Optimized synthesis process of tofacitinib citrate / 中国药科大学学报

@#In order to improve the yield and simplify the operation, the synthesizing process of JAK3 inhibitor tofacitinib citrate was improved based on the analysis of the methods previously published.Using 2, 4-dichloro-7H-pyrrolo [2, 3-d] pyrimidine and (3R, 4R)-1-benzyl-N, 4-dimethylpiperidin-3-amine dihydrochloride as starting materials, tofacitinib citrate was obtained through four steps of nucleophilic substitution, catalytic transfer hydrogenation, cyanide acetylation and citrate salt, and its crystal form was consistent with the original research.After optimization, the yield was better than those reported in literature, and the mild reaction conditions were suitable for industrial production.

A successful liver transplantation from an 81-year-old donor and literature review / 中华器官移植杂志

Objective:To explore how to optimize selection, acquisition, and matching for the use of an aged donor liver.Methods:A case of 81-year-old senior donor liver transplantation performed at our institution is reported, the donor was an 81-year-old female who was brain-dead and the recipient was a 21-year-old male who underwent liver transplantation because of chronic hepatitis B complicated with hepatocellular carcinoma. Combined with the literature, the preliminary experience of age-related marginal donor liver in clinical liver transplantation was discussed.Results:The recipient recovered smoothly. Aspartate aminotransferase(AST)and glutamate-pyruvate transaminase(ALT)were 1131 U/L and 846 U/L on the first postoperative day, and decreased gradually to normal until 2 weeks later.Total bilirubin(TBIL)56.4umol/L on the first day and decreased to 22.1umol/L on the third day after operation, however, it began to rise on postoperative day 5 to a maximum of 66.0 umol/L, which decreased to normal about 2 months after surgery. During the follow-up, AST, ALT, TBIL and other indexes were normal, and AFP decreased progressively.Conclusions:Using of elderly liver donors may achieve satisfactory results, asifthe elderly donors been evaluatedcarefullyandthe low-risk recipients been selected.

Secondary metabolites from Aspergillus petrakii / 中成药

AIM To study the secondary metabolites from Aspergillus petrakii.METHODS The ethyl acetate extract liquid of A.petrakii fermentation broth was isolated and purified by silica,ODS,Sephadex LH-20 and RP-HPLC column,then the structures of obtained compounds were identified by spectral data and physicochemical properties.RESULTS Thirteen compounds were isolated and identified as R-(-)-mellein (1),3-(1-hydroxyethyl)-7-hydroxy-l-isobenzofuranone (2),(-)-semivioxanthin (3),endocrocin (4),p-hydroxyphenylethanol (5),p-hydroxyphenylacetamide (6),hydroquinone (7),adenosine (8),cyclo (Phe-Val) (9),cyclo (Phe-Ile) (10),cyclo (Tyr-Ala) (11),cyclo (Leu-Ile) (12),cyclo (Leu-Leu) (13).CONCLUSION All the compounds are isolated from A.petrakii for the first time.

Determination of Related Substances in Lorcaserin Hydrochloride by HPLC / 中国药房

OBJECTIVE:To establish a method for the determination of related substances in lorcaserin hydrochloride.METHODS:HPLC method was adopted.The determination was performed on Welch ultimate XB-ODS column with mobile phase consisted of Sodium dihydrogen phosphate (pH =6.5)-acetonitrile (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 220 nm,and column temperature was 35 ℃.The sample size was 20 μL.RESULTS:The linear ranges of impurity 1,2,3 were 0.075 60-7.560 μg/mL(r=0.999 9),0.081 40-8.140 μg/mL(r=0.999 9),0.099 24-9.924 μg/mL(r=0.999 9),respectively.The limits of quantification were 0.075 60,0.081 40,0.099 25 μg/mL.The limits of detection were 0.022 68,0.024 42,0.029 77 μg/mL.RSD of precision test was lower than 2.0％.Impurity 1 was found in stability test and reproducibility test,RSD＜2.0％.The recoveries were 98.53％-102.45％ (RSD=1.06％,n=9),98.26％-101.64％ (RSD=1.03 ％,n=9),100.08％-102.10％ (RSD=0.70％,n=9),respectively.CONCLUSIONS:The method is sensitive,rapid,accurate and reliable,which can be used to determine the related substances of lorcaserin hydrochloride.

