RESUMO
The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid forms were developed. The physicochemical properties of the amorphous and hydrate forms of pemetrexed disodium, as well as new forms of pemetrexed diacid (a key synthetic intermediate) were studied by thermal analysis and powder X-ray diffraction. High-performance liquid chromatography and gas chromatography methods were used for the chemical purity and residual solvents determination. In order to study the polymorphic and chemical stability of the amorphous and hemipentahydrate forms, a hygroscopicity test (25 °C, 80% RH) was performed. Powder diffraction and high-performance liquid chromatography analyses revealed that the amorphous character and high chemical purity were preserved after the hygroscopicity test. The hemipentahydrate form transformed completely to the heptahydrate form of pemetrexed disodium. Both pemetrexed disodium forms were produced with high efficiency and pharmaceutical purity in a small commercial scale. Amorphous pemetrexed disodium was selected for further pharmaceutical development. Two new polymorphs (forms 1 and 2) of pemetrexed diacid were used for the preparation of high purity amorphous pemetrexed disodium.
Assuntos
Conformação Molecular , Pemetrexede/química , Pemetrexede/síntese química , Tecnologia Farmacêutica/métodos , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Difração de Pó , Temperatura , Termogravimetria , Molhabilidade , Difração de Raios XRESUMO
Escin, a complex mixture of pentacyclic triterpene saponins obtained from horse chestnut seeds extract (HCSE; Aesculus hippocastanum L.), constitutes a traditional herbal active substance of preparations (drugs) used for a treatment of chronic venous insufficiency and capillary blood vessel leakage. A new approach to exploitation of pharmacological potential of this saponin complex has been recently proposed, in which the ß-escin mixture is perceived as a source of a hitherto unavailable raw material, pentacyclic triterpene aglycone-protoescigenin. Although many liquid chromatography methods are described in the literature for saponins determination, analysis of protoescigenin is barely mentioned. In this work, a new ultra-high performance liquid chromatography (UHPLC) method developed for protoescigenin quantification has been described. CAD (charged aerosol detection), as a relatively new detection method based on aerosol charging, has been applied in this method as an alternative to ultraviolet (UV) detection. The influence of individual parameters on CAD response and sensitivity was studied. The detection was performed using CAD and UV (200 nm) simultaneously and the results were compared with reference to linearity, accuracy, precision and limit of detection.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Escina/química , Triterpenos Pentacíclicos/isolamento & purificação , Aerossóis , Aesculus/química , Cromatografia Líquida de Alta Pressão/instrumentação , Limite de Detecção , Estrutura Molecular , Triterpenos Pentacíclicos/química , Reprodutibilidade dos Testes , Espectrofotometria UltravioletaRESUMO
New triazole linked conjugates were obtained from protoescigenin monopropargyl ethers and sugar azides, under Cu(II) salt promotion in good yield, without losing isopropylidene protection.
Assuntos
Glicoconjugados/síntese química , Triterpenos Pentacíclicos/química , Triazóis/síntese química , Catálise , Cobre/química , Reação de Cicloadição , Glicoconjugados/química , Estrutura Molecular , Triazóis/químicaRESUMO
Hybrid structures made of metal nanoparticles with liquid crystalline coating attract considerable attention due to their conspicuous self-assembly and potential synergistic properties. Here we report on a new structural parameter that can be used to control the formation of hybrid gold nanoparticles superlattice. A series of Au nanoclusters covered with mixed monolayers of alkyl and liquid-crystalline ligands were obtained. For the first time in such systems the lengths of both alkyl ligands and mercapto-functionalized alkyl spacers of the promesogenic molecules were varied. The physicochemical properties of the obtained materials were investigated by different instrumental techniques, such as X-ray photoelectron spectroscopy (XPS), small-angle X-ray diffraction (SAXRD), and transmission electron microscopy (TEM). Interestingly, the applied variations of the grafting layer composition enabled the formation of 1D (lamellar) and 3D long-range ordered structures with systematically changing thermal stability range. Such behavior is explained based on the structural parameters of the hybrid nanoparticles, namely the separation of the cores and ligand flexibility. This work gives some new insights into the nanoparticle self-assembly subject and points out the critical parameters controlling the degree of order within the self-assembled superstructures.
RESUMO
A two-step chemical process for controlled degradation of escin, affording a mixture of olean-12-ene sapogenins, was elaborated and scaled up. The main component of the mixture--protoescigenin--was isolated and purified, in the form of its corresponding monohydrate, without resource to chromatographic methods. This material was further converted into the high purity 3,24;16,22-di-O,O-isopropylidene derivative in a validated large scale laboratory process.
Assuntos
Escina/química , Escina/isolamento & purificação , Cristalografia por Raios X , Sapogeninas/química , Sapogeninas/isolamento & purificaçãoRESUMO
Critical survey of a selected class of pentacyclic triterpenes--the oleanane family, is presented based on current literature in order to underline their value for medicinal chemistry and drug development potential. Oleanenes may be considered as a renewable resource of valuable research materials which are structurally diverse, inherently biocompatible and have built-in affinity for many categories of functional proteins. Although availability of particular compounds from natural sources may be very low, synthetic methods elaborated by generations of chemists, secure a way to obtaining desirable structures from commercial starting materials.