褪黑素固体脂质纳米粒的制备及理化性质

考察不同的处方对褪黑素固体脂质纳米粒粒径和包封率等理化性质的影响，并进行其体外释放实验。结果表明，以单硬脂酸甘油酯为脂质材料，乳化超声法制备固体脂质纳米粒，平均粒径为（62．4±1．5）nm，ζ电位为（-7．0±0．2）mV，平均包封率为（64．6±3．8）％；药物的体外释放符合Weibull模型。     

复方替硝唑单向速缓二次释放药膜的研制及其释放特性

目的:研究复方替硝唑单向速缓二次释放药膜(以下简称药膜)的制法及其释放特性.方法:药膜由保护膜层、缓释药物膜层和速释药物膜层3部分组成,通过重量-面积法确定药膜的含药量并采用改进的TP-5型渗透池研究药膜单向速释及缓释情况.结果:替硝唑的平均回收率为100.45%,RSD为1.36%(n=5).由A池可知,在10 S时有(45.5±3.4)%的药物释放,自5～(36.3±2.8)min有(65.6±3.2)%～(95.1±2.4)%的药物释放.由B池可知,至10 min时始有(3.6±2.6)%的药物释放,至药物膜层脱落时止,有(7.1±2.1)%的药物释放.结论:该药膜易于制备且具有良好的单向速缓二次释放特性.     

阿魏酸钠对血小板促肥大细胞释放组胺的影响

观察血小板激活前后对肥大细胞释放组胺的影响，发现致敏血小板激活后，与肥大细胞混合，其组胺释放率为８２．３％±５．７％；比未致敏血小板与肥大细胞混合后的组胺释放率５９．０％±９．０％有显著增高（Ｐ＜０．０１），用阿魏酸钠２３ｍｏｌ·Ｌ－１处理血小板后，用药组的肥大细胞组胺释放率３３．４±１５．８％比用药前显著下降（Ｐ＜０．０１），而阿魏酸钠对肥大细胞自身的组胺释放率影响不大，说明阿魏酸钠主要通过抑制血小板激活，而参与抗过敏作用的。     

马来酸噻吗洛尔凝胶剂在不同动物皮肤中的经皮渗透性考察

摘要：目的:探究马来酸噻吗洛尔凝胶在不同动物皮肤中的透过性差异,分析药物经皮渗透动力学特征。方法:通过透皮扩散试验仪模拟药物的透皮释放,采用HPLC法测定凝胶剂在不同动物皮肤的累积释放量。结果:马来酸噻吗洛尔凝胶在SD大鼠、BALB/c-nu裸鼠和巴马小型猪皮肤内的24 h单位面积累积透过量分别为（92.20±4.91）,（70.07±5.52）,（26.68±3.48）μg·cm-2。结论:马来酸噻吗洛尔凝胶在3种动物皮肤内的透过性存在种属间差异:SD大鼠皮肤的透过性最大,其次是裸鼠,猪皮最低。凝胶剂在3种动物皮肤中的体外释放均符合零级动力学过程,即凝胶中药物的释放主要以扩散为主。     

银杏叶提取物对溶血磷脂酰胆碱引起的脑微血管细胞损伤的保护作用

目的：研究银杏叶提取物（ＧｂＥ）对溶血磷脂酰胆碱（ＬＰＣ）引起的小牛脑微血管内皮细胞（ＢＣＭＥＣ）损伤及小牛脑微血管平滑肌细胞（ＢＣＭＳＭＣ）增殖的保护作用。方法：以乳酸脱氢酶（ＬＤＨ）释放量为指标测定ＢＣＭＥＣ损伤，用结晶紫染色法测定ＢＣＭＳＭＣ增殖。结果：ＬＰＣ５０ｎｍｏｌ／Ｌ可明显增加ＬＤＨ的释放，ＧｂＥ０，５，１０，２０，５０和１００ｍｇ／Ｌ，则ＬＤＨ释放率由４７．０％±０．７％分别下降为３９％±３％，３６．０％±１．３％，２７．０％±２．１％，１６％±６％和１３％±３％，表明ＧｂＥ呈剂量依赖性地抑制了ＬＤＨ的释放。ＧｂＥ对ＬＰＣ引起的ＢＣＭＳＭＣ的增殖抑制作用不明显。结论：ＧｂＥ对ＬＰＣ引起的ＢＣＭＥＣ损伤具明显的保护作用     

