Preparation of honokiol-loaded chitosan microparticles via spray-drying method intended for pulmonary delivery

It has been demonstrated that spray-drying is a powerful method to prepare dry powders for pulmonary delivery. This paper prepared dispersible dry powders based on chitosan and mannitol containing honokiol nanoparticles as model drug. The results showed that the prepared microparticles are almost spherical and have appropriate aerodynamic properties for pulmonary delivery (aerodynamic diameters was between 2.8–3.3 μm and tapped density ranging from 0.14–0.?18?g/cm³). Moreover, surface morphology and aerodynamic properties of the powders were strongly affected by the content of mannitol. Fourier transform infra-red (FTIR) spectrum of powders indicated that the honokiol nanoparticles were successfully incorporated into microparticles. In vitro drug release profile was also observed. The content of mannitol in powders significantly influenced the release rate of honokiol from matrices.     

苗药冠盖藤不同部位挥发性成分的GC-MS分析

目的研究冠盖藤不同药用部位的挥发性成分。方法采用水蒸气蒸馏法提取了冠盖藤不同部位中的挥发性成分,采用GC-MS对其进行分析鉴定。结果鉴定出冠盖藤根茎挥发性化学成分35种,叶的挥发性成分53种。根茎中化合物类型主要为烷烃(20.96%)、有机酸类(5.06%)、酯(4.46%)、醇(3.28%);叶中化合物类型主要为酯(15.11%)、醇(13.92%)、有机酸(9.85%)以及酰胺(6.29%)、异丁基异硫氰酸盐(5.46%)、甲基-2-氧-苯甲酰-d-呋喃糖苷(5.91%)、酮(5.11%)。结论采用GC-MS对冠盖藤不同部位挥发性化学成分进行了分析,为苗药冠盖藤的进一步开发利用提供实验依据。     

北京三家综合医院抗高血压用药方案组成及主要治疗患者分析

本研究旨在调查不同抗高血压药物如何组成治疗方案及其治疗结果。我们在北京三家医院回顾性收集了974张用于治疗高血压的处方, 并从其中一家医院收集了219份病历以研究不同类型的高血压用药方案及患者之间的关系。抗高血压用药方案按照其中降压药的亚类组合分类。几乎所有的处方均可被分到11组抗高血压用药方案, 其中大部分为多药联合治疗。包含CCB类和RAAS抑制剂 （ARB或ACEI）的治疗方案较其他方案显著倾向于治疗高血压III级患者（P〈0.001）。β受体阻滞剂的方案中最常与CCB组成联合治疗方案。氢氯噻嗪的使用不及指南推荐的广泛。     

痛风性关节炎急性发作的中西医结合治疗研究

目的研究以化痰解郁通淋汤为主的中西医结合方法治疗急性痛风性关节炎的临床疗效和安全性。方法 133例急性痛风性关节炎患者,随机分为中西医结合组(治疗组)72例和对照组61例,两组均予以低嘌呤饮食、多饮水、禁酒、禁用利尿剂,并予碳酸氢钠及醋酸泼尼松治疗。对照组予秋水仙碱。治疗组用中药化痰解郁通淋汤,中药口服1日1剂,每周5剂,休息2日;共观察2周。治疗前后分别比较患者的临床症状与体征的变化,并取血清样本,测定血尿酸(SUA)、白细胞(WBC)总数及超敏C反应蛋白(hs-CRP)、血肌酐(SCr)、血尿素氮(BUN)、丙氨酸氨基转移酶(ALT)等实验室指标。结果治疗组总有效率为87.5%(63/72),对照组为81.9%(50/61),治疗组疗效优于对照组(P<0.05)。(2)两组治疗前后中医症状体征积分比较差异有统计学意义(P<0.05),且治疗组优于对照组(P<0.01)。(3)治疗后治疗组SUA、TWBC及hs-CRP等指标均明显改善。两组SUA水平均显著降低(P<0.01),且治疗组优于对照组(P<0.01);(4)在药物安全性方面,治疗组1例、对照组2例出现食欲减退、上腹部饱胀不适、恶心、呕吐,肝功能示谷丙转氨酶轻度升高,发热、皮疹等不良反应,经过对症处理后不良反应减轻,均能坚持服药。两组不良反应比较差异无统计学意义(P>0.05)。结论化痰解郁通淋汤结合常规西药治疗急性痛风性关节炎有较好的疗效和安全性。     

