Raw Drug Research Articles

Assessment of Trans-Environmental Transitions of Heavy Metals and Arsenic in Herbal Drugs and Herbal Medicinal Products of Valerian Rhizomes with Roots and Motherwort Herb

Scientific relevance. In the context of pharmacopoeial harmonisation, the available methods for quantifying the total heavy metal content in tinctures are not sufficient to demonstrate the safety of liquid dosage forms based on herbal drugs. However, the establishment of individual limits for the heavy metal content requires analysing the patterns of environmental toxicant transitions from plant raw materials to herbal medicinal products in finished dosage forms.Aim. This study aimed to analyse the trans-environmental transitions of heavy metals and arsenic from the soil through plants to herbal medicinal products using a case study of aqueous and alcoholic extracts of valerian and motherwort herbal drugs.Materials and methods. The study focused on motherwort herb and valerian rhizomes with roots, the corresponding herbal medicinal products, and the rhizospheric soil. The elemental composition of the studied samples was determined by inductively coupled plasma mass spectrometry.Results. The authors determined the content of 15 elements (Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Cd, Sb, Hg, and Pb) in plant raw materials, the rhizosphere, and herbal drug infusions and tinctures. The concentrations of elements were 0.002–109.884 mg/kg in motherwort herb samples and 0.017–866.618 mg/kg in the samples of valerian rhizomes with roots. Pb, Cd, and As were detected in all plant raw materials, while Hg was found only in 25% of the study samples. The content of these elements was within acceptable limits. Valerian and motherwort infusions contained all elements, except for Hg; valerian tinctures were free from Fe and Hg; and motherwort tinctures included no Fe, Hg, Sr, Cd, and Pb. The concentrations of elements in the infusions did not exceed 3.169 mg/kg, while the concentrations of elements in the tinctures were below 1.27 mg/kg. In the tinctures, Zn, Cu, Mg, and Ti were the most abundant elements, and Sb and Cd were present in minimum amounts.Conclusions. Valerian and motherwort plants can concentrate Cu, Cr, Fe, and V from the soil. The transition of heavy metals and arsenic into infusions did not exceed 65% of the content of these elements in herbal drugs, while tinctures contained less than 30% of the content of heavy metals and arsenic in herbal drugs. Some elements passed into infusions 1.5–5 times more efficiently than into tinctures.

Active fraction of Polyrhachis vicina (Roger) alleviated cerebral ischemia/reperfusion injury by targeting SIRT3-mediated mitophagy and angiogenesis

