Inhibitory effect of benzocaine from Schisandra chinensis on Alternaria alternata.

The clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.

Advancing ocular safety research: A comprehensive examination of benzocaine acute exposure without animal testing.

Benzocaine is a widely employed local anaesthetic; however, there is a notable dearth of preclinical and clinical evidence regarding its safety in ophthalmological products. To address this, a comprehensive strategy incorporating in silico and in vitro methodologies was proposed for assessing benzocaine's ocular toxicity without animal testing. To collect the in silico evidence, the QSAR Toolbox (v4.5) was used. A single exposure to two benzocaine concentrations (2% and 20%) was evaluated by in vitro methods. Hen's Egg Chorioallantoic Membrane Test (HET-CAM) was performed to evaluate the effects on the conjunctiva. To study corneal integrity, Short Time Exposure test (STE) and Bovine Corneal Opacity and Permeability (BCOP) assay, followed by histopathological analysis, were carried out. Results from both in silico and in vitro methodologies categorize benzocaine as non-irritating. The histopathological analysis further affirms the safety of using benzocaine in eye drops, as no alterations were observed in evaluated corneal strata. This research proposes a useful combined strategy to provide evidence on the safety of local anaesthetics and particularly show that 2% and 20% benzocaine solutions do not induce eye irritation or corneal damage, supporting the potential use of benzocaine in the development of ophthalmic anesthetic products.

Novel Microemulsion Containing Benzocaine and Fusidic Acid Simultaneously: Formulation, Characterization, and In Vitro Evaluation for Wound Healing.

Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion formulations for wound healing that contained both fusidic acid (FA), an antibacterial agent, and benzocaine (BNZ), a local anesthetic. Studies on characterization were carried out, including viscosity, droplet size, and zeta potential. The drug-loaded microemulsion had a stable structure with -3.014 ± 1.265 mV of zeta potential and 19.388 ± 0.480 nm of droplet size. In both in vitro release and ex vivo permeability studies, the microemulsion was compared with Fucidin cream and oily BNZ solution. According to the drug release studies, BNZ release from the microemulsion and the BNZ solution showed a similar profile (p > 0.05), while FA release from the microemulsion had a higher drug release compared to Fucidin cream (p < 0.001). The microemulsion presented lower drug permeation (p > 0.05) for both active ingredients, on the other hand, provided higher drug accumulation compared to the control preparations. Moreover, according to the results of in vitro wound healing activity, the microemulsion indicated a dose-dependent wound healing potential with the highest wound healing activity at the highest concentrations. To the best of our knowledge, this developed BNZ- and FA-loaded microemulsion would be a promising candidate to create new opportunities for wound healing thanks to present the active ingredients, which have low water solubility, in a single formulation and achieved higher accumulation than control preparations.

Effect of Food Viscosity on Drug Dissolution.

PURPOSE: The purpose of the present study was to investigate the effect of food viscosity on the dissolution rate of a drug. There are two types of viscosity, macroviscosity and microviscosity. Macroviscosity affects the diffusion layer thickness, whereas microviscosity affects the molecular diffusion coefficient. The mass transfer coefficient (kc) in the intrinsic dissolution rate (IDR) depends on the viscosity (η) as kc ∝ ηa (a is an exponent on η). In theory, for rotating flow over a disk, if a thickener increases only macroviscosity, a = -1/6, and if it increases both macroviscosity and microviscosity equally, a = -7/6. METHOD: Benzocaine was used as a model drug. Hydroxypropyl cellulose (HPC) and methylcellulose (MC) were employed as control thickeners that increase only macroviscosity. Sucrose was employed as a control thickener for both macroviscosity and microviscosity. The FDA breakfast homogenate (BFH) was diluted with distilled water or 1 mM HCl with/without pepsin digestion. The IDR value was measured by the paddle-over-disk method. RESULTS: The η value of 30% BFH distilled water was 209 mPa∙s, about 300 times higher than distilled water. It was further increased by HCl (430 mPa∙s), and reduced by pepsin digestion (35 mPa∙s). The kc value was little affected by BFH (a = 0.00 to -0.09), slightly less than those in HPC (a = -0.19) and MC (a = -0.21). Sucrose decreased the kc value more significantly (a = -0.70). CONCLUSION: The IDR and kc values of benzocaine were little affected by BFH, suggesting that BFH increased only macroviscosity.

An overview of local anesthetics in over-the-counter products.

