Recent advances in antimalarial compounds and their patents

Malaria is one of the most severe tropical parasitic disease causing 1-3 million deaths annually. In the last 25 years very few new antimalarial molecules have been developed and only a limited number of them are currently in various stages of clinical development. The presently available antimalarial drugs include artemisinin analogs, quinoline derivatives and antifolates. This review summarizes recent advances in antimalarial drug development and world patents published between 2000-2006 claiming new synthetic antimalarial compounds and their activities. The most over-represented classes of compounds in malaria patent literature in order of frequency are artemisinin analogs, quinoline derivatives, DOXP reductoisomerase inhibitors, antifolates and febrifugine analogues. Many of these patents describe the novelty and potential of these synthetic derivatives with an attempt to identify the next generation antimalarials that may have potential commercial advantages.     

Recent advances in solid organ transplantation

Advances in organ transplantation have come rapidly and consistently in recent years as the result of improved surgical techniques and immunosuppressive drug therapies. Experience gained in renal transplantation over the past 30 years has made this a standard therapeutic approach for treating chronic renal failure. This knowledge has been successfully applied to the transplantation of other organs to produce steadily increasing survival rates and improved quality of life. This article reviews the advances that have been made in solid organ transplantation and immunosuppressive drug therapy.     

3D打印技术在骨科中的应用进展

骨科医生主要通过X线片、CT和MR等影像学资料进行病情分析和诊断治疗,往往依赖医生的经验,且缺乏立体的视触感。近年来,3D打印技术迅猛发展,其可将患者虚拟的影像迅速转换成三维实体物件,并且可实现材料结构的个性化定制以及与病变部位的解剖学匹配,已广泛应用于骨科疾病的诊断、治疗和康复。另外,三维组装细胞和材料的生物打印技术有望实现骨肌组织的再生修复,具有广阔的应用前景。本文旨在综述3D技术在骨科应用的前沿研究,总结存在的问题,展望未来。     

Linezolid in children: recent patents and advances

Linezolid is the first approved member of a new generation of antibiotics, the synthetic oxazolidinones, to become available, with a broad spectrum of in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium. It has an excellent bioavailability both intravenously and orally and a very good safety profile both in adults and in children. With regards to its antimicrobial action, linezolid has a predominantly bacteriostatic action, rather than a bacteriocidal effect and is active against Gram-positive bacteria that are resistant to other antibiotics. Linezolid is currently showing great promise for the treatment of multi-resistant Gram-positive infections, both in the community and in a hospital setting. Clinical indications so far include skin and soft tissue infections, community-acquired or nosocomial pneumonia due to MRSA, VRE bacteremia and community-acquired pneumonia due to penicillin-resistant Streptococcus pneumoniae. We anticipate that this new generation of antimicrobial agents will provide adequate cover in the future for infections that cause significant treatment failures so far, such as VRE- associated endocarditis, bone and joint multi-drug resistant infections and possibly central nervous system infections, both in adult and children populations. Some patents on linezolid are also discussed in this review.     

Recent advances of cowpea mosaic virus-based particle technology

Particles of cowpea mosaic virus (CPMV) have enjoyed considerable success as a means of presenting peptides for vaccine purposes. However, the existing technology has limitations in regard to the size and nature of the peptides which can be presented and has problems regarding bio-containment. Recent developments suggest ways by which these problems can be overcome, increasing the range of potential applications of CPMV-based particle technology.     

热熔挤出技术制备螺内酯固体分散体

目的制备螺内酯固体分散体,提高其体外溶出。方法分别以亲水性高分子材料聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物和乙烯吡咯烷酮-醋酸乙烯酯共聚物为载体,采用热熔挤出技术制备螺内酯固体分散体,以有关物质、体外溶出为指标,筛选、优化处方及工艺,并应用差示扫描量热法、X射线衍射法、红外光谱法、偏振光显微镜表征最优固体分散体。结果采用热熔挤出技术可以制备螺内酯固体分散体;最优处方中,螺内酯以分子或无定型状态分散于载体中;固体分散体显著提高了螺内酯在水中的溶出。结论热熔挤出技术制备的固体分散体显著地提高了螺内酯的体外溶出。     

Recent advances in iron oxide nanocrystal technology for medical imaging

Superparamagnetic iron oxide particles (SPIO and USPIO) have a variety of applications in molecular and cellular imaging. Most of the recent research has concerned cellular imaging with imaging of in vivo macrophage activity. According to the iron oxide nanoparticle composition and size which influence their biodistribution, several clinical applications are possible: detection liver metastases, metastatic lymph nodes, inflammatory and/or degenerative diseases. USPIO are investigated as blood pool agents with T1 weighted sequence for angiography, tumour permeability and tumour blood volume or steady-state cerebral blood volume and vessel size index measurements using T2 weighted sequences. Stem cell migration and immune cell trafficking, as well as targeted iron oxide nanoparticles for molecular imaging studies, are at the stage of proof of concept, mainly in animal models.     