BackgroundDamaged mitophagy and impaired angiogenesis involve in the pathogenic development of ischemic stroke. Active fraction of Polyrhachis vicina (Roger) (AFPR) showed great potential on neurological disease with it's remarkable anti-inflammatory and anti-oxidative effects. PurposeThis study designed to clarify the correlation between Pink1/Parkin-mediated mitophagy and angiogenesis after stroke, and to elucidate the role of SIRT3 in regulating mitophagy and angiogenesis, and to address the mechanism of AFPR on promoting mitophagy and angiogenesis in microvessels endothelium of ischemic brain. Study designA cerebral ischemia/reperfusion (CIR) rat model was developed by middle cerebral artery occlusion procedure. bEnd.3 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic CIR process. Neurological function, mitophagy and angiogenesis related indicators were measured. SIRT3 siRNA and 3-MA were used to verify the interaction between SIRT3-mediated mitophagy and angiogenesis. MethodsCIR rats were orally treated with AFPR (8 and 4 g raw drug /kg) and Nimodipine (10.8 mg/kg) for 12 days to mimic the recovery phase post-stroke. The neurological function assessment, TTC staining, HE staining, TUNEL staining and Nissl staining were performed to assess neuroprotective effects of AFPR against CIR. Then CD31-labeled microvessel density in brain was visualized and quantified by immunofluorescence staining. Mitochondrial ultrastructure was assessed by transmission electron microscope scanning. Expressions of relative proteins,e.g. SIRT3, Pink1, Parkin, LC3-II, p62, VEGFA, involving in mitophagy and angiogenesis, were detected by Western blotting analysis. In vitro, bEnd.3 cells were cultured with AFPR or in combination of autophagy inhibitor 3-MA during the reoxygenation. Then cell viability, and LDH releasing were measured. Angiogenic indicators,such as migration and tube formation activity, VEGFA level were determined. To assess effects of AFPR on mitophagy, mitophagy-related proteins were detected, as well as the autophagosome engulfment and lysosome degradation of mitochondria. To address the role of SIRT3, deacetylation activity of SIRT3 was validated by detecting acetylated FOXO3A level with co-immunoprecipitation (Co-IP) assay. Pre-treatment of siRNA or combination use of 3-MA were used to verify the detailed mechanism. ResultsAFPR remarkably reduced neurological scores and infarct size, alleviated neuron apoptosis in cortex, and increased Nissl density in hippocampus of CIR rats. In addition, AFPR significantly promoted angiogenesis by increasing microvessels density and VEGFA expressions, increased SIRT3 expression, and activated Pink1/Parkin mediated mitophagy. In bEnd.3 cells, the combination use of 3-MA and AFPR further demonstrated that AFPR might promote angiogenesis after OGD/R injury through activating Pink1/Parkin mediated mitophagy. Co-IP assay suggested AFPR reduced acetylated FOXO3A level. This might be correlated with an elevation of SIRT3 expression and it's deacetylation activity. SIRT3 siRNA pretreatment significantly abolished the activation of mitophagy through Pink1/Parkin axis, eventually inhibited angiogenesis. ConclusionAFPR promoted angiogenesis through activating mitophagy after cerebral ischemia reperfusion, which might partially involved in the amelioration of SIRT3-mediated regulation on Pink1/Parkin axis. Our study will shed new light on the role of SIRT3 in ischemic brain, especially in regulating mitophagy and angiogenesis after stroke.

Development of DNA markers using next-generation sequencing approach for molecular authentication of Boerhavia diffusa L. and Tinospora cordifolia (Willd.) Miers

The adulteration of plants and their materials used in herbal formulations poses a severe health concern. Hence, there is a need to establish a reliable, cost-effective, and robust molecular biomarker to distinguish among species and identify herbal plants and raw drugs from adulterants. The present study used suppressive subtractive hybridization and next-generation sequencing technology to identify novel DNA markers for Boerhavia diffusa L. and Tinospora cordifolia (Willd.) Miers. We identified two primer sets for B. diffusa and one for T. cordifolia. The DNA markers were validated in different accessions of B. diffusa and T. cordifolia and their common adulterants to determine the sensitivity and specificity of developed DNA markers. The designed DNA markers showed 100% sensitivity and specificity in detecting B. diffusa and T. cordifolia from their adulterants. The strategy described here can be extrapolated for developing DNA markers to authenticate other plant species.

Evaluation of microstructure, dissolution rate, and oral bioavailability of paclitaxel poloxamer 188 solid dispersion.

Poor solubility is a major challenge for enhancing the oral bioavailability and clinical application of many drugs, including the broad-spectrum chemotherapy drug paclitaxel (PTX). A practical approach to improving the solubility of insoluble drugs is through the use of solid dispersion (SD).This study aimed to investigate the potential of the triblock copolymer, poloxamer 188 (P188), as a carrier for preparing solid dispersion of paclitaxel using spray drying technology. We systematically studied its microstructure, dissolution behavior in vitro, and pharmacokinetics. Our findings demonstrate that PTX exists in an amorphous state in copolymer composed of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) P188, with stronger miscibility with hydrophobic PPO segments. All three in vitro dissolution models revealed that the release rate of drugs in SD was significantly higher compared to that of physical mixtures (PM) as well as raw drugs. Furthermore, our pharmacokinetic results showed that the area under the curve(AUC) of PTX in SD was 6 times higher than that of active pharmaceutical ingredient(API), 4.5 times higher than PM, and the highest blood drug concentration (Cmax) reached 357.51 ± 125.54 (ng/mL), approximately 20 times higher than API.Overall, our findings demonstrate that the dissolution rate of amorphous PTX in SD significantly improves, effectively enhancing the oral bioavailability of PTX.

