Analysis of clinical features of seven patients with granular parakeratosis after benzalkonium chloride exposure / 中华皮肤科杂志

Objective:To summarize clinical manifestations and histopathological features of granular parakeratosis (GP) after exposure to benzalkonium chloride.Methods:A retrospective analysis was performed on 7 GP cases with a history of benzalkonium chloride exposure in the Department of Dermatology at Wuhan No.1 Hospital from April to August 2022. Data were collected on the general condition, skin lesion manifestations, pathological examination, treatment, and follow-up of the patients, and retrospectively analyzed.Results:The 7 adult patients with GP typically presented with erythema and brown scales in the intertriginous area, exhibiting an annular distribution pattern. All the 7 patients reported recent exposure to disinfectants containing benzalkonium chloride. A total of 10 skin biopsies were taken from the 7 patients. Histopathological examination showed characteristic hyperkeratosis and fine blue-gray parakeratotic granules in the stratum corneum. All skin lesions improved 1 month after cessation of exposure to benzalkonium chloride.Conclusion:GP has a distinct clinical pattern and histopathological manifestations, and a history of exposure to benzalkonium chloride can be helpful for the diagnosis of GP.

In vitro evaluation for estrogenic mechanisms of the disinfectant benzalkonium chloride as an emerging contaminant

This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3β‐HSD2, 17β‐HSD1, 17β‐HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism.

Studies on Antimicrobial Preservatives Screening and Antimicrobial Efficacy of Diclofenac Sodium Eye Drops / 中国药学杂志

OBJECTIVE: To evaluate the bacteriostatic efficacy of diclofenac sodium eye drops and to explore the reasonable dose of benzalkonium chloride, ethylparaben and thimerosal in diclofenac sodium eye drops. METHODS: According to the method of bacteriostatis effect test in 2015 edition of Chinese Pharmacopoeia (Ch.P),and Escherichia coli, Staphylococcus aureus, Pesudomonas aeruginosa, Candida albicans and Aspergillus niger as test strains,the bacteriostatis effect of diclofenac sodium eye drops from 10 batches of the samples was determined. Also, the concentration gradient of benzalkonium chloride, ethylparaben and thimerosal in diclofenac sodium eye drops was designed to investigate the optimum bacteriostatic concentration. RESULTS: The samples from 3 manufacturers could reach level B, no sample could reach level A,and those from 7 manufacturers did not comply with the specification. When the concentration of thimerosal was 0.01 mg•mL-1 and the concentration of ethylparaben was 0.3 mg•mL-1 in diclofenac sodium eye drops, the bacteriostatic efficacy could reach level B. When the concentration of benzalkonium chloride was 0.01 mg•mL-1, the bacteriostatic efficacy could reach level A. CONCLUSION: The bacteriostatis effect of diclofenac sodium eye drops from 10 batches of the samples is not good, It is recommended that these manufacturers should optimize the type and concentration of antimicrobial agents and optimize their formulation based on both biological tests and physical-chemical tests to ensure drug safety.

Effects of benzalkonium chloride and cyclosporine applied topically to rabbit conjunctiva: a histomorphometric study / Efeitos do uso tópico do conservante cloreto de benzalcônio e ciclosporina na conjuntiva de coelhos: estudo histomorfométrico

ABSTRACT Purpose: Chronic instillation of benzalkonium chloride, a preservative, has inflammatory effects on the ocular surface. However, addition of the anti-inflammatory agent cyclosporine to a therapeutic protocol may mitigate these effects. This study compared the toxic effects of a 0.1% benzalkonium chloride solution and the possible protective effect of 0.05% cyclosporine when applied topically to the rabbit conjunctiva. Methods: Fifteen age- and weight-matched, female New Zealand white rabbits were categorized into three groups and treated for 30 consecutive days. Group 1, 2, and 3 - benzalkonium chloride received 0.1% every 24 h, 0.05% cyclosporine every 6 h, and both treatments, respectively. In each rabbit, the left eye was subjected to treatment and the right eye was a control. The rabbits were euthanized at after the experiment. Goblet cells and blood vessels were then enumerated in conjunctival tissues stained with periodic acid-Schiff and hematoxylin-eosin, respectively. Differences between treated and untreated eyes and between groups were compared using the t-test and analysis of variance. Results: Benzalkonium chloride treatment, with and without cyclosporine, significantly reduced (p≤0.05) in the number of goblet cells in treatment eyes compared with that in respective control eyes. Alternatively, adding cyclosporine to benzalkonium chloride did not prevent the loss of conjunctival goblet cells, and a significant reduction in the number of goblet cells was noted. Benzalkonium chloride-induced significant increase in the number of new blood vessels was mitigated significantly by the addition of cyclosporine. Conclusion: This study demonstrated the magnitude of conjunctival injury caused by chronic instillation of benzalkonium chloride. Although cyclosporine did not mitigate the effects on goblet cells, its addition minimized inflammatory angiogenesis induced by benzalkonium chloride.

