环糊精和糖淀粉衍生物与1,2-二酮的选择结合及对其氧化断裂反应的调节作用

研究了环糊精和糖淀粉的水溶性衍生物对1,2-二酮的氧化断裂的影响得到受物-宿主不同包结形式的一些结果. 在环糊精场合时, 发现包含物稳定性依赖于环糊精的适配性, 但在用糖淀粉作宿主时, 形成的螺旋包含物的稳定性是由糖淀粉衍生物的取代程度和受物的疏水程度所决定的.     

Study on the supramolecular system of TAPP with cyclodextrins by polarography

The interaction of cyclodextrins with meso- Tetrakis (4-N-trimethylaminobenzyl) porphyrin (TAPP) in 0.1 mol l(-1) phosphate buffer (pH 7.0, 20 degrees C) has been studied by polarography. The TAPP can form the 1:1 inclusion complex with Sulfobutylether-beta-cyclodextrin (SBE-beta-CD) and1:2 inclusion complexes with other four cyclodextrins. A new expression, which is used to calculate the inclusion constant for1:2 inclusion complex by polarography, has been educed and testified firstly in this paper. Furthermore, the inclusion abilities of different kinds of cyclodextrins are compared. The result shows the inclusion ability of anionic cyclodextrin SBE-beta-CD with cationic porphyrin TAPP is very strong. It suggests that the charge attraction between CDs and TAPP plays an important role in the inclusion procedure except for the hydrophobic effect. The inclusion formation of anionic cyclodextrins with drugs can increase released rate of drugs at high pH; therefore, the suparmolecular data for the controlled release of the drugs that owned the similar properties as hematoporphyrin have been offered by polarography in this paper.     

Photochemical and antioxidant properties of gamma-oryzanol in beta-cyclodextrin-based nanosponges

Gamma-oryzanol (GO), a mixture of ferulic acid esters, has recently attracted a great interest as natural antioxidant extracted from rice-bran oil, usually employed to stabilize food and pharmaceutical raw materials, moreover as sunscreen in cosmetic formulations. Its usefulness, however, is limited by its fast degradation. A recently proposed approach to increase the stability and effectiveness of antioxidants is based on the inclusion in supramolecular structures (nanoparticles, cyclodextrins, liposomes, etc.). In this work we studied the inclusion of GO in β-cyclodextrin-based nanosponges which in the last few years have been chosen for their ability to encapsulate a great variety of substances to decrease their side-effects and to protect them from degradation. The inclusion complex was prepared in 1:1 w/w ratio and characterized by DSC, XRPD and membrane diffusion runs. The photodegradation of GO upon either UVA or UVB irradiation was found to be slowed down by inclusion in nanosponges. The antioxidant effectiveness of the inclusion complex was also assessed and in vitro experiments on porcine ear skin revealed a certain accumulation of GO also when entrapped in the host structure.     

Solubilization of itraconazole as a function of cyclodextrin structural space

Cyclodextrins are functional pharmaceutical excipients, which can dynamically include poorly water-soluble drugs and drug candidates resulting in improved solubility, stability and oral bioavailability. A number of formulations containing “natural” and chemically modified cyclodextrins have reached the market and are enjoying widespread attention and use. One such example is itraconazole, a broad-spectrum antifungal agent which is available in an aqueous hydroxypropyl-β-cyclodextrin (HPβCD) vehicle for both oral and parenteral use (Sporanox Oral Solution and Sporanox Intravenous Injection^®). While the interaction of itraconazole and HPβCD is well described, its ability to form complexes with other cyclodextrins is less understood. This creates an intriguing opportunity of screening the structural space of available cyclodextrin derivates by assessing their complexation with a single chemical probe, in this case itraconazole. To this end, a number of cyclodextrin derivatives were assess with regard to their ability to improve the water solubility of the test substrate. In some instances, more detail assessments including the effect of pH and the physical form of the drug probe were also completed. The various cyclodextrins solubilized itraconazole to varying extents (micrograms to milligrams) and by varying inclusion mechanisms and stoichiometries.     