Physicochemical Study, Chemical Profiling and Molecular Docking Study for Standardisation of the Homoeopathic Drug Damiana

Abstract Introduction Damiana has been used as aphrodisiac in ethnomedicine for centuries. However, the use of Damiana in homeopathy is diverse, e.g. for migraine treatment of, amenorrhoea, spermatorrhoea, urinary tract infection and prostate related issues. However, this medicinal plant is non-native to India. Hence, it is imperative to investigate the quality of the medicine samples available and prepared in India. Hence, we undertook in-depth chemical analysis of the raw drugs and the commercially available samples of this medicine. Materials and Methods The reported chemical study includes determination of the physicochemical parameters of the raw drug involving, foreign matter, loss on drying, extractive values in different solvents, ash values total fixed oil and total volatile oil. Also, the study includes the analysis of the in-house and commercial mother tinctures consisting of, pH, organoleptic parameters, total solids, total phenol content, ultraviolet absorption spectroscopy and high performance thin layer chromatography. Phytochemical screening of the mother tinctures and extracts of the raw drugs in different solvents was done. A preliminary molecular docking study was done to evaluate the applicability of apigenin as the homoeopathy-specific marker. Result In-house mother tincture, mother tinctures from Indian and multinational companies show similar quality. Molecular docking revealed that apigenin may be a good candidate for homoeopathy-specific marker. Conclusion Our study provides pharmacopoeial standards which show that even for exotic plants the quality of mother tinctures from Indian and international companies is similar.

Metabolite profiling of Drynariae Rhizoma using 1H NMR and HPLC coupled with multivariate statistical analysis.

Drynariae Rhizoma has been used to treat bone diseases and kidney deficiency in traditional medicine. Recently its aqueous extract was reported to enhance memory function. Although the Japanese standards for non-Pharmacopoeial crude drugs 2022 prescribed Drynaria roosii as the botanical origin, some counterfeits and both raw and stir-fired crude drugs are available in markets. To distinguish Drynariae Rhizoma derived from D. roosii appropriately from others and verify the validity of uses of stir-fried ones, 1H NMR-based metabolite profiling coupled with HPLC were performed. Raw samples derived from D. roosii contained naringin (1), neoeriocitrin (2), 5,7-dihydroxychromone-7-O-neohesperidoside (3), caffeic acid 4-O-β-D-glucoside (4), protocatechuic acid (5), trans-p-coumaric acid 4-O-β-D-glucoside (6), and kaempferol 3-O-α-L-rhamnoside 7-O-β-D-glucoside (8). Stir-fried samples were characterized by presence of 5-hydroxymethyl-2-furaldehyde (13), and were divided into two types; one possessing similar composition to raw samples (Type I) and another without above components except 5 (Type II). Quantitative analyses using qHNMR and HPLC, followed by principal component analysis demonstrated that the raw samples had higher contents of 1 (0.93-9.86mg/g), 2 (0.74-7.59mg/g), 3 (0.05-2.48mg/g), 4 (0.27-2.51mg/g), 6 (0.14-1.26mg/g), and 8 (0.04-0.52mg/g), and Type II had a higher content of 5 (0.84-1.32mg/g). The counterfeit samples derived from Araiostegia divaricata var. formosana were characterized by higher content of ( -)-epicatechin 3-O-β-D-allopyranoside (10) (1.44-11.49mg/g) without 1 and 2. These results suggested that Drynariae Rhizoma samples derived from other botanical origins and Type II stir-fried samples cannot substitute for D. roosii rhizome.

