正交法优选氨茶碱注射液红外光谱鉴别中压片条件

目的:探索一种确定氨茶碱注射液红外光谱鉴别中压片最佳条件的科学方法,以获得最理想的红外光谱图。方法:以3因素3水平,即茶碱:溴化钾(mg:mg)分别为5.0:1000、10.0:1000、2.5:1000,压片压力分别为20MPa、24MPa、28MPa,压片时间分别为2min、3min、4min,按正交设计实验,以输出的红外光谱图的基线值和最强吸收峰的透光率T%为指标,应用Excel处理数据,通过极差和方差分析,确定影响红外光谱图的主次因素,从而确定压片最佳条件。结果:以茶碱与溴化钾比例为5.0:1000,压力为24MPa,压片时间为2min为最佳条件,红外光谱图最理想,基线在98%透光率以上,最强吸收峰在透光率为0。结论:正交法优选氨茶碱注射液红外光谱鉴别中压片条件并以Excel处理数据,能方便快捷地获得理想的光谱图,为确定优化条件提供了科学的方法。     

正交法优选薄荷脑红外光谱鉴别中压片条件

目的探索一种确定薄荷脑红外光谱鉴别中压片最佳条件的科学方法,以获得最理想的红外光谱图。方法以三因素的3个水平,即薄荷脑:溴化钾(m g∶m g)分别为0.8∶100、2.3∶100、1.6∶100,压片压力分别为18mPa、24mPa、30mPa,压片时间分别为2m in、3m in、4m in,按正交设计实验,以输出的红外光谱图的基线值和最强吸收峰的透光率T%为指标,确定影响红外光谱图的主次因素,从而确定压片最佳条件。结果以薄荷脑与溴化钾比例为1.6∶100,压力为24mPa,压片时间为2m in为最佳条件,红外光图谱质量最好,基线在98%透光率以上,最强吸收峰在透光率4%以下。结论正交法优选薄荷脑红外光谱鉴别中压片条件,能以较少次数操作获得满意结果。     

正交法优选阿魏酸钠红外光谱鉴别中压片条件

目的探索一种确定阿魏酸钠红外光谱鉴别中压片最佳条件的科学方法,以获得最佳质量的红外光谱图.方法以阿魏酸钠与溴化钾基质比例、压片压力、压片时间三因素的三个水平,即阿魏酸钠：溴化钾分别为1.0：200、1.5：200、2.0：200,压片压力分别为18MPa、24MPa、30MPa,压片时间分别为2min、3min、4min,按正交设计实验,以输出的红外光谱图的基线值和最强吸收峰的透光率T%为指标,通过极差分析和方差分析,确定影响红外光谱图的主次因素,从而确定压片最佳条件.结果以阿魏酸钠与溴化钾比例为2.0：200,压力为18MPa,压片时间为4min为最佳条件,红外光图谱质量最好,基线在99%透光率以上,最强吸收峰在透光率3%以下.而根据实际情况,最后确定最佳条件为：阿魏酸钠与溴化钾比例为2.0：200,在压力18MPa保持2min.结论正交法优选阿魏酸钠红外光谱鉴别中压片条件,能以较少次数操作获得满意结果,为改变传统经验做法提供了科学的方法.     

正交法优选布洛芬片红外光谱鉴别中压片条件

目的 探索一种确定布洛芬片红外光谱鉴别中压片最佳条件的科学方法 ,以获得最理想的红外光谱图.方法 以三因素的三个水平,即布洛芬:溴化钾(mg∶mg)分别为0.7∶100、1.1∶100、2.4∶100,压片压力分别为18mPa、24mPa、30mPa,压片时间分别为2min、3min、4min,按正交设计实验,以输出的红外光谱图的基线值和最强吸收峰的透光率T%为指标,从而确定压片最佳条件.结果 以布洛芬与溴化钾比例为1.1∶100,压力为30mPa,压片时间为2min为最佳条件,基线在98%透光率以上,最强吸收峰在透光率1%以下.结论 正交法优选布洛芬片红外光谱鉴别中压片条件,能以较少次数操作获得满意结果 ,为改变传统经验做法提供了科学的方法 .     

