Outer-surface adduct formation and selective separation of -type gallated and -type non-gallated catechins using cucurbit[7]uril.

We found that -type gallated and non-gallated catechins form low water solubility outer-surface adducts with cucurbit[7]uril in aqueous solution, with -type gallated catechins showing a higher tendency to precipitate as outer-surface adducts. By exploiting this phenomenon, we achieved the selective separation of -type gallated and non-gallated catechins in solution.

Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency.

4-phenylbutyrate (PB) and structurally related compounds hold promise for treating many diseases, including cancers. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their evaluation and clinical use. This study explores cyclodextrin (CD) complexation as a strategy to address these limitations.

Study of the inclusion complexes formed between 4-phenylbutyrate and α-, β- and γ-cyclodextrin in solution and evaluation on their taste-masking properties.

Objectives: 4-Phenylbutyrate (PB), which is used in the management of urea cycle disorders, has an unpleasant taste leading to poor patient compliance. Existing PB formulations though helpful, have some limitations in their use. This study reports on attempts to mask this unpleasant taste by complexing PB with cyclodextrins (CDs) to improve patient compliance.

Syringe-dispensed omega-3 lipid injectable emulsions should be stored under airtight refrigeration: A proposal for the efficient supply of unapproved precious lipid resources.

Background: Both fish-oil lipid injectable emulsion (FO-ILE) and mixed-oil lipid injectable emulsion (MO-ILE) are key components of parenteral nutrition and require importation into Japan, and they are easily oxidized after opening. Given the small daily volumes of these lipids dispensed in infants and children with intestinal failure (IF), the purpose of the study was to identify the optimal storage method.

Methods: Lipids were prepared in polypropylene syringes in the following manner: air-sealing and photoprotection, air-sealing only, photoprotection only, and uncovered.

Drug-Tea Polyphenol Interaction (III) Incompatibility between Aripiprazole Oral Solution and Green Tea.

The details of incompatibility between aripiprazole (ARIP) oral solution and green tea were examined. When the ARIP oral solution was mixed with a commercial PET bottled green tea beverage, the residual rate of ARIP in the mixed solution decreased to 15.7-17.

Incompatibility between propericiazine oral solution and tea-based drink.

Here, we studied the incompatibility between an oral solution of propericiazine (PCZ), an antipsychotic drug, and various commercially available bottled tea-based drinks. When 0.5 mL of the PCZ oral solution (10 mg/mL) was mixed with 16.

[Mechanism of interaction between risperidone and tea catechin (2) influence of presence of galloyl group in catechin on insoluble complex formation with risperidone].

The influence of the presence of a galloyl group in catechin on complexation with risperidone (RISP) was examined using (--)-epigallocatechin gallate (EGCg) and (--)-epigallocatechin (EGC), which are present in green tea as tea catechins. By quantitative analysis using HPLC, it was found that EGCg formed an insoluble complex with RISP for concentration dependence, whereas EGC did not. The large contribution of the galloyl group of catechin to form an insoluble complex with RISP was recognized in this study.

Determination of digoxin clearance in Japanese elderly patients for optimization of drug therapy: a population pharmacokinetics analysis using nonlinear mixed-effects modelling.

Background: Optimal use of digoxin in the elderly population requires information about the drug's pharmacokinetics and the influence of various factors on the drug's disposition. However, because of sampling restrictions, it is often difficult to perform traditional pharmacokinetic studies in elderly patients.

Objective: This study was conducted to determine the apparent total clearance of digoxin from serum after oral administration (CL/F) and to establish the role of patient characteristics in estimating doses of digoxin for elderly patients (age ≥65 years), using routine therapeutic drug monitoring data.

[Mechanism of interaction between risperidone and tea catechin(1)complex formation of risperidone with epigallocatechin gallate].

The mechanism of complexation between risperidone (RISP) and (-)-epigallocatechin gallate (EGCg) was clarified by ¹H-NMR and molecular modeling studies. RISP and EGCg formed an insoluble complex with a 1 : 1 stoichiometry in aqueous solution. In the ¹H-NMR spectra of RISP in DMSO-d₆, the chemical shifts of protons neighboring the N atom on the piperizine ring clearly moved downfield upon formation of the complex.

Population pharmacokinetic investigation of digoxin in Japanese infants and young children.