Over-the-counter (OTC) local anesthetics have historically been used to alleviate pain in several common conditions including toothache and sore throat. With a rise in chronic conditions and an aging population, there has been an increase in associated chronic pain-related disorders. Individuals with chronic pain often seek OTC treatments for quick and accessible pain relief. There are several common OTC local anesthetics, including benzocaine, lidocaine, and dibucaine, which are readily available to patients in several formulations. In order to appropriately advise patients on the use of local anesthetics, it is important to understand their key characteristics, including the mechanism of action, clinical properties, pharmacokinetics, clinical applications, and adverse reactions, which may occur.

Efficacy of benzocaine and lidocaine bioadhesive patches in various minor oral surgical procedures in children - An evaluative study.

Context: The key to successful management of a child in the dental clinic depends greatly on providing painless anaesthesia. Topical anaesthesia using bioadhesive patches may be a breakthrough in this field. Aims: The purpose of the study was to compare the efficacy of Benzocaine and Lidocaine bioadhesive patches in reducing pain associated with various minor oral surgical procedures in children. Methods and Materials: Hundred subjects, aged 6-9 years, requiring various minor oral surgical procedures such as extractions of primary teeth, nerve blocks, mucocele excision or drainage of abscesses were divided equally into Groups 1 and 2. In Group 1, custom fabricated Benzocaine patches were placed for 5 minutes at the target site prior to the procedure, and in Group 2, Lidocaine patches were used in the same manner. Each subject completed a visual analogue scale (VAS) and Wong-Baker Faces pain scale (FPS) after each procedure. Pulse rate and saturation of peripheral oxygen were assessed using pulse oximeter. The duration of the study was from September 2014 to September 2015. Statistical Analysis Used: The statistical analysis was done using paired t test, ANOVA and Bonferroni post hoc analysis. P value less than 0.05 were considered as statistically significant. Results: A significant difference in pain scores was observed favouring the use of Benzocaine over Lidocaine patches (P < 0.05). However, no significant differences in pulse oximeter readings were observed. Conclusions: A statistically significant reduction in pain rating scores was observed in the Benzocaine group after a five-minute application of the patch.

Intraduodenal nutrient infusion differentially alters intestinal nutrient sensing, appetite, and satiety responses in lean and obese subjects.

BACKGROUND: Intestinal nutrient sensing regulates food intake and energy metabolism by acting locally and relaying nutritional status to the brain. It is unclear whether these mechanisms are altered in obese humans. OBJECTIVES: We aimed to investigate differences in duodenal nutrient sensing in humans with or without obesity and the effects of transiently blocking vagal transmission on nutrient sensing, hunger, and appetite. METHODS: In a single-blinded, randomized, cross-over design, subjects with or without obesity (n = 14 and n = 11, respectively) were infused intraduodenally with saline or a combination of glucose and oleic acid for 90 min (glucose load: 22.5 g, 1 kcal/min; oleic acid load: 10 g, 1 kcal/min) in the presence or absence of local anesthetic (benzocaine). Blood was sampled at 10-min intervals (120-240 min) and 15-min intervals until termination of the study for measurements of gut hormones, insulin, leptin, and C-peptide. Hunger and satiety sensations were scored using the visual analog scale, and hepatic glucose production and glucose oxidation rates were measured. RESULTS: Duodenal nutrient infusion in lean subjects led to a 65% drop in acyl ghrelin release and robustly increased cholecystokinin 8 (CCK-8) release (65%; P = 0.023); benzocaine infusion delayed this response (2-factor repeated-measures analysis of variance, P = 0.0065). In contrast, subjects with obesity had significantly blunted response to nutrient infusion, and no further effects were observed with benzocaine. Additionally, significant delays were observed in peptide YY (3-36), pancreatic polypeptide, glucose inhibitory peptide, and glucagon-like peptide 1 (7-36) response. No significant interactions were found between body mass index (BMI) or baseline hormone levels and areas under the curve for hormones except CCK-8 (BMI, P = 0.018; baseline CCK, P = 0.013). Nutrient-induced hunger and satiety sensations were impeded by benzocaine only in the lean cohort. Hunger and satiety sensations in subjects with obesity were not responsive to nutrient entry into the duodenum, and no additional effects were observed by blocking neural signaling. CONCLUSION: Nutrient-induced gut hormone release and response to transient vagal blockade are significantly blunted in subjects with obesity. This trial was registered at clinicaltrials.org as NCT02537314.

