重组人表皮生长因子软膏对烧伤患者血清表皮生长因子浓度的影响

目的:观察不同深度、不同面积烧伤创面对局部外用重组人表皮生长因子(rhEGF)软膏的吸收作用以及对血清EGF浓度的影响。方法:选择烧伤患者41例,局部外用rhEGF软膏治疗,每日换药一次。浅Ⅱ°创面患者于用药前和用药第4,7天;深Ⅱ°创面于用药前和用药后第7,14天,分别取患者静脉血清,采用放射免疫分析法测定患者各时间点血清中EGF浓度。结果:rhEGF软膏在试验浓度范围内,无论用药面积大小和用药时间长短其血清EGF水平均无明显变化,各时间点用药前后EGF血药浓度无显著差异(P>0.05);血清EGF浓度与创面深度和用药面积无明显的相关性。结论:rhEGF软膏局部外用,通过创面吸收的量甚微,体内无蓄积现象。     

重组人表皮生长因子生物黏附胶囊的体外黏附力评价

目的：考察口服重组人表皮生长因子生物黏附胶囊中黏附颗粒体外黏附性能，确定生物黏附剂配比。方法：采用一种体外黏附力测定装置，以卡波姆(934 PCP)、低取代羟丙基纤维素(L-HPC)、乳糖等不同的配比制成颗粒，测定肠黏膜上颗粒滞留率，并以滞留率的大小评价其黏附性强弱。结果：黏附颗粒中黏附剂配比不同，其黏附力有较大差异。实验结果表明，黏附颗粒中含卡波姆(934 PCP)10％、低取代羟丙基纤维素(L-HPC)8％制成的颗粒具有较好的生物黏附性。结论：以CP和L-HPC等作为黏附剂配以适量乳糖制成的颗粒具有较好的生物黏附性能，CP/L-HPC为54最为合适。     

重组人表皮生长因子对冷冻角膜缘上皮细胞PCNA表达的影响

为探讨重组人表皮生长因子(rhEGF)的浓度对冷冻后兔角膜缘上皮细胞增殖活性的影响，采用器官培养方法和SABC免疫组织化学染色法检测角膜缘上皮细胞的PCNA表达。结果表明，器官培养1周时，冷冻角膜缘上皮细胞核中均可见PCNA表达，染色阳性细胞主要在基底细胞层。EGF组的PCNA染色阳性率显著高于无EGF组(P&;lt;0．01)；而不同浓度的EGF组之间阳性率差异无显著意义(P&;gt;0．05)。结论：在体外器官培养中，EGF能增强超低温冷冻保存的角膜缘上皮细胞PCNA的表达，但无量效依赖性。     

胃康胶囊联合泮托拉唑治疗消化性溃疡的临床研究

目的探讨胃康胶囊联合泮托拉唑钠肠溶胶囊治疗消化性溃疡的临床疗效。方法选取2019年5月—2020年10月在南阳市中心医院就诊的106例消化性溃疡患者,按照随机数字表法将所有患者分为对照组和治疗组,各有53例。对照组口服泮托拉唑肠溶胶囊,40mg/次,1次/d。治疗组在对照组治疗的基础上口服胃康胶囊,1.2g/次,3次/d。两组患者连续治疗6周。观察两组的临床疗效,采用视觉模拟评分法(VAS)对患者主观腹痛程度进行评估,检测两组治疗前后血清白细胞介素-17(IL-17)、白细胞介素-1β(IL-1β)、基质金属蛋白酶-9(MMP-9)、表皮生长因子(EGF)、血管内皮生长因子(VEGF)、转化生长因子-α(TGF-α)水平。结果治疗后,治疗组的总有效率为94.34%,对照组总有效率为81.13%,组间对比有显著性意义(P<0.05)。治疗后,两组VAS评分显著降低(P<0.05),以治疗组VAS评分降低的更明显(P<0.05)。治疗后,两组的IL-17、IL-1β、MMP-9水平显著降低(P<0.05);治疗组的IL-17、IL-1β、MMP-9水平低于对照组,差异有统计学意义(P<0.05)。治疗后,两组的EGF、VEGF、TGF-α水平显著升高(P<0.05),以治疗组EGF、VEGF、TGF-α水平升高的更明显(P<0.05)。结论胃康胶囊联合泮托拉唑钠肠溶胶囊可提高消化性溃疡的临床疗效,减轻患者腹痛程度,降低炎症因子,促进溃疡面愈合,且安全性良好。     

