温控型胰岛素液体肛门栓药剂学研究

目的 温控型胰岛素液体肛门栓药剂学性质的研究。 方法 采用正交试验法,以形成凝胶时间、胶凝强度、生物黏附力、黏度、胶凝温度作为评价指标,对处方中的泊洛沙姆407和泊洛沙姆188的比例、壳聚糖质量分数和pH值3个因素进行考察,确定最优处方工艺;测定最优处方液体栓剂的胶凝强度、生物黏附力、黏度、胶凝温度。 结果 泊洛沙姆407:泊洛沙姆188(15:25),壳聚糖质量分数0.4%,pH值为5±0.2。 结论 经验证结果良好,液体栓剂强度及生物黏附力良好。     

盐酸文拉法辛温敏型原位凝胶的研制

目的确定盐酸文拉法辛温敏型原位凝胶的基质处方。方法以不同质量浓度泊洛沙姆作为温敏材料,用卡波姆、聚乙烯吡咯烷酮、羟丙基甲基纤维素作黏膜黏附剂,考察凝胶的相变温度和黏附力,优选基质处方。结果确定180g·L-1泊洛沙姆407和3.0g·L-1聚乙烯吡咯烷酮组合作为盐酸文拉法辛温敏型原位凝胶的处方基质,其胶凝温度为31.7℃,黏附力98.1g·cm-2。结论选定的基质处方可用于制备盐酸文拉法辛温敏型原位凝胶。     

N-三甲基壳聚糖(TMC60)对液体栓基质的体外性质影响研究

目的：考察季胺化程度为60％的N-三甲基壳聚糖（TMC60）对以泊洛沙姆为基质的液体栓剂的物理化学性质的影响，为两者的配伍使用提供试验依据。方法：将5种不同浓度的TMC60（0％，0．2％，0．4‰，0．6‰，0．8％）合并泊洛沙姆溶液（P407：P188=15％：19％）作为液体栓剂的基质，测定不同浓度TMC60对液体栓剂基质的胶凝温度、胶凝强度和生物粘附力的影响。结果：当TMC60的浓度从0％上升至0．8％时，基质的胶凝温度（℃）依次为27．2，28．2，28．8，29．6，30．8；胶凝强度（s）依次为10，30，66，97，146；生物粘附力值（×10^2dyne／cm^2）依次为35．0，46．5，50．2，60．2，82．6。表明随着TMC60浓度增高，泊洛沙姆液体栓剂基质的胶凝温度、胶凝强度和生物粘附力均逐渐升高（P〈0．05）。结论：TMC60可改善以泊洛沙姆为基质的液体栓剂的体外物化性质，值得进一步研究。     

替硝唑温敏性阴道用原位凝胶的制备及其质量控制

目的：制备替硝唑温敏性阴道用原位凝胶,并对其体外性质进行考察,为其体内研究奠定基础。方法：以泊洛沙姆P407与P188为基质,用冷法制备替硝唑原位凝胶。对其胶凝温度、胶凝强度及生物黏附性等主要物理性质进行考察,并对其质量进行控制。结果：本品具有合适的胶凝温度,胶凝强度理想,生物黏附性较强,适合阴道给药。主要质量评价指标简单易行。符合相关规定。结论：替硝唑温敏性阴道用原位凝胶制备简单,性质理想,值得进一步研发。     

喷昔洛韦眼用温度敏感原位凝胶的制备及质量控制

目的 制备喷昔洛韦(penciclovir,PCV)温度敏感原位凝胶,对其进行了处方优化筛选,并建立其质量控制方法.方法 考察含有不同泊洛沙姆407(Pluronic F127)和泊洛沙姆188(Pluronic F68)浓度配比的处方对原位凝胶胶凝温度、流变学性质、质构特性和体外药物释放行为等的影响,从而设计和优化处方.结果 得到最佳凝胶基质组成为19%F127/0.3%F68,其胶凝温度33.7℃;达到34℃时粘度和胶凝强度明显增大;PCV自凝胶中的释放具有一定的缓释效果.结论 喷昔洛韦眼用温度敏感原位凝胶有望开发成为一种新型眼部给药制剂.     