RESUMO Objetivo: A instilação crônica de cloreto de benzal­cônio, um conservante, tem efeitos inflamatórios na superfície ocular. No entanto, a adição do agente anti-inflamatório ciclosporina a um protocolo terapêutico pode atenuar esses efeitos. Este estudo comparou os efeitos tóxicos de uma solução de cloreto de benzalcônio a 0,1% e o possível efeito protetor de ciclosporina a 0,05% quando aplicado topicamente à conjuntiva de coelho. Métodos: Quinze coelhos fêmeas brancos da raça Nova Zelândia, pareados por idade e peso, foram categorizados em três grupos e tratados por 30 dias consecutivos. Os grupos 1, 2 e 3 - receberam cloreto de benzalcônio 0,1% a cada 24h, ciclosporina a 0,005% a cada 6h e ambos os tratamentos, respectivamente. Em cada coelho, o olho esquerdo foi submetido a tratamento e o olho direito foi controle. Os coelhos foram submetidos à eutanásia após o experimento. Células caliciformes e vasos sanguíneos foram então enumerados em tecidos conjuntivais corados com ácido periódico-Schiff e hematoxilina-eosina, respectivamente. As diferenças entre os olhos tratados e não tratados e entre os grupos foram comparadas usando o teste t e análise de variância. Resultados: O tratamento com cloreto de benzalcônio, com e sem ciclosporina, reduziu significativamente (p£0,05) o número de células caliciformes nos olhos tratados em comparação com os olhos controle correspondentes. Alternativamente, a adição de ciclosporina ao cloreto de benzalcônio não impediu a perda de células caliciformes conjuntivais, e foi observada uma redução significativa no número de células caliciformes. O aumento significativo induzido pelo cloreto de benzalcônio no número de novos vasos sanguíneos foi significativamente mitigado pela adição da ciclosporina. Conclusão: Este estudo demonstrou a magnitude da lesão conjuntival resultante da instilação crônica de cloreto de benzalcônio. Embora a ciclosporina não tenha atenuado os efeitos nas células caliciformes, sua adição minimizou a angiogênese inflamatória induzida pelo cloreto de benzalcônio.

A new experimental model of intrinsic denervation in ileum from wistar rats through intramural microinjections of benzalkonium chloride / Um novo modelo experimental de desnervação intrínseca em íleo de ratos wistar através de micro injeções intramurais de cloreto de benzalcônio

Extensive literature is available about the intrinsic denervation of segments of the digestive tube through the application of CB in the serosa of the viscera. However, this technique has some disadvantages like causing peritonitis, flanges and high mortality, limiting its use in humans. The aim of the present study was to evaluate the feasibility of benzalkonium chloride (CB) to induce intrinsic chemical denervation, through applications of CB in the intramural ileum of wistar rats, as well as deepen the knowledge about the evolution of neuronal injury caused in the process. We used 40 rats, divided into two groups (control-GC and benzalkonium-GB) of 20 animals each, divided into four sub-groups according to the time of postoperative assessment of 24, 48 hours, 30 and 90 days. The animals were submitted to intramural microinjections of sterile saline solution 0.9% (GC) or benzalkonium chloride (GB) in ileal portion, and subsequent histopathological analysis and immunohistochemistry for evaluation of neuronal injury. A significant decrease (p<0.05) was found of the neuronal myenteric count over time in groups, GB3, GB4 and GB2. The specific positive immunolabeling for H2AX and Caspase-3 confirmed the results obtained in the histopathological evaluation, denoting the ignition of irreversible cell injury in 24 hours, evolving into neuronal apoptosis in 48 hours after application of the CB 0.3%. Under the conditions in which this work was conducted, it can be concluded that the application of CB 0.3% by means of microinjections intramural in the ileal wall is able to induce intrinsic chemical denervation of the diverticulum of wistar rats and that the main mechanism of neuronal death is induction of apoptosis.(AU)