rhEGF对猪断层皮肤创面表皮和真皮修复的影响

创伤愈合是一个极其复杂的生物学过程。据报道外源性表皮细胞生长因子(EGF)具有促进创伤修复的作用。本实验将探讨重组人表皮细胞生长因子(rhEGF)对中国五指山小型猪断层皮肤缺损创面表皮和真皮的修复作用,为临床使用提供理论依据。     

胃宁胶囊对胃溃疡大鼠胃黏膜EGF及EGFR mRNA表达的影响

目的:探讨胃宁胶囊抗溃疡的作用机理.方法:采用大鼠幽门结扎法致胃溃疡模型;RT-PCR法观察胃宁胶囊对大鼠胃黏膜表皮生长因子(EGF)及表皮生长因子受体(EGFR) mRNA表达水平的影响.结果:胃宁胶囊能提高胃黏膜组织中EGF及EGFR mRNA的表达水平.结论:胃宁胶囊对胃黏膜的保护作用与提高胃黏膜组织中EGF及EGFR mRNA表达水平有关.     

我院2019年门诊口服抗生素应用分析

目的 分析2019年医院门诊口服抗生素使用情况,评价抗生素使用的合理性,为规范抗生素合理使用提供参考。方法 采用限定日剂量(DDD)方法,回顾性对医院2019年门诊口服抗生素的用药频度(DDDs)、限定日费用(DDDc)和药物利用指数(DUI)进行统计分析。结果 医院门诊β-内酰胺类抗生素的用量和金额构成比最大。DDDs排序前5位分别是头孢丙烯片、盐酸多西环素肠溶胶囊、克拉霉素缓释片、罗红霉素胶囊和盐酸左氧氟沙星片。DDDc排序后5位分别是盐酸左氧氟沙星片、盐酸多西环素肠溶胶囊、头孢拉定胶囊、罗红霉素胶囊和罗红霉素缓释片。大部分抗生素DUI≤1,但盐酸多西环素肠溶胶囊和阿奇霉素肠溶胶囊的DUI> 1。结论 医院门诊抗生素的使用基本符合抗菌药物临床应用指导原则,但仍需要加强对阿奇霉素肠溶胶囊的临床规范使用管理。     

硫普罗宁肠溶胶囊人体生物等效性研究

目的:研究硫普罗宁肠溶胶囊与片剂在健康人体的生物等效性。方法:18例健康受试者采用双用期交叉试验,单剂量口服硫普罗宁肠溶胶囊剂或片剂300mg,LC-MS法测定血清中硫普罗宁浓度,3P97软件拟合主要药动学参数,并进行2种制剂的生物等效性评价。结果:硫普罗宁肠溶胶囊与片剂的主要药动学参数分别为:t_(1/2)(2.8±0.5)和(2.6±0.4)h,C_(max) (1453.0±263.1)和(1526.8±288.1)ng·ml~(-1),T_(max)(3.3±0.3)h和(3.1±0.5)h,AUC_(0-1)(7414.3±1248.3)和(7347.2±1286.8)ng·h·ml~(-1),AUC_(0-∞)(8102.0±1310.9)和(7902.8±1346.7)ng·h·ml~(-1)。肠溶胶囊与片剂比较相对生物利用度为(101.2±5.4)%。两药T_(max)差异无统计学意义,肠溶胶囊AUC_(0→t)和C_(max)的90%可信限分别落在片剂的98.8%～103.4%和93.1%～97.5%。结论:两种制剂生物等效。     

