Preparation of New Risperidone Depot Microspheres Based on Novel Biocompatible Poly(Alkylene Adipate) Polyesters as Long-Acting Injectable Formulations

Risperidone (RIS)-loaded microspheres based on poly(alkylene adipate)s derived from dicarboxylic acids and different aliphatic diols were prepared by the oil in water emulsion and solvent evaporation method. Specifically, 3 polyesters, namely poly(ethylene adipate), poly(propylene adipate), and poly(butylene adipate), were prepared with the aid of a 2-stage melt-polycondensation method and characterized by gel permeation chromatography, proton nuclear magnetic resonance (¹H NMR), differential scanning calorimetry, and X-ray diffraction analysis. Results showed that the molecular weight of the polyesters increased as the diol molecular weight increased, while all polymers were of semi-crystalline nature and the melting temperature was varying from 49.1°C to 51.8°C and 65.9°C for poly(propylene adipate), poly(ethylene adipate), and poly(butylene adipate), respectively. The particle size of the RIS-loaded microspheres varied from 10 to 100 μm depending on the polyester type and the drug loading, while X-ray diffraction analysis revealed amorphous active pharmaceutical ingredient in the cases of high drug-loaded microspheres. In vitro drug release studies along with scanning electron microscopy images of microspheres after the completion of dissolution process showed that in all cases RIS release was controlled by the glass transition temperature of polyesters and physical state of active pharmaceutical ingredients via diffusion.     

分析对比奥氮平与利培酮治疗老年精神分裂症的疗效及安全性

目的：对奥氮平、利培酮治疗老年精神分裂症患者的有效性、安全性进行对比分析。方法：90例老年精神分裂症患者,随机（数字表法）分成观察组和对照组各45例。观察组应用奥氮平治疗,对照组则应用利培酮治疗。以BPRS评分、MCCB评分、TESS评分对2组患者治疗的效果、认知功能、安全性分别进行评价,并对2组患者治疗前、治疗8周后的体质指数（BMI）、血清空腹血糖（FBG）、餐后2 h血糖（2hPBG）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、催乳素（PRL）、瘦素（LP）水平进行比较。结果：在BPRS评分方面2组差异无显著性（P>0.05）。2组治疗后的MCCB评分均较治疗前显著上升,且观察组上升更为显著（P<0.05）。观察组的TESS评分显著低于对照组（P<0.05）。2组治疗后的血糖、血脂及BMI水平均较治疗前变化显著,且对照组在TC、TG、LDL-C方面的变化更为显著（P<0.05）。2组治疗后的PRL、LP水平较治疗前显著变化,且对照组变化更为显著（P<0.05）。结论：奥氮平、利培酮治疗老年精神分裂症效果相当,但奥氮平更有助于患者认知功能的改善,不良反应更少,并且对血脂、PRL、LP的影响轻于利培酮,安全性更高。     

阿立哌唑与利培酮治疗自闭症谱系障碍与注意缺陷多动障碍共病患儿的疗效与安全性评价

目的：评价阿立哌唑与利培酮治疗自闭症谱系障碍（ASD）与注意缺陷多动障碍（ADHD）共病患儿的疗效与安全性。方法：选取在某院精神科治疗的ASD和ADHD共病患儿68例,根据随机数字表法将患儿分为阿立哌唑组（n=34）和利培酮组（n=34）。阿立哌唑组患儿接受起始剂量为5 mg·d^-1的阿立哌唑片口服治疗,最终剂量增加至15 mg·d^-1。利培酮组患儿接受起始剂量为1 mg·d^-1的利培酮片口服治疗,最终剂量增加至2 mg·d^-1;2组患儿均治疗12周。在基线（T₀）、治疗6周（T₁）与12周（T₂）时,采用注意缺陷/多动评定量表（ADHD-RS）评价患儿总体ADHD症状变化情况;采用康纳斯行为评定量表（CRSR）教师用量表多动因子（CRSR-I）评价患儿多动症的改善情况;采用CRSR不注意缺陷-冲动因子（CRSR-H）评价患儿注意力缺陷的改善情况;采用临床整体印象-严重程度量表（CGI-S）及儿童总体评估量表（C-GAS）评分评价患儿整体功能。对患儿的相关临床指标进行常规监测,比较2组患儿药物不良事件与安全性。结果：与T₀时比较,阿立哌唑组患儿T₁与T₂时,ADHD-RS、CRSR-I、CRSR-H与CGI-S评分均显著降低（均P<0.05）,C-GAS评分显著提高（P<0.05）。利培酮组患儿T₂时,ADHD-RS、CRSR-I、CRSR-H与CGI-S评分均显著降低（均P<0.05）,C-GAS评分显著提高（P<0.05）。2组患儿的ADHD症状显著改善,多动症状与不注意缺陷-冲动症状显著改善,患儿的整体功能也显著改善。2组患儿主要的不良事件是食欲增加、体质量增加与嗜睡,但均没有发生严重的不良事件。T₂时,利培酮组患儿催乳素水平显著提高（t=9.619,P<0.001）,其他临床指标没有显著性差异（均P>0.05）。结论：阿立哌唑和利培酮能够通过减少ASD和ADHD共病患儿的注意力涣散和多动症症状来改善患儿整体功能,具有较高的疗效、安全性,值得临床推广应用。     

