Preparation and evaluation of a new erythromycin derivative -- erythromycin taurate

Erythromycin taurate, a new derivative of erythromycin, was prepared by reacting erythromycin base with tauric acid and its physico-chemical and biological properties were evaluated. The derivative has reasonably good solubility in organic solvents. The partition coefficient values in chloroform/water 1.17 and octanol/water 1.16 systems indicate its good distribution in various tissues in vivo. The in vitro antimicrobial potency of the derivative (833.33 microg mg(-1)) is higher than that of the existing derivatives such as erythromycin estolate, erythromycin stearate, erythromycin ethyl succinate, erythromycin gluceptate, erythromycin lactobionate. The antimicrobial spectrum is comparable to that of the parent compound. Our results indicate that erythromycin taurate has a high potential for possible clinical application and is more efficient against Escherichia coli and Klebsiella pneumoniae than the parent base.     

Diagnostic significance of semiquantitative and quantitative parameters of Tc99m-Ethylenedicystine renal allograft scintigraphy

OBJECTIVES: No objective parameters for renal allograft evaluation have yet been described for Tc99m-Ethylenedicystine. This study evaluates the diagnostic significance of different quantitative and semi-quantitative parameters of renal allograft scintigraphy using Tc99m-Ethylenedicystine. METHODS: A total of 72 renal dynamic scintigraphic studies were performed within 2-weeks of renal transplantation in 42 patients. The graft perfusion, kidney/aorta ratio, washout index and retention index were derived from all studies. All these parameters were evaluated for their ability to distinguish between a normal graft, a graft with acute rejection (AR), and a graft with acute tubular necrosis (ATN). Histopathological verification of diagnosis was obtained in all cases. RESULTS: Studies were subdivided into 3 groups according to histopathological findings: acute rejection (n = 42), normal (n = 18) and acute tubular necrosis (n = 12). Normal allografts were visualized with in 2.66 +/- 0.59 seconds of visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 15.22 +/- 6.86, 1.67 +/- 0.45, and 5.48 +/- 0.98 respectively. Allografts with ATN were visualized with in 3.36 +/- 0.80 seconds of visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 12.73 +/- 6.74, 0.60 +/- 0.14, and 9.18 +/- 1.48 respectively. In AR, allografts were visualized 15.18 +/- 9.48 seconds after visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 7.07 +/- 2.15, 0.63 +/- 0.11, and 2.26 +/- 1.28 respectively. CONCLUSIONS: Retention index can separate all the three condition of normal, acute rejection and acute tubular necrosis from each other. Retention index of < 4 suggests acute rejection, a value between 4 and 7 suggests normal allograft and a value of > or = 7 is suggestive of acute tubular necrosis. However, perfusion, K/A ratio and washout index can not segregate all the three groups.     

Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents

Primaquine ( PQ ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side‐effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco‐conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside ( 15a ), galactoside ( 15b ) and mannoside ( 15c ) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.     

Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres

The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.