Beckmann Rearrangement of Erythromycin A 9(E)-Oxime

Deoxo 6 deoxy 6,9 epoxy 9,9 a didehydro 9 a aza 9 a homoerythromycin A (1), 9 deoxo 11 deoxy 9,11 epoxy 9,9 a didehydro 9 a aza 9 a homoerythromycin A (2) and 9 a aza 9 a homoerythromycin cyclic lactam (3) were synthesized by the Beckmann rearrangement of erythromycin A 9 (E) oxime (4). The structures of compounds (1), (2) and (3) have been identified by their spectral data. The reaction mechanism was also discussed. The yield of the Beckmann rearrangement of compounds (4) was better than that reported in literatures.

Comparative Process for the Preparation of 9-Oxime Erythromycin A

The comparative process for preparing 9-oxime erythromycin A (EMAO) is investigated. EMAO was synthesized and compared by the reaction of erythromycin and hydroxylamine hydrochloride with various bases such as sodium acetate, triethylamine, etc. A new synthetic method is established. The oximation is performed under dynamic buffer system; less degradation impurities are formed. The yield of EMAO reaches more than 95%, HPLC analysis shows that the purity of EMAO is more than 90%, and the E/Z isomeric ratio preponderates over 7∶1.

Non-Isothermal Desolvation Kinetics of Erythromycin A Acetone Solvate

The desolvation of erythromycin acetone solvate was investigated under non-isothermal conditions by a thermogravimetric analyzer. This paper emphasized the kinetic analysis of non-isothermal TG-DTA data by Achar method and Coats-Redfern method to fit various solid-state reaction models, and to achieve kinetic parameters of desolvation. The mechanism of thermal desolvation was evaluated using the kinetic compensation effect. The results show that kinetics of desolvation of erythromycin acetone solvate was compatible with the mechanism of a two-dimensional diffusion controlled and was best expressed by Valensi equation. Corresponding to the integral method and the differential method, the activation energy of desolvation of erythromycin acetone solvate was estimated to be 51.26—57.11 kJ/mol, and the pre-exponential factor was 8.077×106 s-1—4.326×107 s-1, respectively.

Chiral Separation of Erythromycin as a New Chiral Selector on CE

Erythromycin as a new chiral selector was first used for chrial separation of four derivatives of biphenyldimethylester enantiomers on CE. The influence of pH, the chiral selector concentration and organic modifiers were preliminarily studied. Experiments show that the erythromycin as chiral selector is useful to CE.

Synthesis and Antibacterial Activities of Erythromycin Derivatives

Aim To synthesize 4″-carbamate derivatives of erythromycin and test their antibacterial activities in vitro. Methods New erythromycin antibacterial agents containing 4″-carbamate group were designed and synthesized from azithromycin via protection, aminoformylation, amination and deprotection. Their antibacterial activities against Staphylococcus aureus strains were tested. Results Nine compounds were synthesized. Their structures were confirmed by MS, IR, ~ 1 H NMR and ~ 13 C NMR, and the synthetic conditi...

Effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy

AIM： To determine the effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy. METHODS： Consecutive patients who underwent capsule endoscopy during the 16-mo study period were either given 250 mg oral erythromycin, 1 h prior to swallowing the capsule endoscope or nothing. The gastric and small bowel transit time, and the small bowel image quality were compared. RESULTS： Twenty-four patients received oral erythromycin whereas 14 patients were not given any prokinetic agent. Patients who received erythromycin had a significantly lower gastric transit time than control （16 min vs70 min, P= 0.005）, whereas the small bowel transit time was comparable between the two groups （227 rain vs 183 min, P= 0.18）. Incomplete small bowel examination was found in three patients of the control group and in one patient of the erythromycin group. There was no significant difference in the overall quality of small bowel images between the two groups. A marked reduction in gastric transit time was noted in two patients who had repeat capsule endoscopy after oral erythromycin. CONCLUSION： Use of oral erythromycin significantly reduces the gastric transit time of capsule endoscopy.

