Antifungal activity of silver nanoparticles and clotrimazole against Candida spp

Abstract The aim of present study was calculate the Minimum inhibitory concentrations (MICs) of silver nanoparticles and clotrimazole for Candida species and their interaction by the adaptation of standarized methods. The MICs values of clotrimazole were 9 E-04-3 E-03 ug/ml, 0.1-0.6 ug/ml, 3 E-03- 0.1 ug/ml and 3 E-03-0.3 ug/ml for Candida albicans susceptible to fluconazole, Candida albicans resistance to fluconazole, Candida krusei and Candida parapsilosis respectively. The MICs values of silver nanoparticles were 26.50- 53 ug/ml; 26.50-106 ug/ml; 106-212 ug/ ml and 26.50- 53 ug/ml for Candida albicans susceptible to fluconazole, Candida albicans resistance to fluconazole, Candida krusei and Candida parapsilosis respectively. Synergism between clotrimazole and silver nanoparticles was measured by checkerboard BMD (broth microdilution) test and shown only for C. albicans susceptible to fluconazole because the fractional inhibitory concentrations (FICs) values were 0.07 - 0.15 ug/ml. Indifference was shown for the other species tested because the FICs values were between 0.5 - 2- 3.06 ug/ml. The results suggest synergistic activity depending on the fungus species analysed, however we recommend the incorporation of others measurement methodologies to confirm our results. As for measurement methodologies of MICs of silver nanoparticles and clotrimazole international normative were respected to guarantee reproducible and comparable results.

Analysis of resistance and sensitivity of 1 200 strains of vulvovaginal candidiasis in China to five common antifungal drugs / 中华妇产科杂志

Objective:To test the antibiotic susceptibility of vulvovaginal candidiasis pathogenic strains to 5 antifungal drugs commonly used in clinic.Methods:A total of 1 200 vulvovaginal candida patients from 23 gynecological and family planning outpatient departments in China were enrolled. Their vaginal secretions were collected for candida strain isolation and species identification. According to Clinical and Laboratory Standards Institute (CLSI) M27-S3, the sensitivity of 1 200 strains to clotrimazole, fluconazole, miconazole, itraconazole and nystatin was tested.Results:(1) The sensitivity and resistance of 1 200 vulvovaginal candidiasis pathogens to 5 antifungal drugs were statistically different ( χ2=3 513.201, P<0.01). (2) All strains had higher sensitivity to nystatin [99.92% (1 199/1 200)], followed by miconazole [92.25% (1 107/1 200)] and clotrimazole [87.17% (1 046/1 200)]. All strains had higher resistance to fluconazole [69.17% (830/1 200)], while itraconazole was 50.83% (610/1 200). (3) There was no significant difference between candida albicans and non-candida albicans in drug sensitivity to nystatin ( P=0.315) and miconazole ( P=0.425). (4) Candida albicans and non-candida albicans showed different sensitivity to clotrimazole, fluconazole and itraconazole, respectively. Compared with non-candida albicans, candida albicans showed higher sensitivity to clotrimazole [susceptibility rate: 73.01% (165/226) vs 90.45% (881/974); P<0.001] and higher resistance to fluconazole [resistance rate: 50.88% (115/226) vs 73.41% (715/974); P<0.001]. Although the drug sensitivity of itraconazole was not high, the susceptibility rate of candida albicans to itraconazole was slightly higher than that of non-candida albicans [37.68% (367/974) vs 23.89% (54/226)], and the drug resistance rate was lower [49.28% (480/974) vs 57.52% (130/226)]. Conclusions:The sensitivity of 1 200 strains of candida to 5 antifungal drugs is significantly different, the sensitivity rate of nystatin, miconazole and clotrimazole are higher, but the resistance rate of fluconazole and itraconazole are higher. The sensitivity of candida albicans and non-candida albicans to the same drug is also significantly different. It is suggested that in clinical diagnosis and treatment, we should pay attention to the identification of candida and drug sensitivity test, so as to select antifungal drugs rationally.

New Derivatives of (E)-3-(5-((substitutedphenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styryl quinazolin-4(3H)-one: Searching for New Antifungal and Antibacterial Agents

