Gastrointestinal Irritation Research Articles

Evaluating the Antidote Action of Nimbuk Swarasa and Peya in Jayapala Toxicity: A Critical Review

Jayapala (Myristica fragrans), a plant-based toxin, is recognized for its therapeutic importance despite its toxic properties. Improper administration or insufficient purification can lead to adverse effects, including gastrointestinal irritation, salivation, and even death. The management of Jayapala poisoning is well-documented in classical Ayurvedic texts, with specific antidotes such as Nimbuk Swarasa (lemon juice) and Peya (rice water) being highlighted. This review critically evaluates the mode of action of Nimbuk Swarasa and Peya in Jayapala poisoning, to establish their therapeutic efficacy and practical applicability as antidotes. The study highlights the antidotal potential of Nimbuk Swarasa and Peya in enhancing digestive function, alleviating symptoms, and providing a cost-effective solution for managing Jayapala toxicity. The findings indicate that these preparations not only mitigate harmful effects but also embody a practical approach to addressing accidental poisoning

Extraction, pharmacological prediction and experimental verification of Coreopsis tinctoria flowers

Coreopsis tinctoria (C. tinctoria) is a traditional plant with high medicinal value and edible value. It has the effect of invigorating spleen and stomach and has the potential to develop into flower tea. Therefore, the extraction process of C. tinctoria extract (CTA) was optimised by analytic hierarchy process (AHP) combined with orthogonal test, and its activity was predicted by network pharmacology and verified by experiments. The optimal extraction conditions: temperature of 80 °C, extraction period of 10 min, solid-liquid ratio of 1:70 and times 2. CTA had no gastrointestinal irritation and can significantly increase the faecal water content of mice, inhibit amylase activity, increase protease, xylanase and cellulase activity, increase the number of intestinal Lactobacillus and Bifidobacterium, reduce the number of Escherichia coli and Enterococcus. In summary, CTA can effectively improve the intestinal digestive enzyme activity and the number of probiotics and has the potential to treat gastrointestinal diseases.

A review of the botany, metabolites, pharmacology, toxicity, industrial applications, and processing of Polygalae Radix: the "key medicine for nourishing life".

Polygalae radix (PR) is the dried root of Polygala tenuifolia Willd. and Polygala sibirica L. and enjoys the reputation as the "key medicine for nourishing life." In this study, information about "Polygala tenuifolia Willd.," "Polygala sibirica L.," and "Yuanzhi" was retrieved from scientific databases, including Google Scholar, Baidu Scholar, Web of Science, PubMed, CNKI, and Wan Fang Data. Information from Chinese herbal medicine classics, Yaozhi Data, and the Gaide Chemical Network was also collected. Information related to botany, phytochemistry, pharmacology, toxicity, industrial applications, and processing is summarized in this paper to tap its potentialities and promote its further development and clinical application. More than 320 metabolites have been isolated from PR; saponins, xanthones, and oligosaccharide esters are the main functional metabolites. Pharmacological research shows that its pharmacological action mainly focuses on resisting nervous system diseases, and it also has the functions of anti-oxidation, anti-inflammation, anti-tumor, anti-pathogenic microorganisms and others. The gastrointestinal irritation of its saponins impeded its application, but this irritation can be reduced by controlling the dosage, compatibility with other herbs, or processing. The future progress of PR faces opportunities and challenges. More attention should be paid to the traditional application and processing methods of PR recorded in ancient books. The lack of safety and clinical studies has limited its application and transformation of achievements. Moreover, it is one-sided to take the content of only a few metabolites as the index of processing optimization and quality control, which cannot reflect the full pharmacological and toxicological activities of PR.

Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs) are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery of BPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolving and hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawley rats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkaline phosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls. Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVX controls and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. In the distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21 % in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. This proof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternative for weekly osteoporosis management.

Advanced Delivery Strategies of Nintedanib for Lung Disorders and Beyond: A Comprehensive Review.