Effect of erythromycin on image quality and transit time of capsule endoscopy: A two-center study

AIM: To compare the effect of oral erythromycin vs no preparation with prokinetics on the transit time and the image quality of capsule endoscopy (CE) in evaluating small bowel (SB) pathology. METHODS: We conducted a retrospective, blinded (to the type of preparation) review of 100 CE studies, 50 with no preparation with prokinetics from one medical center (Group A) and 50 from another center with administration of a single dose of 200 mg oral erythromycin 1 h prior to CE (Group B). Gastric, SB and total transit times were calculated, the presence of bile in the duodenum was scored, as was cleanliness within the proximal, middle and distal intestine. RESULTS: The erythromycin group had a slightly shorter gastric transit time (21 min vs 28 min, with no statistical significance). SB transit time was similar for both groups (all P > 0.05). Total transit time was almost identical in both groups. The rate of incomplete examination was 16% for Group A and 10% for Group B (P = 0.37). Bile and cleanliness scores in different parts of the intestine were similar for the two groups (P > 0.05). CONCLUSION: Preparation for capsule endoscopy with erythromycin does not affect SB or total transit time. It tends to reduce gastric transit time, but it does not increase the cecum-reaching rate. Erythromycin does not adversely affect image quality. We consider the routine use of oral erythromycin preparation as being unjustified, although it might be considered in patients with known prolonged gastric emptying time.

Metabolism of Praziquantel in Erythromycin, Acetylspi-ramycin and Dexamethasone Induced Rat Liver Micro-somes

Our results show that in liver microsomes from erythromycin,acetylspiramycin and dexamethsone pretreated rats,the rate of praziquantel( PQT)disappearence was increased as compared with control rat When microsomes from erythromycin-treated rats were exposed to PQT in the presence of potassium ferricyanide which broke down the cytochrome P-450 Fe(Ⅱ)-metabolite complexes and restored the functional cytochrome P-450,PQT metabolism was further increased. Acetylspiramycin did not form the complexes, so potassium ferricyanide showed no effect on the PQT metabolism in microsomes from acetylspiramycin-treated rats. Triacetyloleandomycin,a specific inhibitor of cytochrome P-450ⅢAI, inhibited PQT metabolism by 53% in liver microsomes from dexamethasone-treated rats.These results indicate the cytochrome P-450ⅢA seems to be involved in metabolism of PQT in rat liver microsomes.

EFFECT OF ERYTHROMYCIN ON GASTRIC DYSMOTILITY AND NEUROENDOCRINE PEPTIDES IN RATS WITH DIABETES MELLITUS

Objective To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin （SS）, vasoactive intestinal peptide （VIP）, motilin （MTL）, and substance P （SP） in plasma and isolated gastric antrum tissue of diabetes mellitus （DM） rat models. Methods Thirty male Sprague-Dawley rats were divided into three groups： control group （n = 10）, DM group （n = 10）, and erythromycin group （DM models with erythromycin treatment, n = 10）. A single dose of streptozotocin （100 mg/kg, dissolved in 0. I mol/L citric acid buffer, pH4.5） was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be （＋＋＋ ） to （＋＋＋＋） over one week were considered successful DM models. The resting tension, mean contractile amplitude and fi＇equency of spontaneous change in isolated longitudinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and gastric antrum tissue were measured using radioimmunoassay. Results （1） In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile fi＇equency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension （P 〈 0.01 ）. （2） Plasma SS, VIP, and MTL concentrations in DM group were higher than those in control （P 〈 0.05）, while the SP level decreased （P 〈 0.05）. In the gastric antrum, SS of DM group was significantly higher than that of control group （P 〈 0.01 ）, while SP and MTL levels were lower than those of control group （P 〈 0.05 and P 〈 0.01, respectively）. However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group （P 〈 0.05）. （3） The blood glucose was lower in erythromycin group than DM group （P 〈 0.01 ）. Conclusions Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.

Myasthenia gravis exacerbation and diarrhea associated with erythromycin treatment

An important problem in management of the case with myasthenia gravis (MG) is the control of exacerbation. There are several possible causes of exacerbation of MG including the use of drug. Here, the authors report a case of MG exacerbation and diarrhea associated with erythromycin treatment.