When it is too much: Identifying butamben excess on the surface of pharmaceutical preformulation samples by Raman mapping.

Butamben is a topical local anesthetic which formulation in lipid-based drug delivery systems (DDS) is challenging due to its affinity for hydrophilic excipients. This means that a medium polarity excipient is preferred for the development of a stable nanostructured lipid carrier (NLC) formulation. In turn, in NLC, the type and number of excipients will determine the active pharmaceutical ingredient (API) solubility and the maximum drug upload. To solve this dilemma and get the best formulation, a throughout screening study to evaluate API solubilization in different excipients was carried out. Subsequently, excipients with different solubilization capacities were selected for microscopic evaluation by Raman mapping, and in turn analysis of the distributional homogeneity index (DHI) and standard deviation of the histograms allowed solving the posed question. Design of experiments (DoE) was employed to understand better the interactions between the excipients; linear and higher-order models were obtained with R2 above of 0.8824. Even though DHI is a good parameter to be used as response, an API concentration higher than 30% (w/w) provided a homogeneous surface in case of good miscibility and, in this case, this parameter needs to be employed with an inspection and/or evaluation of other parameters. A curve of concentration vs. mean scores of images proved to be an alternative to identify the saturation/limit of linear range.

Acquired Methemoglobinemia in the Surgical Intensive Care Unit.

Acquired methemoglobinemia is a potentially lethal medical condition caused by exposure to oxidizing xenobiotics, including antibiotics such as dapsone and inhaled anesthetics such as benzocaine. In this case report, we describe two presentations of acquired methemoglobinemia which presented to our surgical intensive care unit within one month. This highlights the potential connection between an emergent surgery or procedure and the development of methemoglobinemia in an environment where it is presumed that this condition would be extremely rare. High clinical suspicion for methemoglobinemia is warranted if the patient develops cyanosis or a decreased oxygen saturation unresponsive to supplemental oxygen when another etiology is not identifiable. If methemoglobinemia is suspected, a direct measurement of blood methemoglobin levels can be obtained to confirm the diagnosis. Prompt treatment with intravenous methylene blue is highly effective.

Controllable formation of polydopamine on carbon dots for ultrasensitive detection of alkaline phosphatase and ratiometric fluorescence immunoassay of benzocaine.

Sensing alkaline phosphatase (ALP) activity with high sensitivity and accuracy is critical for both ALP-related health and food safety supervision and the development of ALP-triggered immunoassay platforms. Herein, an ultrasensitive ratiometric fluorescence (RF) sensing system based on the controllable formation of luminescent polydopamine and efficient quenching of carbon dots was proposed for the ALP activity assay, achieving quantitative detection in the range of 0.01-100 mU/L. Furthermore, this RF sensing system was integrated with an ALP-based ELISA platform to construct an RF-ELISA for benzocaine, a potentially abused anesthetic in edible fish, and ultrasensitive assay at the level of fg/mL was realized. This ratiometric strategy-based platform effectively shields various interferences through the self-calibration effect, thus providing more accurate and reliable quantification results. This study not only offers an efficient method for ultratrace detection of ALP and benzocaine but also proposes a universal platform for ultrasensitive detection of diverse targets in food analysis by replacing the recognition unit.

Hemolysis and acquired methemoglobinemia associated with lidocaine and benzocaine topical application: a case report.

BACKGROUND: Topical anesthetics are commonly used over the counter, and one of the adverse effects of these medications is methemoglobinemia, which is a serious and life-threatening condition. CASE PRESENTATION: We describe a 25-year-old Persian male presenting with generalized weakness, dizziness, headache, and cyanosis. In addition, he had genital warts starting 3 weeks ago, which were self-treated with podophyllin, resulting in itching and pain. He used over-the-counter topical anesthetics, including benzocaine and lidocaine, to reduce the symptoms. According to the lab data, signs and symptoms of methemoglobinemia and hemolysis were diagnosed. Considering the hemolysis, ascorbic acid was used for treatment. The patient was discharged after 5 days with normal arterial blood gas and pulse oximetry and no signs and symptoms. CONCLUSION: This case highlights that self-administration of some topical anesthetics may lead to potentially fatal conditions.

Topical Pharyngeal Anesthesia in Sedated Pediatric Patients Undergoing Esophagogastroduodenoscopy.