Polysorbate Analysis in Biopharmaceutical Applications—A Snapshot of the Analytical Toolbox

Polysorbates (PS) are added to biopharmaceutical formulations to stabilize proteins and monoclonal antibodies (mAbs) and to prevent aggregation, denaturation, and surface adsorption. Polysorbate analysis can be challenging because of their inherent complexity, polydispersity, and their presence in matrices containing high concentrations of proteins and other excipients such as sugars, amino acids, salts, and buffers. This instalment of “Biopharmaceutical Perspectives” provides an overview of different approaches for the qualitative and quantitative analysis of polysorbates, its impurities and degradants in raw material, intermediate dilutions, drug substance, and drug products. Various gas (GC) and liquid chromatography (LC) methods and accompanying detection techniques are briefly discussed and illustrated with results obtained at the authors’ laboratory.

A One-Year Environmental and Microbiological Monitoring of Storage Areas and Production Room of a Pharmaceutical Industry from Northern Nigeria

The degradation and reduction of the potency of both raw materials and finished pharmaceutical products (FPPs) are of great concern to pharmaceutical industries, making the environmental monitoring of storage areas and production rooms a must. In this study, a one year monthly data for environmental and microbiological monitoring for storage areas (raw materials quarantine room, raw materials approved room, finished product quarantine room and finished product approved room) and production room were collected and analyzed using IBM SPSS Statistics Version 23. The results revealed that the lowest temperature (21.01oC) was obtained from the raw materials approved room. At the same time, the highest (29.50oC) was recorded from the finished product quarantine room. In contrast, the lowest relative humidity of 11.11% was obtained from raw materials quarantine room while raw materials approved room had the highest relative humidity of 33.33%. The results obtained for microbial loads showed that Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Pseudomonas aeruginosa recorded 0.00cfu/ml each. In contrast, the value obtained for total viable aerobic mesophilic bacteria plate count ranges from 0.00-28.67 cfu/ml and fungi range from 0.67-5.00 cfu/mL respectively. The significant difference was determined at p<0.05. However, the results obtained for the temperature, relative humidity and microbial loads were within the stated specifications. This shows that the temperature and relative humidity of the storage areas and the production room were controlled and well monitored in line with the current good manufacturing practice which will eventually positively impact the quality, marketability and stability of raw materials and drug products. Environmental monitoring of storage areas and production room should be highly encouraged in pharmaceutical industries to curb the menace of speedy degradation and loss of potency experienced in raw materials and finished pharmaceutical products.

Deriving breast cancer chemotherapy patterns from real-world data.

e13586 Background: Real World Data (RWD) collected during routine medical practice can help in clinical trial design, planning and execution. In addition, it can provide a compelling picture of safety of medical products, and account for all potential adverse events that can be encountered in routine clinical practice. However, raw drug information about chemotherapy in cancer care is not readily understandable in the format it is collected. Analytical techniques need to be applied to extract regimen information, which includes drugs, dosage, number of cycles and cycle length. Methods: A retrospective study was performed using data on 7,798 breast cancer patients from the TriNetX Network, a federated network of de-identified, HIPAA-compliant, health data from 21 healthcare organizations across North America as of May 2022. We investigated a method built on rule-based algorithm and clustering analysis to extract regimens and their patterns of administration and align them into lines of treatment (LOT). To derive drug administration patterns, we clustered administration time periods using three features: total number of drug administrations, median number of days between drug administrations, and standard deviation of the days between drug administrations. Results: The patterns of administration that correspond to the two most common regimens for Erb-B2 receptor tyrosine kinase 2 negative group (ERBB2-) stages 1, 2 and 3 are shown. We looked at patients with Hormone Receptor (HR+) positive and Triple Negative (TN) breast cancer. Results of our analysis were in a close agreement with NCCN Guidelines. However, regimen administration patterns varied. This information can be useful to characterize patients based on the adherence to the expected chemotherapy regimens. It can also provide meaningful insight into burden of illness, such that patients who have higher variability of the drug administration might be faced with clinical problems such as drug tolerability or side effects. The variability might also signify access to care challenges. Conclusions: Understanding regimen LOT and administration patterns is central to research based on RWD, but it can also be useful for clinical trial design, execution, as well as site selection and patient recruitment for clinical trials. [Table: see text]

