樟柳碱的扩瞳与调节麻痹作用

目的：观察樟柳碱眼药水对人眼的扩瞳作用与调节麻痹作用。方法：３０例观察对象（男性２２例，女性８例；年龄１６±ｓ５ａ）均一眼滴用０．２％樟柳碱眼药水，另一眼作空白对照；观察扩瞳作用，用调节卡测定剩余调节力。结果：瞳孔扩至最大时间为４５±５ｍｉｎ，瞳孔恢复正常时间为７５±４ｈ；在药物作用高峰期，剩余调节力为１．７±０．５Ｄ。结论：樟柳碱的扩瞳与调节麻痹作用有临床应用价值；樟柳碱眼药水的应用是安全的     

Nanocarriers for ocular delivery for possible benefits in the treatment of anterior uveitis: focus on current paradigms and future directions

Introduction: Many therapeutic strategies have been adopted in the treatment of anterior uveitis, and it includes corticosteroids and NSAIDs. But, the successful delivery of these drugs is restricted due to limitations of conventional formulation. This review emphasizes on the possible benefits and strategies for development of various novel nanocarriers.

Areas covered: The article explores the various polymers involved in the preparation of novel nanocarriers like polymeric nanoparticles, micelles, microemulsion, liposomes and cubosomes. Reported clinical experimental findings are screened and also discussed in this review.

Expert opinion: The principle behind the development of different nanocarriers is to overcome the limitations imposed by conventional formulations. Several efforts have been made by the researchers in achieving these objectives, but the major challenge with nanosystems remains the requirement of excipients that have unknown or objectionable toxicity profile and are not approved by regulatory authorities. This review is an attempt to provide comprehensive information for the scientists working in the concerned research area.     

Role of Dopamine Receptors on Electroencephalographic Changes Produced by Repetitive Apomorphine Treatments in Rats

Repeated psychostimulants induce electroencephalographic (EEG) changes, which reflect adaptation of the neural substrate related to dopaminergic pathways. To study the role of dopamine receptors in EEG changes, we examined the effect of apomorphine, the dopamine D1 receptor antagonist, SCH-23390, and the D2 receptor antagonist, haloperidol, on EEG in rats. For single and repeated apomorphine treatment groups, the rats received saline or apomorphine for 4 days followed by a 3-day withdrawal period and then apomorphine (2.5 mg/kg, i.p.) challenge after pretreatment with saline, SCH-23390, or haloperidol on the day of the experiment. EEGs from the frontal and parietal cortices were recorded. On the frontal cortex, apomorphine decreased the power of all the frequency bands in the single treatment group, and increased the theta (4.5~8 Hz) and alpha (8~13 Hz) powers in the repeated treatment group. Changes in both groups were reversed to the control values by SCH-23390. On the parietal cortex, single apomorphine treatment decreased the power of some frequency bands, which were reversed by haloperidol but not by SCH-23390. Repeated apomorphine treatment did not produce significant changes in the power profile. These results show that adaptation of dopamine pathways by repeated apomorphine treatment could be identified with EEG changes such as increases in theta and alpha power of the frontal cortex, and this adaptation may occur through changes in the D1 receptor and/or the D2 receptor.     

Formulation,in Vitro Dissolution,and Ocular Bioavailability of High- and Low-Melting Phenylephrine Oxazolidines

The in vitro dissolution and the relative ocular bioavailability of high- and low-melting phenylephrine oxazolidines (HMP and LMP) from a nonaqueous suspension (silicone fluid) were compared. Stability-indicating HPLC assays were developed for evaluation of the prototype formulations, in which a normal-phase HPLC method was necessary for analysis of PO, while a reverse-phase HPLC method was required for analysis of the primary degradation product, phenylephrine (PE), following its separation from the formulation using a short silica gel column. PO was formulated as an ophthalmic suspension in silicone fluid (20 cs) because of its property of undergoing rapid hydrolysis in aqueous media. An experimental test system for measuring the dissolution characteristics of a water-immiscible multiparticulate suspension was designed to obtain the dissolution profiles of suspensions of HMP and LMP. The dissolution rates, which were nearly identical for LMP and HMP, were obtained assuming a quasi-infinite reservoir. A reverse-phase HPLC assay with fluorescence detection was used for measuring the concentrations of PE in aqueous humor and corneal samples. Statistical analysis of the bioavailability data showed that suspensions containing HMP and LMP were equal in extent of absorption following a single topical application to the rabbit eye. The results correlated well with the in vitro dissolution rates of the suspensions of HMP and LMP.     