OBJECTIVES: Pediatric patients undergoing esophagogastroduodenoscopy (EGD) commonly receive procedural sedation for comfort and to facilitate the procedure. EGD with procedural sedation carries the risk of several airway incidents and/or adverse events (AIAE). Topical pharyngeal anesthetics (TPAs) can blunt the airway reflexes and decrease the incidence of laryngospasm but has not been well studied with EGD under procedural sedation. We aimed to study the effect of adding a TPA to propofol-based sedation on the rate of AIAE. METHODS: This is a single-center, retrospective, observational cohort study. We compare AIAE rates (coughing, gagging, apnea, airway obstruction, and laryngospasm) in children who received TPA as part of their propofol-based procedural sedation for EGD with those who did not receive TPA. RESULTS: In 2021, 73 patients received TPA as part of the procedural sedation for EGD and 123 did not. The overall rate of AIAE was high with 75 (38%) patients experiencing 1 or more AIAE. Patients who received benzocaine spray experienced more AIAE than the control group [adjusted odds ratio (aOR) = 1.16; 95% confidence interval (CI): 1.01-1.34; P = 0.037]. Coughing, gagging, apnea with desaturation rates, and laryngospasm were similar in both groups (coughing aOR = 1.01; 95% CI: 0.91-1.13; P = 0.814; gagging aOR = 1.01; 95% CI: 0.91-1.13; P = 0.814; apnea aOR = 0.99; 95% CI: 0.95-1.04; P = 0.688; laryngospasm OR = 1.01; 95% CI: 0.95-1.07; P = 0.71). The rate of airway obstruction requiring jaw thrust was higher in the benzocaine group but did not reach statistical significance (aOR = 1.11; 95% CI: 0.97-1.26; P = 0.133). CONCLUSION: The use of topical pharyngeal benzocaine in children undergoing EGD with propofol-based sedation is associated with a higher overall AIAE rate. Most of the AIAE were mild incidents and only 7 patients experienced true adverse events.

Injectable and topical local anesthetics for acute dental pain: 2 systematic reviews.

BACKGROUND: Local anesthesia is essential for pain control in dentistry. The authors assessed the comparative effect of local anesthetics on acute dental pain after tooth extraction and in patients with symptomatic irreversible pulpitis. TYPES OF STUDIES REVIEWED: The authors searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and the US Clinical Trials registry through November 21, 2020. The authors included randomized controlled trials (RCTs) comparing long- vs short-acting injectable anesthetics to reduce pain after tooth extraction (systematic review 1) and evaluated the effect of topical anesthetics in patients with symptomatic pulpitis (systematic review 2). Pairs of reviewers screened articles, abstracted data, and assessed risk of bias using a modified version of the Cochrane risk of bias 2.0 tool. The authors assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Fourteen RCTs comparing long- vs short-acting local anesthetics suggest that bupivacaine may decrease the use of rescue analgesia and may not result in additional adverse effects (low certainty evidence). Bupivacaine probably reduces the amount of analgesic consumption compared with lidocaine with epinephrine (mean difference, -1.91 doses; 95% CI, -3.35 to -0.46; moderate certainty) and mepivacaine (mean difference, -1.58 doses; 95% CI, -2.21 to -0.95; moderate certainty). Five RCTs suggest that both benzocaine 10% and 20% may increase the number of people experiencing pain reduction compared with placebo when managing acute irreversible pulpitis (low certainty). PRACTICAL IMPLICATIONS: Bupivacaine may be superior to lidocaine with epinephrine and mepivacaine with regard to time to and amount of analgesic consumption. Benzocaine may be superior to placebo in reducing pain for 20 through 30 minutes after application.

Supramolecular assembly of benzocaine bearing cyclodextrin cavity via host-guest complexes on polyacrylonitrile as an electrospun nanofiber.

Nanofibers (NFs) can be encapsulated with cyclodextrins (CDs) based host-guest complexes (HCs) in order to enable many biological applications. Here, benzocaine (BNZ) forms HCs with ß-cyclodextrin (ß-CD) that are co-precipitated and further added to polyacrylonitrile (PAN) solution for making BNZ:ß-CD-HCs/PAN NFs material with the aid of electrospinning technique. The marginal increase in absorbance and fluorescence intensity along with the shift in spectral maxima of BNZ in the presence of ß-CD suggested the host-guest interaction between BNZ and ß-CD. NFs showed a uniform and clean morphology in SEM images and interestingly, the ICs revealed that significantly thinner in terms of average fiber diameter (AFD) than those of free BNZ on PAN medium. BNZ molecule is completely included in the PAN surface as the result of NFs and thus, the original sharp peaks for the BNZ have vanished and the peaks are much broader for the BNZ and BNZ:ß-CD-HCs. BNZ is also found to be a good candidate for anti-inflammatory, anti-oxidant, and anti-diabetic. The results showed an improved activity when it is in the form of HCs on a PAN medium. Making HCs of drugs could be significant in biological applications.

