国产环丙氟哌酸(Ciprofloxacin)体内抗菌作用研究

本文观察了北京、天津研制的两个国产环丙氟哌酸对大肠杆菌、痢疾杆菌、克雷伯氏肺炎杆菌、绿脓杆菌各2株及金黄色葡萄球菌2株感染小鼠的体内抗菌作用。国产环丙氟哌酸对2株金葡菌感染小鼠具有体内抗菌活性,ED_(50)分别为1.54,1.37;1.56,1.60 mg/kg,低于氟哌酸(norfloxacin)的ED_(50)2.78,4.28 mg/kg的结果,是苯唑青霉素(oxacillin)的1/3—1/8。国产环丙氟哌酸对大肠杆菌、痢疾杆菌感染小鼠的体内抗菌作用很强,ED_(50)值在0.026—0.032mg/kg之间,氟哌酸的ED_(50)值是前者的5—10倍,头孢唑啉(cefazolin)及氨苄青霉素(ampicillin)的ED_(50)值是环丙氟哌酸ED_(50)值的近百倍。环丙氟哌酸对克雷伯氏肺炎杆菌感染小鼠的ED_(50)值为0.115与0.158mg/kg,明显低于头孢唑啉相应的ED_(50)值2.16与2.81mg/kg。环丙氟哌酸对绿脓杆菌的ED_(50)低于1mg/kg,明显低于庆大霉素的ED_(50),后者的ED_(50)为3.37—4.42mg/kg。国产环丙氟哌酸具有广谱体内抗菌活性,对5种临床致病菌ED_(50)资料统计分析表明,环丙氟哌酸的体内抗菌作用明显优于氨苄青霉素、头孢唑啉、庆大霉素及苯唑青霉素(p<0.01)。两个国产环丙氟哌酸的体内抗菌作用相似,两个药的ED_(50)值差异不显著。

环丙沙星(ciprofloxacin)在鸡蛋中残留的研究

应用高效液相色谱法(HPLC)检测了鸡蛋中环丙沙星的残留.鸡蛋经乙腈溶液提取,提取液真空干燥后用流动相溶解.以0.015 mol/L四丁基溴化铵/乙腈(94/6,V/V)作流动相,用SymmetryC18柱(5 μm,3.9 mm×150 mm),在激发波长280 nm、发射波长455 nm处,用荧光检测器检测.将环丙沙星以0.05、0.50、1.00 mg/kg分别添加到空白鸡蛋样品中,测得鸡蛋样品中环丙沙星的回收率分别为(82.2±6.8)%、(84.5±5.9)%、(87.9±4.7)%,相对标准差均低于8.3%.用该方法测定鸡蛋中环丙沙星的最低检测限为0.01 mg/kg.各试验组产蛋鸡给药剂量分别按10.0、20.0mg/kg(体质量)内服环丙沙星水溶液,每天给药1次,连续5 d.停药后鸡蛋中环丙沙星残留消除缓慢;休药8～9 d时,鸡蛋中环丙沙星残留量低于0.03mg/kg;休药9～10 d时,鸡蛋中环丙沙星残留量均低于最低检测限(0.01 mg/kg);且随着环丙沙星给药剂量的增大,环丙沙星在鸡蛋中的残留量也相应增大.

Preparation, Characterization and in Vitro Release of Ciprofloxacin Polylactic Acid Microspheres

Aim Ciprofloxacin polylactic acid microspheres (CFX-PLA-MS) were preparedusing solvent evaporation method from a solid-in-oil-in-water emulsion system. Methods Orthogonalexperiment was used to optimize the method of CFX-PLA-MS preparation. Microspheres werecharacterized in terms of morphology, size, encapsulation efficiency, drug loading and in vitro drugrelease. Results The physical state of CFX-PLA-MS was determined by scanning electron microscopy(SEM) and differential scanning calorimetry (DSC) . Microspheres formed were spherical with smoothsurfaces. Drug was enveloped in microspheres without mixing physically with PLA. The averageparticle size was 280.80 ± 0.15 μm, with over 90% of microspheres falling in the range of 250 -390 μm. The encapsulation efficiency was 65.8% ± 0.58% and the drug loading was 34.1% ± 0.51% .In vitro release study revealed a profile of sustained release of Ciprofloxacin from CFX-PLA-MS. Theaccumulated release percentage and half-life (T_(1/2) of Ciprofloxacin microspheres were 84.0% in53.2 h, and 31.9 h, respectively. Higuchi equation was Q= -0.0043 + 0.003 9 t^(1/2), r = 0.9941.Conclusion Ciprofloxacin microspheres have been successfully prepared and sustained release of CFXfrom microspheres is achieved.