Nintedanib, a primary treatment for lung fibrosis, has gathered substantial attention due to its multifaceted potential. A tyrosine kinase inhibitor, nintedanib, inhibits multiple signalling receptors, including endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) and ultimately inhibits fibroblast proliferation and differentiation. Therefore, nintedanib has been studied widely for other ailments like cancers and hepatic fibrosis, apart from lung disorders. Commercially, nintedanib is available as soft gelatin capsules for treatment against idiopathic pulmonary fibrosis. Since it has very low oral bioavailability (4.7%), high doses of a drug, such as 100-150mg, are administered, which can cause problems of gastrointestinal irritation and hepatotoxicity. The article begins with exploring the mechanism of action of nintedanib, elucidating its complex interactions within cellular pathways that govern fibrotic processes. It also emphasizes the pharmacokinetics of nintedanib, clinical trial insights, and the limitations of conventional formulations. The article mainly focuses on the emerging landscape of nanoparticle-based carriers such as hybrid liposome-exosome, nano liquid crystals, discoidal polymeric, and magnetic systems, offering promising avenues to optimize drug targeting, address its efficacy issues and minimise adverse effects. However, none of these delivery systems are commercialised, and further research is required to ensure safety and effectiveness in clinical settings. Yet, as research progresses, these advanced delivery systems promise to revolutionise the treatment landscape for various fibrotic disorders and cancers, potentially improving patient outcomes and quality of life.

Lipid-based systems with precipitation inhibitors as formulation approach to improve the drug bioavailability and/or lower its dose: a review.

Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (m/m). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.

Analısıs Kualıtatıf Rhodamın B pada Perona Mata (Eyeshadow) yang Beredar dı Toko Kosmetık Kota Tarakan

Both adults and teenagers often use eyeshadow as a common cosmetic. The paint and textile industry often uses a red synthetic dye known as rhodamine B. Apart from having carcinogenic properties, continued use of rhodamine B can cause liver problems and gastrointestinal irritation which has the potential to hurt health. This research aims to answer the problem, of whether or not eyeshadow preparations sold in Tarakan City beauty shops contain Rhodamine B. The method in this research uses a wool thread technique and a rhodamine B rapid test kit to carry out qualitative analysis using eleven samples. The results showed that of the eleven eyeshadow samples examined at the Tarakan City cosmetics shop, three samples experienced a color change from red to dark red or purplish. Two of the eyeshadows are not registered, while one is registered with BPOM. Based on these findings, it can be concluded that three of the eleven eyeshadow samples tested positive for rhodamine B.

#1301 Orellanine intoxication—a case report

Abstract Background and Aims This is a case report presenting a patient with orellanine-caused acute kidney failure. Cortinarius rubellus is a mushroom containing orellanine which is a selective nephrotoxin that destroys the proximal tubule cells of the kidney. Intake of just a few mushrooms is enough to cause irreversible damage and furthermore lead to severe kidney failure. Symptoms as gastrointestinal irritation usually occur 3-7 days after intake. Anti-oxidative medication and steroids have been evaluated but have not shown any effect on the kidney damage. The aim of this case report was to raise awareness about the clinical manifestations of orellanine poisoning, diagnostic challenges, and potentially severe consequences. Method The junior doctors (IA, LT, AS) and the senior doctor (JM) took care of the patient at the ED, the internal medicine ward and the dialysis clinic. All data was extracted from the medical record. Informed consent was obtained from the patient. An attempt to analyze orellanine in the kidney biopsy was made. Results A 40-year-old male entered the emergency department with abdominal pain, fever, nausea and vomiting. The creatinine concentration was 278 µmol/L (3.14 mg/dl) where acute kidney failure due to prerenal cause was suspected. The patient was recommended to stay but declined due to personal reasons, and instead a follow-up next day was planned. The following day, the creatinine concentration was increased to 477 µmol/L (5.39 mg/dl). The junior doctor specifically asked for mushroom intake. The patient confirmed that three days before, he had been in the forest picking mushrooms, of which he consumed two raw and the rest in a stew. Acute renal failure from mushroom poisoning was now suspected. The patient was admitted, and serum creatinine increased to 817 µmol/L (9.24 mg/dl) the following day. The urine production decreased, and the patient was anuric 7 days after intake. Hemodialysis was initiated due to uremic symptoms and volume overload. After showing the patient different photos of mushrooms it was suspected that he had consumed Cortinarius Rubellus. A renal biopsy was performed 12 days after the mushroom intake, which showed a fulminant acute tubular necrosis, no sign of glomerulonephritis, vasculitis, or interstitial nephritis. The attempt to analyze orellanine in the kidney biopsy material was not successful. Orellanine would not be detected in the urine or blood samples because they were collected 72 hours after intake. The half-life of orellanine in otherwise healthy humans is considered to be around 2-4 hours. The patient stayed at the hospital for a total of 14 days. He was on hemodialysis for 14 months and was then successfully kidney transplanted. Conclusion Orellanine is a very potent toxin leading to severe damage of the kidney tubules. Due to the diagnostic challenges, it is important to keep this in mind when managing a patient with acute renal failure.

