Chem. Pharm. Bull.(オピニオン)

Coumarin compounds represent an important type of naturally occurring and synthetic oxygen-containing heterocycles with typical benzopyrone framework. This type of special benzopyrone structure enables its derivatives readily interact with a diversity of enzymes and receptors in organisms through weak bond interactions, thereby exhibit wide potentiality as medicinal drugs. So far, some coumarin-based drugs such as anticoagulant and antineurodegenerative agents have been extensively used in clinic. Coumarin-containing supramolecular medicinal agents as a new increasing expansion of supramolecular chemistry in pharmaceutical science have also been actively investigated in recent years. Coumarin-derived artificial ion receptors, fluorescent probes and biological stains are growing quickly and have a variety of potential applications in monitoring timely enzyme activity, complex biological events as well as accurate pharmacological and pharmacokinetic properties. This review provides a systematic summary and insight of the whole range of medicinal chemistry in the current developments of coumarin compounds as anticoagulant, antineurodegenerative, anticancer, antioxidative, antibacterial, antifungal, antiviral, antiparasitic, antiinflammatory and analgesic, antidiabetic, antidepressive and other bioactive agents as well as supramolecular medicinal drugs, diagnostic agents and pathologic probes, and biological stains. Some rational design strategies, structure-activity relationships and action mechanisms are discussed. The perspectives of the future development of coumarinbased medicinal chemistry are also presented.

Current Developments of Coumarin Compounds in Medicinal Chemistry

Pharmaceutical applications of various natural gums, mucilages and their modified forms

Drug dosage forms contain many components in addition to the active pharmaceutical ingredient(s) to assist in the manufacturing process as well as to optimise drug delivery. Due to advances in drug delivery technology, excipients are currently included in novel dosage forms to fulfil specific functions and in some cases they directly or indirectly influence the extent and/or rate of drug release and absorption. Since plant polysaccharides comply with many requirements expected of pharmaceutical excipients such as non-toxicity, stability, availability and renewability they are extensively investigated for use in the development of solid oral dosage forms. Furthermore, polysaccharides with varying physicochemical properties can be extracted from plants at relatively low cost and can be chemically modified to suit specific needs. As an example, many polysaccharide-rich plant materials are successfully used as matrix formers in modified release dosage forms. Some natural polysaccharides have even shown environmental-responsive gelation characteristics with the potential to control drug release according to specific therapeutic needs. This review discusses some of the most important plant-derived polymeric compounds that are used or investigated as excipients in drug delivery systems.

https://www.mdpi.com/1420-3049/14/7/2602/pdf

Polymeric Plant-derived Excipients in Drug Delivery

Improved method of and apparatus for joining and aggregating data elements integrated within a relational database management system (RDBMS) using a non-relational multi-dimensional data structure (MDD). The improved RDBMS system of the present invention can be used to realize achieving a significant increase in system performance (e.g. deceased access/search time), user flexibility and ease of use. The improved RDBMS system of the present invention can be used to realize an improved Data Warehouse for supporting on-line analytical processing (OLAP) operations or to realize an improved informational database system or the like.

Relational database management system having integrated non-relational multi-dimensional data store of aggregated data elements

This study was performed to design bilayer regioselective floating tablets of atenolol and lovastatin to give immediate release of lovastatin and sustained release of atenolol. Bilayer floating tablets comprised two layers, i.e immediate release and controlled release layers. The immediate release layer comprised sodium starch glycollate as a super disintegrant and the sustained release layer comprised HPMC K100M and xanthan gum as the release retarding polymers. Sodium bicarbonate was used as a gas generating agent. Direct compression method was used for formulation of the bilayer tablets. Accelerated stability studies were carried out on the prepared tablets inaccordance with ICH guidelines. Roentgenography was carried out to study the in vivo buoyancy of the optimized formulation. All formulations floated for more than 12 h. More than 90% of lovastatin was released within 30 min. HPMC K100M and xanthan gum sustained retarded the release of atenolol from the controlled release layer for 12 h. After stability tests, degradation of both drugs were found but the drugs, contents were found to be within the range. Diffusion exponents (n) were determined for all the formulations (0.53-0.59). The release of atenolol was found to follow a mixed pattern of Korsmeyer-Peppas, Hixson-Crowell and zero order release models. The optimized formulation was found to be buoyant for 8 h in stomach. Therefore, biphasic drug release pattern was successfully achieved through the formulation of floating bilayer tablets inthis study.

http://ijpr.sbmu.ac.ir/article_783_151defda377529d3b970ec85cdf46fc4.pdf

Development and evaluation of regioselective bilayer floating tablets of Atenolol and Lovastatin for biphasic release profile