To establish the role of patient characteristics in estimating doses of digoxin for infants and young children using routine therapeutic drug monitoring data, the steady-state blood-level data (n = 245) after repetitive oral administration in 117 hospitalized infants and young children were analyzed using nonlinear mixed effects modeling (NONMEM), a computer program designed for analyzing drug pharmacokinetics in study populations through pooling of data. Analysis of the pharmacokinetics of digoxin was accomplished using a 1-compartment pharmacokinetic model. Estimates generated by NONMEM indicated that the clearance of digoxin (CL/F; L/h) was influenced by the following demographic variables: total body weight (TBW), presence of congestive heart failure (CHF), and infant-young children clearance factor (trough serum concentration of digoxin; Conc).

Ab initio molecular orbital study of the reactivity of active alkyl groups. VII. Solvent effects on the formation of enolate isomers from 2-butanone with methoxide anion in methanol.

The mechanism of the deprotonation of 2-butanone (1) with methoxide anion (2) was studied by ab initio molecular orbital (MO) methods. Calculations of the thermodynamic stabilities of each complex and the regioselectivity of the reaction were performed using a static isodensity surface polarized continuum model (IPCM) which takes the solvent effect into consideration. The calculated energies of the complexes lead ultimately to the conclusion that the major deprotonation pathway in protic solvents is dependent upon thermodynamically stable complexes with small activation energies under equilibrium control.

Ab initio molecular orbital study of the reactivity of active alkyl groups. VI. Modified reaction model for the elimination process of nitrosation reaction.

The mechanisms of nitrosation of acetone through sodium enolate [CH3COCH2]- Na+ (1) or naked enolate [CH3COCH2]- (2) with tert-butyl nitrite (CH3)3CONO (3) were studied using ab initio molecular orbital (MO) methods. When the modified complex model was used in the elimination process, our results demonstrated the predominant formation of E-1-hydroxy-imino-2-oxo-propane CH3COCH=NOH (4E), in which a counter-cation of the base catalyst did not participate during the reaction. On the other hand, participation of the counter-cation during the reaction contributed to the formation of the Z-isomer of 4 (4Z).

Differentiation of a pair of diastereomeric tertiarybutoxycarbonylprolylproline ethyl esters by collision-induced dissociation of sodium adduct ions in electrospray ionization mass spectrometry and evidence for chiral recognition by ab initio molecular orbital calculations.

The fragmentation of the sodium adduct ions for tert-butoxycarbonyl-L-prolyl-L-proline ethyl ester (Boc-L-Pro-L-Pro-OEt) was compared with that for Boc-D-Pro-L-Pro-OEt in positive-ion electrospray ionization (ESI) mass spectrometry. In the collision-induced dissociation (CID) mass spectra of the [M + Na](+) ions, the abundance of the [M + Na - C(CH(3))(3) + H](+) ion, which is due to the loss of a tert-butyl group from the [M + Na](+) ion for Boc-D-Pro-L-Pro-OEt, was about eight times higher than that for Boc-L-Pro-L-Pro-OEt. In addition, in the CID spectra of the sodium adduct fragment ion ([M + Na - Boc + H](+)), the abundance of the [M + Na - Boc - prolylresidue + H](+) ion, which is due to the loss of prolyl residue from the [M + Na - Boc + H](+) ion for Boc-L-Pro-L-Pro-OEt, was about five times higher than that for Boc-D-Pro-L-Pro-OEt.

Ab initio molecular orbital study of the reactivity of active alkyl groups. V. Nitrosation mechanism of acetone with syn-form of methyl nitrite.

The mechanisms of nitrosation of acetone through sodium enolate [CH3CO1CH2]-Na+ (1) or naked enolate [CH3CO1CH2]- (2) with methyl nitrite CH3O3NO2 (3), and the reactivity of the syn-form of 3 (syn-3) during the C-N bond formation process were investigated using ab initio molecular orbital (MO) methods. Our results have demonstrated the predominant formation of E-1-hydroxyimino-2-oxo-propane CH3COCH=NOH (4E) when the complex [CH3CO1CH2NO2(O3CH3)]-Na+ was produced kinetically via a metal-chelated pericyclic transition state (TS(CHELATED)), in which the O3 atom of syn-3 was coordinated to the Na+ atom of 1.

Solvent effect on photoisomerisation of 3-methyl-1-phenylbutane-1,2-dione 2-oxime.

Photoisomerisation of (2E)- and (2Z)-3-methyl-1-phenylbutane-1,2-dione 2-oxime (MPBDO) in several solvents was studied. With increasing dielectric constants of solvents, kinetic constants of forward reactions (E-form-->Z-form) did not change appreciably but those of reverse reactions (Z-form-->E-form) decreased. The positive correlation was found between equilibrium constants of photoisomerisation and dielectric constants of solvents.