复方烟酸辛伐他汀双层缓释片的制备及Beagle犬体内药代动力学

以烟酸和辛伐他汀为模型药物制备复方双层缓释片,并评价其体外释放特性。采用双周期双交叉给药方案,LC-MS/MS法同时测定自制制剂和市售制剂中烟酸和辛伐他汀的血药浓度,对6只Beagle犬进行了药代动力学和生物利用度的初步研究。自制制剂和市售制剂给药后烟酸的c_max分别为（6.43±0.80）和（6.38±0.47）μg/mL,t_max分别为（2.80±1.00）和（2.50±1.00）h,AUC分别为（30.16±4.51）和（27.49±4.04） μg·h/mL;辛伐他汀的c_max分别为（38.65±1.71）和（40.54±2.33）ng/mL,t_max均为（1.50±0.40）h,AUC分别为（118.76±11.83）和（115.76±5.46）ng·h/mL。结果表明两种制剂中烟酸和辛伐他汀的AUC,c_max和t_max都等效,说明自制制剂和市售制剂在Beagle犬体内具有生物等效性。     

格列齐特缓释片在比格犬体内的药动学及生物等效性

目的 研究自制格列齐特缓释片在比格犬体内的药动学行为和体内外相关性。方法 取6条比格犬随机分成两组,采用自身对照交叉方式给药,分别灌胃给予自制格列齐特缓释片和参比制剂达美康,给药剂量为30 mg。给药后于不同时间点采血,采用高效液相色谱法测定血药浓度,计算药动学参数,考察自制格列齐特缓释片的药动学特征和相对生物利用度,评价其生物等效性,计算其体内外相关性。结果 达美康的药时曲线下面积（AUC_0-∞）为（101.74±20.29）μg/（mL·h）,自制制剂格列齐特缓释片的AUC_0-∞为（95.40±28.68）μg/（mL·h）,两者间各药动学参数差异均无统计学意义（P>0.05）。自制格列齐特缓释片对达美康的相对生物利用度为93.77%,两者具有生物等效性。将制剂在犬体内的吸收分数与体外累积释药率作线性回归,达美康与自制格列齐特缓释片的相关系数分别为0.912和0.894,均大于临界值（r_0.05,7=0.754）,两者的体外释放速率与犬体内吸收速率均相关。结论 自制格列齐特缓释片在比格犬体内具有缓释特征,其与参比制剂达美康生物等效。本研究建立的体外释放度测定方法可用于预测格列齐特缓释片在体内的吸收行为。     

HPLC法测定丹皮酚制剂在犬体内血药浓度及生物利用度

目的 研究丹皮酚3种制剂在犬体内的药动学及生物利用度。方法 6条犬采用三制剂三周期随机交叉试验设计,分别单剂量口服对照制剂丹皮酚片（R）40 mg;被试制剂丹皮酚软胶囊（T₁）;被试制剂丹皮酚滴丸（T₂）;HPLC测定血药浓度。结果 T₁、T₂与R的主要药动学参数：t_max分别为(1.42±0.38)、(0.96±0.10)、(1.08±0.20) h; C_max分别为(2.23±0.50)、(2.56±0.58)、(1.94±0.40) μg/mL; t_1/2(ke)分别为(3.09±0.40)、(2.88±0.51)、(2.62±0.52) h; AUC_0~12分别为(11.62±1.07)、(12.57±1.80)、(10.32±1.63) h·μg/mL; AUC_0~∞分别为(14.56±1.41)、(15.41±1.70)、(12.70±2.12) h·μg/mL。相对生物利用度为：T₁(114.1±14.3)%和(116.3±15.1)%,T₂(122.6±12.4)%和(122.8±13.9)%。结论 药动学参数经多因素方差分析显示AUC_0~12、AUC_0~∞、C_max和t_max在药物间有显著的统计学差异（P<0.05）,双单侧t检验表明,两种被试制剂与参比制剂不等效。     

基于粉末直接压片工艺的硝苯地平缓释片：制备、体外释放度及比格犬体内药动学评价

目的 选用粉末直接压片工艺,以羟丙基甲基纤维素为骨架材料制备日服1次的硝苯地平缓释片。方法 建立24 h的释放度测定方法并进行硝苯地平缓释片的体外评价;应用液相色谱 质谱联用技术研究缓释片在比格犬体内药代动力学,与市售参比制剂对比并计算相对生物利用度。结果 受试制剂和参比制剂有相似的药代动力学参数,相对生物利用度为（100.9±12.4）%;药物体外累积释放百分数与体内吸收百分数有较好的相关性,r=0.962 5。结论 本工艺制得的硝苯地平缓释片可以达到缓释24 h的要求。     

