Determination of equilibrium solubility and n-octanol/water partition coefficient of pulchinenosiden D by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To determine the equilibrium solubility of pulchinenosiden D in different solvents and its n-octanol/water partition coefficients.</p><p><b>METHOD</b>Combining shaking flask method and high performance liquid chromatography (HPLC) to detect the n-octanol/water partition coefficients of pulchinenosiden D, the equilibrium solubility of pulchinenosiden D in six organic solvents and different pH buffer solution were determined by HPLC analysis.</p><p><b>RESULT</b>n-Octanol/water partition coefficients of pulchinenosiden D in different pH were greater than zero, the equilibrium solubility of pulchinenosiden D was increased with increase the pH of the buffer solution. The maximum equilibrium solubility of pulchinenosiden D was 255.89 g x L(-1) in methanol, and minimum equilibrium solubility of pulchinenosiden D was 0.20 g x L(-1) in acetonitrile.</p><p><b>CONCLUSION</b>Under gastrointestinal physiological conditions, pulchinenosiden D exists in molecular state and it has good absorption but poor water-solubility, so increasing the dissolution rate of pulchinenosiden D may enhance its bioavailability.</p>

Preparation, formation mechanism and preliminary evaluation of oral absorption of a Bicyclol-phospholipid complex / 药学学报

Bicyclol with benzyl alcohol structure, is a poorly water-soluble drug, used for the treatment of chronic hepatitis B. To increase the drug solubility and oral bioavailability, a Bicyclol-phospholipid complex was studied on its preparation, formation mechanism, and the influence on drug physicochemical properties and oral absorption. The complex was prepared by a solvent evaporation method. The optimal formulation was selected by orthogonal experimental design, and a reasonable evaluating method of the complexation rate was established. Various methods, such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and 31P nuclear magnetic resonance (31P-NMR), were used to explore the phase state and formation mechanism of the complex. The solubility of drug in complex was investigated in water/n-octanol. Preliminary study of its absorption and liver tissue distribution in rats was also carried out. The results showed that Bicyclol and phosphatidylcholine can be complexed entirely in the molar ratio 1 : 2. Bicyclol was dispersed in phospholipids as amorphous state. They were combined by intermolecular hydrogen bond due to charge transfer effect which occurred between the two polarities of the double bond between phosphorus and oxygen (P=O) of phosphatidylcholine and benzalcohol group of Bicyclol. The solubility of the complex compared to the active pharmaceutical ingredient (API) was effectively enhanced 5.75 times in water and 7.72 times in n-octanol, separately. In addition, drug concentrations were also enhanced 43 times in plasma and 13 times in liver with one hour after administering the complex to rats via oral gavage. All of these indicated that Bicyclol with benzalcohol group can interact with phospholipids to form complex, improving drug's physicochemical properties, thus further increasing its absorption and target tissue distribution. This study also provided theoretical reference for the research of other benzalcohol derivatives complexed with phospholipids.

Synthesis, radioiodination and biodistribution evaluation of 5-[2-amimo-4-styryl pyrimidine-4-yl]-4-methoxybenzofuran-6-ol

This study describes the organic synthesis of 5-[2-amimo-4-styryl pyrimidine-4-yl]-4-methoxy benzofuran-6-ol [SPBF] as an example of a benzofuran derivative used as a new series of amyloid imaging agents. These benzofuran derivatives may be useful amyloid imaging agents for detecting B-amyloid plagues in the brain of Alzheimer's disease. The precursor is 1-[6-hydroxy-4-methoxybenzofuran-5-yl]-phenyl butadiene ketone, which react with guanidine hydrochloride. The purification process was done via crystallization using solvent ethanol. The overall yield was 75% and the structure of the synthesized compound was confirmed by correct analytical and spectral data. Also, The synthesized compound was labeled with radioactive iodine -125 via electrophilic substitution reaction, in the presence of iodogen as an oxidizing agent, the labeling process was carried out at 95°C for 20min. The radiochemical yield was determined by using a thin layer chromatography and the yield was equal to 80%. Preliminary an in-vivo study examined normal mice after intravenous injection through the tail vein and the data showed the labeling compound was quickly cleared from most body organs. The radioiodinated compound showed high brain uptake. The results of this study suggest that radioiodinated [SPBF] may be useful as a brain imaging agents

Purification of wet-process phosphoric acid by solvent extraction

High grade phosphoric acid can be obtained using liquid-liquid extraction technique. The influence of type of solvent, solvent concentration, organic/aqueous phase ratio, temperature, shaking time and phosphoric acid concentration on P2O5 extraction was studied. Scrubbing and stripping were also investigated, n-octanol proved to be the most efficient and selective. The temperature has a slight positive effect and the extraction was enhanced by increasing P2O5 and with the increase of organic/aqueous phase ratio. The stripping efficiency slightly increased with shaking time and the optimum organic/aqueous phase ratio was determined to be 2.0. For 9.2 M H3PO4, 99.90% of iron, 97.99% of fluoride and 99.99% of manganese were removed whereas complete removal of copper, cadmium and zinc was attained

[Estimation of Bio-accumulation by a group contribution method]