正交法优选葡萄糖红外光谱鉴别中压片条件

目的探索一种确定葡萄糖红外光谱鉴别中压片最佳条件的科学方法,以获得最理想的红外光谱图。方法以3因素的3个水平,即葡萄糖:溴化钾(mg∶mg)分别为0.3∶100、0.5∶100、1.0∶100,压片压力分别为180MPa、24MPa、30MPa,压片时间分别为2min、3min、3min,按正交设计实验,以输出的红外光谱图的基线值和最强吸收峰的透光率T%为指标,从而确定压片最佳条件。结果以葡萄糖与溴化钾比例1.0∶100,压力为30MPa,压片时间为2min为最佳条件,基线在94%透光率以上,最强吸收峰在透光率5%以下。结论正交法优选葡萄糖红外光谱鉴别中压片条件,能以较少次数操作获得满意结果,为改变传统经验做法提供了科学的方法。     

硼替佐米为基础的治疗方案治疗华氏巨球蛋白血症15例的临床分析

目的 探讨以硼替佐米为基础的方案治疗华氏巨球蛋白血症（Waldenström macroglobulinemia,WM）的临床疗效及安全性。方法 回顾性分析2008年12月至2015年10月收治的15例采用以硼替佐米为基础方案治疗的WM患者的临床资料。其中1例采用硼替佐米+地塞米松（BD）方案,3例采用硼替佐米+地塞米松+美罗华（RBD）方案,11例采用硼替佐米+地塞米松+环磷酰胺（BCD）方案,评价上述三方案的疗效及不良反应,并进行生存分析。结果 治疗的总反应率及主要反应率分别为93.3%和80%[其中完全缓解（CR）1例、非常好的部分缓解（VGPR）2例、部分缓解（PR）9例、微小反应（MR）2例]。不良反应包括胃肠道副作用（53.3%）、白细胞减少（20%）、感染（20%）及外周神经病变（26.7%）。随访时间为3~85个月（中位数21个月）,无进展生存（PFS）时间为3~36个月（中位数21个月）,1年的PFS率分别为83.3%。生存分析显示IPSSWM分级为高危组（P=0.015）及用药后治疗反应小于PR（P=0.024）是影响WM患者PFS的危险因素。结论 以硼替佐米为基础的治疗方案可有效治疗WM患者,IPSSWM分级体系及治疗反应可作为判断以硼替佐米为基础的治疗方案的WM患者疾病进展预后的参考因素。     

HPLC法测定硼替佐米原料药中的异构体

摘 要 目的：建立同时测定硼替佐米原料药中3种光学异构体含量的方法。 方法: 采用HPLC法,色谱柱：ChiralPAKAY-H正相手性柱（250 mm×4.6 mm,5 μm）;流动相：正己烷 乙醇 甲醇 三氟乙酸（90∶7.5∶2.5∶0.1）;流速：0.8 ml·min^-1;检测波长：270 nm;柱温：40℃;进样量：5 μl。结果: 硼替佐米与3种光学异构体之间的分离度均大于2.0;3种光学异构体的线性范围均为0.6～20 μg·mL^-1（r≥0.999 7）;平均回收率分别为104.1%,105.5%,92.0%,RSD分别为2.3%,2.4%,2.7%（n=9）;定量限和检测限均分别为3 ng和1 ng。结论:该方法快速、准确度高,可用于测定硼替佐米中的光学异构体。     

地塞米松联合硼替佐米对老年多发性骨髓瘤的治疗效果

目的 分析地塞米松联合硼替佐米对老年多发性骨髓瘤的治疗效果。方法 选择2014年1月—2016年12月在宿州市市立医院血液科进行诊治的41例老年多发性骨髓瘤患者,随机分为两组,观察组21例,对照组20例。两组均给予沙利度胺和环磷酰胺进行治疗,分别口服沙利度胺100 mg,1次/d,并分别于第1、8、15天静滴环磷酰胺300 mg/m²。同时,对照组于第1~4天静脉滴注地塞米松20 mg。观察组在对照组基础上皮下注射硼替佐米1.3 mg/m²,1次/周,1个疗程为4周,2个疗程后进行综合评价。比较两组的临床治疗效果,检测两组治疗前后的β2微球蛋白、骨髓瘤细胞以及免疫球蛋白水平及不良反应。结果 观察组的有效率为85.71%,明显高于对照组的60.00%,差异有统计学意义（P<0.05）。两组治疗后的β2微球蛋白、骨髓瘤细胞以及免疫球蛋白水平均明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组明显低于对照组,差异有统计学意义（P<0.05）。两组间各不良反应的发生率无统计学差异,且各不良反应通过停药或给予相应对症处理后均可得到缓解。结论 地塞米松联合硼替佐米治疗老年多发性骨髓瘤的临床效果明显,可作为初治、难治或复发老年多发性骨髓瘤患者的一线治疗方案。     

