硫酸氢氯吡格雷亚微乳注射液的制备及其性质考察

目的:制备硫酸氢氯吡格雷亚微乳注射液,并对其性质进行考察。方法:以注射用大豆油和注射用中链脂肪酸三酰甘油为混合油相,以蛋黄卵磷脂、泊洛沙姆188和聚山梨酯-80为复合乳化剂,采用高压均质法制备硫酸氢氯吡格雷亚微乳注射液,通过粒度和粒度分布、Zeta电位、pH值、渗透压和含量测定以及稳定性考察等对其性质进行研究。结果:制备的乳剂外观为乳白色,略带蓝色乳光。3批样品的粒径分别为(158±22)、(160±22)和(161±33)nm,平均Zeta电位为(-37.70±0.79)mV,平均pH值为(7.51±0.03),平均渗透压为(279.33±0.58)mmol.kg-1,平均含量为(99.19±1.68)%,在(6±2)和(25±2)℃条件下放置6个月稳定。结论:制备工艺可行,制剂理化性质稳定,符合静脉注射要求。     

新型阿霉素热敏脂质体的研制

目的:探讨以二棕榈酰磷脂酰胆碱(DPPC)和单棕榈酰磷脂酰胆碱(MPPC)为原料制备的温度敏感阿霉素脂质体的制备工艺和理化性质.方法:采用膜过滤挤压法和pH梯度法制备阿霉素脂质体,以紫外分光光度法检测样本中阿霉素含量,计算阿霉素热敏脂质体在不同温度下的药物释放特性,并对其包裹率、粒径,pH值进行研究.结果:阿霉素热敏脂质体在39℃下迅速释放,前20 s内释放药物50%,42℃下药物释放达到60%以上.包封率99.5%,平均粒径90.8 nm,pH值为6.5.结论:制备的热敏感阿霉素脂质体优于常规脂质体,具有良好的温度控释特性.     

罗格列酮氧钒配合物的合成及表征

目的:合成罗格列酮氧钒配合物并进行表征。方法:取罗格列酮与五水硫酸氧钒(VOSO4·5H2O)在适当的条件下(溶剂为乙醇,反应pH值为6)合成罗格列酮氧钒配合物,运用核磁共振氢谱和红外光谱等分析方法对配合物的结构进行了初步确证。结果与结论:确证形成了新的化合物即罗格列酮氧钒配合物,配合物中罗格列酮的化学结构未发生变化,其中2个氧钒均与1个罗格列酮和3个水分子结合。     

β-榄香烯微乳的制备及理化性质考察

目的制备β-榄香烯微乳,并对微乳理化性质进行考察。方法通过在25℃下绘制伪三元相图选择合适的微乳液组分制备β-榄香烯微乳,考察不同油相、表面活性剂、助表面活性剂、水相pH、离子强度、添加剂以及温度对微乳区域的影响;采用离心法及染色法鉴别所制备的微乳。结果制备了Labrafac cc-磷脂-HS15-1,2-丙二醇-水的β-榄香烯微乳,所制备微乳为O/W型微乳;理化性质为:pH值为7.32±0.01、渗透压为(279±3)mOsm.kg-1、黏度为(5.56±0.11)×10-3Pa.s、电导率为(1.14×10-2±7.9×10-5)s.m-1、折光率为(1.458±0.004)、zeta电位为(-2.64±0.06)mV、平均粒径为(38.3±4.3)nm。结论所制备的β-榄香烯微乳粒径小,分布均匀,理化指标稳定。     

百合多糖铁(Ⅲ)配合物的制备及一般性质研究

目的百合多糖铁配合物(LPC)的制备及其性质的研究。方法热水浸泡法提取百合多糖;在碱性条件下,百合多糖水溶液与三氯化铁反应制备LPC。结果LPC为深棕红色无定型粉末,含铁量为20.1%,易溶于水,在pH3~12较稳定。结论LPC铁有望开发成为口服补铁剂。     