Existe vasta literatura sobre a desnervação intrínseca de segmentos do tubo digestório através da aplicação de CB na serosa da víscera. Entretanto, essa técnica tem a desvantagem de causar peritonite, formação de bridas e alta mortalidade, não sendo factível para eventuais utilizações em humanos. O objetivo do presente estudo foi avaliar a viabilidade do Cloreto de benzalcônio (CB) induzir desnervação química intrínseca, por meio de aplicações intramurais em íleo de ratos wistar, além de aprofundar o conhecimento sobre a evolução da lesão neuronal causada neste processo. Foram utilizados 40 ratos, distribuídos em dois grupos (controle- GC e benzalcônio- GB) de 20 animais cada, subdivididos em quatro subgrupos de acordo com o tempo de avaliação pós-operatória de 24, 48 horas, 30 e 90 dias. Os animais foram submetidos à microinjeções intramurais de solução salina estéril 0,9% (GC) ou de cloreto de benzalcônio (GB) em porção ileal, e posterior análise histopatológica e imuno-histoquímica, para avaliação da lesão neuronal. Houve diminuição significativa (p<0,05) na contagem neuronal mientérica ao longo do tempo nos grupos GB2, GB3 e GB4. A imunomarcação específica positiva para H2AX e Caspase-3 confirmou os resultados obtidos na avaliação histopatológica, denotando início da lesão celular irreversível em 24 horas, evoluindo para apoptose neuronal em 48 horas após a aplicação do CB 0,3%. Nas condições em que este trabalho foi conduzido, é possível concluir que a aplicação de CB 0,3% por meio de microinjeções intramurais na parede ileal é capaz de induzir desnervação química intrínseca da porção ileal de ratos wistar e que o principal mecanismo de morte neuronal é a indução de apoptose.(AU)

Benzalkonium chloride effectiveness as a disinfectant against hospital associated methicillin-resistant Staphylococcus aureus (HA-MRSA)

Aims@#Benzalkonium chloride is used to disinfect hospital instruments to prevent nosocomial infection caused by microorganisms, such as Methicillin Resistant Staphylococcus aureus (MRSA). There are strains of MRSA isolated from hospitals that were found to be resistant towards benzalkonium chloride. This research was aimed to compare the affectivity of different concentrations of benzalkonium chloride to inhibit the growth of Hospital-Associated MRSA (HA-MRSA) and determine the Minimum Inhibitory Concentration (MIC) of benzalkonium chloride against HA-MRSA. @*Methodology and results@#The samples were five HA-MRSA isolates obtained from Dr. Soetomo Hospital Surabaya. It was identified by amplification of SCCmec genes. The HA-MRSA with SCCmec type III was divided into six flasks based on the concentration of benzalkonium chloride in their inoculation media (0 μg/mL, 0.625 μg/mL, 1.25 μg/mL, 2.5 μg/mL, 5 μg/mL, and 10 μg/mL). The growth of HA-MRSA in media was determined by the number of colonies after treatment. The result showed that the MIC of benzalkonium chloride for HA-MRSA was 5 μg/mL, where no growth of bacterial was observed. There was significant difference in MRSA colony count between different groups of benzalkonium chloride concentrations (p = 0.001), and there was negative correlation between benzalkonium chloride concentration and HA-MRSA growth (p = 0.0001 and r = -0.880). @*Conclusion, significance and impact of study@#The concentration of benzalkonium chloride influences the growth of HA-MRSA. The higher the concentration, the fewer HA-MRSA growth. Application of benzalkonium chloride according to MIC will prevent HA-MRSA resistance towards benzalkonium chloride.

Effect of Chronic Benzalkonium Chloride Exposure on Senescence in Trabecular Meshwork Cells

