小剂量异维A酸联合2%超分子水杨酸治疗中重度痤疮疗效观察

目的:探讨口服小剂量异维A酸联合外用2%超分子水杨酸治疗中重度痤疮的临床疗效。方法:共选取74例中重度痤疮患者作为研究对象,口服小剂量异维A酸10mg,1次/d。治疗组:37例,联合外用2%新型超分子水杨酸治疗;对照组:37例,联合外用夫西地酸乳膏及阿达帕林凝胶治疗。对两组患者治疗前后的皮损数量变化及治疗效果进行对比分析。结果:经过8周的治疗,两组研究对象的总皮损数量较治疗前均显著减少(P<0.05),且治疗组与对照组比较,无明显差异(P>0.05)。针对不同类型的皮损,治疗组对粉刺的疗效比对照组更具优势,对丘疹与结节的疗效无明显差异。结论:治疗中重度痤疮,小剂量异维A酸联合外用2%超分子水杨酸临床疗效较好,副作用小,可作为痤疮治疗的新选择。     

超分子水杨酸治疗痤疮的效果及对皮肤屏障的影响

目的:观察超分子水杨酸对于痤疮的疗效及皮肤屏障的影响。方法:采用随机对照实验。选取痤疮患者40例,随机分为实验组和对照组,每组20例。实验组:给予30%超分子水杨酸换肤治疗,1周1次并配合外用特护霜,共治疗4次;对照组:仅每日给予特护霜外用。疗程结束4周后随访观察。治疗前及随访时使用CK无创皮肤检测仪检测两组患者面部皮肤生理指标,计数面部皮损。使用VISIA皮肤分析仪拍照留存。结果:实验组总有效率90%,对照组总有效率15%,两组比较有显著性差异(P<0.05)。同治疗前相比,实验组治疗后经皮水分丢失量(TEWL)、红斑值、角质层含水量及p H值均有改善,差异均有统计学意义(P<0.05)。与对照组比较,实验组治疗后TEWL、角质层含水量及p H值均有改善,差异均有统计学意义(P<0.05)。两组患者均未出现色素沉着、瘢痕等不良反应。结论:超分子水杨酸治疗痤疮疗效确切,同时具有修复皮肤屏障的作用。     

基于超分子理论探索古代经典名方的质量控制模式

古代经典名方是基于疗效优、毒副作用小、临床上广泛应用的特点进行研发,其发展将切实推动中医药的应用,具有重要的社会效益和经济效益。中药及中药复方是多成分体系,通过多成分、多靶点和多途径作用于人体,其疗效是多成分协同作用的结果,如何在中药多成分的生物学性质基础上,阐述药材-饮片-制剂制备过程及质量属性显得非常关键。中药和人体均是巨复超分子体,其成分是反映原生物体"印迹模板"特征聚集客体,具有遗传多态性。中药质量属性、炮制、制剂制备与质量属性评价都受到超分子化学的影响,最终反映到"印迹模板"的制备及其质量属性的传递规律上。因此,经典名方研发时运用超分子"印迹模板"理论来研究中药生物遗传多态性,以及药材炮制、制剂制备与质量属性评价,可提高研发成功的可获得率。     

Photosensitive drugs: a review on their photoprotection by liposomes and cyclodextrins

Abstract

Nowadays, an exciting challenge in the drug chemistry and technology research is represented by the development of methods aimed to protect molecular integrity and therapeutic activity of drugs from effects of light. The photostability characterization is ruled by ICH (The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use), which releases details throughout basic protocols of stability tests to be performed on new medicinal products for human use. The definition of suitable photoprotective systems is fundamental for pharmaceutical manufacturing and for human healthy as well, since light exposure may affect either drugs or drug formulations giving rise even to allergenic or mutagenic by-products. Here, we summarize and discuss the recent studies on the formulation of photosensitive drugs into supramolecular systems, capable of entrapping the molecules in a hollow of their structure by weak noncovalent interactions and protecting them from light. The best known supramolecular matrices belong to the ‘auto-assembled’ structures, of which liposomes are the most representative, and the ‘host-guest’ systems, of which cyclodextrins represent the most common ‘host’ counterpart. A relevant number of papers concerning the use of both liposomes and cyclodextrins as photoprotection systems for drugs has been published over the last 20?years, demonstrating that this topic captures interest in an increasing number of researchers.     

Size‐Stable Supramolecular Hyperbranched Polymer Vesicles for Redox‐Triggered Double‐Drug Release

Supramolecular polymer vesicles (SPVs) with stimuli‐responsive features are promising multifunctional nanocarriers; however, improving the stability and developing multiple‐drug‐loaded SPVs remain key issues in this field. In this work, cross‐linked supramolecular hyperbranched polymer vesicles (SHPVs) with redox‐responsiveness are first constructed based on an AB₂‐type macromonomer‐synthesized SHP. The obtained cross‐linked SHPVs exhibit much better size stability than those of non‐cross‐linked branched self‐assemblies, and higher double‐drug‐loading capacity compared with linear supramolecular polymer self‐assemblies. Particularly, these cross‐linked SHPVs exhibit a redox‐triggered, controlled double‐drug release behavior upon the addition of H₂O₂.     