Flavonoids from Millettia nitida var. hirsutissima with their anticoagulative activities and inhibitory effects on NO production

Two new compounds, (2R)-7,3′-dihydroxy-6,4′-methoxyflavan (1) and (3R)-7,4′-dihydroxy-2′-methoxyisoflavan (2), along with 12 known flavonoids (3–14), were isolated from the vine stems of Millettia nitida var. hirsutissima. The structures of the isolated compounds were elucidated based on spectroscopic analyses and comparison of literature data. All of the isolates were evaluated for their effects on in-vitro anticoagulative assay and on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. As a result, all compounds showed weak antiplatelet aggregation activities and compounds 4, 5, 7, 8 and 9 demonstrated antithrombin activity with a good dose–effect relationship from 5 to 100 μg mL^?1 in rabbit plasma. Compounds 8, 9, 10 and 14 exhibited inhibitory effects on LPS-induced NO production in RAW264.7 macrophages with IC₅₀ values of 4.79 ± 0.20, 8.23 ± 0.35, 5.23 ± 0.11 and 6.30 ± 0.30 μg mL^?1, respectively.     

Design,Synthesis and Biological Evaluation of Cinnamic Acyl Shikonin Derivatives

Inducing apoptosis is an important and promising therapeutic approach to overcome cancer. Here, we described a series of novel synthesized compounds, cinnamic acyl shikonin derivatives ( 1b – 19b ), which were synthesized starting from shikonin and cinnamic acids, which exhibit anticancer activity via inducing apoptosis in vitro. Our flow cytometry results showed that compound 8b ((E)‐1‐(5,8‐dihydroxy‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)‐4‐methylpent ‐3‐enyl‐3‐(3‐(trifluoromethyl) phenyl)acrylate) (IC₅₀ = 0.69, 0.65, 1.62 μm for human SW872‐s, A875 and A549 cell lines, respectively) exhibited conspicuous anticancer activities and has low cell toxicity in vitro. Therefore, we considered that compound 8b is potentially to be a candidate of anticancer agent. The proliferation inhibitory effect of compound 8b was associated with its apoptosis‐inducing effect by activating caspase‐3, caspase‐7, caspase‐9, and PARP. When the level of cleaved caspase‐3, cleaved caspase‐7, cleaved caspase‐9, and cleaved PARP are rise, apoptosis of cancer cells will be induced.     

Influence of formulation composition and processing on the content uniformity of low-dose tablets manufactured at kilogram scale

The purpose of this study was to investigate the impact of processing, API loading, and formulation composition on the content uniformity of low-dose tablets made using direct compression (DC) and roller compaction (RC) methods at 1?kg scale. Blends of 1:1 microcrystalline cellulose/lactose or 1:1 microcrystalline cellulose/dicalcium phosphate anhydrous with active pharmaceutical ingredient (API) at loadings of 0.2, 1 and 5% were processed either by DC or RC. A statistical analysis showed that DC produced comparable content uniformity results to RC. Microcrystalline cellulose/lactose formulations had improved average potency compared to microcrystalline cellulose/dicalcium phosphate anhydrous formulations for both DC and RC. The impact of segregation in the DC blends and adhesion to equipment surfaces was assessed to aid in understanding potency trends. DC may be as suitable as RC for low-dose regime (e.g. <?1?mg) when manufacturing clinical supplies at small scale provided the API has a suitable particle size and potency loss to equipment is negligible.     