Study of inclusion complexes of cyclodextrin by cyclic voltammetry

The inclusion complexes of a series of organometallic compound-cyclodextrin and aromatic compound-cyclodextrin have been studied by cyclic voltammetry using glassy carbon electrode. The variations of peak potential and peak current are showed on cyclic voltammogram when the electroactive guest molecules are complexed by cyclodextrins. Dissociation constants of cyclodextrin inclusion complexes have been calculated on the basis of this variation by both potential and current methods. According to the magnitude of dissociation constants the relationship between the stability of cyclodextrin inclusion complex and the degree of matching host molecule with guest molecule has been discussed.     

The complexation efficiency

Studies have shown that cyclodextrins form both inclusion and non-inclusion complexes and that several different types of complexes can coexist in aqueous solutions. In addition, both cyclodextrins and cyclodextrin complexes are known to form aggregates and it is thought that these aggregates are able to solubilize drugs through micellar-type mechanism. Thus, stability constants determined from phase-solubility profiles are rarely true stability constants for of some specific drug/cyclodextrin complexes. A more precise method for evaluation of the solubilizing effects of cyclodextrins is to determine their complexation efficiency (CE). CE can be determined by measuring the solubility of a given drug at 2–3 cyclodextrin concentrations in pure water or a medium constituting the pharmaceutical formulation such as parenteral solution or aqueous eye drop formulation. Based on the CE value the drug:cyclodextrin ratio in the complexation medium can be determined as well as the increase in the formulation bulk in a solid dosage form. Determination of CE is a simple method for quick evaluating the solubilizing effects of different cyclodextrins and/or the effects of excipients on the solubilization. Here we report the CE of 43 different drugs with mainly 2-hydroxypropyl-β-cyclodextrin but also with randomly methylated β-cyclodextrin as well as few other cyclodextrins. Calculation of CE, drug:cyclodextrin molar ratio and the increase in the formulation bulk is discussed, as well as the influence of the intrinsic solubility and drug lipophilicity on the CE.     

State‐of‐the‐art applications of cyclodextrins as functional monomers in molecular imprinting techniques: a review

As a versatile tool in separation science, cyclodextrins and their derivatives, known as emerging functional monomers, have been used extensively in molecular imprinting techniques. The attributes of cyclodextrins and their derivatives are widely known to form host–guest inclusion complex processes between the polymer and template. The exploitation of the imprinting technique could produce a product of molecularly imprinted polymers, which are very robust with long‐term stability, reliability, cost‐efficiency, and selectivity. Hence, molecularly imprinted polymers have gained popularity in chemical separation and analysis. Molecularly imprinted polymers containing either cyclodextrin or its derivatives demonstrate superior binding effects for a target molecule. As noted in the previous studies, the functional monomers of cyclodextrins and their derivatives have been used in molecular imprinting for selective separation with a wide range of chemical compounds, including steroidals, amino acids, polysaccharides, drugs, plant hormones, proteins, pesticides, and plastic additives. Therefore, the main goal of this review is to illustrate the exotic applications of imprinting techniques employing cyclodextrins and their derivatives as single or binary functional monomers in synthesizing molecularly imprinted polymers in areas of separation science by reviewing some of the latest studies reported in the literature.     

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。     

Cyclodextrin based novel drug delivery systems

The versatile pharmaceutical material cyclodextrin’s (CDs) are classified into hydrophilic, hydrophobic, and ionic derivatives. By the early 1950s the basic physicochemical characteristics of cyclodextrins had been discovered, since than their use is a practical and economical way to improve the physicochemical and pharmaceutical properties such as solubility, stability, and bioavailability of administered drug molecules. These CDs can serve as multi-functional drug carriers, through the formation of inclusion complex or the form of CD/drug conjugate and, thereby potentially serving as novel drug carriers. This contribution outlines applications and comparative benefits of use of cyclodextrins (CDs) and their derivatives in the design of novel delivery systems like liposomes, microspheres, microcapsules, nanoparticles, cyclodextrin grafted cellulosic fabric, hydrogels, nanosponges, beads, nanogels/nanoassemblies and cyclodextrin-containing polymers. The article also focuses on the ability of CDs to enhance the drug absorption across biological barriers, the ability to control the rate and time profiles of drug release, drug safety, drug stability, and the ability to deliver a drug to targeted site. The article highlight’s on needs, limitations and advantages of CD based delivery systems. CDs, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes.     