pH敏感的肿瘤靶向聚合物胶束的体外性质

目的 制备肿瘤微环境敏感、具有肿瘤细胞靶向能力和穿膜能力的融合肽FQSIYPpIKRRRRRRRRHHHHC (FRH)修饰的聚合物胶束,并对其体外性质进行初步考察.方法 采用FRH修饰N-(2-羟丙基)-甲基丙烯酰胺(HPMA)聚合物-β-谷甾醇(β-SITO),形成HPMA聚合物胶束(FRH-M),考察其理化性质、肿瘤细胞的摄取和抑制肿瘤细胞生长的效果.结果 透射电镜显示:胶束为均匀的类球形.FRH-M胶束粒径约为55 nm,阿霉素载药量8.3％.该胶束在pH7.4条件下,Zeta电位为-3.01±0.05 mV,在pH6.4条件下,电荷翻转为5.27-0.32 mV.FRH-M的药物释放速度随释放介质的pH降低而加快.FRH-M的细胞摄取较未经修饰胶束的P-M提升了1.9倍;且在pH6.4条件下的细胞摄取明显高于pH7.4的,FRH-M的IC50值为1.40 ±0.41 μg·mL-1,明显低于未经配体修饰的胶束(5.08±0.33 μg· mL-1).结论 经FRH多肽修饰的聚合物胶束具有良好的肿瘤微环境响应能力,且有更好的细胞摄取能力和体外抗肿瘤活性,极具发展前景.     

姜黄素脂质体的制备及理化性质考察

目的:制备姜黄素脂质体,并进行理化性质初步研究。方法:选用薄膜法制备姜黄素脂质体,以单因素考察优选最佳制备工艺;观察脂质体粒径和形态特征,同时考察其贮存条件。结果:确定最佳工艺卵磷脂和胆固醇的比例为3∶1,磷酸缓冲盐溶液的pH值为6.6,离子浓度为0.01moL.L-1。姜黄素脂质体外观呈完整圆球形或椭圆形的球粒,粒径主要分布于140~425nm,表面电性为负,pH为(6.58±0.2),包封率为69.79%,最佳的贮存条件为3~5℃冷藏保存。结论:薄膜法制备姜黄素脂质体方法可行,其理化性质基本稳定,为进一步研究姜黄素在肿瘤治疗中的应用提供了理论基础。     

羧甲基壳聚糖金属配合物的研制

应用水溶性的羟甲基壳聚糖与Ca^2 、Fe^2 、Zn^2 进行络合制备金属配合物,探讨反应时间、温度、羧甲基取代度、溶液离子强度、pH等反应条件对络合的影响,考察金属配合物的性质。结果表明：络合反应的最佳pH值为5－7;室温下反应10min络合量趋于饱和;羧甲基壳聚糖对各金属离子络合能力随羧甲基取代度的增大而增强,随着体系的离子强度增大而减弱。     

裸体方格星虫甲醇提取物的化学成分研究

目的 对裸体方格星虫(Sipunculus nudus Linnaeus)甲醇提取物的化学成分进行分离鉴定.方法采用溶剂萃取,硅胶柱色谱及半制备HPLC等分离手段对其甲醇提取物的化合物进行分离,通过理化性质及波谱学手段对所得化合物进行化学结构鉴定.结果与结论分离并鉴定了4个化舍物:胆甾醇(1)、硬脂酸(2)、环(丙氨酸-脯氨酸)(3)、脱氧胸苷(4).这4个化合物均为首次从裸体方格星虫中分离得到.     

藻酸双酯钠缓释片的制备及体外释放特性研究

目的　制备藻酸双酯钠(PSS)的缓释片;建立PSS缓释片体外药物释放度的测定方法,并对其体外释放特性进行考察。方法　以羟丙基甲基纤维素(HPMC)、羧甲基纤维素钠(CMC-Na)和十八醇为骨架材料,采用熔融制粒法制备PSS缓释片,并采用正交设计优化PSS缓释片的处方;采用高效液相色谱法测定PSS缓释片的体外释放度。结果　建立了测定PSS缓释片药物释放度的柱前衍生高效液相色谱法,在0.3~12 mg/mL浓度范围内与峰面积呈现良好的线性关系(R₂=0.9983),各辅料不影响PSS的含量测定。在低,中,高三个浓度下的加样回收率分别为103.6%,93.3%,104.8%,平均RSD为2.1%(n=6),精密度RSD为1.4%(n=5),重复性RSD为3.4%(n=5),24 h内稳定性良好,RSD为1.92%。采用正交设计确定了制备PSS缓释片的最优处方为：HPMC、CMC-Na和十八醇的用量分别为片重的15%,10%和10%,在最适条件下制备的PSS缓释片在2 h、6 h、12 h内可分别释放药物30.3%,70.9%和95.5%,体外药物释放行为符合一级模型,ln(1-Q)=-0.2756t 4.8141,r=0.9888。 结论　建立的柱前衍生高效液相色谱法具有专属性强,精密度和重现性好的特点,可用于PSS缓释片体外释放度的测定。采用熔融制粒法制备的PSS缓释片体外释放特性良好。     