湘葛一号总黄酮与气候因子的灰色关联度分析

目的运用灰色关联法筛选出影响湘葛一号总黄酮含量的气候主导因子。方法利用紫外分光光度法测定不同采收期湘葛一号不同部位总黄酮含量,采用灰色关联法对其与气候因子的相关性进行分析。结果湘葛一号不同部位、不同采收期总黄酮含量有较大区别。月平均气温、月极端最高气温、月极端最低气温、月平均相对湿度、月降水量、日照时数6个气候因子与湘葛一号根、茎、叶中总黄酮含量关系密切,灰色关联系数均达到0．50以上。其中月平均相对湿度、月极端最高气温和日照时数与根、茎、叶的灰色关联系数达到0．75以上。结论月平均相对湿度、月极端最高气温和日照时数是影响湘葛一号不同部位总黄酮含量的主导因素,实验结果可为湘葛一号的规范化种植提供科学依据。     

Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production

Aim:

To investigate the effects and underlying mechanisms of 118, a novel derivative of mycophenolic acid, in a murine allogeneic skin graft model.

Methods:

Skin grafts were conducted by grafting BALB/c donor tail skin into C57BL/6 skin beds (allograft) or by grafting female C57BL/6 donor tail skin into female C57BL/6 skin beds (syngraft). The mice were treated with the derivative 118 (40 mg·kg⁻¹·d⁻¹, po) for 13 d (3 d before and 10 d after transplantation). Skin grafts, splenocytes and graft-infiltrated lymphocytes were isolated and examined ex vivo. The effects of the derivative 118 on naive CD4⁺ T cell differentiation were examined in vitro.

Results:

Treatment with the derivative 118 dramatically increased the survival rate of murine allogeneic skin grafts. Flow cytometric analysis and H&E staining showed that the derivative significantly decreased inflammatory cell infiltration into the grafts. The levels of the chemokines CXCL1, CXCL2, CCL7, and CCL2 were reduced in the derivative 118-treated grafts. Additionally, the derivative 118 significantly suppressed the IL-17 levels in the grafts but did not affect the differentiation of systemic helper T cells in the murine allogeneic skin graft model. Furthermore, IL-23p19 expression was suppressed in the grafts from the derivative 118-treated group, which might be due to decreases in TLR4 and MyD88 expression. Finally, the derivative 118 did not exert direct influences on helper T cell differentiation in vitro.

Conclusion:

Treatment with the mycophenolic acid derivative 118 improves murine allogeneic skin grafts by decreasing IL-23 expression and suppressing local IL-17 secretion in the grafts, rather than directly inhibiting Th17 differentiation.     

Practical considerations for the use of sodium–glucose co-transporter type 2 inhibitors in treating hyperglycemia in type 2 diabetes

Sodium–glucose co-transporter type 2 (SGLT2) inhibitors are a new class of oral anti-diabetic agents with a unique, insulin-independent mode of action. In patients with diabetes who have adequate renal function, SGLT2 inhibitors reduce hyperglycemia by blocking renal glucose reabsorption and increasing urinary glucose excretion. These agents are indicated for the treatment of hyperglycemia in type 2 diabetes mellitus (T2DM), as an adjunct to diet and exercise. In terms of efficacy, they are comparable to most other oral agents, and carry a low risk of hypoglycemia unless combined with sulfonylureas or insulin. They may be used in combination regimens with metformin, sulfonylureas, or insulin. Beyond glucose lowering, SGLT2 inhibitors are associated with modest weight loss and mild anti-hypertensive effects. Emerging cardiovascular and renal outcomes data suggest other potentially beneficial non-glycemic effects, although these findings await confirmation from further studies. The main adverse effects are increased risk of volume depletion and of genitourinary infections, although these can be managed with standard interventions. Rare cases of euglycemic ketoacidosis have been reported in a subset of patients treated with these agents, an issue currently under investigation. SGLT2 inhibitors represent a promising alternative treatment option for T2DM patients in whom the effectiveness of oral anti-hyperglycemic therapy is limited by the risk of hypoglycemia, weight gain, or other adverse effects. Safety and efficacy (up to 4 years) have been demonstrated in a range of T2DM patient populations, although more studies will be needed to determine whether treatment with SGLT2 inhibitors improves patient-important outcomes in the longer term.