PURPOSE: To determine the possible effects of chronic exposure of low dose benzalkonium chloride (BAK) on trabecular meshwork cells, and to characterize the pathways involved in the effects. METHODS: Trabecular meshwork cells were treated with 0.0005%, 0.00075%, 0.001%, and 0.0025% BAK for 10 minutes; then, the cells were transferred to a new medium for 24 hours. This process was repeated three times. Cell survival was assessed using the MTT assay to determine the non-apoptotic BAK concentration. Senescence-associated (SA)-β-gal staining was performed to compare quantitatively the cellular senescence of BAK-treated cells with the control group. Cells treated with BAK were analyzed by western blot to determine whether the expressions of cell cycle regulators were affected. RESULTS: Two concentrations (0.0005% and 0.00075%) showed persistent cell viability and were chosen for further experiments. After SA-β-gal staining, cells treated with 0.0005% and 0.00075% BAK showed 28% (± 2.08), 37% (± 2.08) increases in cellular senescence expression, respectively, when compared with control cells (p < 0.05). To identify the molecular pathways involved in cell cycle arrest via BAK, western blot analysis was performed on trabecular meshwork cells, resulting in decreased expressions of cyclin E/CDK2, and increased expressions of the upper stream control molecules, p53 and p21. CONCLUSIONS: Chronic exposure to low dose BAK accelerated cell senescence through cell cycle arrest. Because senescent cells of the trabecular meshwork can inhibit its outflow pathway function and ultimately worsen the glaucomatous process, long-term usage of topical glaucoma medications containing BAK should be conducted with caution.

Effects of Several Cosmetic Preservatives on ROS-Dependent Apoptosis of Rat Neural Progenitor Cells

Benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea are commonly used preservatives in cosmetics. Recent reports suggested that these compounds may have cellular and systemic toxicity in high concentration. In addition, diazolidinyl urea and imidazolidinyl urea are known formaldehyde (FA) releasers, raising concerns for these cosmetic preservatives. In this study, we investigated the effects of benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea on ROS-dependent apoptosis of rat neural progenitor cells (NPCs) in vitro. Cells were isolated and cultured from embryonic day 14 rat cortices. Cultured cells were treated with 1–1,000 nM benzalkonium chloride, and 1–50 μM diazolidinyl urea or imidazolidinyl urea at various time points to measure the reactive oxygen species (ROS). PI staining, MTT assay, and live-cell imaging were used for cell viability measurements. Western blot was carried out for cleaved caspase-3 and cleaved caspase-8 as apoptotic protein markers. In rat NPCs, ROS production and cleaved caspase-8 expression were increased while the cell viability was decreased in high concentrations of these substances. These results suggest that several cosmetic preservatives at high concentrations can induce neural toxicity in rat brains through ROS induction and apoptosis.

Preventive effect of Angelica gigas Nakai extract oral administration on dry eye syndrome

Objective:To identify the preventive effect of Angelica gigas Nakai (A. gigas Nakai) extract in a benzalkonium chloride-induced dry eye model.Methods:A total of 28 mice were divided into 4 groups: 1) Normal group: mice received only saline; 2) positive control group: mice received an oral solution without A. gigas Nakai extract at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m.; 3) A. gigas Nakai extract (5 mg); 4) A. gigas Nakai extract (10 mg). Both group 3) and group 4) received an oral solution with A. gigas Nakai extract (either 5 mg/kg or 10 mg/kg) at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m. After 14 d of follow-up, tear volume measurement and fluorescein staining were evaluated for the recovery effects on ocular surface. Histologic analysis was conducted by hematoxylin and eosin staining. Apoptosis on ocular epithelium layer was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of TNF- α was also measured using western blot analysis.Results:An increase in both the tear volume and the sustained fluorescein staining scores was observed, demonstrating the preventive effects of A. gigas Nakai extract. Structure changes such as irregularity of the epithelial layer and corneal epithelial cell death were inhibited in the A. gigas Nakai extract groups. Expression of TNF- α moderately declined; however, its expression level was still higher, compared to the normal group.Conclusions:Results from the current study show the significant preventive effect of A. gigas Nakai extract in a mouse model of benzalkonium chloride-induced dry eye syndrome. Thus, A. gigas Nakai extract could be considered as an oral preventive agent for dry eye syndrome in the future.

Preventive effect of Angelica gigas Nakai extract oral administration on dry eye syndrome