兰索拉唑肠溶微丸胶囊人体生物等效性研究

目的:研究兰索拉唑肠溶微丸胶囊与兰索拉唑肠溶胶囊的人体生物等效性.方法:20名男性健康志愿者随机交叉单剂量口服兰索拉唑肠溶微丸胶囊(受试制剂)或兰索拉唑肠溶胶囊(参比制剂)30mg后,采用HPLC法测定血药浓度,用DAS软件计算药动学参数,并评价其生物等效性.结果:单剂量口服受试制剂兰索拉唑肠溶微丸胶囊和参比制剂兰索拉唑肠溶胶囊的主要药动学参数分别为:t1/2(1.93±0.58)、(2.21±0.84)h;tmax(1.7±0.4)、(1.7±0.4)h;Cmax(1 067.49±321.71)、(1 034.72±291.14)ng·ml-1;AUC0~12(3 655.16±1 635.82)、(3 571.70±1 434.56)ng·h·ml-1;AUC0~∞(3783.13±1 691.29)、(3 735.80±1 541.56)ng·h·ml-1.受试制剂的相对生物利用度为(106.72±13.53)%.结论:2制剂具有生物等效性.     

非言肠溶微粒胶囊的药代动力学和生物等效性研究

考察了永信药品工业（昆山）有限公司生产的非言肠溶微胶囊的相对生物利用度和药物动力学参数。方法：以台湾永信药品工业股份有限公司生产的百炎肠溶微粒胶囊为对照品,采用自身对照法进行单剂量口服给药,血样经预处理后采用高效液相色谱法测定浓度。     

Insulin and C-peptide levels following oral administration of insulin in intestinal-enzyme protected capsules

1. Crystalline beef insulin was administered orally in capsules composed of a methacrylic acid copolymer which prevented breakdown of the insulin by enteric and pancreatic peptidases. 2. In studies performed in 3 individuals blood was sampled before oral ingestion of the insulin (40 144 units), and at 15 or 30 min intervals thereafter for 5.5 hr for measurement of immunoreactive insulin and C-peptide concentrations. 3. Following the administration of oral insulin, plasma immunoreactive insulin concentrations became elevated 4-5 hr after ingestion. 4. The rise in plasma insulin concentrations was associated with a corresponding fall in the concentration of C-peptide. 5. The data suggest that this preparation of oral insulin can produce significant enteric absorption of the peptide, and that further investigation of agents that facilitate insulin absorption from the gut might render the use of methacrylic acid copolymer coated capsules a physiologically sound and a commercially feasible method of oral insulin administration.     

Pharmacokinetics and bioavailability of indoprofen in man

Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 ) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vd ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.     

Duodenum-specific drug delivery: in vivo assessment of a pharmaceutically developed enteric-coated capsule for a broad applicability in rat studies

Targeting new oral drug formulations in the intestine has a broad applicability in animal studies. Enteric-coated capsules are gastroresistant and specific drug delivery systems useful for the evaluation of new pharmaceutical formulations during pre-clinical validations in rats. The purpose of this study was to develop and validate in a large-scale, reliable, reproducible capsules, to offer a safe and standardized duodenum-specific delivery system adapted for studies in rats. The reproducibility of the coating method, the coating layer uniformity and thickness, the external capsules integrity and their enteric properties after in vitro dissolution in simulated gastric and intestinal media were already evaluated and validated. This study presents the in vivo tests of the gastroresistance and of the location of the disintegration. Micro-computerized tomography and a pharmacokinetic study of acetaminophen-filled capsules showed that the enteric-capsules were resistant in the stomach with no apparent leak of the capsules, and were disintegrated in the early duodenum 1-1.5h after oral administration. A positive impact on the bioavailability of acetaminophen in coated capsules was attested. In conclusion, this work, developed with a rigorous pharmaceutical technology, presents a tool adapted for duodenum-specific delivery of new formulations in rats.     