Synthesis of 1-(4-methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride / 中国药科大学学报

@#1-(4-Methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride(1)is the key intermediate to prepare a new type of antitussives agent phosphate dimemorfan. 4-methyl-phenylacetic acid as a raw materials, was chlorinated with thionyl chloride to obtain 4-methyl-phenylacetyl chloride, followed by reaction with 2-cyclohexenyl amine, then cyclization, reduction, methylation and salt formation by HCl were taken out to give the desired product 1. The total yield is 54%, and the purity is greater than 98%. This synthetic process is characterized with available raw materials, simple in operation with high yield and purity, and suitable for large-scale production.

Preliminary study on morphology of proximal femoral medullary cavity and design of artificial furcal interior locking joint / 中国组织工程研究

The irregular anatomic morphology of proximal femoral medullary cavity does not match the current regular prosthetic stem,which is a primary cause of prosthesis loosening post-surgery. The newly designed artificial furcal interior locking joint features irregular prosthetic stem, which adapts to the irregular medullary cavity in the proximal femur. The artificial furcal interior locking joint is anchored in a multi-plane and multi-point manner. Together it can prevent prothetic early peristalsis and late loosening in the medullary cavity post-surgery. Therefore, artificial furcal interior locking joint is promising for prosthetic replacement.

STRUCTURAL ELUCIDATION OF A NEW PERYLENEQUINONE / 药学学报

AIM　To study the chemical constituents from the mycelia of Hypomyces sp. METHODS Silica gel column chromatography was employed for the isolation and purification. The structure of compound 1 was elucidated on the basis of spectral analysis. RESULTS and CONCLUSION　A new perylenequinone, named hypomycin B 1, was isolated from the mycelia of Hypomyces sp.

Studies on chemical constituents of fungus producing perylenequinones Ⅰ / 中草药

Object To study the chemical constituents in the mycelia of Hypomyces sp Methods The mycelia were extracted with acetone and the chemical constituents of the extract were isolated and purified on silica gel column Chemical and spectral methods were used to determine the structures of the isolated compounds Results Five compounds were obtained and identified as: hypocrellin A (Ⅰ),hypocrellin C (Ⅱ), elsinochrome C (Ⅲ), 1 phenazinecarboxylic acid (Ⅳ), and 1,8 dihydroxy 9,10 anthraquinone (Ⅴ) Conclusion Compounds Ⅱ～Ⅴ were obtained from the mycelia of Hypomyces sp for the first time

Determination of Aripiprazole in Human Plasma by HPLC / 中国药房

OBJECTIVE: To establish a HPLC method for the determination of aripiprazole in human plasma by HPLC. METHODS: The plasma sample was determined by HPLC after subjected to liquid- liquid extraction .The separation was carried out on C18 column with clolumn temperature at 40℃. The mobile phase consisted of 0.03mol?L-1 ammonium acetate-acetonitrile(34:66) with a flow rate of 0.8mL?min-1 and detective wavelength of 257nm.The sensitivity was 0.01 AUFS. RESULTS:The linear range of aripiprazole was 5.0～600.0ng?mL-1(r=0.999 5) .The recovery rate was above 90% .CONCLUSION:The method is sensitive,accurate and rapid,and suitable for the determination of aripiprazole in human plasma.

Effects of Yiqi Yangyin Qingre Oral Liquid,a TCM fomulation on insulin resistance in hyperglycemic fatty rats / 中国药理学通报

Aim To investigate the Yiqi Yangyin Qingre Oral Liquid(YYQ) on insulin resistance in hyperglycemic fatty rats.Methods The model of hyperglycemic fatty rats was induced by intravenous injection with a low dose of streptozotocin(STZ) and a fed high fat and high caloric diet.The YYQ was given via gavage for a period of 4 weeks.The fasting blood glucose(FBG),oral glucose tolerance(OGT),serum insulin(INS),triglyceride(TG),total cholesterol(TC),free fatty acid(FFA)levels,glucose infusion rate(GIR) by euglycemic hyperinsulinemic clamp technique as well as erythrocyte insulin receptors(INSR)of rats were tested when the experiment was finished.The weight of the epididymal fat pads and the perirenal fat pads were measured.The IR,IRS-1mRNA expressions in liver tissue were measured by RT-PCR technology.Results YYQ treatment decreased the levels of FBG,TC,TG,LDL-C,FFA and increased the level of HDL-C in hyperglycemic fatty rats.As compared with the model rats,glucose tolerance was improved and body weight was reduced in hyperglycemic fatty rats treated with YYQ.Moreover,YYQ treatment upregulated IR,IRS-1mRNA expressions in liver tissue and increased insulin receptor amounts on the erythrocytes surface as well as GIR in the hyperinsulinemic euglycemic clamp experiment.Conclusions YYQ ameliorated insulin resistance in hyperglycemic fatty rats,and its mechanism might be related to increment of INSR and stimulation of insulin pathway.