Objective: To identify the preventive effect of Angelica gigas Nakai (A. gigas Nakai) extract in a benzalkonium chloride-induced dry eye model. Methods: A total of 28 mice were divided into 4 groups: 1) Normal group: mice received only saline; 2) positive control group: mice received an oral solution without A. gigas Nakai extract at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m.; 3) A. gigas Nakai extract (5 mg); 4) A. gigas Nakai extract (10 mg). Both group 3) and group 4) received an oral solution with A. gigas Nakai extract (either 5 mg/kg or 10 mg/kg) at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m. After 14 d of follow-up, tear volume measurement and fluorescein staining were evaluated for the recovery effects on ocular surface. Histologic analysis was conducted by hematoxylin and eosin staining. Apoptosis on ocular epithelium layer was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of TNF- α was also measured using western blot analysis. Results: An increase in both the tear volume and the sustained fluorescein staining scores was observed, demonstrating the preventive effects of A. gigas Nakai extract. Structure changes such as irregularity of the epithelial layer and corneal epithelial cell death were inhibited in the A. gigas Nakai extract groups. Expression of TNF- α moderately declined; however, its expression level was still higher, compared to the normal group. Conclusions: Results from the current study show the significant preventive effect of A. gigas Nakai extract in a mouse model of benzalkonium chloride-induced dry eye syndrome. Thus, A. gigas Nakai extract could be considered as an oral preventive agent for dry eye syndrome in the future. http://www.apjtm.org/article.asp?issn=1995-7645;year=2018;volume=11;issue=6;spage=369;epage=375;aulast=Lee;type=2.

Simultaneous Determination of 4 Preservatives in Marketed Eye Drops by HPLC / 中国药房

OBJECTIVE:To establish a method for simultaneous determination of residual methylparaben,ethylparaben,nipa-sol and benzalkonium chloride in marketed eye drops. METHODS:HPLC method was adopted. The determination was performed on Hypersil GOLD C18 column with mobile phase consisted of 0.005 mol/L ammonium acetate(10 mL triehtylamine in 1 L solu-tion,pH adjusted to 5.0±0.5 with glacial acetic acid)-acetonitrile(45:55,V/V)at the flow rate of 1.0 mL/min. The detection wave-length was 262 nm(methylparaben,ethylparaben,nipasol)and 214 nm(benzalkonium chloride),respectively. The column tem-perature was 30 ℃ and sample size was 20 μL. RESULTS:The linear range were 1.2350-15.4380 μg/mL for methylparaben(r=0.9999),1.3170-16.3836 μ g/mL for ethylparaben (r=0.9997),1.2072-15.0894 μ g/mL for nipasol (r=0.9996) and 17.776-222.0 μg/mL for benzalkonium chloride(r=0.9999),respectively. Limits of quantitation were 2.0,2.0,2.0,1.11 μg,re-spectively;limits of determination were 0.375,0.375,0.375,0.333 μg,respectively. RSDs of precision,stability and reproducibili-ty tests were all lower than 2.0%. The average recoveries were 98.14%-102.48%(RSD=1.6%,n=9),98.79%-102.42%(RSD=1.3%,n=9),98.19%-102.49%(RSD=1.5%,n=9)and 98.76%-100.53%(RSD=0.6%,n=9),respectively. CONCLUSIONS:The method is accurate,reproducible,simple and suitable for the determination of residual methylparaben,ethylparaben,nipasol and benzalkonium chloride in marketed eye drops.

High-throughput determination of preservatives in eye drops and antimicrobial effectiveness assessment / 中国药学杂志

OBJECTIVE: To establish an HPLC method for rapid screening and simultaneous determination of 10 preservatives in eye drops and assess their antimicrobial effectiveness. METHODS: A Waters XBridge C18 column (4.6 mm × 150 mm, 5 μm) was used, and the mobile phase was 0.1% phosphoric acid-methanol-THF eluted in gradient mode at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 214 nm. The antimicrobial effectiveness of the preservatives was assessed according to Ch. P 2015. RESULTS: The calibration curves were linear in the range of the corresponding test concentrations (r=0.999 3 -1.000 0). The recoveries were between 96.1%-101.8%. One of the eye drops products did not meet the requirement of Ch. P 2015. CONCLUSION: The established method is rapid and inexpensive. And it ensures excellent simplicity, sensitivity, specificity, and reproducibility and can be used for rapid screening and determination of the contents of preservatives in eye drops. The amount of preservatives should be established during the R&D period or determined according to the results of antimicrobial effectiveness test rather than using empirical values.

