舒马曲坦的合成

目的合成抗偏头痛药舒马曲坦。方法以对硝基氯苄为起始原料,经取代、胺化、还原、重氮化、环合等10步反应得到目标化合物舒马曲坦,总收率为18%。结果与结论目标化合物的结构经1H-NMR、IR和MS确证。该合成方法,反应条件温和,操作简便,原料易得,适合工业化生产。     

4-氯丁醛缩二甲醇的制备

4-氯丁醛缩二甲醇(1)是合成色胺类药物,如佐米格(zomitriptan)、舒马曲坦(sumatriptan)和褪黑激素(melatonin)等的中间体[1,2].文献[3]用对甲苯磺酰氯保护1,4-丁二醇的单羟基后,进行选择性氧化得醛,再经缩醛化、氯化制得1,总收率低于20%.     

药用1,3-二甲基戊胺盐酸盐的合成工艺改进

目的合成1,3-二甲基戊胺盐酸盐并改进其工艺。方法 以乙酰乙酸乙酯和2-溴丁烷为原料,经4步合成反应得到1,3-二甲基戊胺盐酸盐,并采用单因素考察法对合成工艺进行改进。结果1,3-二甲基戊胺盐酸盐各步反应的收率均>40%,产物总收率达到12.3%。结论产物结构经1 H-NMR和13 C-NMR确认为1,3-二甲基戊胺盐酸盐。     

7-甲氧基-4-(2-甲基-4-喹唑啉基)-3,4-二氢喹噁啉-2(1H)-酮的合成工艺改进

目的:改进7-甲氧基-4-(2-甲基-4-喹唑啉基)-3,4-二氢喹噁啉-2(1H)-酮的合成工艺。方法:以2-甲基-4(3H)-喹唑啉酮为起始原料,通过氯代、亲核取代、二芳胺烷基化和硝基还原环合等反应对7-甲氧基-4-(2-甲基-4-喹唑啉基)-3,4-二氢喹噁啉-2(1H)-酮的合成工艺进行改进,并考察其收率。结果:7-甲氧基-4-(2-甲基-4-喹唑啉基)-3,4-二氢喹噁啉-2(1H)-酮的结构经核磁共振氢谱和电喷雾质谱确证,总收率为43.5%,较改进前的20.2%提高了23.3%。结论:改进后的工艺更简单,条件更温和,适合实验室研究的批量制备。     

临时配制舒马曲坦琥珀酸盐口服液的稳定性

舒马曲坦（sumatripta）是治疗急性偏头痛的5－羟色胺激动剂。本文研究了它的玻璃酸盐临时配制口服液的稳定性，以Ora－Sweet，Ora－SweetSF，和Syrpaltasyrups临时混合制成舒马曲坦浓度为5mg／ml的3种舒马曲坦琥珀酸盐混悬液。每种混悬液一式3份。混是液置于琥珀色玻璃瓶内在4℃条件下贮存60天。在开始和第2、7、14、21、28、35和60天从每瓶中各取出两份1ml的样品，采用高效液相色谱法测定舒马曲坦的浓度。这些样品还要通过肉眼检查和微生物试验。所有的舒马曲坦混悬液中的平均浓度均可保留起始浓度的90％以上，达21天。到第28天时所有…     

6-甲基-4-苯基-3,4-二氢香豆素的制备

目的: 改进6-甲基-4-苯基-3,4-二氢香豆素的制备方法;方法:以对甲酚和肉桂酸为原料,经脱水、环合制得标题化合物;结果:合成产物经熔点确证,收率达94%;结论:此合成工艺简便,更有利于工业化生产.     

吉非罗齐的合成

目的:合成吉非罗齐,并进行工艺改进。方法:以2 ,5-二甲基苯酚为起始原料,与1-氯-3-溴丙烷反应,得3-( 2 ,5-二甲基苯氧基)-1-氯丙烷,再与异丁酸钠锂作用,制得吉非罗齐。结果:通过两步反应制得产物,总收率4 3.8%。醚化反应经优化后收率较文献提高30 %以上。合成产物经红外光谱、核磁共振谱及质谱确证。结论:缩短了反应步骤,提高了反应收率。     