Objective: The objective of the paper was to evaluate the antifungal and antibacterial potential of new derivatives of ((E)-3-(5-((substitutedphenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styryl quinazolin-4(3H)-one. Materials and Methods: Various syntheses of (E)-3-(5-(substitutedaminomethyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one derivatives have been synthesized by reacting 2-substituted benzoxazin-4-one with (E)-2-(4-Substituedstyryl)-4H-benzo[d] [1,3]oxazin-4-one. All synthesized compounds have been characterized by the infrared, 1HNMR, and mass spectral analysis. Proposed compounds have been evaluated for antifungal and antibacterial activity. The antimicrobial activity of synthesized compounds (QNM-1 to QNM-15) has been carried through the serial dilution method. For bacterial screening, bacterial species were taken includes Staphylococcus aureus (MTCC-96), Bacillus subtilis (MTCC-441), Pseudomonas aeruginosa (MTCC-424), and Escherichia coli (MTCC-40). Norfloxacin (1-Ethyl-6-fluoro-1,4,dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid) was used as the standard drug for antibacterial study. For antifungal screening, the following fungal species were used includes Aspergillus niger (MTCC-281), Candida albicans (MTCC-227), and Fusarium oxysporum (MTCC-284). Clotrimazole was selected as a standard drug for antifungal study. Results and Discussion: QNM-1, QNM-2, QNM-3, QNM-5, QNM-7, QNM-9, QNM-12, QNM-14, and QNM-15 were the most active compounds [Table 1] in the synthesized series which were active against both Gram-positive and Gram-negative organisms by the antibacterial screening. In the case of antibacterial activity, the presence of electronegative group (Cl, Br, F, and NO2) at both R may enhance the activity when they are p-substituted, but the compounds QNM-6 (R1=-C6H5Br (o); Ar=-C6H5), QNM-10 (R1 = -C6H5F (o); Ar= -C6H5F), QNM-11 (R1 =-C6H5NO2 (p); Ar=-C6H5F), and QNM-4 (R1 =-C6H5F (m); Ar=-C6H5) with given substitution may result in diminishing the activity. In case of antifungal activity, compounds QNM-1, QNM-5, QNM-7, QNM-9, QNM-11, QNM-12, QNM-14, and QNM-15 were the most active compounds in the synthesized series which were active against both Gram-positive and Gram-negative organisms. In that series, compounds QNM-14, QNM-11, QNM-5, and QNM-7 have shown the highest activity. Compounds QNM-3, QNM-6, QNM-10, and QNM-13 have the least active. This result has also concluded that o-substituted compounds, i.e., -C6H5Cl(o), -C6H5Cl (m), -C6H5Br(o), -C6H5F (o), -C6H5F (p) at R1 position my resulted in diminishing or lower the activity

Efficacy of topical clotrimazole vs. topical tolnaftate in the treatment of otomycosis. A randomized controlled clinical trial / Eficácia do clotrimazol tópico versus tolnaftato tópico no tratamento da otomicose: um ensaio clínico controlado randomizado

Abstract Introduction: Otomycosis, an infection of the ear canal by fungi, is prevalent in hot and humid weather. Nevertheless, there is not sufficient evidence for the effectiveness of different topical antifungal treatments. Tolnaftate, is a topical antifungal agent described to be effective in the treatment of otomycosis. Currently there are not sufficient studies that prove its efficacy. Objectives: To compare the efficacy of clotrimazole and tolnaftate administration in the treatment of otomycosis. Material and methods: A controlled, randomized and open clinical trial included patients diagnosed with fungal external otitis who were treated with topical antifungals, randomized into two treatment groups: (1) clotrimazole cream; (2) tolnaftate solution. They were microscopically evaluated at one and two weeks of treatment to determine resolution of disease. Recurrence and complications were recorded. Demographic and clinical variables were collected and analyzed. Follow-up and final outcomes (absence of infection) were compared between groups. Results: Forty eight patients were included, 28 in the clotrimazole group and 20 in the tolnaftate group. Spring was the weather most commonly associated with otomycosis, while otic manipulation was the risk factor more common in both groups. Predominant symptoms were itching and otic fullness. Aspergillus niger organism was isolated most frequently. Treatment with clotrimazole resulted in 75% resolution vs 45% resolution with treatment with tolnaftate at one week of treatment (p = 0.007). The Tolnaftate treatment group demonstrated higher recurrence rates and treatment failures, 20% and 15% respectively. Conclusions: Clotrimazole cream treatment is more effective than tolnaftate for uncomplicated otomycosis. More studies are needed to corroborate our results.