肉仔鸡静注和内服环丙沙星(ciprofloxacin)的药物动力学

16只健康 AA肉仔鸡 ,随机分成 2组 ,每组 8只 ,按 10 mg/ kg剂量分别进行静注和内服单剂量环丙沙星药动学试验。血浆中药物浓度用高效液相色谱法测定 ,血药浓度 -时间数据用 MCPKP药动学计算机程序处理。结果表明 ,静注给药后的药时数据符合无吸收二室开放模型 ,主要动力学参数分别为 :t1 /2α为 (0 .2 34± 0 .0 49) h,t1 /2β为 (10 .118±0 .2 71) h,VB为 (1.374± 0 .12 4) L/ kg,CLB为 (0 .0 94± 0 .0 0 9) L· kg- 1 · h- 1 ,AUC为 (10 7.0 6 8± 10 .6 40 ) mg· L- 1· h。内服给药后的药时数据符合一级吸收一室开放模型 ,主要动力学参数分别为 :t1 /2 kα为 (0 .114± 0 .0 0 8) h,t1 /2 k为(7.784± 0 .5 14) h,Tp 为 (0 .70 2± 0 .0 31) h,Cmax为 (5 .736± 0 .5 15 ) m g/ L,AUC为 (6 8.6 2 2± 8.147) mg· L- 1· h,F为 (6 4.0 92± 7.6 10 ) %。肉仔鸡静注环丙沙星在其体内消除较慢 ,分布广泛 ;内服给药吸收迅速 ,消除较静注给药快。

Determination of Ciprofloxacin Lactate by Sodium Tetraphenylboron Method

This paper describes an effective method for determining ciprofloxacin lactate. An excess of sodium tetraphenylboron was added to precipitate ciprofloxacin lactate in HAc-NaAc buffer solution (pH=4.0). After filtering off the precipitate, the excessive sodium tetraphenylboron in the filtrate was titrated with cetyltrimethylammonium bromide standard solution, with bromophenol blue as indicator. The method is simple and rapid, it has been applied to the determination of ciprofloxacin lactate raw material with satisfactory results. The recovery was between 99.66% and 100.2%, the relative error was less than ±0.40%. Experiments showed that the method gave the same results as the approach using nonaqueous titration (ChP).

用Ciprofloxacin去除传代细胞株中的支原体污染的研究

在应用细胞培养手段的生物学研究和生物工程产品中,支原体污染仍是一个非常棘手的问题。对Vero和SP 2/0-Ag 14等细胞,应用Ciprofloxacin,10μg/ml处理14天,支原体检测全部转阴,经4个月的培养、传代、冻存、复苏,每次支原体检测均保持阴性。对去除了支原体的Vero和LSC-116细胞株,测试了其生长特征和功能,均未见受影响。

Safety and efficacy of levofloxacin versus ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients

Levofloxacin is a synthetic fluoroquinolone that is usually used to treat chronic bacterial prostatitis. We investigated the safety and efficacy of levofloxacin compared with ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients. This was a multicenter, open-label, randomized controlled non-inferiority trial. Four hundred and seventy-one patients with clinical symptoms/ signs were enrolled into the study, and 408 patients were microbiologically confirmed chronic bacterial prostatitis, who were randomized to either oral levofloxacin （500 mg q,d.） or ciprofloxacin （500 mg b.i^d.） for 4 weeks. Bacterial clearance rate, clinical symptoms/signs, adverse reactions and disease recurrence were assessed. The clinical symptoms and signs （including dysuria, perineal discomfort or pain） and bacteria cultures in 209 patients treated with levofloxacin and 199 patients treated with ciprofloxacin were similar. The most common bacteria were Escherichia cofiand Staphylococcus aureus. One to four weeks after the end of 4 weeks treatment, the bacterial clearance rate （86.06% vs. 60.03%; P〈O.05） and the clinical efficacy （including clinical cure and clinical improvement（93.30% vs. 71.86%; P〈0.05）） were significantly higher in the levofloxacin-treated group than in the ciprofloxacin-treated group. The microbiological recurrence rate was significantly lower in the levofloxacin-treated group than in the ciprofloxacin-treated group （4.00% vs. 19.25%; P〈0.05）. Rates of adverse events and treatment-related adverse events were slightly lower in the levofloxacin-treated group than in ciprofloxacin-treated group. Levofloxacin showed some advantages over ciprofloxacin in terms of clinical efficacy and disease recurrence, with a low rate of adverse events, for the treatment of chronic bacterial prostatitis in Chinese patients.

