The Hemolytic Properties of Chemically Modified Cyclodextrins

The hemolytic properties of naturalcyclodextrins, especially of the more commoncyclomaltoheptaose entity, severely hamper theirpotential use as carriers in pharmaceuticalapplications where parenteral administration isconcerned. A systematic investigation on the role ofchemical modifications with regard to the hemolyticcharacter was carried out involving C-6 branchedneutral, anionic, cationic and amphoteric derivatives.From these data, conclusions have been drawnabout the charge and the geometry of the modification: (i)Substitution at primary hydroxyl groups usuallydecreases the hemolytic character and the geometry ofthe substituent affects the hemolytic property; (ii)introduction of an amino group, resulting in apositive charge at physiological pH, decreases thehemolytic character; (iii) negative charges arecomparatively less effective in reducing the hemolyticcharacter; (iv) zwitterionic groups seem to enhancethe hemolytic character of the cyclodextrin molecule.     

超分子环糊精两亲分子

本文综述了“超分子环糊精两亲分子”的最新研究进展。超分子环糊精两亲分子主要包括疏水性修饰的环糊精衍生物(第一类)、环糊精衍生物与两亲分子的包合物(第二类)和环糊精衍生物与疏水性客体分子的包合物(第三类)。针对超分子环糊精两亲分子及其自组装体系的研究不但丰富了由诺贝尔化学奖得主Lehn等所提出的超分子化学的内涵,实现了多学科的交叉,而且在生物模拟、智能材料以及可控的、具有疗效的药物输运与缓释等领域具有潜在的应用前景。     

环糊精及其衍生物在手性识别中的应用

详细地论述了环糊精及其衍生物在手性识别中的应用,并对环糊精超分子体系手性识别中的进一步研究提供了依据。     

Cyclodextrins in Eye Drop Formulations

Ideally, eye drop formulations are aqueous solutions. Many drugs that are useful in topical application to the eye are not sufficiently water soluble to be dissolved in simple aqueous solutions. This problem is approached through hydrophilic prodrugs, suspensions, lipid based solutions and excipients such as cyclodextrins. Cyclodextrins can be used to form aqueous eye drop solutions with lipophilic drugs, such as steroids. The cyclodextrins increase the water solubility of the drug, enhance drug absorption into the eye, improve aqueous stability and reduce local irritation. Cyclodextrins are useful excipients in eye drop formulations of various ophthalmic drugs, including steroids of any kind, carbonic anhydrase inhibitors, pilocarpine and cyclosporins. Their use in ophthalmology has already begun and it is likely to expand the selection of drugs available as eye drops. In this paper we review the use of cyclodextrins in eye drop formulations. The use of cyclodextrins to formulate dexamethasone eye drops is an example of their usefulness. Cyclodextrins have been used to formulate eye drops containing corticosteroids, such as dexamethasone, with concentration and ocular absorption, which in human and animal studies is many fold that seen with presently available formulations. Such formulations offer the possibility of once a day application of corticosteroid eye drops after eye surgery, and more intensive topical steroid treatment in severe inflammation.     

基于环糊精包结络合作用的大分子自组装

本文综述了基于环糊精包结络合作用的大分子自组装的研究进展,包括：（1) 线型、梳型、多臂星型或超支化聚合物与环糊精或其二聚体自组装形成多聚轮烷（分子项链）、多聚准轮烷、双多聚（准）轮烷、分子管、双分子管、超分子凝胶及其应用;（2）桥联环糊精与桥联客体分子自组装制备线型或超支化超分子聚合物;（3）温度、pH值、光及客体分子刺激响应智能体系; （4) 通过亲水性的环糊精线型均聚物与含金刚烷的疏水性聚合物之间的包结络合作用来制备高分子胶束及其空心球等。     