Resumo Introdução: Otomicose, uma infecção fúngica do canal auditivo externo, é prevalente em climas quentes e úmidos. No entanto, a literatura não apresenta evidências suficientes sobre os diferentes tratamentos antifúngicos tópicos. O tolnaftato é um antifúngico tópico descrito como eficaz no tratamento da otomicose; entretanto, sua eficácia não está suficientemente comprovada. Objetivo: Comparar a eficácia do uso de clotrimazol e tolnaftato no tratamento da otomicose. Material e método: Ensaio clínico controlado e randomizado; incluiu pacientes diagnosticados com otite externa fúngica tratados com antifúngicos tópicos, randomizados em dois grupos de tratamento: 1) clotrimazole (creme); 2) solução de tolnaftato. Eles foram avaliados microscopicamente uma e duas semanas após o início do tratamento para avaliar a resolução da doença. Recorrência e intercorrências foram registradas; além disso, as variáveis demográficas e clínicas foram coletadas e analisadas. Os dados do acompanhamento e desfechos finais (ausência de infecção) foram comparados entre os grupos. Resultados: O estudo incluiu 48 pacientes, 28 dos quais foram alocados ao grupo clotrimazole e 20 ao grupo tolnaftato. A primavera foi a estação mais comum; a manipulação foi o fator de risco mais comum em ambos os grupos. Os sintomas mais comuns foram coceira e plenitude auricular. Aspergillus niger foi o micro-organismo mais comumente isolado. Após uma semana, o tratamento com clotrimazol apresentou uma taxa de resolução de 75% vs. 45% com o tratamento com tolnaftato (p = 0,007). O tratamento com tolnaftato apresentou maiores taxas de recidiva e falhas: 20% e 15%, respectivamente. Conclusões: Em casos de otomicose não complicada, o uso de clotrimazol (creme) é mais eficaz do que o de tolnaftato. Mais estudos são necessários para corroborar os presentes resultados.

Formulation and Evaluation Thermoreversible Gel of Antifungal Agent for Treatment of Vaginal Infection

Aims:TheaimthisresearchworkistoformulateandevaluatethermoreversiblegelofantifungalagentClotrimazolefortreatmentofvaginalinfection.PlaceandDurationofStudy:DepartmentofBiopharmaceutics,GovernmentCollegeofPharmacy,Karad,Maharashtra,India,betweenJune2009andJuly2010.Methodology:DifferentFormulationsofthermoreversiblegelofantifungalagentClotrimazolewerepreparedbyusingvariousconcentrationsofethanol,PEG400,sodiumdodecylsulphate,polycarbophilandpluronicF127andpluronicF68.Thegelformulationsweresubjectedforevaluationonthebasisofrheologicalbehaviour,mucoadhesivebehaviour,in-vitroperformance.Results:TheresultsindicatethatPolymerssuchaspolycarbophil,PEG-400invariousconcentrationstoprepareformulationswerefoundtoreleasedrugforperiodover12hrs.Withoutgettingdislodged.Theformulationshavesatisfactoryrheologicalbehaviorandtheirdiffusionprofileiscomparabletothemarketedgelformulation.Significantdifferencewasobservedintherheologicalbehaviorofformulations.Gelstrength,spreadability,mucoadhesivestrengthofformulationBandCweredesirable.DrugdiffusionofformulationBandCwere95.2%releaseafte 11hrs98.5%releaseafter11hrs,respectivelywhichwasgoodascomparedtomarketedformulationshowingdrugdiffusionof102.2%after10hrs.Conclusion:OnbasisoftheresultsweconcludedthatdevelopedthermoreversiblegelofClotrimazolewillbebetteralternativetoconventionaldosageformClotrimazole&willimprovepatientcompliance

Study of onychomycosis

Background: Onychomycosis is one of the most common fungal nail infections caused by Dermatophytes, Non-Dermatophytic Molds (NDM) and Yeast. Though it is not life-threatening, can cause pain, discomfort, and disfigurement. It decreases the nail growth rate. Objectives: This study was carried out to document the clinico-mycological pattern and antifungal susceptibility pattern of onychomycosis.Methods: The study group included 130 consecutive patients with suspected fungal nail infections, attending Dermatology outpatient department of King George Hospital, Visakhapatnam, Andhra Pradesh during November 2012 to August 2014. The nail clippings of the patients were collected and subjected to KOH mounts for direct microscopy and fungal culture and antifungal susceptibility tests.Results: Onychomycosis was common among males (66.92%) than females (33.08%) with highest incidence was in age group 31-40 years (41.37%). Finger or toenails were exclusively involved in 32.18% and 55.18% patients respectively while these were involved concurrently in the rest of the 12.65% patients. Distal and lateral subungual onychomycosis seen in 64.36% of the patients was the most common clinical type. KOH and culture positivity were recorded in 56.92% and 48.46% cases respectively. Dermatophytes (50.58%) were predominant isolate followed by NDM (27.58%) and yeast (21.84%). Clotrimazole and ketoconazole were most effective antifungals against dermatophytes. For NDM, itraconazole, nystatin and amphotericin B and for yeast fluconazole and itraconazole were effective.Conclusions: The present study gives an insight about the aetiological agents causing onychomycosis and their anti-fungal susceptibility pattern in this region. Thus, it can help in taking adequate control measures to prevent it.