正交法优选盐酸吡硫醇红外光谱鉴别中压片条件

目的探索一种确定盐酸吡硫醇红外光谱鉴别中压片最佳条件的科学方法,以获得最理想的红外光谱图。方法以三因素的三个水平,即盐酸吡硫醇:氯化钾(m g:m g)分别为1.9∶100、1.6∶100、1.3∶100,压片压力分别为20M Pa、26M Pa、32M Pa,压片时间分别为2m in、3m in、4m in,按正交设计实验,以输出的红外光谱图的基线值和最强吸收峰的透光率T%为指标,从而确定压片最佳条件。结果以盐酸吡硫醇与氯化钾比例为1.9∶100,压力为20M Pa,压片时间为2m in为最佳条件,基线在95%透光率以上,最强吸收峰在透光率1%以下。结论正交法优选盐酸吡硫醇红外光谱鉴别中压片条件,能以较少次数操作获得满意结果,为改变传统经验做法提供了科学的方法。     

硼替佐米对卵巢癌SKOV-3/DDP细胞增殖和耐药逆转的影响

目的:探讨硼替佐米对卵巢癌SKOV-3/DDP细胞增殖和耐药逆转的影响和作用机制。方法:采用MTT法检测不同浓度硼替佐米和顺铂(DDP,cisplatin)对SKOV-3/DDP不同作用时间的细胞生长抑制率,以及硼替佐米和DDP合用和单独应用时的细胞生长抑制率;流式细胞术检测细胞凋亡和细胞周期的变化。结果:硼替佐米能够有效抑制SKOV-3/DDP细胞增殖,硼替佐米与DDP合用组的SKOV-3/DDP细胞抑制率较硼替佐米和DDP单用组均明显增强。单独应用硼替佐米细胞周期阻滞于G2/M期,单独应用DDP细胞周期阻滞于S期,两药联合出现更明显的S期阻滞。结论:硼替佐米与DDP具有协同作用,能够逆转SKOV-3/DDP细胞对DDP的耐药性。     

杭白菊提取物中辅料麦芽糊精的中红外快速定量分析

目的建立一种对杭白菊提取物中麦芽糊精含量进行快速定量的中红外分析方法。方法以78份不同麦芽糊精含量的杭白菊提取物为实验对象,对采集到的已知麦芽糊精含量的样品谱图进行图谱预处理,以偏最小二乘法建立含量测定模型。结果所建含量测定模型的决定系数R²为0.9987,预测标准差为1.137。结论所建含量测定模型测定效果较好、稳定性强、检测精度高,可用于杭白菊提取物中麦芽糊精含量的快速分析。     

Stability of Bortezomib 2.5 mg/mL in Vials and Syringes Stored at 4°C and Room Temperature (23°C)

Background:

Solutions of bortezomib 1.0 mg/mL for IV administration are reportedly stable for up to 42 days. Recent publications have reported that the safety profile of bortezomib is better with subcutaneous administration than with IV administration.

Objective:

To evaluate the stability of higher-concentration bortezomib solutions for subcutaneous administration (i.e., 2.5 mg/mL in 0.9% sodium chloride [normal saline or NS]).

Methods:

On study day 0, twelve 3.5-mg vials of powdered bortezomib were each reconstituted with 1.4 mL of NS to prepare solutions with concentration 2.5 mg/mL. Half of the solutions were subsequently stored in the original vials and half were transferred to syringes. Three of each type of container were stored in the refrigerator (4°C) and the other 3 of each type were stored at room temperature (23°C). Concentration analysis and physical inspection were completed on study days 0, 1, 2, 8, 12, 14, 19, and 21. The concentration of bortezomib was determined by a validated liquid chromatographic method with ultraviolet detection. The expiry date was determined according to the time to achieve 90% of the initial concentration, based on the fastest degradation rate calculated from the 95% confidence interval of the observed degradation rate.