Recent trends in neuropathic pain patents

Introduction: Neuropathic pain (NP) is one of the most important health problems faced nowadays. NP is a chronic disease that cannot be treated like other pain conditions because it is developed from a nerve injury that evolves into a permanent dysfunction of the central and/or peripheral nervous system. Therefore, it involves the participation of several systems and should be viewed as a multi-factorial disease that needs a whole new pharmacological strategy in order to achieve the desired pain relief.

Areas covered: The Espacenet site was used as the main source in order to perform the patent research for NP treatment. This review covers the patents with relevant approaches for NP treatment from 2014 until today.

Expert opinion: Our patent research has shown that there is not a consensus approach to treat NP in any of its forms. In our opinion, the approach regarding NP needs to be like cancer’s approach. As there are different types of cancer and different ways to treat them, the same needs to be done for NP. Currently, there are several promising targets, which corroborates that this is a wide-open research area. For these reasons, neuropathic pain is a therapeutic field full of potential for innovation.     

Recent overview of ocular patents

Ocular drug therapy has always been considered as a major challenge in the field of drug delivery. The presence of blood ocular barriers and efflux pumps has imposed a great concern as well. Various vision threatening disorders require a long term therapy of drug molecules, especially for the diseases that affect the posterior segment. Pharmaceutical companies and other research institutes have adopted a multidisciplinary approach to meet the current challenges which is evidenced by the trends seen in the published and filed U.S. patents. Various strategies have been employed to achieve long term sustained and targeted delivery for both the anterior and the posterior segments of the ocular diseases. These strategies include formulating drugs into implant, micro or nanoparticulate systems and hydrogel-based systems. Transporter targeted approach has also allowed scientists to deliver drugs to both the segments of the eye. Recent developments such as delivery of drugs utilizing ultrasound, iontophoresis and microneedle based devices have been promising. Genebased therapeutics has opened a new avenue for vision threatening disorders. In all, the current developments in the entire field have been very exciting for finding out new strategies to treat vision threatening disorders.     

速释型葛根素固体分散体工艺处方的优化

目的:获得速释型葛根素固体分散体的最优工艺处方.方法:采用溶剂-熔融法制备速释型固体分散体,以体外溶出度为指标,考察不同基质与配比对葛根素溶解特性与溶出速度的影响,从而确定葛根素固体分散体的最优制备处方.结果:当葛根素固体分散体的处方为:葛根素:PEC6000:pluronicF- 68=1:4:1时,葛根素的累积溶出...     

Fundamental aspects of solid dispersion technology for poorly soluble drugs

The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Since a solid dispersion is basically a drug–polymer two-component system, the drug–polymer interaction is the determining factor in its design and performance. In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.KEY WORDS: Solid dispersion, Poorly soluble drug, Phase separation, Drug–polymer interaction     

采用固体分散技术制备尼群地平缓释片

目的：制备具有良好体外释放的尼群地平缓释片。方法：以羟丙甲纤维素（HPMC）为凝胶骨架材料制备缓释片,对骨架材料用量、制备工艺等因素进行考察。结果：随着HPMC用量的增加药物释放明显减慢,固体分散工艺可改善药物的体外释放释药行为。结论：通过固体分散工艺及HPMC用量的适当调整可制备具有良好释放的NT缓释片。     

Recent patents in pressurised metered dose inhalers

In this paper recent patents in pressurised metered dose inhalers have been reviewed. The patents are related to novel valves, dose-counters, formulations, add-on devices, reduction of propellant leakage and inkjet technology. Recently patented dose-counters provide mechanisms that are less susceptible to inaccuracy, and are battery-less electronic dose-counters with the help of miniature electromechanical generators. Regarding the formulation aspect, recent patents provide methods for combinational pMDIs and more stable products. Advantages of recently patented valves are being spring-free and less subject to loss of prime. Recent developments in micromachining have allowed patents that incorporate inkjet technology to develop inhalers that are similar to pMDIs, but produce uniform aerosol droplets. Coating canisters with suitable polymers has reduced need for excipients. Recently patented add-on devices reduce aerosol deposition in the spacer by creating turbulence on the walls of the chamber. Blockage of nozzles in actuators is prevented by providing tapered nozzle channels. In conclusion, these patents show better understanding of pMDIs and provide methods to achieve products with much improved reliability, aerosol performance and stability.     