Investigation of the extraction method and content determination of the active components from oral ulcer film / 药学实践杂志

Objective To investigate the extraction methods for active components from oral ulcer film and optimize the determination methods of active components dexamethasone sodium phosphate and metronazole. Methods Different extraction solvents(methanol, water and 70% methanol aqueous) were applied to extract the active components dexamethasone sodium phosphate and metronazole from oral ulcer film, which contents were quantified by a HPLC method. Results the extraction solvent water had the best efficacy and more simpler compared to the other two solvents. Clotriazole showed a good linear relationship within 5.014 5-200.5800 μg/ml (r=0.999 8), and the average extraction recovery was (104.23±0.63)%, and for dexamethasone sodium phosphate, a good linear relationship was obtained in the range of 0.482-16.328 μg/ml (r=0.9999), and the average extraction recovery was (103.97±1.02)%. Conclusion The water extraction method established in this study was simple and efficient, which showed features of simplicity, accuracy and repeatable.

Comparison of response to treatment of otomycosis using topical betadine and clotrimazole drops

INTRODUCTION:Otomycosis is the fungal infection of EAC (External Auditory Canal) that is very commonly seen in Ear , Nose and Throat clinics .Local debridement and antifungals , topical or systemic is the treatment of choice but recurrences are very common and resistant to treatment.METHODS:Total 220 patients, divided into two groups each 110 in 'A' and 'B' were subjected to betadine (povidone - iodine )10% solution and Clotrimazole (1 %) drops treatment and response of treatment assessed on 5th , 10th and 20th day and analyzed.RESULTS :Out of 110 patients in each group on 5th day 21.8 % patients in group 'A', and 23.6 % in group B' showed no response. 70.9 % in group 'A' and 72.7 % in group 'B' were showed good response at evaluation of 20th day of treatment.CONCLUSION :In our study, betadine (10% solution) and Clotrimazole (1 %) drops were equally effective in treatment of otomycosis. Betadine(10% solution) is low cost, non-ototoxic, nonresistant and equally effective in bacterial and fungal infection. That's why this study support betadine 10% solution as treatment of choice for otomycosis specially in developing countries

Single Dose Topical Application of Clotrimazole for the Treatment of Otomycosis: Is This Enough?

BACKGROUND AND OBJECTIVES: To determine the efficacy of filling the external auditory meatus with 1% clotrimazole at a single visit for the treatment of otomycosis. SUBJECTS AND METHODS: This prospective study included 40 patients who were referred to our clinic with complaints of ear itching, pain, and fullness, and were diagnosed with unilateral otomycosis. After cleaning the mycotic hyphae from the external auditory meatus, the ear canal was filled with 1% clotrimazole, using an intravenous catheter and syringe. The patients received follow-up examinations on post-treatment days 7, 15, and 45. RESULTS: The follow-up otomicroscopic examinations revealed that 95% of the ear canals were entirely clean and that all symptoms had resolved. The post-treatment scores of pain, aural fullness and itching were significantly lower than the pre-treatment scores (p < 0.01). CONCLUSIONS: Filling the external auditory meatus with 1% clotrimazole at a single visit is an easy, efficient, and cost-effective treatment for otomycosis. Additionally, high patient compliance makes this treatment superior to long-term topical therapy.

Synergistic activity of lawsone methyl ether in combination with some antibiotics and artocarpin against methicillin-resistant Staphylococcus aureus, Candida albicans, and Trychophyton rubrum / 中草药·英文版

Objective: One appealing strategy to overcome and prevent resistant problem is the use of combined two or more antibacterial substances. Lawsone methyl ether (LME) is the naphthoquinone found in the leaves of Impatiens balsamina. The objective of this study is to determine the interaction of LME with some antibiotics (ampicillin, tetracycline, norfloxacin, and clotrimazole) and a natural compound, artocarpin against methicillin-resistant Staphylococcus aureus (MRSA), Candida albicans, and Trychophyton rubrum. Methods: A broth microdilution method was used to determine the minimum inhibition concentration (MIC). Synergistic effects were evaluated at their own MIC using the checkerboard method and time-kill assay. Results: LME showed moderate antibacterial activity against MRSA with MIC value of 15.6 µg/mL, and exhibited strong antifungal activities against T. rubrum and C. albicans with MIC values of 7.8 and 3.9 µg/mL, respectively. The interaction of LME with the natural compound artocarpin against MRSA produced a synergy with fractional inhibitory concentration index (FICI) value of 0.31, while the combination of LME and clotrimazole exhibited synergy against C. albicans and T. rubrum with FICI values of 0.38 and 0.24, respectively. The time-kill assays confirmed that the compounds in combination enhanced their antimicrobial activities against the resistant microorganisms with different degrees. Conclusion: LME in combination with clotrimazole exhibited synergy effect against C. albicans and T. rubrum. In combination with artocarpin, it showed synergy effect against MRSA.