Molecular Epidemiological Analysis of Group A Streptococci Isolated from Children in Chaoyang District of Beijing, 2011:emm Types, Virulence Factor Genes and Erythromycin Resistant Genes

Group A streptococcus （GAS） causes a wide range of diseases in the human population. GAS diseases are more common in children than in adults, with clinical manifestations ranging from pharyngitis and impetigo to invasive infections and post streptococcal sequelae, such as acute rheumatic fever and acute post-streptococcal glomerulonephritis[1]. GAS harbors a host of virulence factors that contribute to its complex pathogenicity and differences in the disease severity and frequency. M protein, one of the major virulence factors, is encoded by the emm gene induces a type of specific host immune response and confers antiphagocytic properties.

Preparation, Characterization, and in vitro Release of Biodegradable Erythromycin-gelatin Microspheres

Blank and erythromycin-loaded gelatin microspheres were successfully fabricated via emulsion chemical- crosslinking technique. The surface morphology of the microspheres was characterized by scanning electron microscope（SEM） and optical microscope. The results show that the microspheres were spherical and smooth. The particle average size of erythromycin-loaded microspheres was found to be 20.6 μm, with a high purity of more than 90% and with a good dispersibility. The microspheres could be obtained in a high yield. Erythromycin released from the microspheres was monitored in buffer and artificial body fluid at 37 ℃. Average drug content was 27.2%, and erythromycin-loaded gelatin microspheres showed good release profiles with a nearly constant release during 4-8 h in artificial body fluid in vitro degradation studies. These gelatin microspheres are useful for studying and developing various drug-delivery systems.

Synthesis and Antibacterial Activities of Erythromycin Derivatives

Ten new erythromycin antibacterial agents containing amidino group were designed and synthesized from erythromycin via oximation, reduction and condensation. Their structures were confirmed by MS and 13C NMR; the synthetic condition(reaction medium)was explored; and their in vtiro antibacterial activities were tested. Compound HMA-3 showed antibacterial activity against staphylococcus aureus, which is equivalent to that of erythromycin A. Compounds HMA-8 and HMA-4 also showed an antibacterial activitiy. But no compound showed bactericidal activity.

Effects of erythromycin on pressure in pyloric antrum and plasma motilin and somatostatin content in dogs

ＥｆｅｃｔｓｏｆｅｒｙｔｈｒｏｍｙｃｉｎｏｎｐｒｅｓｓｕｒｅｉｎｐｙｌｏｒｉｃａｎｔｒｕｍａｎｄｐｌａｓｍａｍｏｔｉｌｉｎａｎｄｓｏｍａｔｏｓｔａｔｉｎｃｏｎｔｅｎｔｉｎｄｏｇｓＨＵＡＮＧＹｕＸｉｎ１，ＣＨＥＮＹｕｅＸｉａｎｇ１，ＨＵＩＤｅＳ...

Antitumor Activity of Erythromycin on Human Neuroblastoma Cell Line(SH-SY5Y)

Antitumor effects of erythromycin and the related mechanism were investigated in the present study.Neuroblastoma cells（SH-SY5Y） were exposed to erythromycin at different concentrations for different durations.Cell proliferation was measured by cell counting,and cell viability was examined by MTT assay.Cell cycle phase distribution and the cytosolic calcium level were detected by flow cytometry.Mitochondrial membrane potential was measured by the JC-1 probe staining and fluorescent microscopy.The expression of an oncogene（c-Myc） and a tumor suppressor [p21（WAF1/Cip1）] proteins was analyzed by using Western blotting.Erythromycin could inhibit the proliferation of SH-SY5Y cells in a concentration-and time-dependent manner.The cell cycle was arrested at S phase.Mitochondrial membrane potential collapsed and the cytosolic calcium was overloaded in SH-SY5Y cells when treated with erythromycin.The expression of c-Myc protein was down-regulated,while that of p21（WAF1/Cip1） protein was up-regulated.It was concluded that erythromycin could restrain the proliferation of SH-SY5Y cells.The antitumor mechanism of erythromycin might involve regulating the expression of c-Myc and p21（WAF1/Cip1） proteins.

