注射用尿素的制备工艺研究

目的:优选注射用尿素的最佳制备工艺。方法:以尿素结晶纯度为指标,以乙醇浓度、乙醇与尿素的处方配比、除母液方法、结晶干燥方法为考察因素,采用正交试验优选制备工艺,并进行验证试验。结果:优选出的制备工艺为乙醇浓度75%,乙醇与尿素的处方配比1∶1,离心机甩干除母液,结晶采用真空干燥法;所制3批尿素结晶纯度平均为99.94%。结论:优选的制备工艺可行、重现性好,尿素结晶纯度稳定且较高。     

tianagliflozin与L-脯氨酸的共结晶研究

目的 研究新型钠–葡萄糖协同转运蛋白2抑制剂tianagliflozin与L-脯氨酸的共结晶,制备一种稳定的可供药用的共结晶。方法 在乙醇中共结晶制备tianagliflozin与L-脯氨酸的共结晶,并采用核磁共振氢谱、粉末X衍射、热重/差热分析及红外光谱测定共结晶物的特征。初步考察了共结晶对光、温度和湿度的稳定性。结果 制备了tianagliflozin与L-脯氨酸稳定的1∶1共结晶,初步稳定性考察表明该共结晶对光照、高温和低中湿稳定,高湿条件下发生分解。结论 tianagliflozin与L-脯氨酸的共结晶在稳定性和制备重现性方面较好,为其成药性研究提供了参考。     

利福布丁的晶型Ⅰ及其制备方法

目的 制备一种具有结晶形态的利福布丁.方法 以无定形利福布丁为原料,采用正己烷或者正己烷与羧酸酯的混合物为溶剂,通过梯度降温法制备具有结晶形态的利福布丁.结果 首次制备得到了具有结晶形态的利福布丁,并命名为利福布丁晶型Ⅰ.结论 通过选择适当的溶剂和结晶方法,可以将无定形利福布丁制备成为具有结晶形态的利福布丁,这种具有结晶形态的利福布丁流动性好、稳定性高.     

用球形结晶技术改善甲苯磺丁脲的溶出速率

用球形结晶技术将难溶性药物甲苯磺丁脲在羧甲基纤维素钠(CMC—Na)的溶液中制成球形结晶聚集体(简称球晶)。用扫描电镜法观察到原药结晶为棱状结晶,而球形结晶为小片状及小梭状结晶的聚集体。用粉末X线衍射谱检测了球晶与原晶,发现衍射峰有不同之处,说明有部分晶型发生改变。其球晶的溶解过程由Hixson—Crowll方程式描述,溶解比原药快。     

两面针结晶-8镇痛作用机理的研究

作者前文报道了两面针Zanthoxylum nitidum(Roxb.)DC.根提取物N-4及从N-4中分离出的结晶-8(分子式为C_(20)H_(18)O_6,结构待定,下简称结晶-8)的解痉镇痛作用。并证明结晶-8的解痉作用是直接作用于肠平滑肌。而镇痛作用具有中枢性,并与脑内单胺类递质有关,但与脑内吗啡受体无直接关系。本文仅就结晶-8镇痛作用与中枢某些递质的作用关系加以研究。     

索拉非尼无定形体系结晶动力学稳定性评价及结晶抑制剂筛选

目的 制备索拉非尼无定形体系，评价其结晶动力学稳定性，探讨聚合物对无定形的抑制结晶效应。方法 旋转蒸发法制备索拉非尼无定形态，非等温多速率差式扫描量热分析法研究无定形形成能力和结晶动力学稳定性，溶解度和体外溶出实验考察聚合物对无定形的抑制结晶效应。结果 动力学脆性指数48,玻璃化转变温度与熔融温度之比0.8,降低结晶温度0.51,结晶活化能152.15 kJ·mol^-1,Avrami指数约为2,含有50μg·mL^-1甲基纤维素M450溶液，无定形体系溶解度与累积溶出度分别提高1.43和2.17倍。结论 索拉非尼无定形具有较高的动力学稳定性，甲基纤维素可延长无定形体系过饱和时间。     

夫西地酸钠的结晶工艺研究

目的 以夫西地酸为原料，与氢氧化钠溶液反应成盐后，采用溶析剂丙酮进行溶析结晶得到夫西地酸钠晶体。方法 本研究通过考察夫西地酸钠结晶工艺中的酸溶解浓度、氢氧化钠溶液浓度、溶析剂用量、结晶温度对夫西地酸钠结晶的影响，最终确定了夫西地酸钠结晶新工艺。结果 该工艺制备的夫西地酸钠晶体呈短粗棒状，粒度均匀，晶型稳定，易于分装。     

