Effects of polyvinylpyrrolidone and poly (ethylene glycol) on preparation of ibuprofen pharmaceutical cocrystal

Abstract In this study, we investigated the effects of polymers on the pharmaceutical cocrystal formation process. Ibuprofen (IBU) was selected as the active pharmaceutical ingredient (API), nicotinamide (NIC) and saccharin (SAC) as the cocrystal coformer (CCF), ethanol/water as the solvent, polyvinylpyrrolidone (PVP) and poly (ethylene glycol) (PEG) as the representative polymers. We prepared IBU-NIC and IBU-SAC cocrystals in ethanol-water cosolvent in the absence or presence of polymers. Cocrystal screening products were characterized by FTIR, DSC, PXRD, and HPLC. The results showed that the mixture of IBU and IBU-NIC cocrystal can be prepared in ethanol-water cosolvent without polymers. The addition of PVP facilitates the formation of pure IBU-NIC cocrystal; however, no cocrystal was formed in PEG solutions. SAC could not cocrystallize with IBU in the ethanol-water solvent in the absence of polymers. Neither PVP nor PEG could facilitate the formation of the IBU-SAC cocrystal.

Early fluid therapy guided by optimal urine output threshold in patients with acute pancreatitis / 中华急诊医学杂志

Objective:To investigate the urine output threshold of acute kidney injury in patients with acute pancreatitis(AP) and to guide early fluid therapy.Methods:The clinical data of AP patients from Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) were collected. The 24-h urine output rate [24-h urine output·kg-1·24-h-1, 24-UR mL/ (kg·h) ] and 48-h urine output rate [48-h urine output·kg-1·48-h-1, 48-UR mL/ (kg·h) ] were calculated, and according to the occurrence of acute kidney injury within 7 days (7-AKI), AP patients were divided into the 7-AKI group and non-7-AKI group. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of 24-UR and 48-UR on 7-AKI in AP patients. 24-UR and 48-UR were grouped according to the optimal cut-off value obtained from the ROC curve. Logistic regression was used to analyze the risk factors of 7-AKI, and Kaplan-Meier (KM) survival curve was drawn to analyze the effect of 24-UR and 48-UR on in-hospital mortality of AP patients.Results:A total of 713 AP patients were included, ROC curve analysis showed that the area under the ROC curve (AUC) of 24-UR in predicting 7-AKI in AP patients was 0.76. Based on the maximum Youden index, the cut-off value of 24-UR was 0.795 mL/ (kg·h) , and the AUC of 48-UR was 0.78 and the cut-off value of 48-UR was 0.975 mL/ (kg·h) . Logistic regression analysis showed that 24-UR≤0.795 mL/ (kg·h) was an independent risk factor for 7-AKI compared with 24-UR>0.795 mL/ (kg·h) ( OR: 4.22, 95% CI:1.50-11.85, P=0.006). Similarly, compared with 48-UR>0.975 mL/ (kg·h) , 48-UR0.975 mL/ (kg·h) was an independent risk factor for 7-AKI ( OR: 3.75, 95% CI: 1.45-9.72, P=0.007). The KM survival curve showed that the cumulative in-hospital survival rate in the high 24-UR group was higher than that in the low 24-UR group. Conclusions:24-UR can be used to guide early fluid therapy in AP patients.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris.</p><p><b>METHODS</b>Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina.</p><p><b>RESULTS</b>The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).</p>

Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cells in vitro

To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken (Gallus gallus) primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKα/β and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis. GA significantly inhibited Akt expression and p-IKKα/β level, but not STAT-3 quantity, while the colocalization of Akt and STAT-3 with Hsp90 was weakened, followed by lower cell viability and higher apoptosis. Aspirin after GA treatment partially improved the stress response and apoptosis rate of tested cells caused by the recovery of Akt expression and colocalization, rather than the level of STAT-3 (including its co-localization with Hsp90) and p-IKKα/β. Therefore, Hsp90 expression has a positive effect on cellular capacity to resist heat-stressed injury and apoptosis. Moreover, inhibition of Hsp90 before stress partially attenuated its positive effects.