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.     

Anticancer Drugs: Recent Strategies to Improve Stability Profile,Pharmacokinetic and Pharmacodynamic Properties

In past decades, anticancer research has led to remarkable results despite many of the approved drugs still being characterized by high systemic toxicity mainly due to the lack of tumor selectivity and present pharmacokinetic drawbacks, including low water solubility, that negatively affect the drug circulation time and bioavailability. The stability studies, performed in mild conditions during their development or under stressing exposure to high temperature, hydrolytic medium or light source, have demonstrated the sensitivity of anticancer drugs to many parameters. For this reason, the formation of degradation products is assessed both in pharmaceutical formulations and in the environment as hospital waste. To date, numerous formulations have been developed for achieving tissue-specific drug targeting and reducing toxic side effects, as well as for improving drug stability. The development of prodrugs represents a promising strategy in targeted cancer therapy for improving the selectivity, efficacy and stability of active compounds. Recent studies show that the incorporation of anticancer drugs into vesicular systems, such as polymeric micelles or cyclodextrins, or the use of nanocarriers containing chemotherapeutics that conjugate to monoclonal antibodies can improve solubility, pharmacokinetics, cellular absorption and stability. In this study, we summarize the latest advances in knowledge regarding the development of effective highly stable anticancer drugs formulated as stable prodrugs or entrapped in nanosystems.     

Study on the Inclusion Complex of Major Component of Rhubarb with Cyclodextrins

The inclusion complexes of major component of rhubarb using cyclodextrins as host molecules have been studied by phase solubility method. Rhubarb (rheum officinale Baill.),a common Chinese traditional medicine, has antibacterial, diminish inflammation and resist decrepitude effect etc,its further use is limited due to its low solubility.     

超分子体系中的分子识别研究(Ⅻ)──环糊精及环糊精双核铜配合物对4-取代苯酚的分子识别

用分光光度滴定法在25.0℃时测定了不同pH值下α-,β-,γ-环糊精以及1mol/LNaOH水溶液中α-和β-环糊精双核铜配合物与4-取代苯酚形成超分子配合物的稳定常数.化学计量法表明,主体环糊精及环糊精双核铜配合物与客体4-取代苯酚形成了1：1的超分子配合物.从主-客体间的尺寸关系、pH值、多点识别和诱导契合作用等因素讨论了环糊精及环糊精双核铜配合物对客体4-取代苯酚的分子识别机制.结果表明,β-环糊精双核铜配合物对4-取代苯酚具有特殊的键合能力和分子选择性。     

Preference Prediction for the Stable Inclusion Complexes between Cyclodextrins and Monocyclic Insoluble Chemicals Based on Monte Carlo Docking Simulations

Cyclodextrins (CDs) are useful functional excipients, which are being used to camouflage undesirable pharmaceutical characteristics, especially poor aqueous solubility, through the inclusion complexation process with insoluble drugs. The selection of more efficient cyclodextrin is important to improve the bioavailability of drugs. In this study, the complexing and solubilizing abilities toward poorly water-soluble monocyclic molecules of natural CDs (α-CD, β-CD, and γ-CD) were investigated using Monte Carlo (MC) docking simulations studies. These theoretical results closely agree with the experimental observation of the complex stability in water of the various guests–CD complexes. Host preferences, based on the experimentally determined stability constants between host CDs and guest molecules, show excellent correlation with the calculated interaction energies of corresponding complexes. The inclusion complex with the lower MC docking interaction energy shows a higher value of stability constant than that of the other complex, and the prediction accuracy of the preferred complex for 21 host–guest pairs is 100%. This result indicates that the MC docking interaction energy could be employed as a useful parameter to select more efficient cyclodextrin as a host for the bioavailability of insoluble drugs. In this study, β-CD shows greater solubilizing efficacies toward guest molecules than those of α-CD and γ-CD, with the exception of one case due to the structure of a guest molecule containing one lipophilic cyclic moiety. The surface area change of CDs and hydrogen bonding between the host and guest also work as major factors for the formation of the stable complex.     