一种治疗牙周疾病的温控凝胶剂的制备

目的：采用泊洛沙姆作为基质,制备一种治疗牙周疾病的温控凝胶剂。方法：调整泊洛沙姆407和188的比例,使凝胶剂在36℃开始胶凝。结果：本凝胶剂中,泊洛沙姆407质量分数为22%,泊洛沙姆188质量分数为12%时,凝胶剂的胶凝温度为36℃。结论：本方法制备温控凝胶剂简单可靠,可行性大。     

甲硝唑阴道用原位凝胶的处方设计及体外质量评价

目的:研制甲硝唑阴道用原位凝胶,并考察其体外质量.方法:以卡波姆及泊洛沙姆为混合凝胶基质,筛选其最佳配比,制备甲硝唑阴道用原位凝胶.对其体外流变性、黏附性进行考察,并与上市甲硝唑阴道用凝胶做对照,考察其阴道滞留性.结果:原位凝胶的最佳基质配比为泊洛沙姆407的质量分数为17.5%,卡波姆971P的质量分数为1.5%.黏附力测定结果表明其具有较大的温度敏感性.与上市产品相比,原位凝胶可显著增加阴道滞留性.结论:该原位凝胶具有显著的温度敏感性,本品值得进一步研发.     

泊洛沙姆407水溶液的流变学性质

本文对泊洛沙姆407(商品名为普朗尼克F127)进行了流变学性质的考察。通过剪切速率触变性实验、温度敏感性实验和多次升温后表观黏度复原性实验得到了泊洛沙姆407各项流变学参数。结果表明,随着泊洛沙姆407水溶液浓度的提高,其由牛顿流体转变为假塑性流体,触变性和胶凝温度均逐渐降低(15.25%泊洛沙姆407可在体温下形成凝胶)。本文为泊洛沙姆407作为凝胶剂基质的应用提供了可参考的流变学数据。     

异烟肼原位凝胶的研制及质量控制

目的：制备异烟肼原位凝胶,并建立其质量控制方法。方法：采用搅拌子法测定胶凝温度并用黏度计测定黏度。建立异烟肼原位凝胶的质量控制方法。结果：以泊洛沙姆407和卡波姆940为混合基质制备异烟肼原位凝胶,得到优化处方：浓度为20％的泊洛沙姆407,0．2％的卡波姆940,1．0％的异烟肼溶液30ml,内合1ml甘油（保湿剂）。搅拌子法测得胶凝温度为29℃。结论：制备的异烟肼原位凝胶处方合理,质量稳定,且具有温度敏感型反相凝胶的性质,在体温条件下可以发生相变成为凝胶,可用于结核患者病灶内注射给药,以期达到靶向及缓释给药目的。     

复方甲硫酸新斯的明眼用原位凝胶的处方工艺研究

目的 筛选用于治疗近视的复方甲硫酸新斯的明眼用原位凝胶处方。方法 温度敏感型凝胶以泊洛沙姆P407和泊洛沙姆P188为基质;离子敏感型凝胶以去乙酰结冷胶为基质;pH敏感型凝胶以卡波姆P934、卡波姆P940和羟丙基甲基纤维素为基质,以胶凝的黏度与成分的相溶性为考察指标,筛选最佳基质处方。采用美国药典溶出度测定法第三法的改良法,作缓释制剂的释放度考察。结果 以温度敏感型的泊洛沙姆P407 24%和P188 10%合用的基质制备复方甲硫酸新斯的明眼用原位凝胶最为适合。结论 本法制备眼用原位凝胶的工艺可行,并具有较好的缓释效果。     