联合麻醉下施行上腹部手术对病人应激和免疫功能的影响

目的：通过测定儿茶酚胺（CA）、皮质醇、白细胞介素－2（IL－2）可溶性白细胞介素2－受体（SIL－2R）,观察全麻联合硬膜外阻滞对上腹部手术病人应激激素和免疫功能的影响。方法：选择性上腹部手术病人30例,随机分成全麻联合硬膜外阻滞组（n=15)和单纯全麻组（n=15)。两组病人分别于麻醉前、麻醉诱导后切皮前、手术结束前、术后第1天、术后第3天采血,测定血浆中CA、血清中皮质醇、IL－2、SIL－2R浓度。结果：肾上腺素（E）水平在联合组无明显变化,全麻组在手术结束前、术后第1天都升高（P＜0．01）。去甲肾上腺素（NE）浓度在联合组麻醉诱导后出现降低（P＜0．05）,而手术结束前及术后第1、3天与麻醉前相比均无明显变化。全麻组病人在麻醉诱导后无明显变化,而在手术结束前术前术术后第1天升高（P＜0．01）,术后第3天仍未恢复到麻醉前水平。皮质醇浓度两组病人的变化相仿,在麻醉诱导后都呈降低趋势（P＜0．05）。IL－2在联合组的任何采样点与麻醉前比较均无明显变化,而在全麻组,手术结束前降低（P＜0．01）,与联合组相同采样点比也降低（P＜0．05）。两组病人SIL－2R在麻醉诱导后及手术后均无明显变化。结论：在上腹部手术,联合麻醉在抑制病人的应激反应及保护免疫功能方面优于单纯全麻。     

The Myocardial Lesions Produced by the Potassium Channel Opener Aprikalim in Monkeys and Rats Are Prevented by Blockade of Cardiac {beta}-Adrenoceptors

Aprikalim is a potent, specific, and selective opener of ATP-sensitiveK⁺ (K_ATP) channels. By virtue of this pharmacological property,aprikalim affords cardioprotection in experimental models ofischemia/reperfusion injury, and, at higher doses, also causesperipheral or coronary vasodilatation. Direct-acting peripheralvasodilators can cause myocardial lesions, particularly in ratsand dogs. However, unexpectedly, aprikalim produced this effectalso in monkeys. Thus, the primary aim of this investigationwas to assess whether in monkeys these myocardial lesions werethe direct or indirect consequence of the vascular effects ofaprikalim. Cyno-mologus monkeys were given the ß-adrenoceptorantagonist nado-lol (2 mg/kg po, twice daily) for 4 consecutivedays. On the third and fourth day of the experiment, they receivedaprikalim (1 mg/kg po). In another series, two monkeys carryingtelemetry transmitters for blood pressure and heart rate measurementswere also given aprikalim or its vehicle. Finally, aprikalim(1 mg/kg po for 2 days) or its vehicle was administered to ratswhich were concurrently treated with the ß-adrenoceptorantagonist atenolol (5 mg/ kg sc) or its vehicle. In cynomologusmonkeys, aprikalim produced focal and multifocal myocardialnecrosis of minimal to moderate intensity in or near the papillarymuscles of the left ventricle. These effects were abrogatedby nadolol. Similarly, necrotic lesions were caused by aprikalimonly in those rats which had not been pretreated with atenolol.In monkeys, aprikalim produced a marked and long-lasting decreasein aortic blood pressure, accompanied by an even more prolongedtachycardia. These results demonstrate that aprikalim can producemyocardial necrosis not only in rats but also in monkeys. Toour knowledge, this is the first time that such adverse effectsare reported for a vasodilator in monkeys. More importantly,these effects were prevented by blocking cardiac ß-adrenoceptors.Thus, the myocardial lesions produced by aprikalim may be attributedto its profound and prolonged hemodynamic effects.     