Effects of Cyclodextrins on Dodecane Biodegradation

Bioremediation of non-chlorinated hydrocarbon-polluted soils is mainly affectedby low bioavailability, due to hydrophobicity of these xenobiotics. In fact, severalmicroorganisms can use hydrocarbons as energy and carbon sources, but theirdegradative activity takes place into the aqueous phase of the soil, where just tracesof hydrocarbons are found because of their low water solubility. So, natural attenuationusually occurs in hydrocarbon-polluted soils, but this process is very slow. It has alreadybeen demonstrated that cyclodextrins increase hydrocarbon solubility and bioavailabilityand accelerate their biodegradation. In this work it was investigated if their efficacy onbiodegradation of a model hydrocarbon (dodecane) is affected by the kind (,-, - and hydroxypropyl--cyclodextrin) and the concentrationof cyclodextrin and by environmental factors such as temperature and composition ofthe microbial indigenous population. The results obtained show that all the testedfactors influence the biodegradation kinetics. The best results were obtained with-cyclodextrin at a concentration near to its water solubility limit; moreover,biodegradation rate increases with temperature and different microbial strains showdifferent degradative activity and metabolic behaviour.     

The Effect of Cyclodextrins on the Luminol-Hydrogen Peroxide Chemiluminescence

The action of different molar ratios of α, β, γ-cyclodextrin upon the chemiluminescence of the luminol-H₂O₂ in alkaline buffer Tris-HCl, pH=8.5 has been evidenced. It was found out that α, β, γ- cyclodextrin have an antioxidant capacity, probably due to the free radicals (that are generate in the system) encapsulation in the their cavity. This behaviour depends on α, β, γ-cyclodextrin molar ratio; α-cyclodextrin and γ-cyclodextrin protects more efficiently against free radicals than β-cyclodextrin. These findings could be very important regarding the oxidative stress process.     

水溶液中环糊精包结物的包结常数的测定方法

环糊精（CD）是由6，7，8个葡萄糖基构成的环状化合物，分别叫做α、β、γ-CD，它们具有“外亲水，内疏水”的独特性质，可以与多种物质形成包结物，而改变物质的特性，因而被广泛应用于各行各业中，在以往研究的基础上，总结了多种测定环糊精包结常数的方法，以便能更好地研究并开发利用具有极大潜力的环糊精。     

环糊精的理论计算*

环糊精对超分子化学的发展具有重要意义,其特殊的物理和化学性质已经在实验和理论研究中受到广泛关注。本文对近10年来环糊精的理论计算发展情况进行了综述。重点概述了分子动力学模拟结合自由能计算方法在环糊精识别和自组装行为中的应用,最后展望了环糊精未来的理论计算发展方向。     

Study of Inclusion Complexes of Cyclodextrins with Orange II

Inclusion reactions of - and -CD with Orange IIwere measured by means of a stopped-flow method and UV-spectra. The forward rate constants (k₊), backward rateconstants (k_-) and the equilibrium constants (K) for the inclusion reactions were determined. Theinclusion processes of CD with Orange II follow a one-step reaction mechanism. The value of the forward rate constantat neutral and alkaline conditions for Orange II binding to -CD cavity was large. This suggests that thenaphthalene side is partially included in the final complex form. In the case of -CD, only marginal differenceis shown.It is probable that inclusion covers the whole naphthalene group and part of the azo group as well,resulting ina small effect from the pH variation. The results show that the equilibrium constant at pH 7 for the binding ofOrange II to -CD is the largest because the included part of Orange II matches the cavity of -CD well.     

Present Status of Industrial Application of Cyclodextrins in Japan

The application of CDs in the food, cosmetic and textile industrial fields as solubilizing agents, stabilizers, emulsifiers etc., is reviewed briefly. ManyCD-containing commodities that have been put to practical use are introduced. Technical developments of CDs and their commercialization have had a multilateral impact on economic activities in our country. The expansiveeffects of CD production on other industrial fields and the economic impactare discussed.     

Complexation of Ketoconazole by Native and Modified Cyclodextrins

Complexation of ketoconazole (KET), a broad-spectrum antifungal drug, with β- and γ-cyclodextrins (CDs), heptakis (2,6-di-O-methyl)-β-CD (2,6-DM-β-CD), heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), 2-hydroxypropyl-β-CD (2HP-β-CD) and carboxymethyl-β-CD (CM-β-CD) was studied. The stability constants were determined by the solubility method at pH = 6 and for 2,6-DM-β-CD and CM-β-CD at pH = 5. At pH = 6, the stability constants increased in the order: TM-β-D < γ-CD < 2HP-β-CD < β-CD < CM-β-CD < 2,6-DM-β-CD. At pH = 5, due to the increased ionization of KET, the stability constant with CM-β-CD increased and with 2,6-DM-β-CD decreased. For complexes of KET with 2HP-β-CD and 2,6-DM-β-CD, the thermodynamic parameters of complexation were determined from the temperature dependence of the corresponding stability constants. For β–γ and TM-β-CD complexes, calculations using HyperChem 6 software by the Amber force field were carried out to gain some insight into the host–guest geometry.     