羟喜树碱磷脂复合物理化性质的研究

目的研究羟喜树碱磷脂复合物的理化性质。方法用溶剂法制备羟喜树碱磷脂复合物,测定其在水中的溶解度和分散性,以差示扫描量热法研究其热力学性质,以X-射线衍射法研究羟喜树碱在磷脂中的存在状态。结果复合物中羟喜树碱在水中的溶解度显著增大,水中很容易分散形成纳米粒。DSC图谱表明复合物是不同于羟喜树碱、磷脂以及二者物理混合物的新物相。X-射线衍射表明在复合物中羟喜树碱与磷脂作用以无定形形态存在。结论羟喜树碱与磷脂形成复合物后,其理化性质发生明显变化。     

Physico-chemical characterisation and intrinsic dissolution studies of a new hydrate form of diclofenac sodium: comparison with anhydrous form

Diclofenac sodium is a non-steroidal anti-inflammatory drug widely used in painful and inflammatory diseases. In standard conditions, by exposure to relative humidity even below 60% at 25 °C, the anhydrous form DS gives rise to a hydrate species DSH, a tetrahydrate form different from that obtained by crystallisation from water and previously described. The method of preparation and the physico-chemical properties of the hydrate form were investigated. Data from FTIR spectroscopy, X-ray powder diffraction and thermal analysis were used for the identification and the characterisation of DSH. DS and DSH were easily differentiated by their IR spectra, X-ray patterns and thermal behaviour. DSH stability was followed at room temperature over a period of 1 year and under different conditions of temperature to verify the tendency to solid–solid transition and to study its existence range. Solubility and intrinsic dissolution studies were performed to compare the physico-chemical properties of DS and DSH. Differences in solubility and intrinsic dissolution rates were pointed out: these studies showed that DS dissolved faster than DSH. Storage under uncontrolled environmental conditions or contact with water vapour during manufacturing process could thus influence the performance of the final dosage form.     

槲皮素磷脂复合物理化性质的研究

目的研究槲皮素磷脂复合物的理化性质。方法用溶剂法制备槲皮素磷脂复合物,测定其在水与氯仿中的溶解度,以红外光谱扫描研究两者分子可能的结合基团,以X-射线衍射研究槲皮素在磷脂中的存在状态。结果与槲皮素及相应的混合物相比,复合物中的槲皮素在水与氯仿中溶解度均显著增大。红外光谱显示槲皮素分子中的羟基可能与磷脂分子中的磷氧基团相作用形成复合物,X-射线衍射表明在复合物中槲皮素由于磷脂的作用以无定形态存在。结论槲皮素与磷脂形成复合物后,其理化性质发生明显变化,可增大槲皮素的口服吸收。     

运用生物信息学技术分析预测抗氨基末端脂多糖结合蛋白(NH-LBP)单链抗体的结构

应用生物信息学技术预测人工构建的人源化抗氨基末端脂多糖结合蛋白（NH-LBP）单链抗体（scFv）的结构及其生物学活性。利用在线生物信息学工具分析抗NH-LBP的scFv的理化特性及该抗体的二、三级结构。预测结果表明抗NH-LBP的scFv属于较稳定蛋自质，体内半衰期较长；该抗体与数据库中收录的单链抗体的二级结构十分相似；该抗体的三维空间结构为一种球形的蛋白质。通过在线生物信息学工具获得了抗NH-LBP scFv的一、二、三级结构及理论功能，为进一步研究该抗体的体内外生物学活性提供了理论依据。     

