Research on Polymorphs of Edaravone / 医药导报

Objective To study polymorphism of the free radical scavenger edaravone and to find the one which has good advantages to the clinical medication. Methods Preparation of four forms of edaravone through kinds of physical or chemical methods. These polymorphs were characterized by single crystal X-ray diffraction method (SXRD), powder X-ray diffraction method (PXRD), differential scanning calorimetry method (DSC), infrared spectrum method (IR) and melting point method (MP);a variety of influence factors experiment were used to research the stability of polymorphs. Solid edaravone in different forms were orally administered to SD rats respectively, the plasma concentration of the drug was determined by HPLC, and the pharmacokinetic characteristic of different forms was compared according to the HPLC results. Results Four forms(form A, form B, form C, form D) and the preparation of pure crystal forms were obtained by crystal screening technology. These polymorphs were identified by PXRD, DSC and IR. The edaravone polymorphs have an influence on the stability and pharmacokinetic. Conclusion Edaravone research provideds a variety of crystal material composition, preparation methods, stability, solubility and pharmacokinetic characteristic, and form A has been proved of good advantage one. This research provides data and technology support for choice of preponderant pharmaceutical polymorphs and drug quality standard improvement.

Research on Polymorphs of Edaravone / 医药导报

Objective To study polymorphism of the free radical scavenger edaravone and to find the one which has good advantages to the clinical medication. Methods Preparation of four forms of edaravone through kinds of physical or chemical methods. These polymorphs were characterized by single crystal X-ray diffraction method (SXRD), powder X-ray diffraction method (PXRD), differential scanning calorimetry method (DSC), infrared spectrum method (IR) and melting point method (MP);a variety of influence factors experiment were used to research the stability of polymorphs. Solid edaravone in different forms were orally administered to SD rats respectively, the plasma concentration of the drug was determined by HPLC, and the pharmacokinetic characteristic of different forms was compared according to the HPLC results. Results Four forms(form A, form B, form C, form D) and the preparation of pure crystal forms were obtained by crystal screening technology. These polymorphs were identified by PXRD, DSC and IR. The edaravone polymorphs have an influence on the stability and pharmacokinetic. Conclusion Edaravone research provideds a variety of crystal material composition, preparation methods, stability, solubility and pharmacokinetic characteristic, and form A has been proved of good advantage one. This research provides data and technology support for choice of preponderant pharmaceutical polymorphs and drug quality standard improvement.

Gene Ploymorphisms of Angiotensin Converting Enzyme and Endothelial Nitric Oxide Synthase in Patients with IgA Nephropathy / 대한신장학회잡지

To evaluate the association between ACE gene I/D polymorphism and ecNOS gene a/b polymorphism in IgA nephropathy, 158 IgA nephropathy patients and 121 control subjects were examined. In genotype distribution of the ACE gene I/D polymorphism, there was no significant difference in genotype distribution between controls and IgA nephropathy patients. We also examined the association between ACE genotype and clinical characteristics in the patients with IgA nephropathy. The incidence of hypertension in patients with DD genotype was higher than that of other genotypes. There were no significant association between I/D polymorphism distribution and chronic renal failure, nephrotic range proteinuria, and glomerular sclerosis in IgA nephropathy. In genotype distribution of ecNOS gene a/b polymorphism, there was no significant difference between IgA nephropathy patients and controls. There was no significant difference in frequency of chronic renal failure, hypertension, nephrotic range proteinuria and glomerular sclerosis among ecNOS genotypes. In addition, we failed to detect any significant association between the ACE and ecNOS gene-polymorphis ms and the decline of renal function in IgA nephropathy. A further study with larger number of patient population would be necessary.

A genetic linkage study of Wilson disease in Korean families

Wilson disease gene (WND) locus is presumed to be located in chromosome 13q. There are studies on the clinical heterogeneities and variations between ethnic groups in Europe, North America, and the Middle East and it requires the study of another ethnic group, especially Asian population for the confirmation. This study was an anlysis of restriction fragment length polymorphism of the Wilson's disease with the probes on D13S26, D13S31, and D13S59, The subject was 34 persons of seven families. The serum ceruloplasmin and the serum copper were also measured. The results were as follows: 1) The Wilson disease gene was also presumed to be located in chromosome 13q area in Korean patients and D13S25, D13S26, D13S31 and D13S59 gene loci were also linked to Wilson disease of Koreans. The lod score of D13S25 was 1.45 (theta =0: D13S59, 1.13 (theta =0): D13S26, 247 (theta =0). 2) Three siblings of Wilson disease patients were diagnosed as carriers by the analysis of restriction fragment length polymorphism. 3) In Wilson disease patients, the serum ceruloplasmin and copper was 6.8+/1.8dl, and 64.7+/-38.6microg/dl respectively and it is 18.8+/-6.1 mg/dl and 65.3+/-10.6microg/dl respectively in heterozygotes.