[Possibilities of modern forms of antimicrobial peptides in the treatment of inflammatory pathology of the pharynx]. / Vozmozhnosti sovremennykh form antimikrobnykh peptidov v terapii vospalitel'noi patologii glotki.

Inflammatory diseases of the pharynx occupy one of the leading places in the structure of otorhinolaryngological pathology. Acute and chronic inflammatory processes in the pharynx, as well as exacerbations of the latter, are faced by doctors of a wide range of specialties. Oropharyngeal swab laboratory testing is required to identify a specific pathogen, which takes time. In this regard, of particular interest are local drugs with the necessary spectrum of action, the use of which is possible, both as monotherapy and in combination with systemic therapy. The combination of tyrothricin (tyrothricin), benzalkonium chloride (benzalkonium chloride), and benzocaine (benzocaine) (dorithricin) is highly effective in the treatment of bacterial, viral and fungal infections of the pharynx, and microorganisms consistently demonstrate high sensitivity to the components of the drug.

Reagentless Voltammetric Identification of Cocaine from Complex Powders.

Cocaine is one of the most commonly trafficked and abused drugs in the United States, and deployable field tests are important for rapid identification in nonlaboratory settings. At present, colorimetric tests exist for in-field determination, but these fundamentally suffer from interferent effects. Cocaine is an organic salt that is readily water soluble as a cation and almost insoluble in the deprotonated neutral form. Here, we take advantage of the electrochemical window of water to increase the pH at the electrode surface by driving water reduction, effectively electroprecipitating the cocaine base. The precipitate on the electrode surface is then electrochemically oxidized by a voltammetric sweep through sufficiently positive potentials. We demonstrate excellent selectivity to cocaine compared to common adulterants, such as procaine, lidocaine, benzocaine, caffeine, and levamisole. Finally, we detect cocaine on a carbon fiber microelectrode, demonstrating miniaturizability and allowing access to low-resistance media (e.g., tap water).

Case Report: An Uncommon Etiology of Vulvar Irritation and Swelling in an Adolescent Patient.

INTRODUCTION: Vulvovaginal concerns are common among adolescent patients. In postmenarchal patients, common etiologies include poor hygiene, contact irritants, and infection. CASE: A 14-year-old transgender male presented with concerns of vulvar irritation and significant labial enlargement. Comprehensive workup including tissue biopsies and imaging suggested chronic inflammation. His clinical course was complicated by an episode of methemoglobinemia secondary to local anesthetic toxicity, at which time his care team recognized use of large quantities of Vagisil, which contains benzocaine. Ultimately, vulvar changes were recognized to be secondary to chronic Vagisil use. SUMMARY AND CONCLUSION: This case highlights the potential dangers of off-the-shelf products, such as Vagisil. In patients presenting with vulvovaginal complaints, care providers should carefully screen for use of "hygiene products" as part of exposure history.

Determination of Benzocaine in Pharmaceutical Formulations by Indirect SERRS Assay Combined with Azo Coupling.

Coupled with an azo coupling reaction, a simple, rapid, sensitive, and effective surface-enhanced resonance Raman scattering (SERRS) detection method for benzocaine was developed. In our study, benzocaine which is used clinically as a local anesthetic was derived with p-aminothiophenol into a corresponding azo product within 5 min, resulting in a strong SERRS response with the simple addition of Ag NPs excited with a 532 nm laser. The linear correlation between SERRS intensity of dominant bands and logarithm of benzocaine concentration was investigated for quantitative determination. The method reached a limit of detection (LOD) down to 0.139 and 0.0788 µg/mL calculated with two peak intensity ratios (I1568/I2260 and I1331/I2260), which is comparable to most studies reported previously, and meanwhile had superiority in simplicity and rapidness. The quantitative measurements for pharmaceutical preparations with benzocaine were conducted without complex extraction and enrichment processes. It was indicated that the SERRS assay combined with azo derivatization reaction has implications for practical applications in more complicated systems involving biological samples, in which appropriate and simplified pretreatments were conducted to remove interfering components.