The Pharmacological Usage of Panchadeepakini Chooranam for Respiratory Ailments

An old Indian traditional medical practice called Siddha developed in South India. The Lord typically serves as the source of the system. It is believed that Goddess Parvathi, represented by Lord Shiva, received the Siddha system's knowledge from the Almighty, who then passed it on to Nandikeswara. Nandikeswara was appointed to set up for the framework to be spread in the midst of humankind thus, he obediently granted the information to Sage Agastya. Agastya gave all of the relevant information to his various disciples, who helped spread the system around the world. Diet and lifestyle play a significant role in both health and disease treatment, according to the Siddha medicine system. Pathiyam and Apathiyam refer to this Siddha medicine concept, which is essentially a rule-based system with a list of "dos and don'ts.” The aim of this review article is to explore the scientific literary evidence for the therapeutic usage of Panchadeepakini chooranam for (Silethuma Noi/Kaba Noi) as mentioned in Citta Vaittiya Tirattu and to assign effort to entity the pharmacological activity for the curative nature of the drug. Most of the raw drugs used for the preparation of Panchadeepakini chooranam have bronchodilatory activity, anti-tussive activity, anti-allergic activity, immunomodulatory activity, anti-histamine activity hence justifying its usage in respiratory illness.

Greenness Assessment of HPLC Analytical Methods with Common Detectors for Assay of Paracetamol and Related Materials in Drug Products and Biological Fluids

Paracetamol is one of the most widely consumed analgesic and antipyretic medications worldwide. It is frequently analyzed in many quality control (QC) laboratories in pharmaceutical companies, either in raw materials or drug products. It was reported that paracetamol self-toxicity often occurs, leading to the frequent analysis of paracetamol in toxicological centers in biological fluids. Green analytical chemistry (GAC) is growing to be a global philosophy; therefore, the high frequency of paracetamol analysis poses potential concerns. Chromatographic analytical methods used for the daily analysis of paracetamol could be a potential risk to the environment or the health of the analysts if not thoroughly considered. The presented study aims to establish greenness assessments of nine HPLC methods used to assay paracetamol in raw materials and drug products and twenty-one HPLC methods. The reason for selecting HPLC methods of analysis to be the core of the study is the known reproducibility, reliability and availability in most QC laboratories. The most commonly used metric systems for greenness evaluation are the Analytical GREEnness (AGREE), the eco-scale assessment (ESA) and the national environmental methods index (NEMI) which have been used in this comparative study. The greenest chromatographic method for the analysis of paracetamol in raw materials and drug products was introduced by Rao et al. (the obtained scores were ESA = 76 and AGREE = 0.62, while the greenest chromatographic method for the analysis of paracetamol in biological fluids was proposed by Modick et al.). The obtained scores were ESA = 85 and AGREE = 0.7. The NEMI tool proved to have limited performance compared to other metric systems, hence it could not be used alone. Accordingly, the collaboration of NEMI results with ESA and AGREE for greenness assessment is highly recommended to reach appropriate conclusions.

Study on the regulation mechanism of effective glass transition temperature on the crystallization of crystalline solid dispersion.

The focus of this investigation was to determine the mechanism of effective glass transition temperature (TgE) on the crystallization behavior and microstructure of drugs in crystalline solid dispersion (CSD). CSDs were prepared by rotary evaporation using ketoconazole (KET) as a model drug and the triblock copolymer poloxamer 188 as a carrier. The pharmaceutical properties of CSDs, such as crystallite size, crystallization kinetics, and dissolution behavior, were investigated to provide a foundation for studying the crystallization behavior and the microstructure of drugs in CSDs. According to classical nucleation theory, the relationship of treatment temperature-drug crystallite size-TgE of CSD was investigated. Voriconazole, a compound that is structurally similar to KET but with different physicochemical properties, was used to verify the conclusions. The dissolution behavior of KET was significantly enhanced compared to the raw drug due to smaller crystallite size. Crystallization kinetic studies revealed a two-step crystallization mechanism for KET-P188-CSD, in which P188 crystallized first and KET crystallized later. When the treatment temperature was near TgE, the drug crystallite size was smaller and more numerous, which suggests nucleation and slow growth. With the increase of temperature, the drug changed from nucleation to growth, and the number of crystallites decreased and the size of the drug increased. This result suggests it is possible to prepare CSDs with higher drug loading and smaller crystallite size by adjusting the treatment temperature and TgE, so as to maximize the drug dissolution rate. The VOR-P188-CSD maintained a relationship between treatment temperature, drug crystallite size, and TgE. The findings of our study demonstrate that TgE and the treatment temperature can be used to regulate the drug crystallite size and improve the drug solubility and dissolution rate.