甲硝唑牙用缓释药膜的制备及临床应用

利用羧甲基纤维素钠和聚乙烯醇－１２４为载体，甲硝唑为主药制成一种可吸收性牙周炎缓释药膜。此药膜可贴、口含和插入牙周袋内，观察药膜体外释放试验及临床应用。结果显示，体外释放缓慢。２０２例牙周炎患者的牙龈炎指数（ＧＩ）、龈沟出血指数（ＳＢＩ）、牙周袋深度（ＰＰＤ）明显下降，显效９０．１０％，有效７．９２％，无效１．９８％。     

雌二醇控释贴片的释放度研究

采用浆法测定雌二醇控释贴片的释放度,以1％PEG－400为溶剂,温度（32±0．5）℃,转速30r／min。HPLC法定量：Shim－PackC18柱,流动相为甲醇一水（75：25）,检测波长280nm。结果表明：雌二醇控释贴片在24,72,120,168h的累计释放量分别为28.48％,54.91％,69．69％,83．67％。     

布地奈德混悬液吸入治疗儿童哮喘急性发作疗效观察

目的观察布地奈德混悬液雾化吸入治疗儿童哮喘急性发作的疗效。方法将56例哮喘急性发作患儿随机分为两组，观察组（30例）给予布地奈德混悬液加喘乐宁及爱喘乐雾化吸入，对照组（26例）静滴地塞米松加喘乐宁及爱喘乐雾化吸入，观察两组患儿治疗前和治疗后0．5h、1h、2h、24h、72hPEFR值的变化；呼吸困难、咳嗽、喘息、哮鸣音等主要症状、体征消失天数。结果观察组在治疗后1h、2h、24h、72h的PEFR值（占预计值的百分比）分别为（56．4±3．5）％、（61．3±3．8）％、（68．8±5．5）％、（73．2±3．6）％，对照组的PEFR值分别为（55．1±3．9）％、（57．2±4．1）％、（60．7±5．7）％、（62．1±5．1）％，两组24h、72h的PEFR值比较差异有统计学意义（P〈0．01）；观察组比对照组呼吸困难、咳嗽、喘息、哮鸣音等主要症状体征消失天数明显缩短（P〈0．01）。结论对哮喘急性发作患儿，在雾化吸入支气管扩张剂的同时，加用布地奈德混悬液雾化吸入，可明显缩短病程、改善肺功能，较皮质激素静脉用药有明显优越性。     

蒙脱石对6种药物的体外吸附比较

目的：比较蒙脱石对西咪替丁、雷尼替丁、法莫替丁、阿莫西林、甲硝唑、庆大霉素的体外吸附作用。方法：蒙脱石分别加入上述６种药物,用高氯酸滴定法、高效液相色谱法、紫外分光光度法、旋光法测定其吸附率。结果：蒙脱石对６种药物吸附率分别为（３２．１±１．１）％,（８８．８±１．１）％,（７６±４）％,（１４±３）％,（１７．１±１．４）％,（６２±３）％,６种药物分别进行组间比较,经方差分析,显示吸附差异具有显著意义,Ｐ＜０．０１。结论：蒙脱石对雷尼替丁吸附率最强,吸附作用表现为阳离子吸附。     