Homochiral drug design and development by racemization

One of the enantiomers of a racemic drug may be pharmacologically inactive or toxic or ballast and, hence, U.S. FDA and European agencies have issued certain guidelines for marketing of optically active (homochiral) drugs. However, some homochiral drug enantiomers racemize in to human body leading to the generation of other antipodes, which may be toxic or ballast to the human beings. In addition, racemization reduces the administrated dosage concentration when the optically active enantiomer is converted into its inactive form. Therefore, racemization studies of homochiral drugs are the important and urgent need of today. This article reviews in vitro and in vivo racemization of homochiral drugs. The racemization of some homochiral drugs is described considering the affect of different variables such as temperature, concentration of the drug, ionic concentration, pH, addition of cyclodextrins, formation of inclusion complexes, etc. Efforts have also been made to discuss the mechanisms of the racemization process. Attempts have been made to suggest safe dosages of such drugs.     

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...     

Essential oil–cyclodextrin complexes: an updated review

Cyclodextrins, degradation product of carbohydrates, have been extensively exploited by food, pharmaceutical and cosmetic industry by virtue of their ease of availability and their ability to entrap guest moieties. Various cyclodextrin derivatives have been granted generally recognized as safe (GRAS) status by several countries. The most noteworthy characteristic of cyclodextrins is their ability to form inclusion complexes with variety of molecules, imparting protection and enabling solubility, bioavailability and safety enhancement of challenging bioactives. In the last few decades, investigations have revealed anti-microbial, anti-inflammatory, insecticidal, analgesic and sedative properties of essential oils. However, their poor solubility, volatility and sensitivity to environmental factors pose challenge for the formulation scientists. Inclusion complexes of essential oils with cyclodextrins have proved a useful strategy to circumvent these challenges. The success of this approach for essential oils is examplified by the commercial garlic oil/β-cyclodextrin products, available under the trade names Xund, Tegra, Allidex and Garlessence. Here, we present an in-depth account of essential oil loaded cyclodextrin inclusion complexes.     

Investigation of the complexation of essential oil components with cyclodextrins

The formation of inclusion complexes of six essential oil (EO) components (β-caryophyllene, cis-ocimene, trans-ocimene, sabinene hydrate (thujanol), γ-terpinene and α-terpineol) with six cyclodextrins (CDs) (α-CD, β-CD, γ-CD, HP-β-CD, RAMEB and CRYSMEB) was investigated by using static headspace-gas chromatography and UV–visible spectroscopy. Retention studies showed that CDs could efficiently reduce the volatility of EO components except for β-caryophyllene with α-CD. In this case, no inclusion complex was detected while for other compounds the formation of 1:1 inclusion complexes was observed. Results revealed that the inclusion stability mainly depends on geometric complementarity between encapsulated molecule and CD's cavity. Molecular modelling was used to investigate the complementarities between host and guest. Thus, CDs could efficiently be regarded as promising encapsulants for EO components leading to improve their application in cosmetic, pharmaceutical and agriculture fields.     

Inclusion Compounds — possibility of their combination and use in different branches of chemistry

Hofmann-type and related compounds, a natural zeolitic material of the clinoptilolite type, and cyclodextrins have been studied. Different products, useful in the separation of organic mixtures, used with fertilizers and insecticides in agrochemistry, perfumes, and in the detoxication of raw materials, have been prepared by combinations of the inclusion compounds studied. In the Hofmann-type compounds and cyclodextrins the original guest is substituted; in the zeolite the original sorbate, as well as some part of the zeolitic host is substituted. The physical mixtures of the starting materials differed from the products in their thermal, spectral and diffractographic characteristics. Field test results and other supporting evidence are added.     

Crystalline inclusion complexes formed between the drug diflunisal and block copolymers

The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs, and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs. Recently, certain drugs have been found to form crystalline inclusion complexes (ICs) with multiple types of linear polymers, representing a new subcategory of pharmaceutical solids. In this study, we used diflunisal (DIF) as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL). The block length in the guest copolymers showed a significant influence on the formation, thermal stability and dissolution behavior of the DIF ICs. Though the PEG block could hardly be included alone, it could indeed be included in the DIF ICs when the PCL block was long enough. The increase of the PCL block length produced IC crystals with improved thermal stability. The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length. These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.