ERYTHROMYCIN POLYLACTIC ACID MICROSPHERES FOR LUNG TARGETING

AIM: To prepare polylactic acid microspheres of Erythromycin for Lung targeting. METHEDS: The orthogonal test design was used to optimize the technology of preparation. The character of the microspheres, drug release in vitro, stability and tissue distribution were examined. RESULTS: The Erythromycin polylactic acid microspheres was regular in its morphology. Drug was enveloped in microspheres but not physically mixed with PDLLA. The average particle size was 11.65mm with over 94% of the microspheres being in the range of 5~20mm; The drug loading and the incorporation efficiency were 18% and 60% respectively. The microspheres were stable for three month at 4℃ and room temperature. The in vitro release properties could be expressed by the Higuchi抯 equation: y = 28.067 + 3.8515t1/2 (r = 0.9834). Comparing with injection, the drug in microspheres was more concentrated in lung tissue. CONCLUSION: Erythromycin polylactic acid microspheres showed significant sustained release and lung targeting.

Characterization and structure analysis of the heterosolvate of erythromycin thiocyanate

Erythromycin thiocyanate is widely used for the production of other macrolide antibiotics. In this work, a novel heterosolvate of this pharmaceutical compound has been obtained and characterized for the first time, which was transformed from the dihydrate form in the acetone solvent through evaporation crystallization. Thermal behavior together with compositional analysis revealed that both water and acetone molecules participated in the formation of the crystal lattice which is rarely reported before. The general chemical name of the heterosolvate may be defined as erythromycin thiocyanate sesquihydrate hemiacetonate. Furthermore, studies on solid-state spectral analysis provided strong evidence of intermolecular hydrogen bonds in heterosolvate crystals. According to the crystal structure determined by single crystal X-ray diffraction, the formation mechanism of the heterosolvate is proposed in which strong multihydrogen bondings between water and solute molecules form the layer structure. While acetone molecules form single-hydrogen bonds with solutes and reside in channels between layers. This well explains why acetone solvent is easy to escape from the crystal structure during desolvation.

Syntheses and Antibacterial Activities of Novel Erythromycin O-Alkylamidoximes

Nine novel erythromycin O-alkylamidoxime derivatives were prepared in excellent yields via the condensation of different O-alkylhydroxylamines with erythromycin imino ether. The structures of all the compounds prepared were confirmed by ^1 H NMR, 13C NMR, IR and MS, and their in vtiro antibacterial activities were tested. Among the compounds, two of them showed good antibacterial aetivities.

Streptococcus peumoniae in an Egyptian urban community:incidence of erythromycin-resistance determinants and antibiotic susceptibility profile

Objectives:To determine the incidence of resistance of Streptococcus(Strep).pneumoniae isolated in our locality to erythromycin,to screen for the two resistance determinants erm(B) and mef(A) genes,and to identify the susceptibility profile to commonly used antibiotics.Methods:Samples were collected from patients attending the Outpatient Department of Zagazig University Hospital,Zagazig,Egypt,between February 2006 and March 2007.Strep.pneumoniae was identified by conventional procedures.Susceptibilities to erythromycin and 15 antibiotics were identified by disc diffusion method,as outlined by CLSI.E-test was used for MIC determination of erythromycin.erm(B) and mef(A) genes were detected by PCR.Results:Eighty-one Strep. pneumoniae strains were identified.Fifty- one of them(63%) were erythromycin-resistant,and mef(A) gene was the predominant resistance determinant.Vancomycin,imipenem and gatifloxacin had the best activity against the isolates,whereas tetracycline had the least.Forty-two(51.85%) out of the 81 Strep.pneumoniae strains were multidrug-resistant.Conclusions:High incidence of resistance to erythromycin and multiple antimicrobials existed.mef(A) was the principal erythromycin-resistance gene.

Treatment of pediatric Ogilvie’s syndrome with low-dose erythromycin:A case report

Acute colonic pseudo-obstruction is a poorly understood syndrome, characterized by the signs, symptoms and radiological pattern of a large bowel obstruction without evidence for a mechanical obstruction. We report a case of a 2-year old boy who presented with progressive abdominal distention, vomiting and abdominal pain on postoperative d 3. Plain abdominal X-ray showed markedly dilated large bowel. Mechanical colonic obstruction was ruled out with hypaque enema. Ogilvie＇s syndrome was suspected. The patient received treatment with oral erythromycin which had an immediate beneficial effect. During the 6 mo follow-up, no recurrences of symptoms were observed. We provide a safe and effective therapy for Ogilvie＇s syndrome in pediatric individuals.