表皮生长因子治疗鼻中隔粘膜糜烂性鼻出血

目的：观察表皮生长因子治疗鼻中隔粘膜糜烂性鼻出血的疗效。方法：治疗组６２例（男性２９例，女性３３例；年龄３５±ｓ６ａ）用０．２％表皮生长因子明胶海绵敷贴在鼻中隔的糜烂面上，并用该药液滴鼻，每次４滴，ｑｉｄ×１０ｄ。对照组３０例（男性１４例，女性１６例，年龄３２±５ａ）用０．２５％氯霉素明胶海绵敷贴，并用此药滴鼻，每次４滴，ｑｉｄ×１０ｄ。结果：治疗组出血停止，鼻腔干燥，刺痛感消失，粘膜恢复正常的平均天数及复发率均低于对照组（Ｐ＜０．０１），未见不良反应。结论：表皮生长因子可作为治疗鼻中隔粘膜糜烂性鼻出血的满意制剂。     

Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: a preliminary study

The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m^?1 S^?2 and more than 2.5 kg/3 cm², respectively. The percent drug content was 98.5 ± 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically.     

A novel tri-layered buccal mucoadhesive patch for drug delivery: assessment of nicotine delivery

Objectives The aim of this study was to assess the potential of a novel delivery device for administering drugs that suffer from a high degree of first‐pass metabolism. Methods A tri‐layered buccal mucoadhesive patch, comprising a medicated dry tablet adhered to a mucoadhesive film, was prepared and characterized by its physicochemical properties and mucoadhesive strength. Nicotine was used as a model drug for the characterization of drug release and drug permeation. The influence of different adsorbents on the release of nicotine base from the patches was evaluated in vitro. Different molecular forms of nicotine (base and complex salt) were evaluated for their effect on release performance and permeation in vitro. Key findings Results demonstrated acceptable physicochemical and mucoadhesive properties for the tri‐layered patch. Rapid release of nicotine was observed when nicotine base was incorporated with calcium sulfate dihydrate as the adsorbent. Patches incorporating nicotine base showed distinct advantages over those containing nicotine polacrilex, in terms of drug release (complete drug release achieved at 30 vs 60 min) and transmucosal permeation (37.28 ± 4.25 vs 2.87 ± 0.26% of the dose permeating through mucosa within 120 min). Conclusions The novel tri‐layered patch can effectively adhere to, and deliver an active ingredient through the buccal mucosa, confirming its potential for buccal mucoadhesive drug delivery.     

EFFECT OF NICORANDIL ON POST-ISCHAEMIC CONTRACTILE DYSFUNCTION IN THE HEART: ROLES OF ITS ATP-SENSITIVE K' CHANNEL OPENING PROPERTY AND NITRATE PROPERTY

1. This study aimed to characterize the effect of nicorandil (NC) on myocardial stunning and the role of ATP-sensitive K⁺ (K_atp) channel opening property in its cardioprotective action. 2. In open-chest anaesthetized rabbits, myocardial stunning was induced by 10 min of coronary occlusion followed by 30 min of reperfusion. As an index of regional contractile function, systolic thickening fraction (TF) was measured by an epicardial Doppler sensor. The doses of NC (10 μg/kg per min) and nitroglycerin (TNG) (1 μg/kg per min) were selected not to lower the systemic blood pressure significantly. 3. In the untreated controls, TF at 30 min after reperfusion was 46.4 ± 2.9% of the baseline value, indicating myocardial stunning. Both NC and TNG significantly improved post-ischaemic recovery of TF when administered during the pre-ischaemic and post-ischaemic periods (TF = 68.2 ± 6.4%, 64.7 ± 2.3%, respectively). However, when their infusion was restricted to a pre-ischaemic 10 min period, TF recovery was improved by NC, but not by TNG (63.4 ± 7.9%, 40.9 ± 6.2%, respectively). 4. Pretreatment with glibenclamide (GL; 0.3 mg/kg) did not influence the recovery of TF after the 10 rnin ischaemia (TF = 52.4 ± 3.9% at 30 min after reperfusion). However, after the GL injection, a cardioprotective effect from nicorandil pretreatment was not detected (TF = 51.3 ± 1.7%). 5. These results suggest that nicorandil protects the myocardium against stunning by opening the K_atp channel when it is given before ischaemia, and that the nitrate property of nicorandil may also play a role during the reperfusion period in attenuation of post-ischaemic contractile dysfunction.     