多剂量口服硝苯地平缓释片的药动学及生物等效性

目的：研究多剂量口服硝苯地平缓释片在人体内的药动学特点和国产硝苯地平缓释片的生物等效性.方法：健康志愿受试者20名,口服硝苯地平试验品和参比品20mg,用标准二阶段交叉设计自身对照试验方法,采用液相色谱串联质谱方法（LC-MS/MS）测定服药后不同时刻的血药浓度,计算主要药动学参数,并采用方差分析和双单侧t检验（1-2a）90%置信区间进行生物等效性评价.结果：受试者分别口服受试品和参比品后,其主要药动学参数Tmax,Cmax,T1/2和AUCss分别为：（4.10±1.07）,（4.55±1.23）h;（52.64±15.80）,（51.54±12.87）μg/L;（8.44±1.69）,（8.33±2.27）h;（352.96±85.12）,（367.96±71.28）ng/（h·mL）;受试品的相对生物利用度为（96.2±17.3）%.结论：硝苯地平缓释片和硝苯地平缓释片（1）制剂具有生物等效性.     

氧化苦参碱生物黏附缓释片在Beagle犬体内的药动学

目的:考察氧化苦参碱生物黏附缓释片在Beagle犬体内的药动学过程.方法:建立LC-MS法同时测定Beagle犬血浆中的氧化苦参碱及其代谢产物苦参碱.采用BAPP 2.3程序估算犬服用市售普通胶囊(参比制剂)和氧化苦参碱生物黏附缓释片(受试制剂)后的药动学参数.结果:氧化苦参碱血药浓度.时间曲线符合双室模型特征.受试制剂的生物利用度为110.9,且cmsx降低、tmax延长,具有缓释效果.服用受试制剂后测得苦参碱的量为服用参比制剂后测得量的90.5%.结论:氧化苦参碱生物黏附缓释片与市售普通胶囊相比,生物利用度等效,具有明显的缓释效果.     

盐酸安非他酮缓释微丸的制备及生物利用度研究

目的： 研制盐酸安非他酮(bupropion hydrochloride,BH)24 h缓释微丸,并以市售片剂为对照,进行生物利用度研究。方法： 采用挤出滚圆法制备含药丸心,以乙基纤维素水分散体为包衣材料进行流化床包衣,将BH缓释微丸和市售片剂大鼠灌胃后测定生物利用度,用HPLC法测定血药浓度,采用Kinetica软件计算药动学参数。结果： BH缓释微丸在2,12和24 h的体外释放度分别约为10%,80%和95%。药动学结果表明BH缓释微丸的血药浓度经时曲线符合二室模型,市售片剂的血药浓度经时曲线符合一室模型,BH缓释微丸和市售片剂的AUC分别为(1 523.79±323.30) ng·h/mL和 (1 379.67±253.61) ng·h/mL;c_max分别为(163.80±32.93) ng/mL和(451.91±144.54) ng/mL;t_max分别为(4.67±0.52) h和(0.5±0) h。以市售片剂为对照,BH缓释微丸的相对生物利用度为(110.46±17.07)%。结论： 所研制的BH 24 h缓释微丸与市售BH普通片生物等效。     

两种咪唑斯汀缓释制剂体内生物利用度和药动学研究

目的 对两种上市的咪唑斯汀缓释制剂进行人体药动学的研究,以评价两厂家生产的咪唑斯汀缓释片是否具有生物等效性.方法 采用随机交叉试验设计,10名男性健康受试者单剂量口服咪唑斯汀缓释片(皿治林和尼乐)10 mg后于规定时间点取血,用高效液相法测定血药浓度,计算两种缓释制剂的主要药动学参数,进行人体生物利用度的比较.结果 10名男性健康受试者单剂量口服咪唑斯汀缓释片皿治林后的药动学参数分别为tmax为(1.70±0.59)h,cmax为(276.99±67.58)ng/mL,t1/2为(12.68±1.97)h,MRT为(15.29±2.67)h,AUC0→t为(2 555.89±777.52)ng/mL·h,AUC0→∞为(2 724.07±852.60)ng/mL·h;单剂量口服参比制剂尼乐后的药动学参数分别为tmax为(1.95±0.64)h,cmax为(344.56±93.96)ng/mL,t1/2为(12.42±1.89)h,MRT为(13.49±1.60)h,AUC0→t为(2 532.28±776.06)ng/mL·h,AUC0→∞为(2 659.16±818.06)ng/mL·h.统计结果表明药动学参数t1/2、MRT、tmax、AUC0→T、AUC0→∞受试制剂皿治林与参比制剂尼乐相比没有显著性差异,cmax具有显著性差异,与参比制剂cmax相比有所降低.AUC0→t、AUC0→∞、cmax、t1/2和MRT生物等效,tmax生物不等效.受试制剂的相对生物利用度平均为(101.26±9.82)%(n=10,以AUC0→t计算)和(102.52±8.61)%(n=10,以AUC0→∞计算);药动学参数cmax的比值为(82.17±15.32)%.结论 受试制剂皿治林与参比制剂尼乐二者生物等效,但皿治林制剂咪唑斯汀峰浓度略低,达峰时间tmax略短.     

