校对 ---鹿瓜多肽注射剂质量评价与标准优化

通过探索性研究对鹿瓜多肽注射剂质量现状及存在问题进行评价,并对现行质量标准进行优化。首先,对影响终产品新鲜度的因素进行考察。建立丹磺酰氯柱前衍生-HPLC 法测定鹿瓜多肽注射剂中 8 种生物胺的含量,结果显示个别企业的样品中检出较高浓度的尸胺;采用免疫亲和柱净化-柱后光化学衍生-HPLC -FLD 法测定鹿瓜多肽注射剂及中间提取液中黄曲霉毒素 B₁、B₂、G₁ 和 G₂ 的含量,并采用自动电位滴定法测定甜瓜子原料的酸价和过氧化值,结果表明部分企业生产原料甜瓜子存在霉变、酸败等问题,应在新鲜度方面给予重视。其次,优化了鹿瓜多肽注射剂质量标准中高分子量物质和多肽含量测定的方法。采用 Tricine-SDS-PAGE 电泳法代替凝胶色谱法测定高分子量物质,提高了测定的准确性;采用试剂盒法代替福林酚法测定多肽含量,该法操作简便、专属性更强,适用于大批量样品的快速测定。最后,对鹿瓜多肽注射剂质量标准中缺失的溶血与凝聚、生物学活性测定项目进行研究。建立直接观察法结合酶标仪测定法考察溶血与凝聚反应,结果各企业样品均无溶血与凝聚现象;采用 CCK-8 法考察鹿瓜多肽注射剂对 THP-1 细胞增殖的抑制作用,以此评价其抗炎活性,结果显示鹿瓜多肽注射剂对 THP-1 细胞具有增殖抑制作用,各企业样品的体外抗炎效果具有一定差异。探索性研究结果显示,鹿瓜多肽注射剂原材料、中间产品及终产品的安全性均存在一定隐患,表明本品的整体质量水平一般,且现行质量标准存在缺陷,亟待提高。     

Investigation of Drug Delivery in Rats via Subcutaneous Injection: Case Study of Pharmacokinetic Modeling of Suspension Formulations

With the rising cost of drug research, “do more with less” has become a new emphasis in the pharmaceutical industry. Consequently, the early analysis of pharmacokinetic/pharmacodynamic, efficacy, and safety parameters for a new drug target is critical for ensuring informed decision-making as soon as possible during the drug discovery process. When absorption, distribution, metabolism, and excretion properties of compounds are suboptimal which is especially true during the early stages of drug discovery, obtaining the desired exposure can be challenging via the most common routes (oral, intravenous). Therefore, subcutaneous (SC) injection is often explored as an alternate route of delivery. Although SC injection is used widely in the industry, information about how to model and predict the absorption of drugs administered via SC injection is not readily available. In the current research, we analyzed the absorption behavior of 12 model compounds covering a wide range of physicochemical properties following SC injection. We introduced a compound-specific parameter, the absorption factor from single SC injections of suspension doses of each compound, to aid in modeling and predicting of drug absorption profiles. The pharmacokinetic models derived in this study are capable of describing and predicting the absorption properties of SC injection for individual compounds.     

The implementation of overdose prevention sites as a novel and nimble response during an illegal drug overdose public health emergency

BackgroundDrug-related overdoses were declared a public health emergency in British Columbia, Canada in April, 2016 facilitating the scale-up of responses including rapid sanctioning and implementation of overdose prevention sites (OPSs). OPSs are a health service providing supervised injection and immediate overdose response. In BC, OPSs were operational within weeks of sanctioning. In the first year of operation over 20 OPSs were established with approximately 550,000 visits and no overdose deaths at any site. In this paper, we examine the implementation of OPSs as a novel and nimble response to prevent overdose deaths as a result of injection drug use.MethodsA multiple case study design was used with the Consolidated Framework for Implementation (CFIR) informing the analysis. Three sites in a single city were included with each site constituting a case. In this paper, we focus on qualitative interviews with 15 staff and their perceptions of the implementation of the OPSs as well as provincial and local documents.ResultsThe legislative process to implement OPSs was unprecedented as it sanctioned supervised injection services as an extraordinary measure under a declared public health emergency. Innovative and inclusionary practices were possible within state-sanctioned OPSs, as the sites were government-directed yet community-developed, with PWUD centred in service design, implementation and delivery. OPSs lack permanency and may be limited to the duration of the public health emergency.ConclusionThe rapid implementation of OPSs provides an international example of an alternative to lengthy and often onerous sanctioning processes for supervised consumption services (SCSs). Overdose prevention sites provide an example of a novel service design and nimble implementation process that combines the benefits of state-sanctioned injection services with community-driven implementation. Such evidence questions the continued acceptability of governments’ restrictive sanctioning processes, which have limited expansion of SCSs internationally and the implementation of services that are not necessarily aligned with the needs of PWUD.     