柳穿鱼化学成份的研究

从柳穿鱼中分得3个结晶,经鉴定结晶Ⅰ为鸭嘴花碱,本文详细报道结晶Ⅰ提取、分离,鉴定过程,结晶Ⅰ系首次从本植物中分得。     

异位妊娠药物保守治疗的效果观察

目的探讨甲氨蝶吟加米非司酮与天花粉结晶蛋白治疗异位妊娠的有效性。方法将79例确诊为早期异位妊娠患者随机分成两组．分别给予甲氨蝶吟加米非司酮与天花粉结晶蛋白进行治疗,通过临床护理观察并对照研究。结果甲氨蝶吟加米非司酮组治愈率82．93％。天花粉结晶蛋白组治愈率97．37％。结论甲氨蝶吟加米非司酮与天花粉结晶蛋白治疗异位妊娠均有效,但甲氨蝶呤＋米非司酮治疗异位妊娠更安全、副反应小。     

膜分离法回收土霉素结晶母液中的土霉素

土霉素结晶母液经超滤膜预处理后 ,通过反渗透膜所得浓缩液 ,再经超滤膜处理后 ,15 %氨水调p H值从土霉素结晶母液回收土霉素 ,得到的土霉素纯度 82 .9% ,效价 771u/ mg,回收率 6 2 %。此结晶母液为二次母液 ,与车间冲洗水等混合后可较容易地进行生物降解     

盐酸青藤碱红外光谱分析

目的建立盐酸青藤碱的红外光谱分析方法.方法采用红外光谱法测定不同纯度盐酸青藤碱晶形的IR谱图并比较差异.结果与青藤碱标准品IR谱图比较,盐酸青藤碱对照品的羟基进行了缔合,在3 500～3 200 cm 峰形变宽;纯白色样品与对照品峰形一致;灰白色样品与淡黄色样品在2 400～2 300cm1有一∞=N吸收峰,且淡黄色样品的吸收峰较灰白色样品峰强.结论盐酸青藤碱IR谱图与其晶形纯度有关,运用红外光谱法进行分析,快速、简便、专属性强,为盐酸青藤碱质量控制提供参考.     

A potential function for conformational analysis of proteins

We have devised a residue-residue potential function for low resolution protein conformational calculations. The interactions between residues near in sequence maintain correct secondary structure, while the long-range terms in the potential govern the larger packing features and overall globularity. The short-range terms were calculated by comparing the observed distributions of distances between C^α atoms in 35 protein crystal structures to the expected distributions and assigning the discrepancies to a Boltzmann distribution due to an effective potential. Long-range terms were adjusted to ensure that the crystal structure of bovine pancreatic trypsin inhibitor has a lower total energy than perturbed conformations of the same molecule. Thus the empirical potential function implicity contains solvation and conformational entropy effects along with the usual Van der Waals and electrostatic energies. Extensive testing of the potential on trypsin inhibitor and other proteins establishes that it is generally applicable to small proteins, it does not attempt to compress or expand the conformations found by X-ray crystallography, standard secondary structural features are maintained under the potential, and there are so many local minima that local minimization can be trusted to return a perturbed structure to the native conformation only if they differ initially by less then 1 Ad?.     

Synthesis and Crystal Structure of Anhydrous Analog of 1,25-Dihydroxyvitamin D3

As predicted by single crystal X-ray crystallography, and contrary to the reported suggestions, the anhydrous form of calcipotriol, a therapeutically important vitamin D analog, was found stable enough to be used as an active pharmaceutical ingredient. The crystal and molecular structure of calcipotriol anhydrate was solved and refined using single crystal X-ray diffraction. The analog was obtained by a novel convergent synthesis from the vitamin D C-22 sulfone, as an advanced intermediate and a side-chain fragment. The homo-chiral side-chain aldehyde was obtained from cyclopropanecarboxyaldehyde by the chromatographic separation of the intermediate diastereomeric salts with (S)-naproxen. Calcipotriol anhydrate showed a single peak in differential scanning calorimetry and the absence of a peak from a water molecule, typical for the monohydrate. Calcipotriol anhydrate, as the only 1,25-dihydroxylated analog of vitamin D₃, exists as a mixture of both α- and β-forms of the A-ring, present in the asymmetric part of the unit cell of the crystal lattice. The intermolecular hydrogen bonding between both conformers in the crystal lattice indicated that the stability of calcipotriol anhydrate might be at least the same as for the known monohydrate. The usefulness of calcipotriol anhydrate as an active pharmaceutical ingredient was confirmed by the stability study in the standard conditions used for the storage of vitamin D analogs.     

