SHORT NOTE | doi:10.20944/preprints202006.0348.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Nutraceuticals; pharmaceuticals; medical approach; therapeutic; therapies; emerging companies
Online: 28 June 2020 (20:10:09 CEST)
Nutraceuticals are combination of nutrients and pharmaceuticals and these are derived from various plants, microbes and animals too. The food products that are considered as nutraceuticals are categorised based on the availability in the market. It is a medical approach to improve health and remedy for illness. Nowadays there is an increase in shift towards use of nutraceuticals as its usage provides preventive therapies to various chronic diseases. Various natural nutraceuticals are based on extracts from Ginger, turmeric, garlic, amla, cinnamon, aloe vera etc. A wide variety of therapeutic values are provided by them such as anti-inflammatory, antibacterial, antifungal properties, allergy relief, antidiabetic and cardiovascular problems. India is in its infancy stage but have many emerging companies that are trying to meet the demand of growing population. Overall ‘Nutraceuticals’ has been known as a new era of well being, in which the food industry has become a main player.
ARTICLE | doi:10.20944/preprints201812.0084.v1
Subject: Biology, Ecology Keywords: mixture toxicity; concentration addition; pesticide; pharmaceuticals; Aliivibrio fischeri
Online: 6 December 2018 (11:08:43 CET)
This work introduced the potential synergistic toxicity of binary mixtures of pesticides and pharmaceuticals, which have been substantially detected in major river basins in South Korea. Different dose-response curve functions were employed in each experimental toxicity dataset for Aliivibrio fischeri. We tested the toxicity of 30 binary mixtures at two effect concentrations: high effect concentration [EC50] and low effect concentration [EC10] ranges. Thus, the toxicological interactions were evaluated at 60 effected concentration data points in total and based on model deviation ratios (MDRs) between predicted and observed toxicity values (e.g., three types of combined effects: synergistic (MDR > 2), additive (0.5 ≤ MDR ≤ 2), and antagonistic (MDR < 0.5)). From the 60 data points, MDRs could not be applied to 17 points, since their toxicities could not be measured. The result showed 48 %-additive (n = 20), 40 %-antagonistic (n = 17), and 12 %-synergistic (n = 6) toxicity effects from 43 binaries (excluding the 17 combinations without MDRs). In this study, EC10 ratio mixtures at a low overall effect range showed a general tendency to have more synergistic effects than the EC50 ratio mixtures at a high effect range. We also found an inversion phenomenon, which detected three binaries of the combination of synergism at low concentrations and additive antagonism at high concentrations.
ARTICLE | doi:10.20944/preprints201811.0383.v1
Subject: Life Sciences, Biochemistry Keywords: ADCC; glycosylation; kifunensine; plant made pharmaceuticals; monoclonal antibody
Online: 16 November 2018 (07:24:35 CET)
N-glycosylation has been shown to affect the pharmacokinetic properties of several classes of biologics including monoclonal antibodies, blood factors, and lysosomal enzymes. In the last two decades, N-glycan engineering has been employed to achieve a N-glycosylation profile that is either more consistent or aligned with a specific improved activity (i.e. effector function or serum half-life). In particular, attention has focused on engineering processes in vivo or in vitro to alter the structure of the N-glycosylation of the Fc region of anti-cancer monoclonal antibodies in order to increase antibody-dependent cell-mediated cytotoxicity (ADCC). Here we applied the mannosidase I inhibitor kifunensine to the Nicotiana benthamiana transient expression platform to produce an afucosylated anti-CD20 antibody (rituximab). We determined the optimal concentration of kifunensine used in the infiltration solution, 0.375 µM, which was sufficient to produce exclusively oligomannose glycoforms, at a concentration 14 times lower than previously published levels. The resulting afucosylated rituximab revealed a 14-fold increase in ADCC activity targeting the lymphoma cell line Wil2-S when compared with rituximab produced in the absence of kifunensine. When applied to the cost-effective and scalable N. benthamiana transient expression platform, the use of kifunensine allows simple in-process glycan engineering without the need for transgenic hosts.
