Inclusion Complex of Paclitaxel in Hydroxypropyl-β-cyclodextrin

Introduction Paclitaxel （as Taxol） is a kind of diterpenoid natural product extracted from Chinese yew. It has been reported to have high anti-tumor effects, such as the activity against oophorama, mammary cancer, encephaloma, cervical carcinoma, and non- small-cell lung carcinoma. One of the major problems of paclitaxel applied to therapy is its extremely low solubility in water. In addition, paclitaxel is administered as a slow infusion in a vehicle consisting of Cremophor EL （ polyoxyethylated castor oil ）. However, Cremophor has been observed to cause severe, occasionally fatal hypersensitivity reactions in animals and humans. Therefore, paclitaxel therapy includes a prophylactic regimen of antihistamines and corticosteroids , along with a prolonged infusion time to reduce the severity and incidence of hypersensitivity reactions. Because of the reasons mentioned above, currently its preparation needs to be improved further.

Identification of Composition From Volatile Oil in Genseng Flower Bud and Studies on Inclusion Complex of β-Cyclodextrin (β-CD)

The Genseng abounds in Jilin Province, which is very helpful to the human health. But large amount of the Genseng flower bud, which has not been utilized sufficiently by now, goes to waste every year. Recently we have made a study of the Genseng flower bud and its volatile oil (FGVO) was extracted, in which 56 compounds were separated and identified by GC/MS. The relative content of sesguiterpenoid is 44.4％ of the ex-

Method for quantification of prazosin in dog plasma and its application to pharmacokinetic study

A simple and sensitive high performance liquid chromatography method using fluorescence detection （HPLC- FLD） and a one-step single solvent extraction for the determination of prazosin（PZS） in dog plasma is developed and validated. After extraction with ether, the chromatographic separation of PZS is carried out using a reverse phase C18 column （ 150 mm ×4.6 mm, 5 μm） with a mobile phase of 30% acetonitrile and 70% acetic acid-sodium acetate buffer solution （pH = 3.6） and quantified by fluorescence detection operated with an excitation wavelength of 258 nm and an emission wavelength of 387 nm. The flow rate of the mobile phase is 1.0 mL/min and the retention time of PZS and the internal standard is found to be 4. 4 and 5. 8 rain, respectively. The calibration curve is linear within a concentration range from 1.0 to 1 000.0 ng/mL （ P 〉 0. 998）. The limit of detection is 0.4 ng/mL. The inter-day coefficient of variation （COV） of the calibration standards is below 5.0% and the mean accuracy is in the range from 92. 7% to 104. 2%. Moreover, by analyzing quality control plasma samples for three days, the results show that the method is precise and accurate, for the intra- and inter- day COV within 10% and the accuracy from 95.9% to 112.7%. The developed and validated method is successfully applied to phannacokinetic study for the preclinical evaluation of a new peroral PZS-sulfobutyl ether beta-cyclodextrin （PZS-SBE-β-CD） inclusion complex tablets （test preparation）, which demonstrates that the test preparation released PZS is conducted in a slow and controlled way, and the relative bioavailability of the test preparation is found to be 105.0%.

Effect of Complexation with Hydroxylpropyl-β-Cyclodextrin on Solubility, Dissolution Rate and Chemical Stability of Prostaglandin E1

Aim To study the effect of complexation with hydroxylpropyl-β-cyclodextrin(HP-β-CD) on the solubility, dissolution rate and chemical stability of prostaglandin E_1 (PGE_1) ,thereby providing a basis for preparing a stable solid or aqueous preparation of PGE_1 formulatedwith HP-β-CD. Methods The effect of HP-β-CD on the solubility of PGE_1 was studied by phasesolubility method. The formation of inclusion complexes of PGE_1 with HP-β-CD in the aqueoussolution was confirmed by UV spectra, circular dichroism spectroscopy, and that in the solid stateby IR spectra and X-ray diffractome-try. An solid inclusion complex of PGE_1 with HP-β-CD wasprepared by lyophilization. The dissolution rate and stability of the inclusion complex weredetermined and compared with those of PGE_1 alone. Meanwhile, the stability of PGE_1 aqueoussolutions in the presence of HP-β-CD was studied under different pH conditions. Results Thesolubility of PGE_1 increased linearly with increasing HP-β-CD concentration in various pH bufferedsolutions, showing typical A_L-type phase solubility diagrams. The stability and dissolution rateof the solid inclusion complex of PGE_1 were significantly increased, compared with those of purePGE_1 . The stability of PGE_1 in HP-β-CD solutions was also obviously improved under acidic andbasic conditions, but the stabilizing effect was absent under neutral conditions. Conclusions Thesolubility,dissolution rate and chemical stability of PGE_1 are markedly improved by complexationwith HP-β-CD: It is quite possible to prepare a stable PGE_1 inclusion complex-containing soliddosage forms, but almost impossible to obtain a stable aqueous preparation of PGE_1 formulated withHP-β-CD.