The antibacterial activity and release of quaternary ammonium compounds in an orthodontic primer

The aim of this study was to evaluate the impact of 10 wt% benzalkonium chloride (TBBAC) or 10 wt% cetylpyridinium chloride (TBCPC) on the antimicrobial properties of the orthodontic adhesive primer, Transbond XT™ (TB). Antimicrobial activity was assessed using a zone of inhibition diffusion test and the release of the antimicrobial compounds was monitored by high performance liquid chromatography (HPLC). Shear bond strength (SBS) was tested using bovine enamel. Control, TB, specimens failed to demonstrate intrinsic antibacterial activity at 1, 7 and 14 days; whereas, TBBAC and TBCPC showed antibacterial effects at all times. HPLC analysis indicated no significant differences in the release behaviour of TBBAC and TBCPC (ttest, p > 0.05), except for the 7day release which was higher for TBBAC (p < 0.05). By 14 days the extents of release were 27 ± 2% and 25 ± 5% of the total initial loading for TBBAC and TBCPC, respectively. The incorporation of 10 wt% BAC or CPC in Transbond XT™ adhesive primer also resulted in superior shear bond strength at 7 and 14 days (Fisher's LSD, p < 0.05) with no significant change in the mode of bracket failure under shear stress (Pearson's chisquared, p > 0.05) (AU)

El objetivo de este estudio fue evaluar el impacto del cloruro de benzalconio al 10% en peso del peso (TBBAC) o de cloruro de cetilpiridinio al 10% del peso (TBCPC) con propiedades antimicrobianas presentes en el adhesivo acondicionador ortodóncico, Transbond XT ™ (TB). La actividad antimi crobiana se evaluó usando una zona de prueba de difusión de inhibición y la liberación de los compuestos antimicrobianos se controló mediante cromatografía líquida de alta resolución (HPLC). La resistencia de adhesión al corte (SBS) se probó usando esmalte bovino. Las muestras control, TB no lograron demostrar actividad antibacteriana intrínseca a 1, 7 y 14 días; mientras que TBBAC y TBCPC mostraron efectos antibac terianos en todo momento. El análisis por HPLC no indicó diferencias significativas en el comportamiento de liberación de TBBAC y TBCPC (prueba t, p> 0,05), excepto en la liberación a los 7 días que fue más alta para TBBAC (p <0,05). A los 14 días, los grados de liberación fueron de 27 ± 2% y de 25 ± 5% de la carga inicial total para TBBAC y TBCPC, respectivamente. La incorpora ción de 10% en peso de BAC o CPC en el imprimador adhesivo Transbond XT ™ también dio como resultado una resistencia superior corte a los 7 y 14 días (Fisher's LSD, p <0.05) sin cambios significativos en el modo de falla del bracket bajo tensión de corte (Pearson's chicuadrado, p> 0.05) (AU)

Determination of Benzalkonium Chloride in Ophthalmic Solutions by Stability-Indicating HPLC Method: Application to a Stability Study.

A simple HPLC method for determination of Benzalkonium chloride in various ophthalmic solutions was developed. The chromatographic analysis was achieved using CN column (250 mm, 4.6 mm i.d., 5 μm) with isocratic mobile phase consisting of acetonitrile - phosphate buffer (pH 5.5; 0.05 M) (70:30, v/v) at a flow rate of 1 mL/minute. The column temperature was maintained at 25°C and the detection wavelength was 210 nm. The proposed HPLC method was successfully validated according to the ICH guideline and proved to be stability-indicating. This method was applied to quantify Benzalkonium chloride during in-use stability study of two ophthalmic solutions. Antimicrobial effectiveness of Benzalkonium chloride in these solutions was also evaluated. The developed method is suitable for the routine analysis of Benzalkonium chloride in many ophthalmic solutions as well as for the stability studies.

Comparison of the Related Substances in Benzalkonium Chloride at Home and Abroad / 中国药师

Objective:To determine the related substances in benzalkonium chloride used as a pharmaceutical adjuvant, and com-pare the quality at home and abroad. Methods:An HPLC method was used with an ODS-HYPERSIL C18 column(250 mm × 4. 6 mm, 5 μm). The detection wavelength was 210 nm and 257 nm. The flow rate was 1. 0 ml· min-1 and the column temperature was 30℃. The injection volume was 20 ml. The mobile phase was A ( dissolving 1. 09 g sodium1-hexanesulfonate and 6. 9 g sodium dihydrogen phosphate in water, adjusting pH to 3. 5 with phosphoric acid and diluting to 1 000. 0 ml) and B ( methanol) with gradient elution. Results:The content of benzaldehyde in the samples at home and abroad was low. The content of benzyl alcohol in the samples from a-broad was qualified, which was significantly higher than that in the domestic samples. The content of benzyl chloride in the domestic samples was higher than that in the samples from abroad. Conclusion:The method is simple and fast, which is suitable for comparing the related substances of domastic and imported samples. At the same time, the study provides basis for enterprises to choose benzalko-nium chloride rationally.