REVIEW | doi:10.20944/preprints202111.0057.v1
Subject: Chemistry, Organic Chemistry Keywords: Catalysis; Suzuki-Miyaura; Buchwald-Hartwig amination; Palladium; Pharmaceuticals, Process Chemistry
Online: 2 November 2021 (22:56:37 CET)
Cross coupling reactions have changed the way complex molecules are synthesized. In particular, Suzuki-Miyaura and Buchwald-Hartwig amination reactions have given opportunities to elegantly make pharmaceutical ingredients. Indeed, these reactions are forefront at both the stages of drug development, medicinal chemistry, and process chemistry. On one hand, these reactions have given medicinal chemists a tool to derivatize the core molecule to arrive at scaffold rapidly. On the other hand, these cross couplings have offered the process chemists a smart tool to synthesize the development candidates safely, quickly, and efficiently. Generally, the application of cross coupling reactions is broad, and this review will specifically focus on their real (pharma) world applications in large scale synthesis those appeared in last two years.
ARTICLE | doi:10.20944/preprints202009.0562.v1
Subject: Materials Science, Biomaterials Keywords: adsorption; graphene oxide; methylene blue; pharmaceuticals; kinetics, isotherms and thermodynamics
Online: 24 September 2020 (04:27:52 CEST)
The remarkable adsorption capacity of graphene derived materials has prompted their examination in composite materials suitable for deployment in treatment of contaminated waters. In this study, crosslinked calcium alginate – graphene oxide beads were prepared and activated by exposure to pH 4 by using 0.1M HCl. The activated beads were investigated as novel adsorbents for the removal of organic pollutants (Methylene Blue dye and the pharmaceuticals Famotidine and Diclofenac) with a range of physicochemical properties. Effects of initial pollutant concentration, temperature, pH and adsorbent dose were investigated and kinetic models were examined for fit to the data. Maximum adsorption capacities qmax obtained were 1334, 35.50 and 36.35 mg g-1 for the uptake of Methylene blue, Famotidine and Diclofenac respectively. The equilibrium adsorption had an alignment with Langmuir isotherms while the kinetics were most accurately modelled using a pseudo- first –order and second order models according to the regression analysis. Thermodynamic parameters such as ΔG◦, ΔH◦ and ΔS◦ were calculated and the adsorption process was determined to be exothermic and spontaneous.
ARTICLE | doi:10.20944/preprints201902.0016.v1
Subject: Chemistry, Analytical Chemistry Keywords: liquid chromatography–tandem mass spectrometry; pharmaceuticals; wastewater analysis; solid phase extraction
Online: 2 February 2019 (03:21:04 CET)
The present work describes the optimization and validation of a highly selective and sensitive analytical method using solid phase extraction and liquid chromatography tandem mass spectrometry (SPE LC-MS/MS) for the determination of some frequently prescribed pharmaceuticals in urban wastewater received and treated by Sharjah sewage treatment plant (STP). The extraction efficiency of different SPE cartridges was tested and the simultaneous extraction of pharmaceuticals was successfully accomplished using hydrophilic-lipophilic-balanced reversed phase Waters® Oasis HLB cartridge (200 mg/ 6 mL) at pH 3. The analytes were separated on an Aquity BEH C18 column (1.7 µm, 2.1 mm x 150 mm) using gradient elution and the mass spectrometric analysis were performed in multiple reactions monitoring (MRM) selecting two precursor ions to produce ion transition for each pharmaceutical using positive electrospray ionization (+ESI) mode. The correlation coefficient values in the linear calibration plot for each target compound exceeded 0.99 and the recovery percentages of the investigated pharmaceuticals were more than 84%. Limit of detection (LOD) varied between 0.1-1.5 ng/L and limit of quantification (LOQ) was 0.3-5 ng/L for all analytes. The precision of the method was calculated as the relative standard deviation (RSD%) of replicate measurements and was found to be in the ranges of 2.2% to 7.7% and 2.2% to 8.6% for inter and intra-day analysis, respectively. All of the obtained validation parameters satisfied the requirements and guidelines of analytical method validation.
ARTICLE | doi:10.20944/preprints201811.0091.v1
Subject: Chemistry, Applied Chemistry Keywords: polyacrylonitrile; chemical modification; thiourea; polar pharmaceuticals; sulphonation; dispersion-solid phase extraction
Online: 5 November 2018 (08:48:52 CET)
Pharmaceuticals contain biologically active components that can pollute water courses as a result of the excretions from individuals and/or uncontrolled release of residues from chemical plants, and they can pose a hazard to health. Pharmaceutical residues can persist at low concentrations in the environment, and thus may be potentially harmful to aquatic animals and to humans. Controlling and monitoring such residues are therefore a prime interest, for example, a solid-phase extraction uses solid sorbents to purify and preconcentrate the residues prior to their chemical analysis. In the present study, poly (acrylonitrile-co-divinylbenzene-80) sorbents are synthesised by varying the comonomer feed ratios under precipitation polymerisation conditions to deliver a family of porous polymer microspheres. Acrylonitrile confers polar characters onto the sorbents, and the acrylonitrile-derived nitrile groups can be chemically transformed via polymer-analogous reactions into thioamide and sulfonated residues which make the sorbents even more suitable for the capture of polar analytes, including selected pharmaceuticals. The utility of the porous thioamide-sulfonated containing sorbents is demonstrated via the dispersion-solid phase extraction of mefenamic acid from aqueous media; mefenamic acid is an anthranilic acid derivative which is a potent, non-steroidal anti-inflammatory drug which is found in environmental waters at low concentrations.