Patient-focused programable release indomethacin tablets prepared via conjugation of hot melt extrusion (HME) and fused depositional modeling (FDM) -3D printing technologies

Indomethacin (IND) eases the chronic pain caused by Juvenile idiopathic arthritis (JIA) in clinic, but it was reported that it has dose-related side effects such as gastrointestinal irritations and potential damage to nervous system. So, there is a considerable demand for offering effective, safety, and quality IND dosages for individual pediatric and youth patients. The main aim of this work is to on-demand manufacture personalized and programmable release IND tablets via combining hot melt extrusion (HME) and 3D printing technologies based on the structure-release correlations. IND loaded filaments were extruded and then the tablets were designed and printed. A series of physical and chemical characterization studies were also conducted, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot stage polarized light microscopy (PLM), texture analysis, and in vitro drug release studies. The results showed that IND was dispersed in HPMCAS matrix and formed amorphous solid dispersions (ASDs). Additionally, the in vitro drug release studies demonstrated that the release of IND can be programmed via manipulating 3D structure design. The mathematical model to predict the IND from structural designed tablets was obtained and two tablets (T-v1 and T-v2) were printed to validate such model, where the fitting coefficient are 0.9964 and 0.9965, respectively. This study suggested that combining HME and 3D printing technologies could be an optimal approach for personalized and precision drug delivery dosage development.

A novel approach to exploit Small-Molecule glucagon-like Peptide-1 receptor agonists with high potency

Small-molecule glucagon-like peptide-1 receptor (GLP-1R) agonists are recognized as promising therapeutics for type 2 diabetes mellitus (T2DM) and obesity. Danuglipron, an investigational small-molecule agonist, has demonstrated high efficacy in clinical trials. However, further development of danuglipron is challenged by a high rate of gastrointestinal adverse events. While these effects may be target-related, it is plausible that the carboxylic acid group present in danuglipron may also play a role in these outcomes by affecting the pharmacokinetic properties and dosing regimen of danuglipron, as well as by exerting direct gastrointestinal irritation. Therefore, this study aims to replace the problematic carboxylic acid group by exploring the internal binding cavity of danuglipron bound to GLP-1R using a water molecule displacement strategy. A series of novel triazole-containing compounds have been designed and synthesized during the structure–activity relationship (SAR) study. These efforts resulted in the discovery of compound 2j with high potency (EC50 = 0.065 nM). Moreover, docking simulations revealed that compound 2j directly interacts with the residue Glu387 within the internal cavity of GLP-1R, effectively displacing the structural water previously bound to Glu387. Subsequent in vitro and in vivo experiments demonstrated that compound 2j had comparable efficacy to danuglipron in enhancing insulin secretion and improving glycemic control. Collectively, this study offers a practicable approach for the discovery of novel small-molecule GLP-1R agonists based on danuglipron, and compound 2j may serve as a lead compound to further exploit the unoccupied internal cavity of danuglipron's binding pocket.

