薄荷油的质量标准研究

目的 修订薄荷素油的指纹图谱检查方法;建立多组分的气相色谱法。方法 气相色谱（GC）法同时测定薄荷素油中柠檬烯、（-）-薄荷酮、乙酸薄荷酯、薄荷脑4种成分的含量,并将这4个成分作为指标性成分考察薄荷素油的指纹图谱。结果 柠檬烯在147.34～1 473.41 ng范围内线性关系良好(r=0.999 8),平均回收率为99.0%,RSD为1.3%(n=9);（-）-薄荷酮在504.35～5 043.49 ng范围内线性关系良好(r=0.999 6),平均回收率为101.4%,RSD为0.6%(n=9);乙酸薄荷酯在151.72～1 517.20 ng范围内线性关系良好(r=0.999 8),平均回收率为99.9%,RSD为0.5%(n=9);薄荷脑在808.40～8 084.00 ng范围内线性关系良好(r=0.999 8),平均回收率为97.0%,RSD为1.5%(n=9);建立了薄荷素油气相指纹图谱,确定6个共有峰,样品的相似度为0.997～0.999。结论 气相色谱指纹图谱结合多成分同时测定的方法简便、准确、可靠,可用于薄荷素油质量的控制。     

GC-MS法测定荆芥挥发油中薄荷酮、胡薄荷酮含量

采用气相色谱-质谱联用法,选用毛细管气相色谱柱H-5MS(5%henyl Methyl Silox-ane,30.0 m×250.0μm×0.25μm),程序升温方法:初始温度50℃,以10℃.min-1速率升至100℃,保持10min,再以5℃.min-1速率升至200℃,保持5min。薄荷酮在0.00517～0.1034mg.mL-1之间呈良好的线性关系(r=0.9999);胡薄荷酮在0.0372～0.744mg.mL-1之间呈良好的线性关系(r=0.9991)。薄荷酮回收率为98.0%,RSD(%)=1.696;胡薄荷酮回收率为99.4%,RSD(%)=2.469。     

气相色谱法测定薄荷素油中薄荷脑、薄荷酮、薄荷脑乙酸酯、柠檬烯的含量

目的采用高效毛细管柱气相色谱法同时测定薄荷素油中主要成分薄荷脑、薄荷酮、薄荷脑乙酸酯、柠檬烯含量。方法色谱柱:HP-FFAP毛细管柱(25m×0.20mm×0.33μm),60℃～230℃程序升温,内标物环己酮。结果各组分线性关系良好,相关系数为1.0000。加样回收率:薄荷脑97.71%,薄荷酮102.18%,薄荷脑乙酸酯98.20%,柠檬烯97.30%。结论该方法简便、准确、可靠,可作为控制薄荷素油质量的方法。     

感冒清热颗粒挥发油特征图谱及薄荷酮和胡薄荷酮的含量测定

目的:建立感冒清热颗粒中挥发油的特征图谱并测定其中薄荷酮和胡薄荷酮的含量。方法:Agilent HP-5毛细管柱(30 m×320 mm,0.25μm);进样口、检测器温度250℃;柱温:初始温度40℃,保持1 min,7℃.min-1升至100℃,保持12min,3℃.min-1升至150℃,保持8 min,10℃.min-1升至240℃,保持2 min;载气为氮气;流速:1 mL.min-1;不分流。结果:特征图谱中标定了6个共有峰。薄荷酮进样量在0.0211～0.422μg,胡薄荷酮进样量在0.0371～0.743μg内均呈良好的线性关系(r=0.9999);平均回收率分别为101.0%和97.5%,RSD均小于3%。结论:建立的气相色谱特征图谱及含量测定方法可从定性和定量两方面控制感冒清热颗粒中的挥发性成分,方法准确、可行,可作为感冒清热颗粒的质量控制方法。     

GC测定荆芥及荆芥油中的薄荷酮和胡薄荷酮

目的 测定荆芥及荆芥油中的薄荷酮和胡薄荷酮.方法 采用GC法.用PEG-20M石英毛细管柱(30 m×0.53 mm×1 μm),FID检测器,氮气为载气,柱温140%,气化室和检测器温度均为250°C,不分流进样.以萘为内标.结果 薄荷酮的线性范围为0.2～2.5 mg·ml-1(r=0.9999),胡薄荷酮的线性范围为0.2～2.5 mg·ml-1(r=0.9992);薄荷酮和胡薄荷酮的平均回收率(n=9)分别为99.0%、99.6%.结论 所建方法简便、准确,可同时测定荆芥以及荆芥油中的薄荷酮和胡薄荷酮.     