The effects of vitamin A on cells of innate immunity in vitro

Retinoid treatment is suggested to promote development of inflammatory bowel disease, although preclinical studies are not supportive. We evaluated the effect of retinoids on cytokine response in in vitro-differentiated human dendritic cells (ivDCs) and macrophages (ivMACs) derived from healthy human donors and in cultured human THP-1 cells. Effect on human intestinal epithelial cell integrity was also assessed. Each cell type was incubated (±lipopolysaccharide [LPS]) with all-trans retinoic acid (ATRA), 13-cis-RA (isotretinoin) and 4-oxo-13-cis-RA. Cytokine analysis was performed by array analysis. Cultured human endothelial colorectal adenocarcinoma (Caco-2) cells were incubated with these retinoids and media analyzed for leakage by spectrofluorometric analysis. ATRA consistently and significantly inhibited LPS-induced release of the pro-inflammatory cytokines tumor necrosis factor, interleukin (IL)-6, macrophage inflammatory protein (MIP)-1α and MIP-1β. All retinoids tested stimulated release of the anti-inflammatory cytokines granulocyte–macrophage colony-stimulating factor and IL-10, and also monocyte chemotactic protein-1, vascular endothelial growth factor and eotaxin-1. Incubation with retinoids did not significantly alter the permeability of Caco-2 monolayers. Pre-treatment of each cell type with retinoids promoted an anti-inflammatory cytokine profile with only minimal effect on intestinal epithelial cell permeability; consistent with in vivo studies.     

盐酸氨溴索缓释片体内外相关性研究

目的考察盐酸氨溴索缓释片体外释放度与体内吸收的相关性。方法应用释放度测定法研究盐酸氨溴索缓释片体外释药行为 ,采用HPLC法测定盐酸氨溴索缓释制剂在家犬体内的血药浓度 ,按照Wagner Nelson公式计算药物的吸收分数。 结果 3种自制盐酸氨溴索缓释片与参比制剂生物等效 ,以药物累积吸收百分数 f(t)与相应时刻的体外累积释放百分数F(t)建立的一元线性回归方程 ,参比制剂与 3种自制制剂的体内外相关系数分别为 0 969、0 979、0 970和 0 983。结论盐酸氨溴索缓释片的体外释放度与体内吸收具有显著的相关性。     

In Vitro-In Vivo Relationship of Oral Extended-Release Dosage Forms

Purpose. A method to establish the in vitro-in vivo relationship of oral extended-release products is proposed. Methods. The approach utilizes incremental amounts of drug released and absorbed within defined time intervals, to construct a ² distributed variable for testing in vitro-in vivo similarity. Results. A case study is used to demonstrate that the similarities between incremental values of in vivo absorbed and in vitro dissolved fractions are distinguishable for different dissolution profiles despite naturally significant linear correlations between cumulative in vivo absorbed and in vitro dissolved fractions (with different dissolution tests) of an oral extended-release product. Conclusions. The method enables investigators to compare different in vitro dissolution profiles of an oral extended-release product to find an optimized dissolution profile to be the surrogate of the in vivo release process of the product.     

黄芩苷化合物现代常用测定方法的分析比较

黄芩的主要有效成分黄芩苷具有抗菌消炎、解热镇痛、抗病毒、抗肿瘤、降压及利尿等作用。黄芩苷是许多复方中药制剂的主要成分,而中药成分复杂,对分析技术也有特定的要求。本文对黄芩苷测定技术分光光度法、色谱法、红外光谱分析法等进行了综述。     

Venoconstrictor responses to ergosine and ergosinine: Evidence for the isomerization of ergosinine