Synthesis and Crystal Structure of Rare Earth Complex withCiprofloxacin

The complex of rare earth with ciprofloxacin has been synthesized and characterized by means of x-ray single crystal diffraction. The structure features of the complex are decribed.

Pharmacokinetics and tissue behavior of enrofloxacin and its metabolite ciprofloxacin in turbot Scophthalmus maximus at two water temperatures

Turbot Scophthalmus maximus, an important aquaculture species in China, currently suffers from epizootic diseases because of high density aquaculture. Enrofloxacin has been used to treat various systemic bacterial fish infections. However, studies concerning the pharmacokinetics of enrofloxacin in turbot are limited. In this study, the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin, were investigated in the turbot following intravenous and oral administration at 10 mg enrofloxacin/kg body weight, at 16℃ and 10℃ water temperatures. The concentrations of enrofloxacin and ciprofloxacin in the main tissues （plasma, muscle, liver and kidney） were detected by HPLC. The results show that the plasma concentration-time data for enrofloxacin were best described as a two-compartment open model after intravenous and oral administration. Three pharmacokinetic equations were established between the concentrations and temperatures. The kinetic profile of enrofloxacin was temperature dependent. The absorption half-life of enrofloxacin was 1.99 h and 2.17 h after oral administration, whereas the elimination half-life of the drug was 98.63 h and 136.59 h at 16℃ and 10℃, respectively. The peak concentration of enrofloxacin in plasma and tissues was higher at 16℃ than that at 10℃, and the peak plasma concentration time in the liver was the shortest at both temperatures among those of other tissues. The plasma ℃/MIC ratio varied between 11.08 and 5 540.00 at 16℃; and between 7.92 and 3 960.00 at 10℃. The AUC/MIC ratio was 467.82-280 690.00 at 16℃, and 359.48-215 690.00 at 10℃. These ratios indicate that it is possible to obtain therapeutic efficacy. Very low levels of ciprofloxacin were detected. The AUC ratios of ciprofloxacin and enrofloxacin in plasma suggest that plasma ciprofloxacin might play a minor role in enrofloxacin treatment for turbot.

Infective severe acute pancreatitis:A comparison of ^(99m)Tc-ciprofloxacin scintigraphy and computed tomography