Evaluation of Cytotoxicity of Various Ophthalmic Drugs, Eye Drop Excipients and Cyclodextrins in an Immortalized Human Corneal Epithelial Cell Line

Purpose. An immortalized human corneal epithelial cell line (HCE) was tested as a screening tool for prediction of topical ocular irritation/ toxicity by pharmaceuticals. Methods. Effects of various drugs, excipients and cyclodextrins (CDs) on viability of HCE cells were evaluated using two in vitrocytotoxicity tests, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye reduction assay and propidium iodide assay. Results. Mitochondrion-based MTT test was a more sensitive indicator of cytotoxicity than the plasma membrane-based propidium iodide test. The tests revealed following cytotoxic rankings for ophthalmic drugs: dipivefrin > timolol > pilocarpine dexamethasone; for excipients: benzalkonium chloride (BAC) > sodium edetate (NA₂EDTA) > poly-vinyl alcohol (PVA) > methylparaben; and for CDs: -CD > dimethyl--cyclodextrin (DM--CD) > sulfobutyl ether (-cyclodextrin ((SBE)_7m--CD) hydroxypropyl--cyclodextrin (HP--CD) > -CD. In consideration of the in vivoclinical situation, the short exposure time (5 min) is more relevant even though toxic effects of some test substances were seen only after longer exposure times (30 and 60 min). Conclusions. Immortalized HCE cells are a promising tool for rapid cytotoxicity assays of ocular medications. The cell line is potentially useful in predicting the in vivocorneal toxicity of ocularly applied compounds.     

再生障碍性贫血患者外周血单个核细胞产生某些细胞因子能力的变化及意义

观察再生障碍性贫血患者外周血单个核细胞（ＰＢＭＮＣ）产生 ＩＬ－１α、ＩＬ－２的能力及外周血清ｓＩＬ－２Ｒ水平,探讨这些变化的意义。方法：应用ＥＬＩＳＡ法测定细胞因子活性。结果〔显示再障患者ＰＢＭＮＣ产生ＩＬ－１α的能力明显低于对照组（Ｐ＜０．０１）;而产生 ＩＬ－２的能力则明显高于对照组（Ｐ＜０．０１）;血清 ｓＩＬ－２Ｒ水平明显高于对照组（Ｐ＜０．０１）。结论：这三项检测结果对于认识再障贫血的发病机制、辅助诊断疾病的严重程度、指导治疗和估计预后有一定意义。     

HPLC法测定甲麻滴鼻液中麻黄碱和甲硝唑的含量

目的建立一种快速、准确的高效液相色谱法同时测定盐酸麻黄碱和甲硝唑的含量。方法采用C18柱,以乙腈-0.1%磷酸(用三乙胺调pH为3.5)(7∶93)为流动相,检测波长为257nm,进样量为20μL。结果盐酸麻黄碱和甲硝唑分别在0.4997~1.499m g.mL-1和0.2907~0.8720m g.mL-1范围内呈良好线性关系(r=0.9998和r=0.9999)。平均回收率分别为98.97%和99.70%,RSD分别为1.77%和1.19%。结论此方法可快速、准确地同时检测甲麻滴鼻液中的盐酸麻黄碱和甲硝唑的含量。     

HPLC法测定大青龙汤颗粒剂中盐酸麻黄碱和盐酸伪麻黄碱的含量

摘 要 目的:建立HPLC测定大青龙汤颗粒剂中盐酸麻黄碱和盐酸伪麻黄碱含量的方法,为该制剂的质量控制提供依据。方法: 采用Agilent Zorbax SB-C₁₈色谱柱(150 mm×4.6 mm,5 μm),以乙腈-含0.3%三乙胺的0.02 mol·L^-1磷酸二氢钾溶液（用磷酸调节至pH=3.0）(5∶95)为流动相,流速:1.0 ml·min^-1,波长：207 nm。结果:盐酸麻黄碱在64～640 μg·ml^-1浓度范围内线性关系良好（r=0.999 6）,平均回收率为101.66%,RSD为2.59%(n=6);盐酸伪麻黄碱在31.8～318 μg·ml^-1浓度范围内呈现良好的线性关系（r=0.999 7）,平均回收率为99.70%,RSD为1.58%(n=6)。结论:该法简便易行,结果准确,可用于大青龙汤颗粒剂的质量控制。     