Hybrid Nanostructured Films for Topical Administration of Simvastatin as Coadjuvant Treatment of Melanoma

This work aims at (1) assessing the potential of repurposing simvastatin (SV) to support the most common therapies against melanoma and (2) developing an innovative topical adhesive film, composed by chitosan-coated nanostructured lipid carriers (Ch-NLC) used as drug vehicle. A factorial design approach was employed as the basis for the formulation development. Optimized Ch-NLC displayed a particle size of 108 ± 1 nm, a polydispersity index of 0.226, a zeta potential of 17.0 ± 0.6 mV, as well as an entrapment efficiency of 99.86 ± 0.08%, and SV loading of 14.99 ± 0.01%. The performance of SV-Ch-NLC films was assessed in terms of release, permeation, and adhesion, as critical quality attributes. Cutaneous tolerability and in vitro cytotoxicity studies were performed to warrant film safety and drug effectiveness, respectively. The topical films provided a sustained release kinetic profile of SV and were classified as nonirritant systems. The encapsulation of SV increased cytotoxicity in melanoma cells. The key role of squalene as nanostructuring agent of the lipid nanoparticle matrix and as permeation enhancer was highlighted, suggesting its key action for potentiating skin permeation and uptake into melanoma cells. Topical SV-Ch-NLC films are thus able to provide an in situ extended drug delivery and useful as coadjuvant treatment of melanoma skin lesions.     

黏膜给药新方法研究

目的：探索黏膜给药新方法——电致孔透黏膜给药。方法：用电致孔给药仪透直肠黏膜给药．与被动扩散给药相比较,通过双室扩散池法、HPLC法检测药物中指标成分栀子苷透过量的变化,摸索适宜的电学参数条件。结果：电致孔条件下栀子苷的累积透过量明显高于被动扩散栀子苷的累积透过量,且栀子苷的累积透过量在电学参数波形为方波、脉冲次数为360个时,透过量增大显著。结论：电致孔透黏膜给药方法可行,优化的电致孔条件应用于中药有效成分透直肠黏膜给药有良好的前景。     

In-vitro nasal drug delivery studies: comparison of derivatised, fibrillar and polymerised collagen matrix-based human nasal primary culture systems for nasal drug delivery studies.

The aim of this study was to establish a collagen matrix-based nasal primary culture system for drug delivery studies. Nasal epithelial cells were cultured on derivatised (Cellagen membrane CD-24), polymerised (Vitrogen gel) and fibrillar (Vitrogen film) collagen substrata. Cell morphology was assessed by microscopy. The cells were further characterised by measurement of ciliary beat frequency (CBF), transepithelial resistance (TER), permeation of sodium fluorescein, mitochondrial dehydrogenase (MDH) activity and lactate dehydrogenase (LDH) release upon cell exposure to sodium tauro-24, 25 dihydrofusidate (STDHF). Among the three collagen substrata investigated, the best epithelial differentiated phenotype (monolayer with columnar/cuboidal morphology) occurred in cells grown on Cellagen membrane CD-24 between day 4 and day 11. Cell culture reproducibility was better with Cellagen membrane CD-24 (90%) in comparison with Vitrogen gel (70%) and Vitrogen film (< 10%). TER was higher in cells grown on Vitrogen gel than on Cellagen membrane CD-24 and Vitrogen film. The apparent permeability coefficient (Papp x 10(-7)cm s(-1)) of sodium fluorescein in these conditions was 0.45+/-0.08 (Vitrogen gel) and 1.91+/-0.00 (Cellagen membrane CD-24). Except for LDH release, CBF and cell viability were comparable for all the substrata. Based on MDH activity, LDH release, CBF, TER and permeation studies, Cellagen membrane CD-24- and Vitrogen gel-based cells were concluded to be functionally suitable for in-vitro nasal drug studies. Vitrogen film-based cultures may be limited to metabolism and cilio-toxicity studies.     