AIM:To evaluate 99mTc-ciprofloxacin scintigraphy compared with computed tomography(CT)for detecting secondary infections associated with severe acute pancreatitis(SAP)in swine.METHODS:Six healthy swine were assigned to a normal control group(group A,n = 6).SAP was induced in group B(n = 9)and C(n = 18),followed by inoculation of the resulting pancreatic necroses with inactive Escherichia coli(E.coli)(group B)and active E.coli(group C),respectively.At 7 d after inoculation,a CT scan and a series of analyses using infecton imaging(at 0.5,1,2,3,4 and 6 h after the administration of 370 MBq of intravenous infecton)were performed.The scintigrams were visually evaluated and semi-quantitatively analyzed using region of interest assignments.The differences in infecton uptake and changes in the lesion-background radioactive count ratios(L/B)in the 3 groups were recorded and compared.After imaging detection,histopathology and bacterial examinations were performed,and infected SAP was regarded as positive.The imaging findings were compared with histopathological and bacteriological results.RESULTS:In group A,6 animals survived without infection in the pancreas.In group B,7/9 swine survived and one suffered from infection.In group C,15/18 animals survived with infection.Hence,the number of normal,non-infected and infected SAP swine was 6,6 and 16,respectively.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of the infecton method were 93.8%(15/16),91.7%(11/12),92.9%(26/28),93.8%(15/16)and 91.7%(11/12),whereas these values for CT were 12.5%(2/16),100.0%(12/12),50.0%(14/28),100.0%(2/2)and 46.2%(12/26),respectively.The changes in L/B for the infected SAP were significantly different from those of the non-infected and normal swine(P < 0.001).The mean L/B of the infectious foci at 0.5,1,2,3,4 and 6 h was 1.17 ± 0.10,1.71 ± 0.30,2.46 ± 0.45,3.36 ± 0.33,2.04 ± 0.37 and 1.1988 ± 0.09,respectively.At 3 h,the radioactive counts(2350.25 ± 602.35 k)and the mean L/B of the infectious foci were significantly higher than that at 0.5 h(P = 0.000),1 h(P = 0.000),2 h(P = 0.04),4 h(P = 0.000)and 6 h(P = 0.000).CONCLUSION:99m Tc-ciprofloxacin scintigraphy may be an effective procedure for detecting SAP secondary infections with higher sensitivity and accuracy than CT.

Antimicrobial activity and synergism of Sami-Hyanglyun-Hwan with ciprofloxacin against methicillin-resistant Staphylococcus aureus

Objective: To investigate the antibacterial activity of SHHextracted with either water or ethanol against methicillin-resistant Staphylococcus aureus(MRSA) and combinatory antimicrobial effect with ciprofloxacin(CIP) by time kill assay and checkerboard dilution test. Methods: The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of Sami-Hyanglyun-Hwan(SHH) water extract(SHHW) and SHH ethanol extract(SHHE) ranged from 250 to 2000 μg/m L and 125 to 1000 μg/m L against MRSA, respectively. Results: In the checkerboard method, the combinations of SHHE with CIP had a partial synergistic or synergistic effect against MRSA. The time-kill curves showed that a combined SHHE and CIP treatment reduced the bacterial counts dramatically after 24 h. Conclusions: The present study demonstrates the therapeutic ability of SHHE against MRSA infections.

Construction of TiO_(2)-pillared multilayer graphene nanocomposites as efficient photocatalysts for ciprofloxacin degradation

We successfully constructed TiO_(2)-pillared multilayer graphene nanocomposites(T-MLGs)via a facile method as follows:dodecanediamine pre-pillaring,ion exchange(Ti4+pillaring),and interlayer in-situ formation of TiO_(2) by hydrothermal method.TiO_(2) nanoparticles were distributed uniformly on the graphene interlayer.The special structure combined the advantages of graphene and TiO_(2) nanoparticles.As a result,T-MLGs with 64.3wt%TiO_(2) showed the optimum photodegradation rate and adsorption capabilities toward ciprofloxacin.The photodegradation rate of T-MLGs with 64.3wt%TiO_(2) was 78%under light-emitting diode light irradiation for 150 min.Meanwhile,the pseudofirst-order rate constant of T-MLGs with 64.3wt%TiO_(2) was 3.89 times than that of pristine TiO_(2).The composites also exhibited high stability and reusability after five consecutive photocatalytic tests.This work provides a facile method to synthesize semiconductor-pillared graphene nanocomposites by replacing TiO_(2) nanoparticles with other nanoparticles and a feasible means for sustainable utilization of photocatalysts in wastewater control.

Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu(Plecoglossus altivelis)to subsequent Pseudomonas plecoglossicida-induced infection