Ergosine and its D-isolysergic acid derivative ergosinine were investigated on canine saphenous veins both in vivo and in vitro. Following local i.v. infusion in vivo, about 5 times higher doses of ergosinine were necessary to produce the same venoconstrictor response as induced by ergosine. When administered orally, however, both ergot alkaloids were equi-effective. In vitro methiothepin, a 5-HT receptor blocker with high affinity for 5-HT₁ receptors, antagonized venoconstrictor responses to 5-HT and ergosine within the same concentration range, being significantly less potent when tested against norepinephrine. The reverse was true for the α₂-selective adrenoceptor blocker yohimbine, which was significantly more potent against norepinephrine and ergosine than against 5-HT, suggesting that ergosine has affinity to both 5-HT₁-like receptors and α₂-adrenoceptors. Concentration-response curves to norepinephrine were shifted to the right in a parallel fashion when ergosine or ergosinine were present in the organ baths, suggesting competitive antagonism. The blocking potency of ergosinine increased with increasing incubation times in Krebs-Henseleit solution becoming similar to that of ergosine when an incubation time of 2 hr was applied. It is suggested that the pharmacological activity of ergosinine is the consequence of an isomerization into its natural stereoisomer ergosine, which may occur both in vivo and in vitro.     

氟罗沙星的体内外试验相关性研究

本文研究了新型喹诺酮类药物氟罗沙星体外溶出与体内吸收之间的相关性。实验表明，本品口服吸收在血清中达峰时间较快，作用持久，消除半衰期为９．６０ｈｒ。在人工胃液中溶出速率较快，在血清达峰之前，体内吸收与体外溶出量之间呈现良好的相关性。     

The action of small doses of lead on erythrocyte D-aminolevulinic acid dehydratase in the mouse

After a single intraperitoneal administration of lead in very small doses [1–100 g Pbac/kg body weight (bw)], there was a dose-dependent, highly significant inhibition of erythrocyte D-aminolevulinic acid dehydratase (D-ALA-D) activity in mice. The maximal inhibition occurred between 3 and 24 h post injection (p.i.). After that, a rapid recovery of the D-ALA-D activity took place so that four days after lead administration, enzyme activity exceeded even the normal value. Only after eight days p.i. did the D-ALA-D value return to the initial level after a biphasic course.After 10 i.p. injections of 0.1 to 10 g Pbac/kg bw, there was again a dose-dependent, highly significant inhibition of the erythrocyte D-ALA-D activity in mice. The maximal inhibition was shown to be 24 h after the last lead injection. In contrast to the single i.p. administration, however, we found a monophasic course for the return of D-ALA-D activity. The D-ALA-D values did not exceed the normal range at any time after 10 i.p. lead injections. Ten and 30 days oral administration of lead corresponding to i.p. doses exhibited similar results in D-ALA-D inhibition.     

制剂体内外相关性研究进展

综述体内外相关性（IVIVC）研究模型的建立、实验方法与步骤以及发展策略的最新研究进展.并指出目前IVIVC研究的局限性和体外实验的新方法.IVIVC研究中不存在通用的体外模型,因此IVIVC研究只能进行逐例建模.综合药物理化性质、生物药剂学特征、剂型设计和它们与消化道的相互作用对IVIVC研究十分重要.     

双嘧达莫胃内漂浮片的研制

双嘧达莫 ( dipyridamole,1 )可抑制血小板聚集 ,有抗血栓形成作用 ,临床上多用于血栓栓塞性疾病 ,也可用于缺血性心脏病。 1生物半衰期短 ,血浆t1/ 2 仅为 2～ 3h,每天需用药 3～ 4次 [1,2 ] ,加上此类患者一般需长期服药 ,故宜制成缓释制剂。考虑到 1主要在胃内吸收 ,若将其制成胃内漂浮片 ,延长其在胃内的停留时间 ,可达到使血药浓度波动性减小、降低毒副作用以及便于患者使用的目的。1　试药与仪器聚丙烯酸树脂 (批号 2 0 0 110 6 2 8- 2 )、聚丙烯酸树脂 (批号 2 0 0 0 32 71)均由连云港云升实业公司提供 ;羟丙甲纤维素 (HPMC,湖州…