艾拉莫德(T-614)的临床前药代动力学研究

目的：研究 T-614 原料在动物体内的吸收、分布、代谢、排泄、蛋白结合及口服原料和片剂的相对生物利用度;研究 T-614 原料对5种人 P450 同工酶的体外抑制作用。方法：采用 HPLC 方法进行大鼠 ig T-614 原料 5、10和20 mg/kg 的药代动力学（吸收、分布、代谢、排泄、蛋白结合率）及 Beagle 犬po T-614 原料及片剂（5 mg/kg）的相对生物利用度研究;采用 LC/MS/MS 方法对大鼠 ig T-614 原料 50 mg/kg 后尿液中的主要代谢转化产物进行了分析;采用高通量 P450 酶抑制剂筛选试剂盒测定了 T-614 原料对人 P450 同工酶 CYP2D6、CYP1A2、CYP2C9、CYP2C19 和 CYP3A4 的体外抑制活性。结果：大鼠 ig T-614 原料 5、10和20 mg/kg 后主要药动学参数t_1/2Ke 分别为（5.41 ± 1.28）、（4.31 ± 0.48）和（4.17 ± 1.04）h,t_1/2Ka 分别为（0.16 ± 0.06）、（0.30 ± 0.19）和（0.58± 0.37）h,t_max 分别为（0.81 ± 0.20）、（1.16 ± 0.60）和（1.78 ± 0.61）h,C_max 分别为（7.83 ± 1.85）、（15.46 ± 2.27）和（30.89 ± 6.54）μg/mL,AUC_0～t 分别为（72.08 ± 11.05）、（127.53 ± 17.68）和（296.24 ± 57.10）μg /mL · h;大鼠 ig T-614 原料 10 mg/kg 后在所有脏器组织中均能检测到原形物质,其中肝、肾、子宫的量最高,脑的量最低;大鼠 ig T-614 原料 10 mg/kg 72 h 后,粪中的排泄率达到 15.75 %,而尿与胆汁的排泄率分别为 0.836 %和 0.677 %;当质量浓度为 5、10和20 μg/mL 时,T-614 原料的蛋白结合率分别为（17.2 ± 5.1）%、（28.6± 7.1）%和（28.9 ± 10.2）%,平均蛋白结合率为（24.9 ± 9.2）%。Beagle 犬口服 T-614 原料和片剂 5 mg/kg,其主要药动学参数t_1/2Ke 分别为（11.10 ± 1.50）和（9.30 ± 3.29）h,t_1/2Ka 分别为（1.18 ± 0.22）和（1.53 ± 1.26）h,t_max 分别为（4.24 ± 0.48）和（4.23 ± 1.75）h,C_max 分别为（0.77 ± 0.13）和（1.01 ± 0.27）μg/mL,AUC_0～t 分别为（12.69 ± 2.77）和（16.81 ± 6.49）μg /mL·h;微粉化片剂相对于原料的相对生物利用度为 132.5 %。大鼠 ig 50 mg/kg T-614 后,尿液中检测到 T-614 的 5 种主要代谢物,包括 T-614 原结构的异构体、苯环羟基化、脱醛基后再羟基化、脱醛基后胺基乙酰化、脱醛基后的产物。体外CYP450酶活性抑制试验结果表明,T-614原料浓度为 20～0.009 1 μmol/L 时,对 CYP2D6、CYP1A2、CYP2C9、CYP2C19 和 CYP3A4 活力抑制的 IC₅₀>20 μmol/L。结论：大鼠 ig T-614 原料 5、10 和 20 mg/kg 剂量的药代动力学特征符合一级吸收。在大鼠体内各组织中分布较广,蛋白结合率低于 30 %。粪、尿、胆汁中原形物质的总排泄量低于 20 %。Beagle 犬口服 T-614 片剂的相对生物利用度为 132.5 %。T-614 对人 P450 同工酶 CYP2D6、CYP1A2、CYP2C9、CYP2C19 和 CYP3A4 活力无抑制作用。T-614 在肾脏中代谢转化的主要产物为原形物质的异构化、羟基化、脱醛基后再羟基化、脱醛基后胺基乙酰化、脱醛基等。     