非晶形醋酸麦迪霉素的制备及其理化性质

以乙基纤维素为稳定剂，三氯甲烷为溶媒，用喷雾干燥法制备较稳定的非晶形醋酸麦迪霉素。探讨了喷雾条件对非晶形转化的影响，同时，进行了其晶形与非晶形理化特性的比较。     

Solution equilibria of deferoxamine amides

The physico-chemical solution properties of deferoxamine were modified by acylating the terminal amino group with short-chain aliphatic, succinic, and methylsulphonic moieties. The analog iron(III)-binding constants and stabilities under physiological conditions were determined to confirm that the iron binding ability of the parent molecule was retained following modification. The proton dissociation constants of the lipophilic deferoxamine analogs were determined by potentiometric titration and nonlinear least-squares analysis. However, because the iron(III) binding complex is fully formed below pH 2, the metal-ligand equilibria could not be studied using potentiometric methods. The iron binding constants of the deferoxamine analogs were determined by spectrophotometrically following the proton-dependent exchange of iron with EDTA in the pH range of 4.0 to 6.5 and solving mass balance equations. The proton-dissociation constants and the iron binding constants of the lipophilic deferoxamine analogs were comparable to those of deferoxamine. However, at physiological conditions, the iron-binding complex of the most lipophilic butylamide derivative was slightly less stable and the succinamide derivative complex was slightly more stable. Like deferoxamine, the hydroxamate groups of the analogs were unhindered and free to form a 1:1 coordination complex with iron(III). Consequently, changes in aqueous solvation, conformation, and steric interference, imparted by the modifications at the terminal amino group of deferoxamine, may have affected the stabilities of the iron(III) complex and the efficiency of iron binding.     

Chiral 1,4-benzodiazepine. VII. Cyclization rates of 2-(n-alpha-ammoniumacyl)-amino-5-chloro-benzophenones in the chiral 1,4-benzodiazepin-2-ones.

Cyclisation rates of some S-alpha-amino acid derivatives (I--VII) into chiral 1,4-benzodiazepin-2-ones were determined under physiological-like conditions (pH, temperature) and plotted against pKa values of the corresponding alpha-amino acids. No correlation between k, i.e. t1/2 values, of the acidic precursors, and pharmacodynamic activity, as determined by some standard tests, were observed, however. Unambiguity of cyclisation, and its t1/2 values reveal benefit for physico-chemical properties of the investigated acyclic precursors as transport-forms of the chiral 1,4-benzodiazepin-2-ones with prolonged pharmacological activity.     

美洛昔康脂质体凝胶剂的研制与质量评价

目的 制备含有美洛昔康的脂质体凝胶,并进行质量初步评价.方法用正交设计优选该脂质体的处方及制备工艺,并用扫描电镜观测其外观、大小及分布,用微型凝胶柱测定其包封率,并进一步制备成凝胶,初步考察该制剂的稳定性.结果所得脂质体外观圆整,分布较均匀,平均包封率(67.8±1.2)%(n=3),所得凝胶剂为半透明黏稠状胶体,稳定性良好.结论 该脂质体凝胶制备工艺可行,具有开发价值.     

Comparison of the polymorphic modifications of famotidine

The polymorphic modifications of famotidine are described and characterized by their spectroscopic (infrared, X-ray) and some physico-chemical data. In addition to the standard physico-chemical data (melting point, solubility, bulk density) some further properties influencing its use in pharmaceutical technology are also characterized. The methods used to prepare the morphologically homogeneous modifications are also given.     

Racemization of L-lysine for pharmaceutical synthesis and its chiral separation by GC-MS spectroscopy

In order to improve physico-chemical properties and to enhance stability of drugs, amino acid salt has been widely adopted in pharmaceutical synthesis. Acetylsalicylic acid lysinate is one of the widely used analgesics and it is a good example of this synthesis. In the case of acetylsalicylic acid lysinate synthesis, racemization of naturally occurred lysine is essential because the racemic lysine salt of the drug shows better yield, crystallinity and dryness than that of the L-lysine salt. To establish a simple, practical and economical process for L-lysine racemization, L-lysine treatments with phosphoric acid and with acetic acid were compared and the optimum conditions for its process and derivatization were investigated by chiral separation methods using GC-MS spectroscopy.