Comparison of the recovery rate of otomycosis using betadine and clotrimazole topical treatment / Comparação da taxa de recuperação de otomicose com o uso de tratamento tópico com betadina e clotrimazol

Abstract Introduction Otomycosis is a common diseases that can be associated with many complications including involvement of the inner ear and mortality in rare cases. Management of otomycosis can be challenging, and requires a close follow-up. Treatment options for otomycosis include local debridement, local and systemic antifungal agents and utilization of topical antiseptics. Objective This study was designed to compare the recovery rate of otomycosis using two therapeutic methods; topical betadine (Povidone-iodine) and clotrimazole. Methods In this single-blind clinical trial, 204 patients with otomycosis were selected using a non-probability convenient sampling method and were randomly assigned to two treatment groups of topical betadine and clotrimazole (102 patients in each group). Response to treatment was assessed at 4, 10 and 20 days after treatment. Data were analyzed using the independent t-test, Chi-Square and Fisher exact test in SPSS v.18 software, at a significance level of p < 0.05. Results The results showed that out of 204 patients with otomycosis, fungi type isolated included Aspergillus in 151 cases (74%), and Candida albicans in 53 patients (26%). On the fourth day after treatment, 13 patients (13.1%) in the group treated with betadine and 10 patients (9.8%) in the group treated with clotrimazole showed a good clinical response to treatment (p = 0.75). A good response to treatment was reported for 44 (43.1%) and 47 patients (46.1%) on the tenth day after the treatment (p = 0.85); and 70 (68.6%) and 68 patients (67.6%) on the twentieth day after treatment (p = 0.46) in the groups treated with betadine and clotrimazole, respectively. The response to treatment was thus not significantly different in the two groups. Conclusion In the present study the efficacy of betadine and clotrimazole was the same for the treatment of otomycosis. The result of this study supports the use of betadine as an effective antifungal in otomycosis treatment, helping to avoid the emergence of resistant organisms.

Resumo Introdução A otomicose é uma das doenças comuns associadas a muitas complicações, como envolvimento da orelha interna e mortalidade em casos raros. O tratamento da otomicose pode ser realmente desafiador e requer um acompanhamento rigoroso. As opções de tratamento para otomicose podem incluir desbridamento local, agentes antifúngicos locais e sistêmicos e uso de antissépticos tópicos, os medicamentos tópicos recomendados para o tratamento da otomicose. Objetivo Comparar a taxa de recuperação de otomicose utilizando dois métodos terapêuticos de betadina tópica (povidona-iodo) e clotrimazol. Método Neste ensaio clínico simples cego, 204 pacientes com otomicose foram selecionados utilizando-se método de amostragem de não probabilidade conveniente e randomizados para dois grupos de tratamento, com betadina tópica e com clotrimazol (102 pacientes em cada grupo). A resposta ao tratamento foi avaliada aos 4, 10 e 20 dias após o tratamento. Os dados foram analisados utilizando o teste t independente, qui-quadrado e teste de Fisher no software SPSS v.18, com nível de significância de p < 0,05. Resultados Os resultados mostraram que dos 204 pacientes com otomicose, os tipos de fungos isolados incluíram Aspergillus em 151 casos (74%) e Candida albicans em 53 pacientes (26%). No quarto dia após o tratamento, 13 pacientes (13,1%) no grupo tratado com betadina e 10 pacientes (9,8%) no grupo tratado com clotrimazol apresentaram boa resposta ao tratamento (p = 0,75). Uma boa resposta ao tratamento foi relatada para 44 (43,1%) e 47 pacientes (46,1%) no décimo dia após o tratamento (p = 0,85); e 70 (68,6%) e 68 pacientes (67,6%) no vigésimo dia após o tratamento (p = 0,46) no grupo tratado com betadina e clotrimazol, respectivamente. Assim, a resposta ao tratamento não foi significativamente diferente nos dois grupos. Conclusão No presente estudo, a eficácia da betadina e do clotrimazol foi a mesma no tratamento da otomicose. O resultado deste estudo apoia o uso de betadina como um antifúngico eficaz no tratamento da otomicose que pode ajudar a evitar o surgimento de organismos resistentes.

Effect observation of cleaning up the external auditory canal by otoendoscope combined with Clotrimazole Ointment in the treatment of pregnancy with otitis externa mycotica / 临床耳鼻咽喉头颈外科杂志