Novel trifluoromethyl ketone derivatives as oral cPLA2/COX-2 dual inhibitors for resolution of inflammation in rheumatoid arthritis

Thirty-five trifluoromethyl hydrazones and seventeen trifluoromethyl oxime esters were designed and synthesized via molecular hybridization. All the target compounds were initially screened for in vitro anti-inflammatory activity by assessing their inhibitory effect on NO release in LPS-stimulated RAW264.7 cells, and the optimal compound was finally identified as 2-(3-Methoxyphenyl)-N'-((6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-ylidene)acetohydrazide (F26, IC50 = 4.55 ± 0.92 μM) with no cytotoxicity. Moreover, F26 potently reduced the production of PGE2 in LPS-stimulated RAW264.7 cells compared to indomethacin. The interaction of F26 with COX-2 and cPLA2 was directly verified by the CETSA technique. F26 was found to modulate the phosphorylation levels of p38 MAPK and NF-κB p65, as well as the protein expression of IκB, cPLA2, COX-2, and iNOS in LPS-stimulated rat peritoneal macrophages. Additionally, F26 was observed to prevent the nuclear translocation of NF-κB p65 in LPS-stimulated rat peritoneal macrophages by immunofluorescence localization. Therefore, the aforementioned in vitro experiments demonstrated that F26 blocked the p38 MAPK and NF-κB pathways by binding to COX-2 and cPLA2. In the adjuvant-induced arthritis model, F26 demonstrated a significant effect in preventing arthritis symptoms and inflammatory status in rats, exerting an immunomodulatory role by regulating the homeostasis between Th17 and Treg through inhibition of the p38 MAPK/cPLA2/COX-2/PGE2 and NF-κB pathways. Encouragingly, F26 caused less acute ulcerogenicity in rats at a dose of 50 mg/kg compared to indomethacin. Overall, F26 is a promising candidate worthy of further investigation for treating inflammation and associated pain with lesser gastrointestinal irritation, as well as other symptoms in which cPLA2 and COX-2 are implicated in the pathophysiology.

Multiple drug-delivery strategies to enhance the pharmacological and toxicological properties of Mefenamic acid

ObjectiveTo improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS). MethodsThe in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer. ResultsWhen the PSs were resuspended in water, MefeGAL’s, MA’s and their mixture’s apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS. ConclusionsThese preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs.

Transdermal Delivery of Ketoprofen for Osteoarthritis Treatment and Management: A Literature Review on Current Progression

Arthritis, a diverse spectrum of joint disorders, is characterized by chronic pain and inflammation. Osteoarthritis (OA), the most prevalent form, leads to disabling pain, functional limitations, and reduced mobility. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for managing OA pain, with ketoprofen recognized as one of the effective options. However, oral administration of ketoprofen may cause gastrointestinal irritation. Addressing this issue, Transdermal Drug Delivery Systems (TDDS) emerge as a promising alternative route of administration. TDDS facilitates delivery of various drugs through the skin without undergoing first-pass metabolism. Recent studies have centered on enhancing ketoprofen’s transdermal delivery, particularly focusing on different methods (such as patches, gels, electroporation technology, and stratum corneum bypass methods), with microneedles emerging as a promising approach for delivering anti-inflammatory drugs through transdermal routes. This review aims to explore recent advancements in transdermal drug delivery systems for managing OA. The utilization of transdermal ketoprofen presents innovative opportunities for future research and development in novel drug delivery systems.

Anodic oxidation of esomeprazole in water by carbon coated titanium (C/Ti) electrode: Optimization and degradation analysis

AbstractEsomeprazole (ESO) is one of the proton pump inhibitors (PPIs) that is commonly used to treat extreme acidity and gastrointestinal irritation. Since it is used at a high rate, it is now classified as a pollutant of emerging concern (CEC). ESO gravely jeopardizes the health of living beings because it persists in water and wastewater sources even after standard treatment. Studies on the effective removal of PPIs, especially ESO, are scarce. In the current study, esomeprazole is disintegrated in water using electrochemical oxidation (EO). Titanium cathode with sodium sulfate electrolyte and carbon coated titanium (C/Ti) anode were used to apply EO. Through optimization studies utilizing COD measurement, it was discovered that 93% of the COD could be removed at pH 3, 60 mM sodium sulfate concentration, 300 min treatment period, and 115 mA cm−2 current density. Whereas TOC research revealed only 44% mineralization, HPLC‐PDA experiments revealed 100% ESO transformation. High resolution mass spectrometry (HRMS) studies were used to propose a degradation mechanism and pathway. The primary processes of degradation included desulfurization, thioperoxole group formation, sulfinyl benzimidazole group breakage, and demethylation. More than 20 reuses of the anode and cathode materials were possible without significantly lowering their oxidation efficiency.