多西他赛磺丁基-β-环糊精包合物的大鼠药代动力学

采用LC-MS/MS法比较研究多西他赛磺丁基-β-环糊精包合物受试制剂与市售参比制剂静脉注射后,药物在大鼠体内的药代动力学及组织分布。结果显示,大鼠静注10 mg/kg受试制剂及参比制剂后,药代动力学参数分别为t_1/2（3.4±0.9）和（4.0±1.0）h,表观分布容积为（31.999±14.16）和（35.526±7.218）L/kg,AUC_0-∞为(1 690±476)和(1 629±213) μg·h/L,多西他赛在大鼠体内的药代动力学过程均符合二室模型的特征。大鼠静注10 mg/kg受试制剂及参比制剂后,骨髓、肺和脾中含量较高,脑、脂肪和睾丸中含量较低。统计学分析显示,两种制剂在大鼠体内主要药代动力学参数及组织分布无显著性差异（P>0.05）。     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Acupuncture Treatment of Vomiting

CASE HISTORY A female patient, 46 years old, head of the foreign affairs department of a certain university in Beijing, paid her first visit on October 9, 2006, with the chief complaint of vomiting for one month. She got vomiting after meals in early September. Before that, she had discomfortable sensation in the stomach due to angry with others, but she didn't pay much attention. Later, it developed into vomiting after eating. After the vomiting, the discomfort would be relieved, but with slight hypodynamia. She was once diagnosed as having 'neurogenic vomiting'. Having taken some western and Chinese drugs, the above symptoms were a little bit improved, but she would have nausea upon eating and with regurgitation. Because of the fear for vomiting, she did not dare to have food intake, with body weight reduction of 6 kilos in one month.     

Qiu Baoguo''''s Experience in Treating Consumptive Syndromes after Radio-Chemotherapies

Radiotherapy and chemotherapy are the important modern medical therapies for malignant tumors,yet they can also bring about serious local and systemic toxic side reactions so to decrease the patient;'s life quality,manifested by a series of consumptive symptoms.Having engaged in the combined work of Chinese and western medicine for nearly 50 years,the research fellow Qiu Baoguo in Henan Provincial Academy of TCM has developed his unique views on the TCM study of consumptive syndromes.The author of this essay had once the fortune tO follow Dr.Qiu in clinic,and specially would like to introduce in the following Dr.Qiu's experience in treating consumptive syndromes after radio-chemotherapies for patients with malignant tumor.     

Insomnia Due to Deficiency of Both the Heart and Spleen Treated by Acupuncture-Moxibustion and Chinese Tuina

OBJECTIVE: To observe therapeutic effects of the comprehensive therapy of acupuncture-moxibustion and Chinese Tuina for treatment of insomnia due to deficiency of both the heart and spleen. METHODS: 92 cases were divided randomly into the treatment group (treated by acupuncture-moxibustion and Chinese Tuina) and the control group (treated by acupuncture-moxibustion). RESULTS: The therapeutic effect of the treatment group was obviously superior to that of the control group (the CHI2 test showed P < 0.01). CONCLUSIONS: The comprehensive therapy of acupuncture-moxibustion and Chinese Tuina can give marked therapeutic effects for treatment of insomnia due to deficiency of both the heart and spleen.     

Analysis of CK-19,PDX-1,Nestin,Ngn3 in different donor islet purity in rats

Objective: To investigate if there are the CK-19, PDX-1, Nestin, Ngn3 positive cells in the donor islets of different purity in rats. Methods: Thirty male adult SD rats were randomly divided into 3 groups. Islets were isolated using digestion by ductal injection of collagenase. Group Ⅰ (n=10): Separating cell preparations were not purified, Group Ⅱ(n=10): Islet sediment was purified with 25% Ficoll400 ,Group Ⅲ (n=10): Islet sediment was purified with 25% and 11% Ficoll-400. The levels of protein of CK-19, PDX-1, Nestin and Ngn3 were detected by immunohistochemistry and the mRNA of CK-19, PDX-1, Nestin, Ngn3 was amplified by RT-PCR. Results: After two different purification methods applied, three islet preparations of different purities were obtained. The difference of islet purity was significant among various groups (P＜0.05). Compared with group Ⅱ and group Ⅲ,the protein and mRNA of CK-19, PDX-1, Nestin,Ngn3 were both higher in group Ⅰ; group Ⅲ was poorly expressed. Conclusions: The three different islet purity donor islet have different CK-19, PDX-1, Nestin, Ngn3 positive cells within them, indicating that there are some islet stem cells in the purified donor islet.     

Dr.Zhang Ren''''s Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

Luo Lingjie''''s Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.