To investigate the clinical effect of cleaning up the external auditory canal under otoendoscope combined with Clotrimazole Ointment in the treatment of pregnancy with otitis externa mycotica.From May 2015 to May 2017,16 cases of pregnant patients(19 ears)with otitis externa mycotica were divided into two groups:pure cleaning up group and cleaning up combined with medication group.In the pure cleaning up group,external auditory canal were only cleaned up under otoendoscope conventionally in 9 patients(11 ears),while in the cleaning up combined with medication group,Clotrimazole Ointment was topically applied after cleaning up the external auditory canal under otoendoscope in 7 patients(8 ears).After treatment of 2 weeks,the clinical curative effect,adverse reaction and average time interval to take effect were compared at the end of treatment.The total effective rate(100%)in cleaning up combined with medication group's was significantly better than that in pure cleaning up group's(81.81%)(<0.05);The average time interval to take effect in cleaning up combined with medication groupwas significantly shorter than that in pure cleaning up group's[(2.71±0.70)d vs(5.40±1.96)d,<0.05].After the two-week treatment,there was a four-week follow-up.Only one patient in pure cleaning up group relapsed.After two-week treatment by Clotrimazole Ointment,this patient was cured.Cleaning up the external auditory canal under otoendoscope combined with Clotrimazole Ointment is effective and safe for the treatment of otitis externa mycotica in pregnant women.The addition of topical application of Clotrimazole Ointment further improve the therapeutic efficacy,as compared to the conventional method of cleaning up the external auditory canal under otoendoscope.We suggest clinical application of this method.

Qualitative and quantitative analysis of related substances in clotrimazole cream / 药学学报

For qualitative and quantitative analysis of related substances in clotrimazole cream, HPLC-Q-TOF spectrometer was used to analyze the fragmentation pathways and identify structures of the related substances. Five related substances named by BP (2018) were identified as impurity A ((2-chlorophenyl)-diphenylmethanol), impurity B (para-clotrimazole isomer), impurity E (2-chlorobenzophenone), impurity F (1-tritylimidazole) and impurity 4 (9-(2-chlorophenyl)-fluorene), respectively, by using impurity references matching and comparison with the literature data. Four related substances were detected in clotrimazole cream except impurity E, and 9-(2-chlorophenyl)-fluorene is the first identified impurity in this preparation. To establish an HPLC method for determination of the related substances in Clotrimazole Cream, the Agilent Poroshell Bonuns RP column was used (100 mm×4.6 mm, 2.7 μm) with UV detection at 215 nm. The mobile phase was acetonitrile-10 mmol·L-1 dipotassium phosphate buffer (adjusted with phosphoric acid to pH of 5.80) with a flow rate of 1.0 mL·min-1. Gradient elution was used. The column temperature was maintained at 40℃. A good linear behavior was achieved between component's concentrations and peak area for impurity A, B, E, F within the range of 0.20-10.02 μg·mL-1, 0.20-10.00 μg·mL-1, 0.20-10.10 μg·mL-1, 0.10-5.01 μg·mL-1 with the correlation coefficients were 0.999 7, 1.000 0, 1.000 0, 0.999 9, respectively. The average recoveries were 94.3%, 95.0%, 100.0%, 99.6% with RSDs were 2.8%, 2.2%, 1.1%, 2.7%, respectively (n=9). LOQ were 200.4, 200.0, 202.0, 100.2 ng·mL-1, respectively. LOD were 57.25, 57.14, 57.71, 28.63 ng·mL-1, respectively. The developed method was simple, rapid, accurate and effective for testing related substances in clotrimazole cream to control its quality, ensuring the safety of clinical medication.

Improvement role of clotrimazole suppositories and fluconazole combined therapy in sex life of patients with candidal vaginitis / 中国生化药物杂志

Objective To investigate the improvement role of clotrimazole suppositories and fluconazole combined therapy in sex life of patients with candidal vaginitis.MethodsThe clinical data of 80 cases of patients with candidal vaginitis in our hospital from January 2015 to January 2017 were retrospectively analyzed, these patients were divided into clotrimazole suppositories and fluconazole combined therapy group (combined treatment group, n=40) and fluconazole single therapy group (single treatment group, n=40) according to the treatment methods, the clinical effects, main clinical symptoms and signs improvement time, quality of life of the two groups were statistically analyzed.ResultsThe total treatment efficiency of the combined treatment group 100.0% (40/40) was significantly higher than the single treatment group 87.5% (35/40) (P<0.05), the vaginal itching, pain, burning sensation, abnormal leucorrhea, abnormal discharge improvement time were significantly shorter than the single treatment group (P<0.05), the sexual desire, sexual arousal, lubrication, orgasm and sexual satisfaction scores were significantly higher than the single treatment group (P<0.05), the pain score was significantly lower than the single treatment group (P<0.05).ConclusionClotrimazole suppositories and fluconazole combined therapy can more effectively improve the sex life of patients with candidal vaginitis than fluconazole single therapy.