The Haloform Reaction in the Presence of Cyclodextrins

Cyclodextrins act as inverse phase transfer catalystsin the oxidation of methyl ketones by hypochloride(the haloform reaction). The reaction is affected by thechoice and the amount of cyclodextrin. The reactionproceeds under mild reaction conditions and itprovides only the corresponding carboxylic acid asreaction product. No organic solvent is required.     

Stabilization and Solubilization of Lipophilic Natural Colorants with Cyclodextrins

The paper provides data on the practical utilization of the benefits of the molecular encapsulation of natural colorants by cyclodextrins. Experimental results on the stability of cyclodextrin complexed curcumin, curcuma oleoresin, -carotene and carotenoid oleoresins against light-, heat- and oxygen prove the benefits of molecular encapsulation of colorants. The parent -cyclodextrin stabilized most effectively the curcumines, while the stability of carotenoids was most effectively achieved by -cyclodextrin complexation. Methylated -cyclodextrin was found to be the most potent solubilizing agent for both carotenoids and curcuminoids.     

Complex Formation between Polyisoprene and Cyclodextrins

Summary: Polyisoprenes were found to form inclusion complexes with cyclodextrins with high selectivity to give crystalline compounds. β‐Cyclodextrin formed complexes only with polyisoprene of low molecular weight, whereas γ‐cyclodextrin formed complexes with polyisoprenes of high molecular weight. α‐Cyclodextrin did not form complexes with polyisoprene of any molecular weight. The yields of γ‐cyclodextrin complexes increased with increasing molecular weights of the polyisoprenes and reached a maximum of around several thousands, and then decreased.

Theoretical depiction of the complex formed between polyisoprene and γ‐CD, as determined by molecular modelling studies. The PIP chain is shown penetrating the γ‐CD cavity, which, in turn, accommodates one to 1.5 monomer units of PIP.     

基于环糊精的新材料的研究进展

从纳米粒子、水凝胶、纤维材料和环糊精高分子等方面介绍了近年来以环糊精为基础研制的新材料的研究进展。目前以环糊精为基础的纳米粒子材料有核壳结构的纳米粒子、环糊精的化学接枝与共聚、环糊精与无机非金属材料的复合和含环糊精的囊泡材料;以环糊精为基础的凝胶材料有水凝胶和有机凝胶两种材料;此外还有以环糊精为基础的纤维材料、环糊精高...     

Physicochemical Properties of Large-Ring Cyclodextrins (CD 18 ∼CD 21

Cyclomaltooctadecaose(CD₁₈),cyclomaltononadecaose(CD₁₉),cyclomaltoeicosaose(CD₂₀) andcyclomaltoheneicosaose(CD₂₁) are cyclic oligosaccharides composed of 18, 19, 20 and 21 D-glucose units, respectively. This report describes the physicochemical properties of CD₁₈, CD₁₉, CD₂₀ and CD₂₁ in terms of aqueous solubility, surface tension, optical rotation and acid-catalyzed hydrolysis.     

Molecular Recognition Studies on Modified Cyclodextrins

This account describes our research progress in recent years in the areas of the molecular recognition studies on modified cyclodextrins, including positively charged cyclodextrins, cyclodextrin derivatives with hydrophobic substituent, and dimeric cyclodextrins. Calorimetric titration and various spectrometric techniques were employed to determine the complex stability constants, as well as the thermodynamic parameters, for their inclusion complexation with diverse guest molecules. The results obtained have been discussed from the viewpoint of size/shape‐matching, induced‐fit, geometric compensation, and multiple recognition. Thermodynamically, the compensatory relationship between ΔH and TΔS was found to be exhibited in the inclusion complexation of modified cyclodextrin.