神经痛大鼠脊髓胶质细胞源性神经营养因子参与多巴胺D2受体激动剂对痛觉过敏的调制作用

目的 研究鞘内注射多巴胺D2受体激动剂喹吡罗对坐骨神经慢性压迫损伤大鼠脊髓水平胶质细胞源性神经营养因子表达的影响,探讨其介导抗伤害作用的可能机制. 方法 实验1：采用完全随机分组方法将30只成年雄性SD大鼠制作坐骨神经慢性压迫损伤（chronic constriction injury of sciatic nerve,CCI）模型分为5组（每组6只）：CCI＋生理盐水（NS组）、CCI＋喹吡罗0.1 μg（Q0.1组）、CCI＋喹吡罗1μg（Q1组）、CCI＋喹吡罗5 μg（Q5组）、CCI＋喹吡罗10 μg（Q10组）,分别在建模后第7天鞘内注射0.1、1、5、10 μg喹吡罗,NS组单次鞘内注射生理盐水10μl.于给药前及给药后0.5、1、2、4、8、16h测定大鼠术侧后足机械缩足反射阈值（paw withdrawal mechanical threshold,PWMT）和热缩足反射潜伏期（paw withdrawal thermal latency,PWTL）.实验2：将54只成年雄性SD大鼠制作CCI模型,并采用完全随机分组方法分为3组（Q5组、Q10组、NS组,每组18只）：Q5组、Q10组分别在建模后第7天鞘内注射5、10μg喹吡罗后0.5、1、2、4、8、16h处死取材,NS组单次鞘内注射生理盐水10μl;另取6只正常大鼠作为模型对照组（M组）,另取6只正常大鼠作为对照组（C组）.采用免疫印迹法测定脊髓背角胶质细胞源性神经营养因子（glial cell line-derived neurotrophic fact,GDNF）蛋白表达的变化. 结果 实验1：与NS组比较,Q0.1组注药后各时间点PWMT和PWTL差异无统计学意义（P＞0.05）,Q1组注药后2 h PWMT[（4.3±1.5）g]及PWTL[（13.2±1.6）s],Q5组注药后1,2、4 h PWMT[（4.7±1.6）、（5.3±1.6）、（4.7±2.1）g]和PWTL[（14.0±1.7）、（15.2±1.5）、（13.4±1.6）s],Q10组注药后1、2、4 h PWMT[（6.0±1.3）、（7.3±1.0）、（5.3±2.1）g]和PWTL [（15.3±1.8）、（17.5±1.2）、（14.9±1.7）s]明显升高（P＜0.05）.实验2：与C组比较,M组GDNF表达（0.95±0.09）明显升高（P＜0.05）.与M组和NS组比较,GDNF的表达Q     

Provider acceptability of Sayana® Press: results from community health workers and clinic-based providers in Uganda and Senegal

Background

Sayana® Press (SP), a subcutaneous formulation of depot medroxyprogesterone acetate (DMPA) in Uniject™, has potential to be a valuable innovation in family planning (FP) because it may overcome logistic and safety challenges in delivering intramuscular DMPA (DMPA IM). However, SP's acceptability is unknown. We measured acceptability of SP among clinic-based providers (Senegal only) and community health workers.

Study design

This open-label observational study was conducted in clinics in three districts in Senegal and community-based services in two districts in Uganda. Providers administered SP to clients seeking reinjection of DMPA IM. We conducted in-depth interviews with 86 providers (52 in Senegal, 34 in Uganda) to assess their experiences providing SP to clients.

Results

Almost all providers (84/86; 98%) preferred SP over DMPA IM. The main reason Uganda providers preferred SP was the prefilled/all-in-one design made preparation and administration easier and faster. Some providers thought the SP all-in-one feature may decrease stock outs (DMPA IM requires syringe and vial). Providers also felt clients preferred the shorter SP needle because it is less intimidating and less painful. Similarly, the main reasons Senegal providers preferred SP were its characteristics (prefilled/all-in-one) and client preference (especially less pain). They also saw a potential to increase access to FP, especially through community-based distribution. Providers from both countries reported SP introduction would be enhanced through client counseling and community engagement. Providers also said SP must be accessible, affordable and in stock.

Conclusion

Almost all providers preferred SP over DMPA IM. Provider recommendations should be considered during SP introduction planning.

