Recent Patents on Biotechnology - Volume 13, Issue 2, 2019

Background: Quantitative susceptibility mapping (QSM) depicts biodistributions of tissue magnetic susceptibility sources, including endogenous iron and calcifications, as well as exogenous paramagnetic contrast agents and probes. When comparing QSM with simple susceptibility weighted MRI, QSM eliminates blooming artifacts and shows reproducible tissue susceptibility maps independent of field strength and scanner manufacturer over a broad range of image acquisition parameters. For patient care, QSM promises to inform diagnosis, guide surgery, gauge medication, and monitor drug delivery. The Bayesian framework using MRI phase data and structural prior knowledge has made QSM sufficiently robust and accurate for routine clinical practice. Objective: To address the lack of a summary of US patents that is valuable for QSM product development and dissemination into the MRI community. Method: We searched the USPTO Full-Text and Image Database for patents relevant to QSM technology innovation. We analyzed the claims of each patent to characterize the main invented method and we investigated data on clinical utility. Results: We identified 17 QSM patents; 13 were implemented clinically, covering various aspects of QSM technology, including the Bayesian framework, background field removal, numerical optimization solver, zero filling, and zero-TE phase. Conclusion: Our patent search identified patents that enable QSM technology for imaging the brain and other tissues. QSM can be applied to study a wide range of diseases including neurological diseases, liver iron disorders, tissue ischemia, and osteoporosis. MRI manufacturers can develop QSM products for more seamless integration into existing MRI scanners to improve medical care.

Background: The orchids are one of the beautiful creations of nature which stand apart from any other assemblage of flowering plants. They are highly evolutionary and ecologically significant group of plants that have effectively occupied almost every habitat on the earth. Indiscriminate collections and extermination of their natural habitats have threatened many species of orchids with extinction, resulting in a severe reduction of their genetic resources in nature according to recent patents. It is necessary to adopt sound scientific protocols for the preservation of orchid species. Method: This cost-effective technique provides large storage time for the conservation of germplasm. Presently, efforts have been made to explore various cryopreservation techniques utilized so far and factors affecting the longevity of the propagules (in vivo and in vitro) while cryopreserving them. The sample to be cryopreserved is freeze-preserved in two ways, a) stepwise at two different subzero temperatures and b) in the rapid method, the samples are placed directly in the liquid nitrogen. Results: The orchid seeds and pollen are the most suitable propagules for cryopreservation of orchids due to their minute size and less space requirement. Conclusion: Among the tissues (such as seeds, pollen, protocorms etc.) seeds are the most reliable. The present article reviews the cryopreservation techniques and factors effecting the cryopreservation, for in vitro conservation of orchid gene pool.

Background: Arginine deiminase (ADI), an arginine catabolizing enzyme, is considered as an anti-tumor agent for the treatment of arginine auxotrophic cancers. However, some obstacles limit its clinical applications. Objective: This review will summarize the clinical applications of ADI, from a brief history to its limitations, and will discuss the different ways to deal with the clinical limitations. Method: The structure analysis, cloning, expression, protein engineering and applications of arginine deiminase enzyme have been explained in this review. Conclusion: Recent patents on ADI are related to ADI engineering to increase its efficacy for clinical application. The intracellular delivery of ADI and combination therapy seem to be the future strategies in the treatment of arginine auxotrophic cancers. Applying ADIs with optimum features from different sources and or ADI engineering, are promising strategies to improve the clinical application of ADI.

Background: The increase of oxidant compounds is the most well-known reasons for the tolerance to the analgesic properties of Morphine. Additionally, the production of proxy-nitrite impairs receptors, proteins and enzymes involved in the signaling pathways of analgesia, apoptosis and necrosis. Also, we revised all patents relating to opioid tolerance control methods. Objective: The aim of this study was to assess the effects of Alpha-tocopherol as an anti-oxidant agent to reduce Morphine tolerance. Method: Forty male rats randomly divided into four groups. 10 mg/kg of morphine was injected subcutaneously to create the desired level of tolerance. After modeling, 70 mg/kg Alpha- Tocopherol was injected intraperitoneal. Also, the hot plate recorded pain threshold alterations was used to evaluate the behavioral test. All tissue samples were extracted from the spinal cord, thalamus and frontal cortex for molecular and gene expression evaluations. Also, the effect of Alpha- Tocopherol on the apoptosis and necrosis parameters was analyzed using nissl staining and tunel test. Results: The time latency results showed that there were no significant differences in the different days in groups treated with Morphine plus Alpha-Tocopherol. However, our data highlighted that the pain threshold and their time latency in respond to it had substantially increased in comparison with the control group. Furthermore, we found that the Alpha-Tocopherol obviously decreased c-fos gene expression, especially in the spinal cord. Conclusion: Thus, co-administration of Alpha-Tocopherol with Morphine can decrease the adverse effects of nitrite proxy, which is released due to repeated injections of Morphine.

Background: The use of dihydroartemisinin (DHA) for effective malaria treatment is challenged by its poor aqueous solubility and inadequate bioavailability leading to treatment failures and emergence of resistant strains. A review of some novel drug delivery systems developed to address these challenges and their patents revealed that no study has reported the application of surface modified lipid nanoemulsions for improved antimalarial activity of DHA. Objective: The main thrust of this study is to develop oral dihydroartemisinin formulations solubilized in surface modified lipid nanoemulsions, characterize, and evaluate their activity against murine malaria. Method: Lipid nanoemulsions containing dihydroartemisinin were formulated by high pressure homogenization using soybean oil, and polyethylene glycol 4000 was employed for surface modification. The formulations were characterized for droplet size, surface charge, pH, fouriertransform infrared spectroscopy, and surface morphology, viscosity and drug content efficiency. In vitro haemolytic study as a function of cytotoxicity using red blood cells as well as in vivo anti-malarial study using murine malaria model was also investigated. Results: Nanoemulsions recorded droplet sizes ranging from 26 – 56 nm, and zeta potential in the range of -28 to -35 mV. The formulations were slightly acidic (pH 4.4 – 5.8) with the drug molecularly dispersed as seen using infrared spectroscopy. The formulations showed non- Newtonian flow with significant drug content efficiency in the range of 77-96%. The formulations did not induce haemolysis of cells and showed good clearance of parasitaemia. Conclusion: Surface-modified lipid nanoemulsion is a perfect carrier system for improving the anti-malarial activity of dihydroartemisinin.