电子自旋共振技术研究吸收促进剂及剂型因素对紫杉醇大鼠小肠黏膜渗透的影响

小肠是大多数药物口服吸收的主要部位,小肠黏膜为类脂质双层结构的生物膜,药物的极性及药物制剂中类脂质成分可以直接影响其吸收。紫杉醇属大环三萜类抗肿瘤药物,其独特的抗肿瘤机制使它成为具有显著疗效的抗肿瘤药物[1,2]。由于强疏水性,紫杉醇口服后几乎不被吸收。目前市售的     

Development of transdermal system containing nicotine by using sustained release dosage design

This study was carried out to develop a membrane-controlled transdermal formulation (TF) of nicotine by using sustained release dosage design (SRDD). TFs were prepared with polyethylene membrane as a rate-controlling barrier; a carbomer was used as the gel reservoir with or without propylene glycol (PG). The in vitro target flux (0.0535 mg cm(-2) h(-1)) was calculated according to SRDD calculations. Nicotine permeation through the membrane with or without transfer adhesive was also studied using diffusion cells. Nicotine permeated through membrane (without adhesive) with a flux of 0.0555 mg cm(-2) h(-1) and this value was similar to that of the in vitro target flux. The release from the TFs and from a commercial product (Nicotinell, 52.5 mg 30 cm(-2)) was studied using the FDA paddle method. The nicotine amount was increased from 22.7 to 56.5 mg in gel reservoir, and a plateau was reached beyond 45.4 mg of drug; the system attained the maximum thermodynamic activity with 56.5 mg of nicotine. The release rate from TFs (without adhesive layer) containing PG in the reservoir was very similar to the target release rate (1.07 mg h(-1)). The fluxes of nicotine from Nicotinell and TF containing 45.4 mg of nicotine were close to the in vitro target release rate.     

Development and characterization of mucoadhesive microspheres bearing salbutamol for nasal delivery

Mucoadhesive drug delivery systems are those that provide intimate contact of the drug with the mucosa for an extended period of time. In our present work, mucoadhesive chitosan microspheres were prepared by emulsion solvent method. Formulations were characterized for various physicochemical attributes, shape, surface morphology, size, and size distribution, drug payload, swelling ability, and mucoadhesion. The effect of drug, citric acid, and permeation enhancer concentration on the physicochemical properties was studied. Crosslinked chitosan microspheres showed very good mucoadhesion, which was decreased on increasing the drug concentration and citric acid concentration, and slightly improved upon incorporation of permeation enhancer. The in vitro drug release and in vitro drug permeability through mucous membrane were performed, and slow release/permeation was noted with chitosan citrate complexed microspheres compared with noncomplexed chitosan microspheres. The in vivo performance of mucoadhesive microspheres formulations showed prolonged and controlled release of salbutamol as compared with oral administration of conventional dosage form.     

Controlled indomethacin release from mucoadhesive film: in vitro and clinical evaluations

To develop a film formulation allowing controlled release for long-term analgesia, we selected ethyl cellulose (EC) as a novel additive, prepared a film formulation using indomethacin (IM film), and evaluated it in vitro and clinically. In the in vitro experiments, the effects of the EC concentration on the release rate of IM and on the adhesion force to the mucous membrane were investigated. The addition of 10% EC resulted in more sustained slow release compared with no EC, and the adhesion of the film with 10% EC added was similar to that of films containing carboxyvinyl polymer, which we reported previously showed significantly increased adhesion. A two-layered film consisting of an adhesive layer with 2% or 1% IM and 10% EC and a nonadhesive layer with 2% polyethylene glycol as a softening agent, was investigated for clinical use. Film consisting of an adhesive layer with 2% IM and 10% EC exhibited rapid onset of potent analgesia and was expected to prolong the duration of analgesia. These results suggest that IM film with EC added may be useful clinically, since it shows both immediate analgesic effects and prolonged duration of release.