The majority of organic pollutants, after their dispersion in water then their ingestion, have a strong tendency to accumulate in greases. That is due to the hydrophobic character of these molecules. To have an idea on the capacity of a substance to accumulate in the alive beings according to their lipidic mass, the modeling of the pollutant behaviour was made by considering its partition coefficient between n-octanol [representing the lipidic mass] and water. Its knowledge represents a very significant information for the petrochemical and the pharmaceutical industries. To dissipate any doubt about confidence concerning the obtained results, it is considered useful to check the effectiveness of UNIFAC method on the monomethylbenzoic acid such as, for example, the 3-methylbenzo'ic acid whose n-octanol - water partition coefficient is already listed in the literature. The small deviations observed between the n-octanol-water partition coefficients listed in the literature and the one calculated according UNIFAC method encouraged us to apply it in order to predict the n-octanol-water partition coefficient of the dimethylbenzoic acid

Application of reversed-phase ion-pair chromatography for universal estimation of octanol-water partition coefficients of acid, basic and amphoteric drugs / 药学学报

This paper is to establish a reversed-phase ion-pair chromatography (RP-IPC) method for universal estimation of the octanol/water partition coefficients (logP) of a wide range of structurally diverse compounds including acidic, basic, neutral and amphoteric species. The retention factors corresponding to 100% water (logk(w)) were derived from the linear part of the logk'/phi relationship, using at least four isocratic logk' values containing different organic compositions. The logk(w) parameters obtained were close to the corresponding logP values obtained with the standard "shake flask" methods. The mean deviation for test drugs is 0.31. RP-IPC with trifluoroacetic acid as non classic ion-pair agents can be applicable to determine the logP values for a variety of drug-like molecules with increased accuracy.

Quantitative structure-activity relationships for the toxicity of substituted benzenes to Cyprinus carpio / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To measure the 96h-LC50 values of 32 substituted benzenes to the carp and to study the relationship between quantitative structure-activity and structural parameters of chemicals.</p><p><b>METHODS</b>The acute toxicity values of 32 substituted benzenes to the carp were determined in a semistatic test. The energy of the lowest unoccupied molecular orbital, and the highest occupied molecular orbital, the dipole moment and the molecular weight of substituted benzenes were calculated by the quantum chemical method MOPAC6.0.</p><p><b>RESULTS</b>The range of the toxicity of studied compounds was broad, and the most toxic compound was pentachlorophenol, while the least toxic compound was 4-methylaniline. By the stepwise regression analyses, a series of Quantitative structure-activity relationships (QSAR) equations were derived from all compounds and subclasses. The equation log1/LC5o=0.759logP + 2.222 (R2 (adj)=0.818) was found to fit well and the average predicted percentage error was 6.16%.</p><p><b>CONCLUSION</b>The toxicity of anilines and phenols to the carp could be modeled well by logP alone, whereas the toxicity of the halogenated benzenes and nitrobenznes not containing hydroxyl or amino group can be controlled by hydrophobic and electronic factors.</p>

Studies on the chemical constituents of the volatile oil from Radix Cudramiae / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of the volatile oil from Radix Cudramiae.</p><p><b>METHOD</b>The oil was obtained by steam distillation. The chemical compositions were separated and identified by GC-MS. The relative contents in the oil were determined by area nomalization.</p><p><b>RESULT</b>Sixty-four compounds were obtained from Radix Cudramiae. The relative contents of twenty-three compounds were more than 1%. The highest relative content was L-linalool (9.852%).</p><p><b>CONCLUSION</b>Sixty-four compounds characterized by GC-MS analysis were obtained from Radix Cudramiae for the first time.</p>

The Changes of Olfactory and Trigeminal Pungency Thresholds in n-Aliphatic Alcohols with Different Carbon Chain in Normal Adults / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Using n-aliphatic alcohols whose physical properties change gradually as their length increases, we investigated the changes of olfactory threshold and trigeminal pungency threshold with the increase of carbon chain length. MATERIALS AND METHOD: Olfactory and trigeminal pungency thresholds were measured in ethanol (C2), 1-butanol (C4), 1-hexanol (C6) and 1-octanol (C8) in 40 normal adults using a two-alternative forced-choice modified by the ascending method of limit (CCCRC) test. Plastic bottles with 30 ml of four n-aliphatic alcohols were diluted threefold successively by mineral oil. Plastic bottles containing only mineral oil were used as controls. RESULTS: The olfactory and trigeminal pungency thresholds decreased and the ratio of olfactory threshold/trigeminal pungency threshold increased with the length of carbon chain in n-aliphatic alcohols. The correlation coefficients among olfactory thresholds in each alcohol were higher than those among trigeminal pungency thresholds. CONCLUSION: Alcohol with long carbon chains showed low olfactory and trigeminal pungency thresholds, indicating that high lipid solubility is an important factor in olfaction and trigeminal chemosensitivity.

Prediction of environmental fate and effects of heteroatomic polycyclic aromatics by QSARs: the position of n-octanol/water partition coefficients / 生物医学与环境科学（英文）

The HPLC and TLC retention, n-octanol/water partition coefficients (log Kow), bioconcentration factors, and acute toxicity data of 29 heteroatomic polycyclic aromatic hydrocarbons and 7 parent polycyclic aromatics were determined experimentally. For the same set of compounds, molecular weights, fragmental log Kow values, and molecular connectivities were calculated. Quantitation of the mathematical relationships between the variables was used to validate the predictive potential of various parameters. The importance of log Kow in predictive studies is highlighted. It is concluded that the internal concentration of a pollutant in the organism should be used as a parameter in future QSAR work.