Long-term follow-up of Chinese herbal medicines combined with conventional treatment in patients with acute coronary syndrome after percutaneous coronary intervention: A multicenter randomized controlled trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the prognosis effect of Chinese herbal medicines (CHMs) for benefiting qi and activating blood circulation adjunctive to conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>A total of 702 patients with ACS who underwent PCI were enrolled and randomly assigned to receive conventional treatment plus CHMs for benefiting qi and activating blood circulation (treatment group, 351 cases) or conventional treatment alone (control group, 351 cases) for 6 months. Six months later, all patients received conventional treatment alone. Follow-ups were scheduled at 6th, 12th, 18th, 24th month after enrollment in April 2008, and the final follow-up visit was during September 2011 and November 2011. The primary endpoint was the composite of cardiac death, nonfatal myocardial infarction or revascularization (PCI or coronary artery bypass grafting); and the secondary endpoint was the composite of re-admission for ACS, congestive heart failure, nonfatal stroke or other thrombus events.</p><p><b>RESULTS</b>A total of 621 (88.59%) patients completed 35.4±3.8 months follow-up, while 80 (11.41%) patients withdrew from the trial (41 in the treatment group and 39 in the control group). The incidence of primary endpoint was 5.7% (20 patients) in the treatment group versus 10.86% (38 patients) in the control group [relative risk (RR): 0.53; 95% confidence interval (CI): 0.30, 0.88; P=0.013; absolute risk reduction (ARR):-0.052, 95% CI: -0.06, 0.01]. The incidence of secondary endpoint was 5.98% (21 patients) in the treatment group versus 10.28% (36 patients) in control group (RR: 0.58, 95% CI: 0.33, 0.97, P=0.037; ARR: -0.043, 95% CI: 0.06, 0.01). Most of the primary and secondary endpoints were occurred in 18 months (84.50% in the treatment group versus 78.10% in the control group).</p><p><b>CONCLUSION</b>CHMs for benefiting qi and activating blood circulation adjunctive to conventional treatment improved clinical outcomes for patients with ACS after PCI in long-term follow-up.</p>

Clinical efficacy of traditional chinese medicine on acute myocardial infarction: a prospective cohort study / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical effects of Chinese medicine (CM) on acute myocardial infarction (AMI) with a prospective cohort study.</p><p><b>METHODS</b>A total of 334 AMI patients from January 2007 to March 2009 were consecutively enrolled, and were assigned to a treatment group (169 cases) treated with combined therapy (CM for at least one month and Western medicine) and a control group (165 cases) with Western medicine alone. Clinical data including age, gender, smoking, medical history, infarction area, heart functional classification, CM syndrome scores, blood-stasis syndrome score, primary end-point (death, nonfatal myocardial infarction, and revascularization) and secondary end-point (ischemic stroke, rehospitalization due to angina, heart failure and shock), were collected. CM syndrome scores, blood-stasis syndrome score, primary end-point and secondary end-point were collected during the 6-month follow-up. Kaplan-Meier method was used for the survival analysis. The multifactor analysis was analyzed by Cox proportional hazards regression.</p><p><b>RESULTS</b>At the end of 6-month the CM syndrome score and bloodstasis syndrome score in the treatment group were lower than those in the control group (P<0.01), especially the symptoms of chest pain, spontaneous perspiration and insomnia. Rehospitalization rate due to angina during the 6-month follow-up in the treatment group (2.96%) was lower than that in the control group (7.88%, P<0.05). Kaplan- Meier survival curve showed that event-free cumulated survival of rehospitalization due to angina during the 6-month follow-up in the treatment group was higher than that in the control group (Log rank 4.700, P=0.03). Cox regression analysis showed that heart dysfunction [hazard ratio (HR)=1.601, 95% CI=1.084-2.364, P=0.018] and diabetes mellitus (HR=1.755, 95% CI=1.031-2.989, P=0.038) were hazard factors to end-point, whereas CM (HR 0.405, 95% CI=0.231-0.712, P=0.002), percutaneous coronary intervention (PCI, HR=0.352, 95% CI=0.204-0.607, P<0.001) and angiotensin converting enzyme (ACE) inhibitors (HR=0.541, 95% CI=0.313-0.936, P=0.028) were protective factors.</p><p><b>CONCLUSIONS</b>CM therapy could decrease CM syndrome scores and blood-stasis syndrome score, reduce the rehospitalization rate during 6-month follow-up due to angina. Heart dysfunction and diabetes mellitus were hazard factors to end-point, whereas CM, PCI and ACE inhibitors were protective factors.</p>