种植、野生薄荷原药材调研考察及分析

目的：考察分析国内不同种植及野生薄荷的质量,为薄荷的标准提高和质量控制提供合理化建议。方法：采用气相色谱质谱联用方法,分析40批次不同产地薄荷挥发油中的主要化学成分;采用薄层色谱方法,分析薄荷及其混淆品的薄层色谱行为;观察植物花序类型,茎、叶、花萼的特征及气味特点。结果：根据挥发油中所含主要成分、薄层色谱行为及植物形态,进行了分类,分为三大类：薄荷类、留兰香类及其他类。薄荷较稳定的特征为轮伞花序腋生,茎、叶、花萼有毛,辛凉味足,挥发油中主成分为薄荷脑、薄荷酮。结论：大多数地区种植的薄荷与药典规定基原相符,个别地区存在留兰香类及同属其他植物当薄荷错种、误种的问题,部分地区野生品植物形态与药典品相近,挥发油主成分为胡薄荷酮、薄荷酮,而薄荷脑含量较低或无,不应作为药用薄荷使用;薄荷的质量控制应采取性状与化学成分相结合的方式。     

HPLC法测定黄连上清片中胡薄荷酮的含量

目的探讨提高黄连上清片质量标准的方法。方法采用HPLC法测定黄连上清片中胡薄荷酮的含量,流动相：甲醇-水（50：50）,检测波长252nm,流速0．8ml·min^-1结果在0．03～0．3μg范围内,胡薄荷酮进样量与其峰面积响应值呈良好的线性关系,r=0．9999;平均回收率为98．3％。结论本法准确、稳定,重复性好,可作为控制黄连上清片质量的有效方法。     

GC法同时测定感冒退烧片中的薄荷酮和胡薄荷酮

目的 采用气相色谱内标法测定感冒退烧片中薄荷酮和胡薄荷酮的含量.方法 采用5％苯基-甲基聚硅氧烷(DB-5)毛细管柱,程序升温(初始温度120℃,以2℃·min-1升温至140 ℃,再以3℃·min-1升温至200℃,保持5 min),进样口温度240℃,检测器温度240℃.结果 2.3074 ～46.1475 ng薄...     

气相色谱法测定复方苦参凝胶中薄荷酮、薄荷脑的含量

目的建立复方苦参凝胶中薄荷酮、薄荷脑的含量测定方法。方法采用GC法测定薄荷酮、薄荷脑的含量,色谱柱为弹性石英毛细管柱（柱长30m,内径0．32mm,膜厚度0．25μm）Supelcowax-10;程序升温;进样口温度260℃,检测器温度280℃;分流比50：1;柱流量1．0mL·min^-1。结果采用C-C法测定薄荷酮、薄荷脑的含量,薄荷酮的量在0．0562～0．4215μg有良好的线性关系（r=0．9997）,平均回收率为97．12％,RSD=1．55％;薄荷脑的量在0．03216～0．2412μg有良好的线性关系（r=0．9992）,平均回收率为98．17％,RSD=1．70％。结论所建立的含量测定方法简便可行、重复性好,可以用来测定复方苦参凝胶中薄荷酮、薄荷脑的含量。     

GC测定5%薄荷凝胶贴膏中薄荷脑的含量

目的 建立气相色谱法用于含5%薄荷凝胶贴膏中薄荷脑的含量测定。方法 首先比较挥发油提取法和超声提取法提取样品的优劣，其次采用GC测定薄荷脑含量：以聚乙二醇20000为固定相的毛细管柱(30 m×0.32 mm，0.25 μm)，氮气载气，柱温为140 ℃，FID检测器。结果 选用超声提取法提取样品更加完全。对薄荷脑凝胶贴膏检测方法的方法学考察结果显示，精密度RSD为0.4%，重复性RSD为0.67%，平均回收率为97.02%及其RSD为0.17%，薄荷脑浓度在0.175~2.1 mg·mL^–1内线性关系良好，回归方程为Y=0.802X–0.000 7(r=0.999 9)。用所建立的方法对11批样品进行含量测定，结果均合格。结论 由于凝胶贴膏特有的交联固化过程影响，前处理使用超声提取法比挥发油提取法更可靠、更稳定，建立的GC测定凝胶贴膏中薄荷脑含量的方法可靠、稳定、重现性好，可用于薄荷脑凝胶贴膏的质量控制。     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate, eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol

Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the beta(2)-adrenoceptor agonist formoterol [eformoterol]. This isomer contains two chiral centres and is being developed as an inhaled preparation for the treatment of respiratory disorders. Sepracor believes that arformoterol has the potential to be a once-daily therapy with a rapid onset of action and a duration of effect exceeding 12 hours. In 1995, Sepracor acquired New England Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the purpose of preparing formulations of levosalbutamol and arformoterol. Phase II dose-ranging clinical studies of arformoterol as a longer-acting, complementary bronchodilator were completed successfully in the fourth quarter of 2000. Phase III trials of arformoterol began in September 2001. The indications for the drug appeared to be asthma and chronic obstructive pulmonary disease (COPD). However, an update of the pharmaceutical product information on the Sepracor website in September 2003 listed COPD maintenance therapy as the only indication for arformoterol. In October 2002, Sepracor stated that two pivotal phase III studies were ongoing in 1600 patients. Sepracor estimates that its NDA submission for arformoterol, which is projected for the first half of 2004, will include approximately 3000 adult subjects. Sepracor stated in July 2003 that it had completed more than 100 preclinical studies and initiated or completed 15 clinical studies for arformoterol inhalation solution for the treatment of bronchospasm in patients with COPD. In addition, Sepracor stated that the two pivotal phase III studies in 1600 patients were still progressing. In 1995, European patents were granted to Sepracor for the use of arformoterol in the treatment of asthma, and the US patent application was pending.     

欧洲刺柏（Juniper）

活性成分与药理作用欧洲刺柏药用部位是其浆果，具有促水排泄、防腐、抗胃肠胀气和抗风湿作用，还可改善胃功能。用作促水排泄药可增加尿量（水丢失），但不增加钠排泄。成分萜品烯-4-醇可增加肾小球滤过率，但刺激肾。欧洲刺柏浆果对单纯疱疹病毒体外显示抗病毒活性，并具抗真菌活性。动物实验显示，欧洲刺柏浆果提取物具有堕胎、抗生育、抗炎、抗胚胎植入、降血压、升血压和降血糖作用。欧洲刺柏浆果油具有兴奋子宫的活性，以及利尿、胃肠道抗菌和刺激作用，该油对平滑肌有阻止解痉作用。     

Oral Presentations (LDD, LPES, LNM, LPAT, LNT, LPPT, LPM)

Probiotic microorganisms have been shown to provide specific health benefits when consumed as food supplements or as food components. The main problem of such products is the poor survival of the probiotic bacteria in the low pH of gastric fluid. However the use of synthetic excipients for enteric coating to prevent the exposure of microorganisms to gastric fluid is limited in food supplementary industry. Therefore the aim of this study was to develop an enteric coating formulation containing shellac as a natural polymer. Shellac possesses good resistance to gastric juice; the major disadvantage of this polymer is its low solubility in the intestinal fluid [1, 2]. Thus films containing different ratios of shellac and water-soluble polymers (sodium alginate, hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidon (PVP)) or plasticizers (glycerol and glyceryl triacetate (GTA)) were prepared in order to analyse the films’ melting temperatures (T_m), the changes in enthalpy (ΔH), their capability of taking up water, and their solubility in different media. The release characteristics of the films were studied by loading pellets with Enterococcus faecium M74 and coating them with formulations containing different amounts of shellac and polymer or plasticized shellac. Using dissolution tests, performed according to USP XXXI paddle method, the resistance of the coatings to simulated gastric fluid (SGF, pH 1.2) and the release of cells in simulated intestinal fluid (SIF, pH 6.8) was investigated.The trials showed that an increasing amount of plasticizer results in a decrease of T_m and ΔH of the films whereat glycerol had a superior plasticization effect to GTA. The compatibility of films made of water-soluble polymers and shellac was also concentration dependent. HPMC and PVP showed superior compatibility with shellac compared to sodium alginate, since films containing shellac and more than 10% [w/w] sodium alginate tended to separate into two phases. In the end five formulations containing shellac and either 5% [w/w] glycerol, 10% [w/w] PVP, 20% [w/w] PVP, 10% [w/w] HPMC, or 5% [w/w] sodium alginate emerged as feasible for enteric coating purposes.