Pharmaceutical Standardisation and Physicochemical Analysis of Krimighatini Vati

Standardization is the process for the establishment of standard for a particular or drug. Standardization in Ayurvedic formulation mainly deals with ensuring standards for the quality and purity of raw materials, quality control during the drug manufacturing process, production of a good quality finished product and storage and distribution to maintain the quality of the final product. Standard of an Ayurvedic product can be assessed only by analyzing the analytical parameters of raw drugs, drugs after preprocessing and the finished products. Krimighatini vati explained in Rasendra chintamani is an antihelminth preparation explained in Rasendra Chintamani krimirogadhikara. It contains Parada- 1part, Gandhaka- 2 parts, Ajamoda -3 parts, Vidanga bheeja- 4 parts, Palaasha bheeja- 5parts, and Kaarsakara beeja- 6 parts. It is similar to Krimimudgara rasa that is available in market but differs in proportion of Palaasha beeja and Karaskara beeja. Present study aims to standardize Krimighatini vati after preparing the medicine according to the method explained in Ayurveda samhithas. Preprocessing of the Gulika includes, Shodhana of Hingula, Gandhaka and Karaskara beeja according to the methods mentioned in Rasasastra books. Parada was extracted from Hingula by Ordhwapaathana vidhi. It was then triturated with Shuddha Gandhaka to get Kajjali. Fine powders of other drugs were mixed with Kajjali and rolled into pills with Honey. Study observed the physicochemical parameters of individual drugs and validated the Gulika by HPTLC method. Analysis of Kajjali was done using XRD so as to prove the complete formation of Kajjali. Pharmaceutical standardization helps in reproducibility of drug paving way for more studies on toxicity and efficacy of drug.

Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes

The technologies for fabrication of nanocrystals have an immense potential to improve solubility of a variety of the poor water-soluble drugs with subsequent enhanced bioavailability. Repaglinide (Rp) is an antihyperglycemic drug having low bioavailability due to its extensive first-pass metabolism. Microfluidics is a cutting-edge technique that provides a new approach for producing nanoparticles (NPs) with controlled properties for a variety of applications. The current study's goal was to engineer repaglinide smart nanoparticles (Rp-Nc) utilizing microfluidic technology (Dolomite Y shape), and then to perform in-vitro, in-vivo, and toxicity evaluations of them. This method effectively generated nanocrystals with average particle sizes of 71.31 ± 11 nm and a polydispersity index (PDI) of 0.072 ± 12. The fabricated Rp's crystallinity was verified by Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD). In comparison to the raw and commercially available tablets, the fabricated Rp's nanoparticles resulted in a higher saturation solubility and dissolving rate (p < 0.05). Rp nanocrystals had a considerably lower (p < 0.05) IC50 value than that of the raw drug and commercial tablets. Moreover, Rp nanocrystals at the 0.5 and 1 mg/kg demonstrated a significant decrease in blood glucose level (mg/dL, p < 0.001, n = 8) compared to its counterparts. Rp nanocrystals at the 0.5 mg/kg demonstrated a significant decrease (p < 0.001, n = 8) in blood glucose compared to its counterparts at a dose of 1 mg/kg. The selected animal model's histological analyses and the effect of Rp nanocrystals on several internal organs were determined to be equivalent to those of the control animal group. The findings of the present study indicated that nanocrystals of Rp with improved anti-diabetic properties and safety profiles can be successfully produced using controlled microfluidic technology, an innovative drug delivery system (DDS) approach.