With the rapid development of intensive farming,the aquaculture industry uses a great many antibiotics for the prevention and treatment of bacterial diseases.Despite their therapeutic functions,the overuse and accumulation of antibiotics also pose a threat to aquaculture organisms.In the present study,ayu(Plecoglossus altivelis)was used as a fish model to study the impacts of ciprofloxacin(CIP)overuse on intestinal homeostasis and immune response during subsequent Pseudomonas plecoglossicida infection.Based on 16S rRNA gene amplification and Illumina sequencing,we found that CIP pre-exposure caused significant variation in intestinal microbiota,including increased species richness,altered microbiota composition and interaction networks,and increased metabolic dysfunction.Furthermore,immunohistochemical analysis indicated that CIP pre-exposure resulted in severe mucosal layer damage,goblet cell reduction,and epithelial cell necrosis of the intestinal barrier in infected ayu.Quantitative real-time polymerase chain reaction(qRT-PCR)showed that disruption of intestinal homeostasis impaired systemic antiinfection immune responses in the intestine,gill,spleen,and head kidney,while inhibiting IL-1β,TNF-α,and IL-10 expression and promoting TGF-βexpression.Our findings indicated that CIP administration can directly affect intestinal microbiota composition and intestinal integrity in ayu fish.This perturbation of intestinal homeostasis is likely responsible for the lower survival rate of hosts following subsequent infection as the capacity to mount an effective immune response is compromised.This study also provides preliminary clues for understanding the effects of antibiotic overuse on higher vertebrates through trophic transfer.

Studies on the Mechanism of Primary Nucleation of Ciprofloxacin Hydrochloride Monohydrate

A general expression for the relationship between induction periodand supersaturation was developed based on polynuclear approach.Different mechanism of primary nucleation in solution can beillustrated by the expression. The results of induction perioddetermined by laser scattering method shows that the crystallizationof ciprofloxacin hydrochloride monohydrate in water/ethanol oraqueous solution is by the mechanism of primary nucleation followedby one-dimensional diffusion growth, and then on-dimensionalcontinuous or 'birth and spread' growth on crystal face. The growthmechanism on the crystal face is affected by temperature and solvent.

Interaction of ciprofloxacin hydrochloride with sodium dodecyl sulfate in aqueous/electrolytes solution at different temperatures and compositions

Interactions of ciprofloxacin hydrochloride(CPFH)with sodium dodecyl sulfate(SDS)were investigated by conductivity measurement in H2O/electrolyte solutions(NaCl,Na2SO4&Na3PO4)over 298.15–318.15 K temperature range(with 5 K interval)considering the human body temperature.In all cases,two critical micelle concentrations(c*)were observed which are increased in the presence of drug and decreased in the presence of salts enunciating the presence of interaction amongst the studied components.For(CPFH+SDS)system in the presence of salt,the c*values at 303.15 K and I=0.50 mmol·kg^-1 followed the order:CNaCl>CNa2SO4>CNa3PO4.TheΔG1,m0 andΔG2,m0values are found to be negative for all systems that show that the micellization process is thermodynamically spontaneous.For(CPFH+SDS)system in water,theΔHm0&ΔSm0 values reveal that the micellization processes is both entropy dominated in almost all cases.In the occurrence of electrolytes,ΔHm0 andΔSm0 values indicate that micellization processes are both entropy&enthalpy restricted at upper temperature but it becomes totally entropy dependent at higher temperature.The higher positiveΔSm0 values indicate the enhanced hydrophobic interaction in presence of salts.The enthalpy-entropy compensation was determined from the linear relationship betweenΔHm0 andΔSm0 values in every state.Different transfer energies as well as compensation temperature and intrinsic enthalpy were also evaluated and the behaviors were comparable to other biological system.

Degradation and mineralization of ciprofloxacin by gas–liquid discharge non-thermal plasma

A typical quinolones antibiotic ciprofloxacin(CIP) in aqueous solution was degraded by a gas–liquid discharge non-thermal plasma system. The discharge plasma power and the emission intensity of the excited reactive species(RS) generated in the gas phase were detected by the oscilloscope and the optical emission spectroscopy. The effects of various parameters on CIP degradation, i.e. input powers, initial concentrations addition of radical scavengers and p H values were investigated. With the increase of discharge power, the degradation efficiency increased but the energy efficiency significantly reduced. The degradation efficiency also reduced under high concentration of initial CIP conditions due to the competitive reactions between the plasma-induced RS with the degradation intermediates of CIP. Different radical scavengers(isopropanol and CCl_4) on ·OH and H· were added into the reaction system and the oxidation effects of ·OH radicals have been proved with high degradation capacity on CIP.Moreover, the long-term degradation effect on CIP in the plasma-treated aqueous solution proved that the long-lived RS(H_2O_2 and O_3, etc) might play key roles on the stay effect through multiple aqueous reactions leading to production of ·OH. The degradation intermediates were determined by the method of electrospray ionization(+)-mass spectroscopy, and the possible degradation mechanism were presented.