REVIEW | doi:10.20944/preprints202112.0380.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: sex differences; drug repurposing; sex-bias; sex-aware; review; therapeutics; pharmaceuticals; computational drug repurposing
Online: 8 March 2022 (10:34:42 CET)
Sex differences are essential factors in disease etiology and manifestation in many diseases such as cardiovascular disease, cancer, and neurodegeneration (1). The biological influence of sex differences (including genomic, epigenetic, hormonal, immunological, and metabolic differences between males and females) and the lack of biomedical studies considering sex differences in their study design has led to several policies. For example, the National Institute of Health’s (NIH) sex as a biological variable (SABV) and Sex and Gender Equity in Research (SAGER)) policies to motivate researchers to consider sex differences (2). However, drug repurposing, a promising alternative to traditional drug discovery by identifying novel uses for FDA-approved drugs, lacks sex-aware methods that can improve the identification of drugs that have sex-specific responses (1,3–5). Sex-aware drug repurposing methods either select drug candidates that are more efficacious in one sex or deprioritize drug candidates based on if they are predicted to cause a sex-bias adverse event (SBAE), unintended therapeutic effects that are more likely to occur in one sex. Computational drug repurposing methods are encouraging approaches to develop for sex-aware drug repurposing because they can prioritize sex-specific drug candidates or SBAEs at lower cost and time than traditional drug discovery. Sex-aware methods currently exist for clinical, genomic, and transcriptomic information (3,6,7). They have not expanded to other data types, such as DNA variation, which has been beneficial in other drug repurposing methods that do not consider sex (8). Additionally, some sex-aware methods suffer from poorer performance because a disproportionate number of male and female samples are available to train computational methods (3). However, there is development potential for several different categories (i.e., data mining, ligand binding predictions, molecular associations, and networks). Low-dimensional representations of molecular association and network approaches are also especially promising candidates for future sex-aware drug repurposing methodologies because they reduce the multiple hypothesis testing burden and capture sex-specific variation better than the other methods (9,10). Here we review how sex influences drug response, the current state of drug repurposing including with respect to sex-bias drug response, and how model organism study design choices influence drug repurposing validation.
ARTICLE | doi:10.20944/preprints202205.0245.v1
Subject: Arts & Humanities, Philosophy Keywords: Disease; Diffusion; Health; Health Impact Fund; Impact Rewards; Incentives; Innovation; Monop-oly Rewards; Pandemic; Patents; Pharmaceuticals; Poverty; Vaccines
Online: 19 May 2022 (03:19:21 CEST)
Globalized in 1995 through the TRIPs Agreement, humanity’s dominant mechanism for encouraging innovations involves 20-year product patents, whose monopoly features enable innovators to reap large markups or licensing fees from early users. Exclusive reliance on this reward mechanism in the pharmaceutical sector is morally problematic for two main reasons. First, it imposes a great burden on poor people who cannot afford to buy patented treatments at monopoly prices and whose specific health problems are therefore neglected by pharmacological research. Second, it discourages pharmaceutical firms from fighting diseases at the population level with the aim of slashing their incidence. These problems can be much alleviated by establishing a supplementary alternative reward mechanism that would enable pharmaceutical innovators to exchange their monopoly privileges on a patented product for impact rewards based on the actual health gains achieved with this product. Such an international Health Impact Fund (HIF) would create powerful new incentives to develop remedies against diseases concentrated among the poor, rapidly to provide such remedies with ample care at very low prices, and to deploy them strategically to contain, suppress, and ideally to eradicate the target disease. By promoting innovations and their diffusion together, the HIF would greatly enlarge the benefits, and thereby also the cost-effectiveness, of the pharmaceutical sector, in favor of the world’s poor especially.