A Strategy for Fabrication of Columnar Supramolecular Polymers by Highly Directional π‐π Stacking and Strong Multiple Ionic Bonds

A columnar supramolecular HDTP/HCTP polymer is prepared by simple addition of two oppositely charged triphenylene‐based monomers. ¹H NMR indicates an ordered aggregate formation with parallel stacking of the aromatic subunits in aqueous solution. UV‐Vis and fluorescence spectra imply that HDTP and HCTP self‐assemble to construct H‐aggregates, in which two monomers have a strict geometric association with each other. A fiber‐like structure (and fiber aggregates) is also found in the solid state. The microstructure of the supramolecular polymer is also studied by WAXS. Based on the analyses, a tentative model for the columnar supramolecular polymer is proposed, which suggests the importance of directional π‐π interactions and strong multiple ionic bonds.

     

Organic Zeolite Analogues Based on Multi-Component Liquid Crystals: Recognition and Transformation of Molecules within Constrained Environments

In liquid crystals (LCs), molecules are confined in peculiar environments, where ordered alignment and certain mobility are realized at the same time. Considering these characteristics, the idea of “controlling molecular events within LC media” seems reasonable. As a suitable system for investigating this challenge, we have recently developed a new class of ionic LCs; the salts of amphiphilic carboxylic acids with 2-amino alcohols, or those of carboxylic acids with amphiphilic 2-amino alcohols, have a strong tendency to exhibit thermotropic LC phases. Because of the noncovalent nature of the interaction between molecules, one of the two components can easily be exchanged with, or transformed into, another molecule, without distorting the original LC architecture. In addition, both components are common organic molecules, and a variety of compounds are easily available. Taking advantage of these characteristics, we have succeeded in applying two-component LCs as chiral media for molecular recognition and reactions. This review presents an overview of our recent studies, together with notable reports related to this field.     

Functional reconstitution of human eukaryotic translation initiation factor 3 (eIF3)

Protein fate in higher eukaryotes is controlled by three complexes that share conserved architectural elements: the proteasome, COP9 signalosome, and eukaryotic translation initiation factor 3 (eIF3). Here we reconstitute the 13-subunit human eIF3 in Escherichia coli, revealing its structural core to be the eight subunits with conserved orthologues in the proteasome lid complex and COP9 signalosome. This structural core in eIF3 binds to the small (40S) ribosomal subunit, to translation initiation factors involved in mRNA cap-dependent initiation, and to the hepatitis C viral (HCV) internal ribosome entry site (IRES) RNA. Addition of the remaining eIF3 subunits enables reconstituted eIF3 to assemble intact initiation complexes with the HCV IRES. Negative-stain EM reconstructions of reconstituted eIF3 further reveal how the approximately 400 kDa molecular mass structural core organizes the highly flexible 800 kDa molecular mass eIF3 complex, and mediates translation initiation.     

Chemoresponsive alternating supramolecular copolymers created from heterocomplementary calix[4]pyrroles

The importance of noncovalent interactions in the realm of biological materials continues to inspire efforts to create artificial supramolecular polymeric architectures. These types of self-assembled materials hold great promise as environmentally stimuli-responsive materials because they are capable of adjusting their various structural parameters, such as chain length, architecture, conformation, and dynamics, to new surrounding environments upon exposure to appropriate external stimuli. Nevertheless, in spite of considerable advances in the area of responsive materials, it has proved challenging to create synthetic self-assembled materials that respond to highly disparate analytes and whose environmentally induced changes in structure can be followed directly through both various spectroscopic and X-ray diffraction analyses. Herein, we report a new set of artificial self-assembled materials obtained by simply mixing two appropriately chosen, heterocomplementary macrocyclic receptors, namely a tetrathiafulvalene-functionalized calix[4]pyrrole and a bis(dinitrophenyl)-meso-substituted calix[4]pyrrole. The resulting polymeric materials, stabilized by combination of donor-acceptor and hydrogen bonding interactions, undergo dynamic, reversible dual guest-dependent structural transformations upon exposure to two very different types of external chemical inputs, namely chloride anion and trinitrobenzene. The structure and dynamics of the copolymers and their analyte-dependent responsive behavior was established via single crystal X-ray crystallography, SEM, heterocomplementary isodesmic analysis, 1- and 2D NMR, and dynamic light scattering spectroscopies. Our results demonstrate the benefit of using designed heterocomplementary interactions of two functional macrocyclic receptors to create synthetic, self-assembled materials for the development of "smart" sensory materials that mimic the key biological attributes of multianalyte recognition and substrate-dependent multisignaling.     

Structural Diversity of Hydrogen-Bonded 4-Aryl-3,5-Dimethylpyrazoles for Supramolecular Materials

The 1H-pyrazoles have high versatility and ability to form hydrogen-bonded supramolecular materials. In this study, the thermal stability, fluorescence, and H-bonding ability of the studied 3,5-dimethyl-4-(4-X-phenyl)-1H-pyrazoles showed large differences depending on the terminal substituent. Supramolecular structures were analyzed using X-ray diffraction and Hirshfeld surface calculations. Compounds were found to arrange in different hydrogen-bonded structures, depending on the substitution at the para position of the phenyl ring (X = OCH₃, NO₂, NH₂). The methoxy-substituted compounds arranged in dimers through methanol bridges, the nitro-substituted compound formed supramolecular polymers or catemers, and the amino-substituted compound gave rise to a new structure based on a 2D hydrogen-bonded network.