Hyperoxaluria due to endogenously synthesized and exogenously ingested oxalates is a leading cause of recurrent oxalate stone formations. Even though, humans largely rely on gut microbiota for oxalate homeostasis, hyperoxaluria associated gut microbiota features remain largely unknown. Based on 16S rRNA gene amplicons, targeted metagenomic sequencing of formyl-CoA transferase (frc) gene and qPCR assay, we demonstrate a selective enrichment of Oxalate Metabolizing Bacterial Species (OMBS) in hyperoxaluria condition. Interestingly, higher than usual concentration of oxalate was found inhibitory to many gut microbes, including Oxalobacter formigenes, a well-characterized OMBS. In addition a concomitant enrichment of acid tolerant pathobionts in recurrent stone sufferers is observed. Further, specific enzymes participating in oxalate metabolism are found augmented in stone endures. Additionally, hyperoxaluria driven dysbiosis was found to be associated with oxalate content, stone episodes and colonization pattern of Oxalobacter formigenes. Thus, we rationalize the first in-depth surveillance of OMBS in the human gut and their association with hyperoxaluria. Our findings can be utilized in the treatment of hyperoxaluria associated recurrent stone episodes.

/pdf/hyperoxaluria-leads-to-dysbiosis-and-drives-selective-1cemzvzsd4.pdf

Hyperoxaluria leads to dysbiosis and drives selective enrichment of oxalate metabolizing bacterial species in recurrent kidney stone endures

The aim of this work was the chemical modification of pectins by limited acetylation of their free hydroxyl groups to yield high ester pectins and to investigate its swelling and erosion behavior along with the effect on the release pattern of drugs. Ibuprofen as a weakly acidic drug was formulated as tablets using chemically modified pectin and its impact on drug release was studied. Optimum concentrations of the modified pectin in such a system protect the tablet throughout the gastrointestinal tract (GIT) for 10–12 hrs. The pectin modified with acetylating agent was found to be promising to modify the release of drugs which are to be delivered throughout GIT. Drug dissolution studies were carried out in buffers of pH 1.2 and 6.8 and the system was designed based on the total GIT transit time concept. This article reviews physicochemical characterization of chemically modified pectins, correlation of the physicochemical characteristics with the drug release pattern of ibuprofen and the potential use of chemically modified pectin for modified release dosage forms.

/pdf/chemical-modification-of-pectins-characterization-and-4rhf5z2t17.pdf

Chemical Modification of Pectins, Characterization and Evaluation for Drug Delivery

A data navigation system and a method that enable a user to selectively view multi-dimensional forecast data in a two-dimensional form. The data navigation system includes a representation means for representing the multi-dimensional data. The system also has a Graphical User Interface that displays the data in two-dimensional form and also enables the user to navigate through the multi-dimensional data through the Interface using an interaction means such as a keyboard, a mouse a voice-command, a touch screen and other such means. The system also has an identification means and an extraction means that identify and obtain the data to be displayed in the Interface from the representation means. The data navigation system can also be used to view any multi-dimensional data in two-dimensional form.

System and method for selectively presenting multi-dimensional data in two-dimensional form

Development of highly engineered and tailor-made pharmaceutical nanocarriers with multifunctional properties is presently under consideration for modified drug delivery. Multifunctionality could help to improve in vivo efficacy as well as therapeutic and diagnostic applications of nanocarriers more significantly. In vitro studies end up with the best formulation for desired in vivo performance. This may not completely avoid the preclinical studies, but surely will reduce the number of animals to a minimum. These include surface topography, size, entrapment efficiency, drug release, sterility testing, etc. In vivo properties include longevity, targetability, cellular uptake, bioavailability, pharmacokinetics, safety, efficacy, toxicity, and specific pathological activity testing, etc. Hence, the development of multifunctional pharmaceutical nanocarriers allows their use as powerful carriers for diagnostic as well as therapeutic applications with high efficacy. Ultimately, it would be a reliable option in future pharmacotherapy by sustained delivery through the direct administration at the site of action.

Manish S. Bhatia

Papers

Development and evaluation of regioselective bilayer floating tablets of Atenolol and Lovastatin for biphasic release profile

Hyperoxaluria leads to dysbiosis and drives selective enrichment of oxalate metabolizing bacterial species in recurrent kidney stone endures

Chemical Modification of Pectins, Characterization and Evaluation for Drug Delivery

System and method for selectively presenting multi-dimensional data in two-dimensional form

Characterization of pharmaceutical nanocarriers: in vitro and in vivo studies