Antipyretic and Antinociceptive Effect of the Methanol Leaf Extract of Ficus asperifolia in Murine Models

Pyrexia occurs as a result of the resetting of the hypothalamic set-point. Non steroidal anti-inflammatory drugs used for the treatment of fever and related illnesses are associated with side effects including gastrointestinal irritation, bleeding, ulcers and perforation. In traditional medicine, many plants have been found to possess antipyretic activity. Ficus asperifolia (Miq), family Moraceae has been traditionally used to treat pain and fevers. The aim of the study was thus to evaluate the antipyretic and antinociceptive activity of the methanol leaf extract of Ficus asperifolia (FME) in murine models. Preliminary phytochemical screening and oral acute toxicity studies were conducted using standard protocols. Antipyretic activity was evaluated using the Brewer’s yeast induced pyrexia model. Antinociceptive effects were investigated using the acetic acid and thermal induced models. The mechanism of action of the plant was also evaluated against several antagonists. FME significantly (p<0.05) and dose dependently reduced yeast induced pyrexia. FME at doses 125, 250 and 500 mg/kg significantly (p<0.05) decreased acetic acid induced abdominal writhes and increased the mean reaction time of mice to thermal-induced pain stimulus. Pre-treatment of mice with naloxone (a non-selective opioid receptor antagonist), glibenclamide (a potassium channel blocker) and L-NNA (a nitric oxide synthase inhibitor) significantly reversed the analgesic action of the extract suggesting that the activity is likely mediated via the involvement of these pathways.

Multi-locus phylogenies revealed a new record of Entoloma species (Basidiomycota, Agaricales) responsible for gastrointestinal poisoning

The frequency of mushroom poisoning has increased worldwide. In Thailand, reports on mycetism between 2013 and 2021 included 18 cases of Entoloma poisoning. Incorrect identification of toxic Entoloma species occurs during wild mushroom foraging, and their consumption results in gastrointestinal irritation. Morphological distinction of mushroom leftovers is difficult; however, we aimed to characterize 40 clinical samples to the genus level using macroscopic and microscopic analyses. Furthermore, species identification of the poisonous Entoloma was performed based on multi-locus phylogenetic analyses of the nuclear internal transcribed spacer region, nuclear large subunit ribosomal DNA, and mitochondrial small subunit ribosomal DNA. Phylogenetic trees reconstructed using maximum likelihood and Bayesian methods demonstrated that forty samples of mushroom remnants formed eight robust clades with six identified species. The findings confirmed the taxonomic identity of E. griseolazulinum as a new record of species causing gastrointestinal poisoning. The use of molecular annotation provided a foundation for the development of accurate methods for identification of toxic mushrooms.

OPTIMIZATION OF DICLOFENAC POTASSIUM TRANSDERMAL PATCH FORMULA USING A COMBINATION OF POLYVYNIL PYRROLIDONE K 30, ETHYL CELLULOSE AND MENTHOL WITH SIMPLEX LATTICE DESIGN METHOD

Diclofenac potassium is one of the NSAID drugs which can cause gastrointestinal irritation and damage to the small intestinal mucosa including erosion and ulceration. The purpose of this study was to determine the effect of the combination of PVP K 30, ethyl cellulose and menthol on organoleptic, thickness, weight uniformity, moisture and folding resistance of diclofenac potassium transdermal patch.This research is an experimental study that includes an experiment to optimize the formulation of a transdermal patch preparation with the active ingredient potassium diclofenac and a combination of PVP K 30, ethyl cellulose and menthol. The optimization method uses the simplex lattice design method. There are 13 formula designs consisting of a combination of PVP K 30, ethyl cellulose and menthol. Each formula was tested for organoleptic, thickness, weight uniformity, moisture and folding resistance. Then the optimum formula was determined and analyzed using the simplex lattice design method. The combination of PVP K 30, ethyl cellulose and menthol with a simplex lattice design has an effect on the transdermal patch of diclofenac potassium which increases the consistency of the patch surface, reduces the thickness directly proportional to the weight of the patch and increases folding resistance. The proportion of PVP K 30, ethyl cellulose and menthol that can produce the optimum formula for diclofenac potassium transdermal patches with the simplex lattice design on the critical parameters of thickness, moisture, folding resistance and penetration tests, namely PVP K 30 of 14.87%, ethyl cellulose of 10.00% and 5.13% menthol.