Interaction of β-Cyclodextrin Catalyst with p-Chlorobenzonitrile for the Synthesis of 5-Substituted 1H-tetrazoles in n,n-Dimethylformamide：a DFT Study

The synthesis of 5-substituted 1H-tetrazoles in n,n-dimethylformamide（DMF） with b-cyclodextrin（β-CD） as catalyst can get an excellent yield in short reaction time.The interaction of β-CD with p-chlorobenzonitrile plays an important role in this process.This paper studies the complex of β-CD with p-chlorobenzonitrile using density functional theory（DFT） method.The minimum energy structure is investigated in water,DMF and DMSO.Hydrogen bonds are researched on the basis of natural bonding orbital（NBO） analysis.The relative position between p-chlorobenzonitrile and β-CD in DMF is confirmed by 1H nuclear magnetic resonance（1H NMR）.The data from 13 C and 15 N spectra indicate that more positive charges focus on the carbon atom of cyanogroup（C11） and more negative charges concentrate on the nitrogen atom of cyanogroup（N12） upon complexation.The results from frontier molecular orbitals and Mulliken charge reveal that β-CD catalyst improves the reactivity and electrophilicity of p-chlorobenzonitrile.Meanwhile,the functional group of p-chlorobenzonitrile is easier to be attacked by azide ions in the presence of β-CD as catalyst.

Effect of β-Cyclodextrin Upon the Sol-gel Transition of Methylcellulose Solutions in the Presence of Sodium Dodecyl Sulfate

The sol-gel transition temperature of methylcellulose （MC） solution in the presence of sodium dodecyl sulfate （SDS） as well as the mixtures of SDS and β-cyclodextrin （β-CD） was mea- sured, and the effect of the two competing interactions, the hydrophobic interaction between SDS and MC and the inclusion interaction between SDS and β-CD, upon the sol-gel transition of MC solution was studied. It has been found that the inclusion interaction between SDS and β-CD is much greater than the hydrophobic interaction between SDS and MC. As a result, in the coexistence of SDS and β-CD, the sol-gel transition temperature of MC solution keeps the same value, independent of the concentration of SDS in solution on con- dition that the concentration of SDS is less than β-CD. Our experimental results not only suggest that the effect of SDS upon the sol-gel transition of MC solution can be screened by β-CD completely but also indicate the inclusion ratio of SDS to β-CD can be determined quantitatively by using rheological measurement. The inclusion ratio of SDS to β-CD is 1：1, which is in good agreement with the inclusion ratio of SDS to β-CD in the presence of poly（vincyl pyrrolidone） determined by the viscosity measurement but is critically different from the inclusion ratio of SDS to β-CD in the presence of the oppositely charged polyelec-trolyte by using the rheological measurement, mainly due to the reason that the mechanism of the interaction between SDS and MC is critically different from the mechanism of the interaction between SDS and the oppositely charged polyelectrolyte.

NMR and IR Investigations of Ternary Inclusion Complexes among β-Cyclodextrin, Rare Earth Metal Ions, and Naphthalenediamines

Ternary inclusion complexes β-cyclodextrin （β-CD）, rare earth metal ions （YbC13, YC13）, and 1,8-naphthalene- diamine/ 1,5-naphthalenediamine are synthesized in basic aqueous media, which are characterized via IH NMR and IR spectroscopy. The stoichiometric proportion of β-CD ： YbC13 ： 1, 5-naphthalenedia- mine is 2：1：2, that of β-CD：YCI3 ： 1,8-naphthalenediamine is 2：1：1, and that of β-CD：YbC13 ： 1,8-naphthalenediamine is 2 ： 1 ： 1. The IR spectroscopy of the ternary inclusion complexes in the range of 935-1 000 cm 1 reveals the existence of the coordinate bond M---O or M---N. The possible conformations of the ternary inclusion complexes are depicted.

Preparation and Characterization of Holmium-Beta-Cyclodextrin Complex

The purpose of this study was to prepare and characterize of holmium-beta-cyclodextrin complex (Ho-β-CD) in order to increase the solubility and stability of Holmium. To achieve this goal, Ho-β-CD complex was prepared by evaporation method of holmium and beta cyclodextrin solutions in a proportion (1:1) and (1:3), respectively. Infrared (IR) and Raman spectroscopy, X-Ray Diffraction were performed to identify the complex. Morphology of the Ho, β-CD, and Ho-β-CD were studied using Scanning Electron Microscopy (SEM).

Spectroscopic and Spectroelectrochemical Studies of Interaction of Nile Blue with DNA

Nile Blue can strongly bind to DNA and its affinity for DNA has beeninvestigated by spectroscopy and spectroelectrochemistry. At low DNA concentrations, Nile Blue canbind to DNA (per nucleotide phosphate) to form a 1:1 association complex with the binding constantof 4.7 * 10~4 L/mol and the major binding model of Nile Blue to DNA is 'electrostatic binding'.However, the major binding model changes into 'intercalative binding' at high DNA concentrations. Inorder to confirm which part of Nile Blue intercalating into DNA, the inclusion action ofβ-cyclodextrin (β-CD) has been used to study the interaction. Nile Blue can be included into thehydrophobic cavity of β-CD to form an inclusion complex with a stability constant of 1.9 * 10~3L/mol. The experimental results indicate that the naphthalene ring part of Nile Blue is includedinto β-CD's hydrophobic cavity and the inclusion complex decomposes at high DNA concentrations. Itmay be deduced reasonably that the naphthalene ring part of Nile Blue molecule intercalates into DNAhelix Strand.