Study on related substances of TSD-1 — a novel P2Y12 receptor antagonist / 药学学报

For quantitative analysis of related substances in TSD-1 active pharmaceutical ingredient, structures of prepared impurities were confirmed by NMR and UHPLC-MS, and a high performance liquid chromatographic method was established to determine the related substances in TSD-1. The analytical column was an Agilent ZORBAX Eclipe XDB-C8 (250 mm × 4.6 mm, 5 µm). The mobile phase A was 50 mmol·L-1 ammonium acetate solution (adjusted pH to 5.8 with acetic acid) and the mobile phase B was acetonitrile. The whole run was carried out by gradient elution at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 240 nm and the column temperature was 30 ℃. The resolutions among peaks of TSD-1, impurity A, impurity B, TSD-D, and TSD-F were good. The calibration curves (n = 7) of TSD-1, impurity A, impurity B, TSD-D and TSD-F were linear in their respective weight ranges of 0.242-48.4 µg·mL-1 (r = 1.000 0), 0.244-9.75 µg·mL-1 (r = 0.999 9), 0.244-4.80 µg·mL-1 (r = 0.999 9), 0.254-1.02 µg·mL-1 (r = 0.999 9), and 0.247-0.987 µg·mL-1 (r = 0.999 9). The lower limits of quantitation were 0.244, 0.244, 0.254, and 0.247 µg·mL-1 for impurity A, impurity B, TSD-D, and TSD-F, respectively, and the average recovery of each impurity ranged from 99.08% to 103.00% with high accuracy. TSD-D and TSD-F were not detected in the three batches of TSD-1 active pharmaceutical ingredients, and impurity A and impurity B were not detected beyond the limit. The established HPLC method is simple, accurate, and suitable for determination of related substances of TSD-1, which can provide a valuable reference for the subsequent development of TSD-1.

Effects of Hydrogen Sulfide on Inflammatory Factors and Mitochondrial Energy Metabolic Disorders After Reperfusion Injury in Rats / 中国医学科学院学报

Objective To explore the effect of hydrogen sulfide on inflammatory factors and energy metabolism of mitochondria after limbs reperfusion injury in rats. Methods Sixty rats were divided into three groups:sham operation group,control group(ischemia-reperfusion injury + saline group),and experimental group(ischemia-reperfusion injury + HS group).Wistar rat models of limb ischemia-reperfusion injury were established.Skeletal muscle samples were collected to determine the levels of necrosis decomposition products [including myoglobin(MB),lipoprotein complex(LPC)and lipid peroxide(LPO)];blood samples were collected to determine the levels of interleukin(IL)-1,IL-6 and tumor necrosis factor-α(TNF-α);mitochondria were extracted for mitochondrial transmembrane potential measurement and ATP content detection.Statistical analysis was made on the test results. Results After ischemia reperfusion injury,the levels of MB,LPO,and LPC in skeletal muscle,liver,lung and renal tissues of the control group were significantly increased(MB:P =0.003,P =0.001,P =0.001,P =0.001;LPO:P =0.001,P =0.001,P =0.001,P =0.002;LPC:P =0.000,P =0.002,P =0.002,P =0.003),and hydrogen sulfide treatment during ischemia reperfusion significantly inhibited the production of MB,LPO,and LPC(MB:P =0.021,P =0.036,P =0.005;LPO:P =0.003,P =0.008,P =0.010,P =0.015;LPC:P =0.002,P =0.026,P =0.007,P =0.006).Ischemia/reperfusion of lower extremity in rats resulted in increased levels of IL-1,IL-6,and TNF-α in the serum of rats,and the levels of IL-1,IL-6,and TNF-increased over time,with statistically significant differences in IL-1,IL-6,and TNF-α among groups at 3 h(IL-1:P =0.019,P =0.011,P =0.009,$P_{12_{h}}$=0.008,and P =0.002;IL-6:P =0.026,P =0.009,P =0.002, $P_{12_{h}}$=0.002,P =0.003;TNF-α:P =0.002,P =0.002,P =0.005,$P_{12_{h}}$=0.002,P =0.003).The levels of IL-1,IL-6,and TNF-α in serum were significantly inhibited during ischemia reperfusion(IL-1:P =0.035,P =0.039,P =0.012,$P_{12_{h}}$=0.005,P =0.006;IL-6:P =0.042,P =0.025,P =0.023,$P_{12_{h}}$=0.006,P =0.005;TNF-α:P =0.005,P =0.003,P =0.022,$P_{12_{h}}$=0.005,P =0.005),and such inhibitory effects became even more obvious over time.After limb ischemia and reperfusion in the control group,the mitochondrial transmembrane potential of skeletal muscle cells significantly decreased compared with that of the sham group(t=6.698;P=0.001).After hydrogen sulfide treatment,the mitochondrial membrane potential energy of the experimental group was significantly higher than that of the control group(t=7.507,P = 0.000).The ATP level in the mitochondria of ischemia reperfusion rats in the control group was significantly lower than that in the sham group(t=7.526,P = 0.000).The content of mitochondrial ATP in the experimental group was significantly higher than that in the control group after hydrogen sulfide treatment(t=8.604,P = 0.000). Conclusions Hydrogen sulfide can alleviate the injury of skeletal muscle and distal organs after limb ischemia-reperfusion and reduce local inflammatory reaction.In addition,it is valuable in alleviating mitochondrial transmembrane potential and energy metabolism disorders during reperfusion injury.

Rotary self-locking intramedullary nail for long tubular bone fractures / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intramedullary nails had been widely used in the treatment of long-bone fractures because of less interference of fractures and center bearing biomechanical advantage. However, it had been also found many shortcomings such as broken nails, delayed healing and was modified in order to achieve better efficacy and reduce complications. The aim of the present study is to compare the efficacy of rotary self-locking intramedullary nails (RSIN) with that of interlocking intramedullary nails (IIN) in the treatment of long-bone fractures.</p><p><b>METHODS</b>A retrospective study investigated 129 cases with long-bone fractures (36 with femoral fracture, 81 with tibial fracture, and 12 with humeral fracture). The fractures were fixed using either an RSIN or IIN. All patients underwent followup for 12-30 months.</p><p><b>RESULTS</b>All patients in both groups achieved a clinical fracture healing standard and the postoperative affected limb muscle strength and joint function were well restored. The RSIN group required a shorter operative time and the fracture healed faster. There was no significant difference in the hospital stay, intraoperative blood loss or postoperative complications between the two groups.</p><p><b>CONCLUSIONS</b>RSIN is used to treat long-bone fractures. Its healing efficacy is equivalent to the IIN. Moreover, the RSIN method is simpler and causes less tissue damage than the IIN, therefore having the advantage of accelerated healing.</p>

The process of Chinese medicine by submerged fermentation of pharmaceutical fungi / 中国中药杂志

The progress of Chinese medicine modernization is slow in china, and one of the reason is the dated process method. The fermentation technology of pharmaceutical fungi is more and more perfect. To process Chinese medicine by pharmaceutical fungi could enhance the effective density of active ingredient in Chinese medicine, and the fungi could produce a variety of active secondary metabolite, moreover, some compounds in Chinese medicine could be bio-transformed to produce new compound by pharmaceutical fungi in the fermentation. So process Chinese medicine by pharmaceutical fungi could produce de novo Chinese medicine preparations which include a variety of bioactive compounds, and it is suitable to produce in a large scale and convenient to control the quality. To process Chinese medicine by submerged fermentation of pharmaceutical fungi provides a new process method for Chinese medicine.