Topical drug delivery strategies for enhancing drug effectiveness by skin barriers, drug delivery systems and individualized dosing.

Topical drug delivery is widely used in various diseases because of the advantages of not passing through the gastrointestinal tract, avoiding gastrointestinal irritation and hepatic first-pass effect, and reaching the lesion directly to reduce unnecessary adverse reactions. The skin helps the organism to defend itself against a huge majority of external aggressions and is one of the most important lines of defense of the body. However, the skin's strong barrier ability is also a huge obstacle to the effectiveness of topical medications. Allowing the bioactive, composition in a drug to pass through the stratum corneum barrier as needed to reach the target site is the most essential need for the bioactive, composition to exert its therapeutic effect. The state of the skin barrier, the choice of delivery system for the bioactive, composition, and individualized disease detection and dosing planning influence the effectiveness of topical medications. Nowadays, enhancing transdermal absorption of topically applied drugs is the hottest research area. However, enhancing transdermal absorption of drugs is not the first choice to improve the effectiveness of all drugs. Excessive transdermal absorption enhances topical drug accumulation at non-target sites and the occurrence of adverse reactions. This paper introduces topical drug delivery strategies to improve drug effectiveness from three perspectives: skin barrier, drug delivery system and individualized drug delivery, describes the current status and shortcomings of topical drug research, and provides new directions and ideas for topical drug research.

Polygalae Radix: review of metabolites, pharmacological activities and toxicology.

Polygalae Radix: is the dried root of Polygala tenuifolia Willd. or Polygala sibirica L., which has the effect of improving memory and cognitive function in traditional Chinese medicine. Modern pharmacological studies indicated that Polygalae Radix has rich pharmacological activities in vitro and in vivo, including protective effects on the nervous system, immune system, cardiovascular system and respiratory system, as well as antioxidant and antiepileptic pharmacological activities. Up to now, more than 160 metabolites from Polygalae Radix were identified, including triterpenoid saponins, xanthones, oligosaccharide esters and et al. The clinical practice of traditional Chinese medicine has proved that Polygalae Radix has a certain irritation to the throat, and a large or long-term use will stimulate the digestive tract, and the main toxic metabolite is saponins. Therefore, Polygalae Radix should be pr ocessed or used in combination with other Chinese herbal medicines to reduce the irritation to the throat and reduce gastrointestinal irritation. This article provides a review of the metabolites, pharmacological activity, and toxicology of Polygalae Radix. It also discusses the future research prospects and existing problems of Polygalae Radix, providing reference for further research on Polygalae Radix.

Plasmapheresis as an Adjunctive Section Therapy for Yellow Phosphorus Poisoning: A Case Report

Yellow Phosphorus (YP) poisoning is an infrequent, yet severe medical condition characterised by multi-systemic toxicity. The ingestion or inhalation of YP can lead to gastrointestinal irritation, hepatic injury, and Acute Liver Failure (ALF). Plasmapheresis, a therapeutic intervention involving the removal and replacement of plasma components, is a potential adjunctive treatment for YP poisoning. This case report aims to explore the mechanistic rationale, clinical efficacy, and safety considerations of plasmapheresis in the management of this toxicological emergency. Here, a 16-year-old female reported to the Emergency Department (ED), having consumed 1-2 g of Ratol poison at two different times of the day. She came to the hospital on day 4 post-consumption. On admission, the patient was jaundiced and Arterial Blood Gas (ABG) analysis was suggestive of respiratory alkalosis with hypokalemia. Treatment focused on fluid therapy, vitamin K therapy, and N-Acetyl Cysteine (NAC). She developed angioedema and urticaria with no airway compromise, in response to intravenous NAC. A diagnosis of acute liver injury secondary to YP poisoning was made. Close monitoring of liver function and coagulation parameters, and bleeding complications was done. Plasmapheresis was considered as NAC reinitiating was not feasible due to potential anaphylaxis. The patient responded well to the treatment and was discharged on day 7 of hospitalisation.