A granular adsorbent-supported Fe/Ni nanoparticles activating persulfate system for simultaneous adsorption and degradation of ciprofloxacin

In this work,Fe/Ni nanoparticles were produced through Fe(II)and Ni(II)reduction by NaBH4 and they were stabilized by a kind of prepared granular adsorbent(Fe/Ni@PGA).Fe/Ni@PGA as an environment-friendly activator was used to activate persulfate(PS)for the removal of ciprofloxacin from aqueous solution.Fe/Ni@PGA was systematically characterized via Brunauer-Emmett-Teller(BET)method,X-ray diffraction(XRD),scanning electron microscopy(SEM),and Fourier transform infrared spectroscopy(FTIR).The effects of PS concentration,initial solution pH,Fe/Ni@PGA dosage,initial ciprofloxacin concentration,reaction temperature,anions,and natural organic matters on the removal of ciprofloxacin by Fe/Ni@PGA/PS were analyzed.The removal efficiency of ciprofloxacin by Fe/Ni@PGA/PS was 93.24%under an initial pH of 3.0,PS concentration of 10 mM,Fe/Ni@PGA dosage of 0.1 g,and reaction temperature of 30℃.Fe/Ni@PGA could still exhibit high catalytic activity after nine cycles of regeneration.The removal mechanisms for ciprofloxacin by the Fe/Ni@PGA/PS system were proposed.In summary,the Fe/Ni@PGA/PS system could be applied as a promising technology for ciprofloxacin removal.

Thermal Behavior and Non-isothermal Kinetics of the Polyoxometalate of Ciprofloxacin with Tungstophosphoric Acid

The polyoxometalate （CPFX-HCl）3H3PW12O40·.8H2O was prepared and characterized by elemental analysis, IR spectra and TG-DTA-DTG. The thermal decomposition mechanism and non-isothermal kinetic parameters of the polyoxometalate were obtained from the analysis of TG-DTG data using the Achar equation, Coats-Redfern equation （CR）, Madhusudanan-Krishnan-Ninan equation （MKN） and Horowitz-Metzger equation （HM）. And their mathematical expressions of the kinetic compensation effect were also calculated.

Vanishing bile duct and Stevens-Johnson syndrome associated with ciprofloxacin treated with tacrolimus

Stevens-Johnson syndrome (SJS) is a serious and potentially life-threatening disease. Vanishing bile duct syndrome (VBDS) is a rare cause of progressive cholestasis. Both syndromes are mostly related with drugs. We report a case of a patient with ciprofloxacin-induced SJS and acute onset of VBDS, and reviewed the related literature. It is the fi rst case of ciprofloxacin-induced VBDS successfully treated with tacrolimus. This case reminds physicians of the importance of drug reactions, their severity, techniques for diagnosis and methods of management.

Theoretical Researches on the Self-assembly System of Ciprofloxacin Imprinted Polymers

A molecular modeling approach was used to elucidate template-monomer interaction and the effect of solvent on the recognition of molecularly imprinted polymers （MIPs）. Ciprofloxacin （CIP） was taken as the template molecule. The methacrylic acid （MAA）, 4-vinyl pyridine （4-Vpy）, acrylamide （AAM）, and 2-（trifluoromethyl） acrylic acid （TFMAA） were taken as the functional monomers, respectively. Density functional theory （DFT） at the LC-WPBE/6-31g（d,p） level has been adopted to investigate the geometry optimization. The NBO charge and the binding energies of CIP with the monomers were carried out. The molecular imprinting mechanism of CIP and the monomers as well as the influence of solvent was also discussed. Results indicate that CIP and the monomers are matchable in steric structure and chemical groups lead to ordered compounds. The interaction between CIP and TFMAA is the strongest, and when the ratio of CIP-TFMA_A is 1：6, the polymer has the lowest energy in toluene. The computational approach has been applied to provide details of interactions between CIP and the monomers. This research will hopefully shed light on the future study of CIP-MIPs.