Physico and phytochemical standardization of nutritionally rich mulberry fruits (Morus indica Linn)

Due to their sweet flavor, impressive nutritional value, and various health benefits, mulberries are gaining popularity worldwide. Mulberries are colorful berries that are eaten both fresh and dried. They're a good source of iron, vitamin C, and several plant compounds and have been linked to lower cholesterol, blood sugar, and cancer risk. Mulberries are the fruits of mulberry trees (Morus sp.) and are related to figs and breadfruit. The trees are traditionally grown for their leaves mainly in Asia and North America as they’re the only food that silkworms eat. They carry colorful berries most commonly black, white, or red that are often made into wine, fruit juice, tea, jam, or canned foods, but can also be dried and eaten as a snack. Mulberries have a decent amount of fiber. The present communication carries an attempt to evaluate the study of phytochemical physicochemical parameters e. g. successive extractive values in different solvents, ash values, alcohol, water, and hexane soluble extractives, moisture contents, loss of weight on drying at 105oC, pH values of 1% and 10 % aqueous solutions, qualitative and quantitative mineral contents, and thin layer chromatography of different extracts. Besides, the qualitative and quantitative analysis of Phyto-constituents like alkaloids, total phenolics, tannins, sugar contents, crude fibers, proteins, and estimation of heavy metals, microbial loads, pesticide residues, and aflatoxins were also carried out which will be useful in the identification and control of the possible adulterations of the raw drug.

Enlarged pore of worm mesoporous silica nanoparticles improves anti-inflammatory drug absorption.

Searching for an effective pore-enlarging agent to form mesoporous silica nanoparticles (MSN) with a creative surface frame is of great importance. Herein, several polymers were attempted to be pore-enlarging agents to form seven types of worm mesoporous silica nanoparticles (W-MSN) and analgesic indometacin that exerted functions on inflammatory diseases (breast disease, arthrophlogosis, etc.) was studied to enhance its delivery efficiency. The porous morphology differences between MSN and W-MSN were that MSN had independent mesopores while the enlarged mesopores of W-MSN were interrelated and shaped as a worm. Among all these W-MSN, WG-MSN templated by hydroxypropyl cellulose acetate succinate HG with the highest drug-loading capacity (24.78%), shortest loading time (10h), drug dissolution improvement of almost 4 times compared to that of the raw drug, and highest bioavailability (5.48 times higher than that of raw drug and 1.52 times higher than that of MSN) was an outstanding drug carrier and can shoulder the mission to deliver drugs with high efficiency.

Renal-friendly Li+-doped carbonized polymer dots activate Schwann cell autophagy for promoting peripheral nerve regeneration.

Activation of autophagy in Schwann cells (SCs) has emerged as a powerful trigger for peripheral nerve injury (PNI) repair. Lithium ion (Li+) is a classical autophagy activator that plays an important role in promoting axonal extension and remyelination. However, the therapeutic window of existing lithium drugs is extremely narrow, and the adverse side effects, especially nephrotoxicity, severely limit their therapeutic value. Herein, Li+-doped carbonized polymer dots (Li-CPDs) was synthesized for the first time to change the pharmacokinetics of Li+ from occupying epithelial sodium channels to lipid raft-mediated endocytosis. The in-vivo results confirmed that Li-CPDs could accelerate the removal of myelin debris and promote nerve regeneration via activating autophagy of SCs. Moreover, Li-CPDs exhibited almost no renal toxicity compared to that of raw lithium drugs. Thus, Li-CPDs could serve as a promising Li+-based nanomedicine for PNI regeneration with improved biosafety. STATEMENT OF SIGNIFICANCE: Regardless of the fact that lithium drugs have been used in treatment of mental illness such as manic depression, the systemic side effects and renal metabolic toxicity still seriously restrict their clinical application. Since Li+ and Na+ compete for ion channels of cell membrane, the cell entry efficiency is extremely low and easily affected by body fluctuations, which seems to be an unsolvable problem. Herein, we rationally exploited the endocytotic features of CPDs to develop Li-CPDs. The Li-CPDs improved the entry pathway, greatly reduced nephrotoxicity, and inherited the biological function of Li+ to activate autophagy for promoting peripheral nerve regeneration. Due to the BBB-crossing property of Li-CPDs, it also showed application prospects in future research on central nervous system diseases.