HPLC法测定通宣理肺颗粒中盐酸麻黄碱及盐酸伪麻黄碱的含量

目的：建立通宣理肺颗粒中盐酸麻黄碱及盐酸伪麻黄碱含量的高效液相色谱测定方法。方法：色谱柱为SymmetryC18（250mm×4．6mm,5μm）,流动相为甲醇-0．1％磷酸（含0．1％三乙胺）（7：93）,流速1．00mL／min,检测波长210nm,柱温30℃,选样量10μL。结果：盐酸麻黄碱在4．46～89．20μg／mL浓度范围内与峰面积线性关系良好,r=0．9995（n=6）,平均回收率为100.7％,RSD为1.6％（n=9）;盐酸伪麻黄碱在2．11-42．20μg／mL浓度范围内与峰面积线性关系良好,r=0．9999（n=6）,平均回收率为100．7％,RSD为1．5％（n=9）。结论：本测定方法简便,结果准确,灵敏度高,重复性好,可用于通宣理肺颗粒的质量控制。     

紫外分光光度测定特麻滴鼻剂的含量

本文采用双波长分光光度法消除组分间干扰进行含量测定,特非那定含量测定波长为261．5,253nm,对应平均回收率99．8％（RSD＝0．9％,n=9),盐酸麻黄碱含量测定波长为254．8nm,对应平均回收率99．5％（RSD＝1．5％,n=9),本方法简便,快速,准确。     

HPLC法同时测定百喘朋中盐酸麻黄碱和盐酸苯海拉明的含量

目的 :建立HPLC法同时测定百喘朋中盐酸麻黄碱和盐酸苯海拉明的含量。方法 :采用DiamonsilC18(5μ,4.6mm×150mm)色谱柱 ,流动相为乙腈 -水 -磷酸 (60∶40∶0 1 ,每1000ml含4 0g 十二烷基硫酸钠 ) ,检测波长为254nm ,采用外标法。结果 :盐酸麻黄碱、盐酸苯海拉明的线性范围分别为2 69μg～32.28μg、2 54μg～30.48μg ,回收率 (n=5)分别为100 4 % (RSD=1.1 % )和99 8 % (RSD=0.9 % )。结论 :本法可同时准确测定百喘朋中盐酸麻黄碱和盐酸苯海拉明的含量。     

高效液相色谱法测定麻黄止嗽胶囊中盐酸麻黄碱及盐酸伪麻黄碱含量

目的：建立测定麻黄止嗽胶囊中盐酸麻黄碱及盐酸伪麻黄碱含量的高效液相色谱法。方法色谱柱为C18柱（250 mm ×4.6 mm,5μm）,流动相为乙腈-0.1%磷酸（3：97）梯度洗脱,流速为1.0 mL/min,检测波长210 nm。结果盐酸麻黄碱进样量在0.02~3.12μg范围内、盐酸伪麻黄碱在0.01~1.52μg范围内与峰面积积分值线性关系良好（ r=0.9999）;3种质量浓度盐酸麻黄碱的加样回收率分别为99.26%,99.44%,105.10%,盐酸伪麻黄碱的加样回收率分别为100.48%,102.75%,100.50%。结论该方法简便、准确,可用于控制该制剂的质量。     

In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan

Gellan gum, kappa-carrageenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use. To achieve this purpose different proportion of the biopolymers were analyzed using a mixture experimental design evaluating their transparency, mechanical properties and bioadhesion in the absence and presence of simulated tear fluid. Tear induces a rapid sol-to-gel phase transition in the mixtures forming a consistent hydrogel. The solution composed by 80% of gellan gum and 20% kappa-carrageenan showed the best mechanical and mucoadhesive properties. This mixture was evaluated for rheological behavior, microstructure, cytotoxicity, acute corneal irritancy, ex-vivo and in vivo ocular toxicity and in vivo corneal contact time using Magnetic Resonance Images (MRI) techniques. Result indicates that the system is safe at ophthalmic level and produces an extensive ocular permanence higher than 6 h.     

Influence of Stabilizers on the Physicochemical Characteristics of Inhaled Insulin Powders Produced by Supercritical Antisolvent Process