足叶乙甙同质异晶的研究

用二种不同工艺制得的足叶乙甙具有不同的差热图谱,测熔点时熔融过程不一,经用粉末X-光衍射检查,确认二种工艺所得产品具有不同晶型,其原因是精制时使用了不同的溶剂。变换溶剂可使二种晶型彼此转变。晶型B测定熔点升温到190℃左右时,出现类似潮解的湿润状态,这是转晶过程的开始,由B型转变成A型。晶型A较之晶型B处于较低能态,应具有较好的稳定性。足叶乙甙的制剂为溶液态,晶型的差异与药效无关。     

Precision and detection limit of quality test for amorphous drug in powder X-ray diffractometry

This report puts forward a method of powder X-ray diffractometry to estimate the precision and detection limit of the crystalline component in an amorphous drug. Cefditoren pivoxil (CP) was employed as a model drug. The major error source of the measurement at low crystal contents is shown to be the random noise in a diffraction pattern (halo pattern) of the amorphous material. For the analysis of the noise, the obstructive halo pattern should be eliminated from the observed pattern. The subtraction of the observed halo pattern from another one derived from the same material, extracts the random noise alone, although the noise is amplified by square root 2 times. The noise in the powder X-ray diffractometry was identified as the white noise. On the basis of the stochastic properties of the extracted noise and signal parameters (peak area) of CP, the relative standard deviations (R.S.D.) of the area measurements of the crystalline diffraction peaks were estimated over a wide range of crystal contents without repeated experiments. The detection limit was determined such that the crystal content at detection limit produced 30% R.S.D. of the measurements. The R.S.D. and detection limit obtained from FUMI theory were in good agreement with the results from the repeated measurements.     

Crystallization of Organic Glasses: Effects of Polymer Additives on Bulk and Surface Crystal Growth in Amorphous Nifedipine

Purpose  

To study the influence of polymer additives on bulk and surface crystal growth in organic glasses (amorphous solids), which are being investigated for delivering poorly soluble drugs and in this role must resist crystallization. Recent studies have discovered new modes of crystal growth that emerge as organic liquids are cooled to form glasses: one existing in the bulk (GC growth) and another at the surface, both leading to crystal growth much faster than predicted by standard theories.     

Studies of polymorphism in three compounds by single crystal X-ray diffraction

The role of single crystal diffraction in the quantitative determination of polymorphism is demonstrated by the examination of three compounds. Two polymorphs were found for each of the compounds bis(2-nitrophenyl) trisulphide (1), 2-amino-5-nitrobenzophenone (2) and bis(2-nitrophenyl) sulphide (3). Only in one polymorph of (1) does molecular symmetry correspond with crystallographic symmetry. In (2) the polymorphs arise in the same crystal class and in the same crystallographic space group whereas in (3) the two polymorphs exist in different crystal classes and hence in different space groups. Crystallographic space group transformation is also discussed.     

Chemical space sampling in virtual screening by different crystal structures

Retrospective virtual screening experiments were carried out to investigate the effects of combining hit lists from different crystal structures of the same target using consensus scoring. An in-house High Throughput Screening (HTS) dataset from PI3K-γ was used and docked against five diverse PI3K-γ crystal structures. The results show that consensus scoring prioritizes compounds that score moderately against individual crystal structures and is thus complementary to individual crystal structure screening leading to an increase in the diversity of hits. Enrichment factors (EFs) of the consensus score for two or three structures are often as high as or higher than the EF of the individual structures used in the consensus score. Combining four or five structures in the consensus score generally yields lower enrichments. Compounds in the top 500 of the consensus score that are also found in the top 500 of an individual X-ray structure used in the consensus score calculations yield the largest number of hits with the lowest number of false positives.     

布南色林的单晶培养和结构确证

目的 培养布南色林的单晶,以验证所合成的化合物为布南色林.方法 通过温度、质量浓度、溶剂的考察,选择合适的条件,培养出大小适合X射线单晶衍射检测的布南色林单晶.结果 通过X射线单晶衍射测定,结果显示所得数据与文献报道一致,证明布南色林的化学结构正确.结论 采用本法可很好地获得大小适合X射线单晶衍射检测的布南色林单晶,并...     

加晶种提高头孢拉定反应结晶产品质量的研究

反应结晶是抗生素生产中常用的一种结晶方法,但目前国内反应结晶技术水平落后,普遍存在产品粒度分布过宽问题。加晶种的控制结晶是一种改善结晶产品粒度分布的有效方法,已广泛用于蒸发结晶、冷却结晶、溶析结晶等结晶体系,而未见报道在反应结晶过程中应用。本文对在头孢拉定反应结晶过程中投加晶种改善产品粒度分布进行了研究,比较了在相同的育晶条件下,超声波法制和制备的晶种、筛分后的成品作为晶种科自然起昌方式对最终产品