Effect of itraconazole capsules combined with clotrimazole vaginal tablets on patients with fungal vaginitis / 中国生化药物杂志

Objective To investigate the effect of itraconazole capsules combined with clotrimazole on the quality of life and the incidence of adverse reactions in patients with fungal vaginitis. Methods From May 2014 to February 2016, 106 cases of fungal vaginitis patients were randomly divided into single drug group and combination drug group, 53 cases each group. The single drug group was treated with clotrimazole vaginal tablets, the combination drug group was treated with itraconazole capsules combined with clotrimazole vaginal tablets, both groups were treated for 15 d. Quality of life score(QOL-100) before and after treatment was compared, and the incidence of adverse reactions and clinical efficacy between the two groups were compared as well. Results The total effective rate was 96.23％ (51/53) in the combination drug group and 81.13％ (43/53) in the single drug group, the difference was statistically significant (P<0.05); The QOL-100 score of the combination group was higher than that of the single drug group, the difference was statistically significant (P<0.05); However, there was no significant difference in the incidence of adverse reactions between the two groups. Conclusion Itraconazole capsules combined with clotrimazole vaginal tablets in the treatment of fungal vaginitis can effectively improve patients' quality of life, the effect is exact and no obvious adverse reactions was observed.

Clinical Observation of Clotrimazole Vaginal Tablet in the Treatment of Pregnancy with Vulvovaginal Candi-diasis / 中国药房

OBJECTIVE:To observe the efficacy and safety of Clotrimazole vaginal tablet in the treatment of pregnancy with vulvovaginal candidiasis. METHODS:106 pregnant patients with vulvovaginal candidiasis were randomly divided into observation group (56 cases) and control group (50 cases). Observation group was given one tablet Clotrimazole vaginal tablet,washed the genital area before treatment to keep clean and one Clotrimazole vaginal tablet was sent to intravaginal 5-6 cm,once every 2 day. Control group was given Lactobacillus vaginal capsule,once a day,washed the genital area before treatment and one Lactobacillus vaginal capsule was sent to intravaginal 5-6 cm. The treatment course for both groups was 8 d. No sexual activities during treatment and no other drugs. Clinical efficacy,clearance rate of candidiasis,pregnancy and incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate and clearance rate of candidiasis in observation group were significantly higher than control group,carrier rate was significantly lower than control group,the differences were statistically significant (P0.05). CONCLU-SIONS:Clotrimazole vaginal tablet shows significant efficacy in the treatment of pregnancy with vulvovaginal candidiasis and can clear candidiasis,with good safety.

The evaluation of the amount and sustain release of antifungal agent clotrimazole incorporated in different polymer matrix in artificial saliva at a pH of 6.2.

Background: Candidiasis in the oral cavity is an opportunistic infections, the most common species involved is Candida albicans. Clotrimazole (CTZ) is the first line broad-spectrum antifungal drug that has been widely used for the prophylaxis and treatment of oral and vaginal candidiasis. It is seen that the effect of drug is better locally as compared to oral intake. The aim of the present study is to find out the quantum release of clotrimazole from the incorporated materials in the artificial salivary medium at the pH of 6.2 and to access the physical properties of the clotrimazole incorporated reliner and tissue conditioner. Methods: The antifungal clotrimazole is incorporated in two types of denture base material used for this study at 2%, 5% and 10% concentration by weight. The release of clotrimazole out of polymer matrix was studied at various pH. The main property of tensile strength of the specimen before and after the chemical release of the clotrimazole was tested. Result: Concentration was maximum on 8th day and uniformly decreased thereafter. The maximum amount of release upto 8th day was 2.52, 4.23, 9.84 mg for 2%, 5% and 10% respectively. Conclusion: Topical release of antifungal agents is more effective than systemic intake, which has adverse effect like renal toxicity and CNS toxicity.

Comparison of efficacy, safety and cost-effectiveness of clotrimazole 1% cream and sertaconazole 2% cream in patients suffering from of mild to moderate tinea corporis, attending tertiary care hospital out-patient department: a randomized, open-labeled, comparative, parallel group trial.

Background: Tinea corporis is a common dermatophytic infection of the body involving keratin layer of skin. This lesion presents as an annular plaque with an advancing border along with central clearing. Clotrimazole is topical, conventional imidazole antifungal drug and has given good efficacy in tinea corporis. Sertaconazole is new topical imidazole antifungal claimed to be superior to old topical imidazoles in tinea corporis. The aim of this study was to compare efficacy, safety and cost effectiveness of topical antifungals, clotrimazole 1% cream and sertaconazole 2% cream in patients suffering from mild to moderate tinea corporis attending out-patient department of tertiary care hospital in Vidarbha region of Maharashtra. Methods: This was a prospective, comparative, randomized trial with 2 parallel treatment arms of 4 weeks duration. Patients were diagnosed on the basis of clinical evaluation and microscopic findings of KOH mount. Hundred patients were randomly assigned into two groups of clotrimazole 1% cream, and sertaconazole 2% cream with 50 patients in each group. Evaluation was carried out at baseline, 1st week, 2nd week and 4th week for efficacy parameters viz. itching, erythema and scaling, physician’s global assessment (PGA), safety and cost effectiveness. Results: Topical sertaconazole 2% cream was highly efficacious and superior to clotrimazole 1% cream in improvement of clinical parameters, PGA and mycological cure at the end of the treatment phase. At end of the follow-up phase both the trial drugs were effective with no recurrence or relapse of tinea corporis. However, clotrimazole 1% cream was safe and cheaper. Conclusions: Topical clotrimazole 1% cream and sertaconazole 2% were effective and well tolerated in patients of tinea corporis. Effectiveness of sertaconazole was early and superior with tolerable side-effects. However, clotrimazole was costeffective.