Results:

The analytical method separated degradation products from bortezomib such that the concentration was measured specifically and accurately (with absolute deviations from known concentration averaging 2.99%), with intraday and interday reproducibility averaging 1.51% and 2.51%, respectively. During the study period, all solutions were observed to retain at least 95.26% of the initial concentration in both types of containers at both temperatures.

Conclusions:

Bortezomib (3.5 mg in manufacturer’s vial) reconstituted with 1.4 mL NS is physically and chemically stable for up to 21 days at 4°C or 23°C when stored in either the manufacturer’s original glass vial or a syringe. Subcutaneous injection of bortezomib represents a change in practice, and there is a potential safety concern if a solution of the increased concentration used for subcutaneous administration (2.5 mg/mL) is inadvertently used to prepare a dose intended for IV administration. Therefore, it is recommended that sites switching to subcutaneous administration of bortezomib eliminate 1.0 mg/mL IV solutions altogether or institute substantial barriers to prevent IV administration of the higher concentration of bortezomib.     

Clinical and investigational use of proteasome inhibitors for transplant rejection

Introduction: The presence of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) in patients experiencing acute cellular rejection and antibody-mediated rejection (AMR) is associated with poor renal allograft survival in kidney transplant recipients. Traditional therapies for AMR provide variable results, and do not deplete the cellular source of antibody production, that is, the plasma cell.

Areas covered: Physiologic effects of proteasome inhibitors (PIs) are reviewed in the context of recent clinical reports of PI therapy in solid organ transplantation for AMR and desensitization.

Expert opinion: PI-based therapy is a novel approach for treating AMR that is being employed with increasing frequency in transplantation. Initial reports of PI-based regimens for treating AMR have demonstrated the ability of bortezomib to significantly reduce DSA levels and improve histology and allograft function. Use of PI agents have recently been evaluated in a large multicenter collaborative consisting of over 100 solid organ transplant recipients treated with a common PI-based regimen. Increasing experience with PI-based regimens for AMR have indicated that PI therapy (similar to other AMR therapies) provides excellent results in early AMR, with late AMR demonstrating a greater degree of therapeutic resistance. A substantial number of strategies exist for enhancement of therapeutic results with PI therapy for AMR.     

干姜挥发油提取优化及GC-MS图谱研究

目的:优化千姜挥发油提取工艺,同时建立干姜挥发油GC-MS指纹图谱.方法:以挥发油得率为指标,采用正交设计,对加水量、超声时间、浸泡时间和提取时间进行优化,并采集GC-MS图谱.结果:确定加17倍量水,超声35 min,浸泡40 min,再提取8 h的效果最优,挥发油得率分别为1.89%,GC-MS图谱稳定、重复.结论:干姜挥发油经过提取优化可以保证得率,获得的GC-MS图谱稳定可靠,并鉴定出的49种化合物.     

Current treatments for renal failure due to multiple myeloma

Introduction: Renal impairment (RI) is a common complication of symptomatic myeloma; 20 – 40% of newly diagnosed patients present with moderate or severe RI and 10% of them may require dialysis. Immediate initiation of specific antimyeloma therapy is crucial in order to improve RI.

Areas covered: There has been a significant improvement in the outcome of patients with RI over the past 15 years. The authors review current data on the role of antimyeloma therapy on the improvement or resolution of RI and the importance of novel regimens, especially those based on bortezomib. IMiDs-based regimens, conventional chemotherapy and high-dose therapy is also reviewed. The role of extrarenal free light chain removal, by means of plasma exchange or extended hemodialysis with the use of high cutoff dialysis membranes, is also discussed.

Expert opinion: Bortezomib/dexamethasone-based regimens are the preferred regimens for most patients with multiple myeloma (MM) who present with RI, especially for newly diagnosed patients; however, other novel agents (thalidomide, lenalidomide) in combination with dexamethasone may also improve RI in several patients. Further investigation is needed for the clarification of the role of plasma exchange or extended high cutoff dialysis. Carfilzomib, which was recently approved, may also be a treatment choice for selected patients with relapsed MM and RI.