盐酸阿洛司琼合成工艺改进

目的 :改进盐酸阿洛司琼的合成工艺 ,以利于工业生产。方法 :以 2 ,4 -哌啶二酮 - 3-羧酸甲酯与 N -甲基苯肼缩合后在硫酸和醋酸存在下环合得制 2 ,3,4 ,5 -四氢 - 5 -甲基 - 1H-吡啶并 [4、3- b]吲哚 - 1-酮 ,然后甲基化 ,再与 4 -羟甲基 - 5 -甲基咪唑在对甲苯磺酸催化下缩合。结果 :制得合格的盐酸阿洛司琼 ,总收率 38%。结论 :经改进的工艺操作简便 ,比原工艺更易于工业化生产     

盐酸美金刚胺的合成工艺改进

目的改进盐酸美金刚胺的合成工艺。方法以1,3-二甲基金刚烷为原料,在叔丁醇、乙腈、浓硫酸存在下,经Ritter反应生成1-乙酰胺基-3,5-二甲基金刚烷,再以聚乙二醇为溶剂,加入氢氧化钠水解得到美金刚胺,然后在异丙醇溶剂中盐酸化得到盐酸美金刚胺。总收率：70%。结果合成了具有良好化学纯度的盐酸美金刚胺（纯度99.9%,总收率70%）。结论改进的工艺明显提高了反应收率,工艺条件温和,合成步骤简洁,适合工业化生产。     

抗疟药中间体4,7-二氯喹啉的工艺研究

目的改进4，7-二氯喹啉的合成工艺，提高收率，降低成本。方法以间氯苯胺和乙氧基次甲基丙二酸二乙酯缩合后高温直接环合，再经水解、脱酸、氯化得4，7-二氯喹啉。结果通过改进工艺制得4，7-二氯喹啉总收率88G。结论改进工艺操作简单，步骤少，成本低，收率提高，更适合工业生产。     

Production of Ultrafine Sumatriptan Succinate Particles for Pulmonary Delivery

PURPOSE: Drug particle physical properties are critical for the efficiency of a drug delivered to the lung. The purpose of this study was to produce ultrafine sumatriptan succinate particles for inhalation. METHODS: Sumatriptan succinate particles were produced via reactive precipitation without any surfactants. Several low toxic organic solvents such as acetone, isopropanol, and tetrahydrofuran were investigated as the reaction medium. And the dry powder was obtained via spray drying. FT-IR, HPLC, SEM and XRD were exploited to characterize the physicochemical properties of the ultrafine sumatriptan succinate dry powder. The aerosol performance of the powder was evaluated using an Aeroliser connected to a multi stage liquid impinger operating at 60 l/min. RESULTS: The mean particle size of the ultrafine sumatriptan succinate particles obtained under optimum conditions was in the range of 630-679 nm and consequently they were in the respirable range. The spray-dried powder whose fine particle fraction was increased up to 50.6 +/- 8.2% showed good aerosol performance whereas the vacuum-dried powder was approximate 18.2 +/- 3.0%. CONCLUSIONS: Good aerosol performance ultrafine sumatriptan succinate particles could be produced by reactive precipitation without any additives followed by spray drying at the optimum parameters.     

炎琥宁的合成工艺研究

目的 研究炎琥宁的合成工艺。方法 以脱水穿心莲内酯二琥珀酸半酯为起始原料，用KHCO3和Na2CO3混合溶液一步成盐法合成炎琥宁。结果 总收率为80．6％。结论 合成工艺操作简便，提高了收率，降低了成本，适合于工业化生产。     

In vivo bioavailability studies of sumatriptan succinate buccal tablets

Back ground and the purpose of study

Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability.

Methods

Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard.

Results

Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%.

Conclusions

Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability.     

醋酸巴多昔芬的合成工艺改进

目的：改进醋酸巴多昔芬的合成工艺。方法：以对羟基苄醇和环己亚胺基乙基氯盐酸盐为起始原料,经过亲核取代、氯代得到侧链,4-苄氧基苯丙酮和4-苄氧基苯肼盐酸盐经缩合得母核,侧链和母核缩合后,经成盐,氢解、中和,与乙酸成盐总计6步得目标化合物。结果：目标化合物经质谱、核磁共振确证其结构。总收率可达53%,产品HPLC纯度99.5%以上。结论：改进后的工艺步骤大大缩短,且操作简单,收率和纯度较高,适合工业化生产。     

抗肝癌药盐酸诺拉曲噻的合成*

目的：改进盐酸诺拉曲噻的合成工艺。方法：以2-溴4-硝基甲苯为原料经Sandmeyer法合成靛红、氧化开环、环合成喹唑啉酮和Ullmann反应合成了盐酸诺拉曲噻。结果：有关中间体及目标化合物的结构经必要的图谱确证，或经含量分析；总收率为28．8％。结论：本合成路线简洁，工业成本低，所得产品纯度高，适合于工业化生产。     