Two‐stage distributionally robust optimization model for a pharmaceutical cold supply chain network design problem

AbstractPharmaceutical safety has received increasing attention from governments and corporations, and building a safe and effective pharmaceutical cold supply chain network has become an important issue. This paper proposes a two‐stage pharmaceutical cold supply chain network design problem considering drug safety, in which the drug demand, transportation costs, and drug safety risk costs are assumed to be random variables. Due to the presence of uncertainty and the fact that information about the distribution of uncertain parameters is often only partially known, a distributionally robust optimization method is used to handle the uncertainty. A two‐stage distributionally robust optimization model is constructed, in which the reliability of the estimation of the demand necessary to satisfy the entire cold chain network is ensured to be greater than a certain predetermined level by introducing an ambiguous joint chance constraint. The decision process for the problem can be divided into strategic and operational decisions with the goal of minimizing the total costs related to facility construction, the purchase of raw materials, drug production, transportation, and safety risks. By introducing an ambiguity set with mean and covariance information to describe the uncertain parameters, the two‐stage model is eventually reformulated as a standard second‐order cone program, thus making it computationally tractable. Finally, numerical experiments are presented to demonstrate the effectiveness of the proposed models and optimization methods.

Preparation and optimization of surface stabilized cryptotanshinone nanocrystals with enhanced bioavailability.

Cryptotanshinone (CTS) is a plant product extracted from Salvia miltiorrhiza Bunge with various pharmacological significances. In addition to its activities against coronary heart disease, hyperlipidemia, stroke, hepatitis and chronic renal failure, it demonstrates antimetastatic effects. However, its clinical use is limited due to its poor aqueous solubility and oral bioavailability. Herein, CTS nanocrystals were prepared with the precipitation method followed by high-pressure homogenization using Poloxamer 407 as the stabilizer. A stable product was further obtained by lyophilization. The particle size of the CTS nanocrystals was 315.67 ± 11.02 nm, and the zeta potential was near 0mV. The crystallinity was confirmed by DSC and PXRD. The saturation solubility was substantially increased from 0.97 ± 0.12μg/ml to 62.29 ± 1.91μg/ml, and the dissolution rate was also significantly accelerated. A pharmacokinetic study in rats revealed an improvement in oral bioavailability (2.87-fold) with CTS nanocrystals compared to the raw drug. In conclusion, the results of this study suggest a feasible formulation for the oral delivery of CTS.

Chemical Composition and Pharmacological Activity of Plants of the Hypericum L. Genus

The purpose of this work was to present the results of summarizing the literature data on the chemical composition and pharmacological activity of the Hypericum L. genus. The chemical composition of St. John’s wort (Hyperici herba) has been studied quite fully within the Eurasian area of the species; more than 80 components have been identified. The main biologically active compounds of raw materials are anthracene derivatives (hypericin), flavonoids (rutin, quercetin, hyperozoid), phenylpropanoids (chlorogenic acid) and hyperforin. The review article presents physical constants and spectroscopic ((-NMR) proton magnetic resonance, (13C NMR) 13C nuclear magnetic resonance, (-UV) ultraviolet, (-IR) infrared) interpretations of biologically active substances obtained from secondary metabolites from species belonging to genus. The results of pharmacognostic and pharmacological studies determine the feasibility of clinical trials of St. John’s wort raw materials drugs and their use in a wide therapeutic range in the complex treatment of diseases. Herba St. John’s wort is a promising source of raw materials for obtaining antibacterial, antiviral, anti-inflammatory, astringent, diuretic, antidepressant, antioxidant, anticarcinogenic, immunotropic and adaptogenic agents.