Neuroprotection of posttreatment with risperidone,an atypical antipsychotic drug,in rat and gerbil models of ischemic stroke and the maintenance of antioxidants in a gerbil model of ischemic stroke

Risperidone, an atypical antipsychotic drug, has been discovered to have some beneficial effects beyond its original effectiveness. The present study examines the neuroprotective effects of risperidone against ischemic damage in the rat and gerbil induced by transient focal and global cerebral ischemia, respectively. The results showed that pre‐ and posttreatment with 4 mg/kg risperidone significantly protected against neuronal death from ischemic injury. Many NeuN‐immunoreactive neurons and a few F‐J B‐positive cells were found in the rat cerebral cortex and gerbil hippocampal CA1 region (CA1) in the risperidone‐treated ischemia groups compared with those in the vehicle‐treated ischemia group. In addition, treatment with risperidone markedly attenuated the activation of microglia in the gerbil CA1. On the other hand, we found that treatment with risperidone significantly maintained the antioxidants levels in the ischemic gerbil CA1. Immunoreactivities of superoxide dismutases 1 and 2, catalase, and glutathione peroxidase were maintained in the stratum pyramidale of the CA1; the antioxidants were very different from those in the vehicle‐treated ischemia groups. In brief, our present findings indicate that posttreatment as well as pretreatment with risperidone can protect neurons in the rat cerebral cortex and gerbils CA1 from transient cerebral ischemic injury and that the neuroprotective effect of risperidone may be related to attenuation of microglial activation as well as maintenance of antioxidants. © 2014 Wiley Periodicals, Inc.     

利培酮与氟哌啶醇治疗儿童抽动障碍对照研究

目的探讨利培酮与氟哌啶醇治疗儿童抽动障碍的临床疗效。方法将78例儿童抽动障碍患儿随机分为利培酮组和氟哌啶醇组各39例,分别予以利培酮和氟哌啶醇治疗8周。采用临床整体印象量表(CGI)、治疗中需处理的不良反应症状量表(TESS)于治疗前、治疗第2周、第4周和第8周末对两组患儿进行评定,并记录用药量。结果治疗8周后,利培酮组和氟哌啶醇组的最高平均治疗剂量分别为(1.4±0.34)mg和(7.3±0.52)mg,治疗总体有效率分别为82%和82.3%,无显著性差异(P>0.05);不良反应的发生率分别为28.2%和76.9%,有非常显著性差异(P<0.01),其中以第2周为明显,两组均未见严重不良反应。结论利培酮和氟哌啶醇对儿童抽动障碍患儿均具有较好疗效,但利培酮的安全性和依从性更高。     

利培酮单药治疗对精神分裂症患者前脉冲抑制和P50的影响

目的:探讨非典型抗精神病药利培酮单药治疗对首发和慢性精神分裂症患者前脉冲抑制(PPI)和P50的影响。方法:采用事件相关电位检测急性期精神分裂症首发患者(首发组,n=81)和慢性精神分裂症患者(慢性组,n=92)利培酮治疗前及治疗6~8周后PPI和P50各项指标,结果与59名健康对照者(正常对照组)比较。结果:与正常对照组比较,首发组与慢性组PPI的单独强刺激的潜伏期显著延长(P均<0.05)。治疗前PPI和P50指标在两患者组之间差异无统计学意义(P>0.05)。精神分裂症患者PPI和P50抑制与阳性和阴性症状量表(PANSS)得分、发作次数、病程之间无相关性(P>0.05)。治疗后,除P50中的S1波幅的组别主效应显著(F=4.97,P=0.016)外,其余P50测量指标以及PPI的主效应及交互作用均不显著(P>0.05);利培酮对PPI和P50测量指标的影响与疗效无关。结论:首发和慢性精神分裂症患者的PPI与P50缺陷与其精神症状严重程度、病程等无关,利培酮无法改善PPI和P50抑制缺陷。