4-吡啶丁醇的合成

目的:合成4-吡啶丁醇。方法:以4-溴吡啶盐酸盐为原料,经缩合、成盐、催化氢化再游离共4步反应得到目标产物。结果与结论:目标产物的化学结构经1HNMR确证,反应条件温和,操作简单,适宜工业化生产,总收率65.1%。     

Development of validated UV spectrophotometric method for <Emphasis Type="Italic">in vitro</Emphasis> analysis of sumatriptan in pharmaceutical preparations in comparison with HPLC

An accurate, simple reproducible and sensitive method for the determination of sumatriptan succinate was developed and validated. According to this, sumatriptan succinate was determined using a UV spectrophotometric (UVS) technique and the results were compared with the data of isocratic HPLC procedure on a Bondapack reversed-phase ODS or C18 Waters column (chemically bonded to Spherisorb⁽particles (5 μm), 4.6 mm × 25 cm,) under conditions of isocratic elution at a flow rate of 1.0 ml/min. The mobile phase composition was acetonitrile – buffer (420 : 580, v/v), pH 7.5. The buffer composition was dibutylamine, 85% phosphoric acid, and doubly distilled water (0.18 : 0.06 : 99.76, v/v), which was adjusted to pH 7.5 with 0.8 N sodium hydroxide solution. Both the proposed UVS procedure and HPLC with UV detection were carried out at 282 nm. The linear range of detection for sumatriptan succinate by means of both UVS and HPLC methods was between 21 and 39 μg/ml of sumatriptan. The UVS method is shown to be linear, reproducible, specific, sensitive and robust.     

Nasal drug delivery of sumatriptan succinate

The purpose of this work was to increase the nasal absorption of sumatriptan succinate by using bile salts. A rat in situ nasal perfusion technique was used to examine the rate and extent of absorption of sumatriptan succinate. In vitro enzymatic drug degradation studies were carried out with rat nasal washings. Various experimental conditions such as nasal perfusion rate, pH of the perfusion medium and concentrations of absorption enhancers such as sodium deoxycholate, sodium caprate, sodium tauroglycocholate and EDTA were optimized. In vivo studies were carried out for the optimized formulation in rabbits and the pharmacokinetics parameters of nasal solution were compared with marketed nasal solutions. Nasal absorption of sumatriptan succinate was pH dependent. It was found maximum at pH 5.5 and decreased at higher pH values. In in vitro enzymatic degradation studies, no measurable degradation was observed during the first week. The extent of drug absorption was increased by absorption enhancers. Sodium deoxycholate appeared to be more effective for enhancing the nasal absorption of sumatriptan succinate than the other absorption enhancers. The order of increasing absorption of sumatriptan succinate caused by theenhancers was sodium deoxycholate > sodium caprate > sodium tauroglycocholate > EDTA.     

Stability-indicating methods for the determination of sumatriptan succinate

Four stability-indicating methods were developed for the determination of sumatriptan succinate in the presence of its degradation products. The first method depends on the quantitative densitometric evaluation of thin-layer chromatography of sumatriptan succinate in the presence of its degradation products without any interference. Cyclohexane–dichloromethane–diethylamine (50:40:10 v/v/v) was used as a mobile phase and the chromatogram was scanned at 228 nm. This method determines sumatriptan succinate in the concentration range l–8 μg per spot with mean percentage recovery 100.52±1.23%. The second and third methods depend on the use of first-derivative (D₁) and second-derivative (D₂) spectrophotometry at 234 and 238 nm, respectively. These methods determine the drug in the concentration range 1.25–10 μg ml⁻¹ with mean percentage recovery 99.91±1.01% and 99.96±1.13% for (D₁) and (D₂), respectively. The fourth method depends on the use of ratio derivative spectrophotometric technique. The amplitude in the first derivative of the ratio spectra at 235 nm was selected to determine the cited drug in the presence of its degradation products. Calibration graph is linear in the concentration range 1.25–10 μg ml⁻¹ with mean percentage recovery 100.19±1.19%. The suggested methods were successfully applied for determining sumatriptan succinate in bulk powder, laboratory-prepared mixtures and pharmaceutical dosage forms (Imigran tablet) with good accuracy and precision. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the reported method.