Implications

We found that SP was acceptable to both clinic-based FP providers and community health workers. Providers' positive attitudes towards SP may facilitate introduction and uptake of this method.     

Management strategies for achalasia

Treatment options for achalasia include oral pharmacologic therapy, endoscopic injection of botulinum toxin, pneumatic dilation, and myotomy (conventionally by laparoscopy, but more recently by an endoscopic approach). Oral pharmacologic agents have fallen out of use because of insufficient efficacy and frequent side effects. Endoscopic injection of botulinum toxin is safe and has good short‐term effectiveness, but as the effect invariably wears off after a few months, this treatment is reserved for patients who are not candidates for more definitive treatments. Pneumatic dilation and surgical myotomy are currently considered the most effective treatments, with similar effectiveness in randomized controlled trials with follow‐up of up to 2 years. The risk/benefit ratio and choice of therapy depend on patient characteristics (age, comorbidities, disease stage, prior treatments), patient's preference, and locally available expertise. Treatment of patients who fail or relapse after initial therapy is challenging and the success rate of pneumatic dilation or myotomy in this group is lower compared with previously untreated patients. The recently developed peroral endoscopic approach to myotomy has achieved excellent results in early uncontrolled studies, but high‐quality randomized trials are needed to ensure widespread adoption is reasonable. Finally, retrospective data suggest that achalasia subtypes as defined by high‐resolution esophageal pressure topography may guide treatment choice, but confirmation in prospective outcome studies is awaited.     

外痔切除内痔注射消痔灵与外剥内扎术治疗混合痔的疗效比较

为观察比较混合痔外痔使用高频电容场痔疮治疗仪电钳切除、内痔注射消痔灵与外剥内扎术两种术式的疗效,将以Ⅱ～Ⅳ期内痔为主的混合痔患者120例随机分为两组,每组60例,治疗组采用高频电容场痔疮治疗仪电钳切除外痔,内痔行消痔灵注射治疗;对照组采用外剥内扎术治疗。分别观察其手术时间、疗效及术后并发症情况。结果显示,两组疗效无明显统计学差异（P〉O．05）;但在手术时间、术后并发症方面治疗组优于对照组（P〈O．01或P〈O．05）。结果表明,两种术式疗效接近,但治疗组操作较简便,术后并发症少。     

PPH加消痔灵注射配合电凝切术治疗混合痔的临床观察

为探讨PPH加消痔灵注射配合电凝切术治疗混合痔的临床疗效,回顾性分析10年来对560例混合痔患者施行PPH加消痔灵注射配合电凝切术治疗的资料,观察其疗效。结果显示,560例患者中,治愈500例（89．3％）,显效53例（9．5％）,有效7例（1．2％）,总有效率i00％。住院时间7～14d,平均（10±1）d。术后随访3个月至10年,吻合口出血3例,均经过再次缝扎止血后治愈;吻合口狭窄4例,予以局麻下行电凝切狭窄松解术后治愈。结果表明,PPH加消痔灵注射配合电凝切术治疗混合痔,术后患者痛苦小,恢复快,并发症少,肛门功能正常,肛门外观平整,近、远期未见复发,疗效确切。     

自制胰岛素注射腹带在居家糖尿病患者胰岛素治疗中的应用

目的 探讨提高居家糖尿病患者胰岛素注射部位准确性、减少注射相关不良反应的有效方法.方法 将103例初次使用胰岛素注射治疗的出院糖尿病患者随机分成观察组52例,对照组51例.两组均采用腹部注射,对照组常规给予胰岛素注射相关知识的指导,观察组除常规指导外,注射胰岛素时佩戴自制胰岛素腹部注射定位腹带.结果 治疗12周后观察组皮下硬结发生率显著低于对照组（P＜0.05）.两组血糖比较,差异无统计学意义（P＞0.05）.结论 胰岛素腹部注射定位腹带能帮助患者在进行腹部注射胰岛素时按照指示部位和位置顺序规律注射,减少皮下硬结发生率.     

左卡尼汀与清开灵注射液联用治疗急性病毒性心肌炎临床观察

目的探讨左卡尼汀联合清开灵注射液治疗急性病毒性心肌炎的临床效果。方法将急性病毒性心肌炎患者98例随机分为观察组与对照组,治疗组50例,应用左卡尼汀和清开灵,对照组48例,给予能量合剂和病毒唑,比较两组的疗效。结果治疗组临床表现、心电图、心肌标志物治疗后的改善与对照组治疗后比较,差异有统计学意义（P〈0.05）。结论左卡尼汀联合清开灵注射液治疗急性病毒性心肌炎疗效显著,值得临床推广。