Quercetin-phospholipids complex solid dispersion and quercetin solid dispersion: preparation and evaluation

Quercetin (QUE) has many beneficial biological activities and pharmacological actions in vitro. However, its oral bioavailability in vivo was very poor due to poor solubility, and severely restricted its clinical applications. In this study, we preparedquercetin solid dispersion (QUE-SD) and quercetin phospholipids complex solid dispersion (QUE-PC-SD) by a solvent evaporationmethod to improve the absorption of QUE in vivo. The results of XRD of QUE-SD and QUE-PC-SD showed that QUE was dispersed homogeneously in an amorphous or molecular state in QUE-SD and QUE-PC-SD, which could contribute to improve the solubility and dissolution of QUE. The solubility of QUE-SD and QUE-PC-SD was enhanced from (4.03±0.02) μg/mL to (26.91±0.06) μg/mL and (30.65±0.06) μg/mL, respectively. The solubility of QUE-PC-SD was higher than that of QUE-SD.In vitro dissolution study, it was showed that the maximum dissolution of QUE (9.57%) from the QUE-SD and QUE-PC-SD was enhanced to 93.81% and 94.16%, respectively. The results of pharmacokinetic experiment indicated that the QUE-SD and QUE-PC-SD exhibited considerable enhancement in the oral bioavailability. The relative bioavailability of QUE-SD and QUE-PC-SD compared with QUE were 149.49% and 198.32%, respectively. In addition, the relative bioavailability of QUE-PC-SD was also higher than that of QUE-SD. Therefore, in regard to drugs with poor solubility and low permeation, an active constituent-PC-SD system could result to a better absorption and higher bioavailability.     

Recent patents therapeutic agents for cancer

Cancer is one of the most dreaded diseases with a complex pathogenesis, which threats human life greatly. Multidisciplinary scientific investigations are making best efforts to combat this disease and put to the identification of novel anticancer agents. Patent anticancer agents registered in China are therefore increasing dramatically during the past ten years, which will be reviewed briefly in this article. platinum complexes anthracycline analogs (including doxorubicin derivatives) quinoline analogs podophyllotoxins analogs taxane analogs camptothecin (CPT) analogs.     

Recent patents on cardiovascular stem cells

Chronic heart failure has emerged as a leading cause of morbidity and mortality worldwide. Conceptually, replacement of akinetic scar tissue by viable myocardium and improvement of neovascularization should improve cardiac function and impede progressive left ventricular remodelling. Experimental and clinical studies suggest that transfer or mobilization of stem and progenitor cells can have a favourable impact on tissue perfusion and contractile cardiac performance. The aim of the present review was to screen various available patent data bases to give an overview on different patent applications of cell-based and non-cell based therapies in regenerative cardiovascular medicine. The first part describes cell based methods and use of growth factors to improve cardiovascular function. Secondly, patents on methods to improve angiogenesis, re-endothelialization and vascular function are presented. Finally, we describe patents describing methods for improved differentiation of stem cells to cardiovascular cells, including the generation of cardiomyocytes from embryonic or adult stem cells. A systematic overview on the current patent situation about use of stem cells in cardiovascular medicine should facilitate future decision making in the development of novel therapeutic strategies in regenerative medicine.     

Recent advances in drug delivery applications of cubosomes,hexosomes, and solid lipid nanoparticles

The use of lipid nanocarriers for drug delivery applications is an active research area, and a great interest has particularly been shown in the past two decades. Among different lipid nanocarriers, ISAsomes (Internally self-assembled somes or particles), including cubosomes and hexosomes, and solid lipid nanoparticles (SLNs) have unique structural features, making them attractive as nanocarriers for drug delivery. In this contribution, we focus exclusively on recent advances in formation and characterization of ISAsomes, mainly cubosomes and hexosomes, and their use as versatile nanocarriers for different drug delivery applications. Additionally, the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo. Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies, further investigations on improved understanding of the interactions of these nanoparticles with biological fluids and tissues of the target sites is necessary for efficient designing of drug nanocarriers and exploring potential clinical applications.KEY WORDS: Biological fate, Cubosomes, Drug delivery, Hexosomes, Inverse non-lamellar liquid crystalline phases, Nano-self-assemblies, Solid crystalline phases, Solid lipid nanoparticles