Purpose  To examine the effect of stabilizers on aerosol physicochemical characteristics of inhaled insulin particles produced using a supercritical fluid technology. Materials and Methods  Insulin with stabilizers such as mannitol and trehalose was micronized by aerosol solvent extraction system (ASES). The supercritically-micronized insulin particles were characterized for size, shape, aerosol behavior, crystallinity and secondary structure. Results  Experimental results indicated that when insulin was incorporated with the most commonly used stabilizer mannitol (insulin/mannitol: 15/85 wt.%, designated IM), the particles formed were irregular and needle-shaped and had a tendency to agglomerate. With the incorporation of a second stabilizer trehalose (insulin/mannitol/trehalose: 15/70/15 wt.%, designated IMT), the particles were relatively uniform, more spherical, less cohesive, and less agglomerated in an air flow, when compared to IM particles. The mass median aerodynamic diameter of the IMT particles was 2.32 μm which is suitable for use in inhalation therapy. In vitro deposition test using micro-orifice uniform deposit impactor showed 69 ± 7 wt.% of the IMT particles was deposited in stage 3, 4, 5 and 6 while 41 ± 15 wt.% of the IM particles was deposited in the same stages. In terms of insulin stability, secondary structures of insulin particles were not adversely affected by the ASES processing studied here. Conclusions  When properly formulated (as in IMT particles), ASES process can produce particles with appropriate size and size distribution suitable for pulmonary insulin delivery.     

回顾性分析本院用更昔洛韦与阿昔洛韦治疗单纯疱疹病毒性角膜炎的疗效

目的 回顾性分析本院用更昔洛韦与阿昔洛韦治疗单纯疱疹病毒性角膜炎的疗效.方法 收集近年在本院门诊就诊的100例(106眼)单纯疱疹病毒性角膜炎患者,其中48例用更昔洛韦眼用凝胶;37例用阿昔洛韦眼液.比较两者疗效.结果 更昔洛韦组与阿昔洛韦组总有效率分别为91.7%,75.7%,显示更昔洛韦眼用凝胶的有效率好于阿昔洛韦眼液(P＜0.05).结论 更昔洛韦眼用凝胶治疗单纯疱疹病毒性角膜炎的效果较好.     

HPLC法测定骨通贴膏中盐酸麻黄碱的含量及含量均匀度

目的：建立HPLC法测定骨通贴膏中盐酸麻黄碱的含量及含量均匀度。方法：采用Kromasil C18柱（250mm×4．6mm,5μm）,乙腈-0．1％磷酸溶液（5：95）为流动相,柱温为30℃,流速1．0ml·min^-1,检测波长为207nm。结果：盐酸麻黄碱在0．0527～2．6350μg的范围内线性关系良好,r=1．0000,平均回收率103．07％,RSD为1．70％（n=6）。结论：该方法操作简便,准确性、重复性好,可用于骨通贴膏中盐酸麻黄碱的含量及含量均匀度测定。     

HPLC法测定麻黄止嗽丸中盐酸麻黄碱及盐酸伪麻黄碱的含量

摘 要 目的: 建立麻黄止嗽丸中盐酸麻黄碱及盐酸伪麻黄碱含量的测定方法。方法: 采用反相高效液相色谱法,色谱柱为Kromasil C₁₈柱(200 mm×4.6 mm,5 μm),流动相为乙腈 0.1％磷酸溶液（含0.1%三乙胺）（4∶96）,流速为1 ml·min^-1,检测波长为207 nm,柱温：室温,进样量：5 μl。结果:盐酸麻黄碱在0.02～0.52 μg 范围内线性关系良好(r=0.999 9),平均回收率为97.8%,RSD为1.6%(n=6);盐酸伪麻黄碱在0.02～0.51 μg范围内线性关系良好(r=0.999 8),平均回收率为99.4%,RSD为0.9%(n=6)。结论:该方法准确可靠,可用于麻黄止嗽丸中盐酸麻黄碱和盐酸伪麻黄碱的含量测定。     

HPLC法同时测定复方诺氟沙星滴鼻液中的诺氟沙星和盐酸麻黄碱

目的　建立一种快速、准确的高效液相色谱法同时测定诺氟沙星 ( NOR)和盐酸麻黄碱 ( EPH)的含量。 方法　使用 C1 8色谱柱 ,流动相为乙腈— 0 .1%磷酸 ( 15 :85 V/V) ,检测波长为 2 5 6nm。结果 　样品测定在 9min内完成。诺氟沙星在 10～ 60μg· ml- 1 浓度范围内 ,r=0 .9999,RSD= 0 .46% ,平均回收率为 99.91% ;盐酸麻黄碱在 2 5～ 12 5 μg· ml- 1浓度范围内 ,r=0 .9992 ,RSD=0 .5 1% ,平均回收率为 10 0 .0 3%。 结论 　方法可快速准确地检测复方诺氟沙星滴鼻液中的诺氟沙星和盐酸麻黄碱含量