Study of Clotrimazole on Cell Apoptosis in Rat Liver After Ischemia-reperfusion Injury / 医药导报

Objective To investigate the effect of clotrimazole on apoptosis of hepatic cells after ischemia-reperfusion injury and its mechanism. Methods Hepatic ischemia-reperfusion rat model was established. Thirty-two male Sprague-Dawley rats were randomly allocated into sham-operated group, model control group, low dose clotrimazole group and high dose clotrimazole group. Apoptosis in hepatic tissue was assessed by TUNEL method. Protein expression levels of CYP3A1,Bcl-2,Bax and PARP were measured by Western blotting. Results As compared with model control group, the apoptosis rate, tissue injury,activity of plasma enzymes and the Bax/Bcl-2 expression ratio were reduced in low and high dose clotrimazole groups. The apoptotic index in both clotrimazole-treated groups was lower than that of model control group with statistically significant difference. CYP3A1 expression was significantly induced by clotrimazole compared to the sham-operated group. Conclusion Clotrimazole may inhibit apoptosis of hepatic cells by up-regulating Bcl-2 and down-regulating Bax, thus produce a protective effect on hepatic ischemia-reperfusion injury and it is also related to the inhibition of PARP shear.

Aspergilosis nasal en un perro: reporte de un caso / Nasal Aspergillosis in a Dog: A Case Report / Aspergilose nasal em um cachorro: reporte de um caso

La aspergilosis nasal es una de las principales causas de afección crónica de las fosas nasales en el canino. La sinología clínica es típica en toda enfermedad nasal crónica. Se presenta sobre todo epistaxis y ocasionalmente dolor. La evaluación rinoscópica de la zona permite encontrar hallazgos asociados con la patología y tomar muestras para citología y cultivo. La terapéutica sistémica con antifúngicos orales ha sido de utilidad variable, pero actualmente se ha remplazado con la medicación tópica directa en el área afectada. Este artículo describe el caso clínico de un canino, macho de cuatro años de edad, que fue presentado a consulta por secreción nasal mucosanguinolenta unilateral con una semana de evolución. El paciente se venía tratando en otro centro veterinario con ciclonamina y vitamina K por un posible trastorno en la coagulación. Después de una serie de exámenes que incluyeron rinoscopia y cultivo para hongos, se diagnosticó aspergilosis nasal. Se realizaron dos aplicaciones de clotrimazol intranasal que permitieron la resolución de los signos clínicos.

Nasal aspergillosis is a major chronic disease affecting the nostrils in dogs. Clinical sinology is typical in every chronic nasal disease. Epistaxis and occasional pain occurs. Rhinoscopic assessment of the area evidences findings associated with the pathology and allows collecting samples for cytology and culture. Systemic therapy with oral antifungals has had variable utility, but now it has been replaced by direct topical medication to the affected area. This article describes the case of a 4-years-old male dog, submitted to consultation by unilateral muco-bloody nasal discharge with a week of evolution. The patient was treated by another vet center with cyclonamine and vitamin K for a possible clotting disorder. After a series of tests that included rhinoscopy and fungal culture, nasal aspergillosis was diagnosed. Intranasal clotrimazole was applied twice and it allowed the resolution of the clinical signs.

A aspergilose nasal é uma das principais causas de afecção crônica das fossas nasais no canino. A sinologia clínica é típica em toda doença nasal crônica. Apresenta-se sobre tudo epistaxe e ocasionalmente dor. O exame rinoscópico da zona permite encontrar achados associados com a patologia e tomar amostras para citologia e cultivo. A terapêutica sistêmica com antifúngicos orais tem sido de utilidade variável, mas atualmente substituiu-se com a medicação tópica direta na área afetada. Este artigo descreve o caso clínico de um canino, macho de 4 anos de idade, que foi apresentado à consulta por secreção nasal muco sanguinolento unilateral com uma semana de evolução. O paciente estava sendo tratado em outro centro veterinário com ciclonamina e vitamina K por um possível transtorno na coagulação. Depois de uma série de exames que incluíram rinoscopia e cultivo para fungos, se diagnosticou aspergilose nasal. Realizaram-se duas aplicações de clotrimazol intranasal que permitiram a resolução dos sinais clínicos.