Morphological changes of corneal and conjunctival epithelia in a rat model of dry eye / 中国比较医学杂志

Objective To evaluate the rat model of dry eye induced by topical administration of benzalkonium chloride and compare the morphological characteristics of corneal and conjunctival tissues of the normal and model rats . Methods Topical administration of benzalkonium chloride (0.3%) twice per day for seven days to induce the rat model of dry eye.Pathology with HE and periodic acid-Schiff staining and transmission electron microscopy were performed to evaluate the corneal and conjunctival changes .Results The corneal and conjunctival epithelial cells were sloughed off , the number of goblet cells was decreased in the dry eye model .Microvilli were obviously lost in the surface epithelial cells of the dry eye rat cornea and conjunctiva compared with the normal rats , as indicated by the amount and size of microvilli . Conclusions The changes in the corneal and conjunctival epithelia of BAC-induced rat dry eye are similar to the changes in human dry eye .This rat model may play an essential role for dry eye studies in the future .

Research on Quality Differences in Benzalkonium Chloride from Domestic and Abroad / 中国药师

Objective:To compare the quality differences in benzalkonium chloride samples from domestic and abroad to provide references for the quality standard revision for benzalkonium chloride in Chinese pharmacopoeia. Methods: The ratio of alkyl compo-nents was determined according to the method described in USP 38, and the total content of benzalkonium chloride was determined ac-cording to the method recorded in Chinese Pharmacopoeia (2015 edition) and USP 38, respectively. Results:According to the results of composition ratio of alkyl, the fraction defective of domestic samples and imported samples was 100% and 50%, respectively. The content difference between the values calculated by the methods in the two pharmacopoeias showed that the total content of domestic samples changed from 3. 86% to 4. 15%, and that of imported samples changed from 1. 15% to 3. 90%. Conclusion:There are sig-nificant differences in the quality of benzalkonium chloride between domestic samples and imported samples. It is recommended that the ratio of alkyl components should be supplemented in our pharmacopoeia referring to the method in USP 38 and the total content calcula-tion formula for benzalkonium chloride should be revised to improve the quality standard for benzalkonium chloride.

An Unpleasant Result of Imprecision: Esophageal Corrosive Injury Due to the Oral Intake of 10% Benzalkonium Chloride.

Benzalkonium chloride is a skin antiseptic agent. It should be diluted before usage for cleaning of mucosal membranes; otherwise it may result in severe damage on mucosa. Herein we will report a 2 months old baby who took 10% Benzalkonium chloride orally by an accident and consequently developed esophageal damage and larynx edema. Our aim was to take attention to the Benzalkonium chloride usage.

The effects of topical benzalkonium chloride on the cornea of the experiment animals / 中国基层医药

Objective To observe the effects of the topical benzalkonium chloride on the cornea of experi-ment animals and evaluate the safety of topical benzalkonium chloride.Methods 36 rabbits were randomly divided into two groups according to the random number table,18 rabbits(36 eyes)in each group.The benzalkonium group was assigned as preservative benzalkonium chloride(0.05%)gutta,the control group was served as blank control. Rabbits were examined by the slit lamp,non-contact corneal endothelial microscope and Ultrasonic Wave instrument for corneal endothelial cell density and corneal thickness before and the 3rd weeks,the 6th weeks after the medica-tion.In vitro cornea was stained by typan blue and alizarin red,corneal endothelial cells were observed and calculate the viability of corneal endothelial cells (CECs).Results The differences of corneal thickness at the 3rd weeks and the 6th weeks were not statistically significant between the two groups(t =1.876,1.876,all P >0.05);The differ-ences of the corneal endothelial cell density and the viability of corneal endothelial cells(CECs)between the two groups at the 3rd weeks and the 6th weeks were not statistically significant(t =0.321,1.541,all P >0.05);The tear meniscus height of the benzalkonium group were lower than the control group at the 6th weeks[(142 ±36)μm vs. (198 ±31)μm,t =2.462,P <0.05].Conclusion Benzalkonium chloride has no impact on the corneal endothelial cells in short period,but the affection on the tear is obvious.

Irritant Contact Dermatitis Induced by Benzalkonium Chloride (Zephanon®) / 대한피부과학회지

No abstract available.