Biopharmaceutics: Different Absorption Profiles of Deramciclane in Man and in Dog

We have studied the dog model for predicting the oral absorption of deramciclane, a novel anxiolytic compound, as a model acid-labile drug. The absorption profile of deramciclane was studied in man and beagle dogs after administration of conventional capsules and enteric coated tablets. Absorption in dogs pretreated with pentagastrin or saline was also studied after administration of conventional capsules. The in-vitro stability of deramciclane was determined over the pH range 1.2–6.0. The rate of degradation of deramciclane increased ten-fold as the pH was reduced from 2.1 to 1.2 (t.β (elimination half-life) 9 h and 39 min, respectively). Deramciclane was stable at pH. 3. The two formulations were bioequivalent in dogs and there were no significant differences between pharmacokinetic parameters measured for dogs pretreated with pentagastrin or saline. In man the mean relative bioavailability and C_max (peak plasma concentration) for the conventional capsules were approximately 75% and 83% of those for the enteric coated tablets (P = 0.0004 and P = 0.0031, respectively). This was probably because of degradation of deramciclane at lower pH of man's stomach compared with that of the dog. Pentagastrin was probably unsuccessful in reducing gastric pH and thus no change in absorption was observed. It is concluded that the absorption of deramciclane, and possibly other acid-labile drugs, cannot be predicted by use of the dog model.     

Bioavailability of flufenamic acid in hard and soft gelatin capsules.

The biological availability of flufenamic acid after oral administration of the drug in both hard and soft gelatin capsules was studied in dogs and humans. The soft gelatin capsules produced consistently higher plasma concentration-time curves.     

阿司匹林缓释胶囊的释放度与生物利用度研究

目的 :制备阿司匹林缓释胶囊 (A -SRC) ,并对其释放度与生物利用度进行研究。方法 :通过测定A -SRC的释放度 ,进行释放机制的研究 ;测定家兔体内血药浓度 ,研究A -SRC的相对生物利用度。结果 :A -SRC体外释放符合零级动力学过程。该制剂相对于其普通片剂释药稳定、生物利用度高。结论 :A -SRC缓释效果明显 ,给药后血药浓度较为平缓 ,持续作用时间长 ,可减少给药次数 ;由于A -SRC采用轻质辅料具漂浮性能 ,缓慢释药 ,因而有利于降低其对胃肠道的刺激性及其他不良反应。     

Bioavailability of metoclopramide in a sustained-release preparation

The aim of this study was to examine the pharmacokinetical behaviour of metoclopramide of Gastronetron retard capsules after a single administration to 8 healthy male volunteers. Determinations of the concentration of metoclopramide in the serum were made up to 24 h p.a. The calculation of the serum concentration curves was based on an open 2-compartment model. It has been proved that already 30 min after oral administration effective serum concentrations could be reached, which are maintained over about 24 h. An approximate value of 71% was obtained for the bioavailability of metoclopramide of Gastronerton retard capsules. The action achieved by the administration of 1 capsule Gastronerton retard per day can be considered equal to that of 3 single administrations of the conventional oral pharmaceutical form.     

普卢利沙星胶囊人体药动学研究

目的:研究单剂量和多剂量口服给予普卢利沙星胶囊的药动学。方法:12名健康成年受试者按3×3拉丁方随机分组,分别单次口服132、264、528mg普卢利沙星胶囊,多次口服264mg普卢利沙星胶囊,连续6d。采用高效液相色谱法测定给药后不同时间普卢利沙星代谢产物NM394的血药浓度。应用DASver1·0软件进行模拟拟合及参数计算。结果:12名受试者全部完成单次给药试验,试验期间未发生任何药品不良反应。各受试者血样中检测不到普卢利沙星,只能测定其代谢产物NM394。高、中、低3个剂量组均符合二室模型,在人体内的药动学过程符合一级动力学,无性别差异。多次给药未见蓄积现象和药动学参数的改变,表明本品无自身酶抑制或诱导作用。结论:本方法灵敏、准确、可靠、特异性强,可满足普卢利沙星临床药动学试验要求,其参数与国外文献报道一致,在我国成人中无性别差异。     

Validation of a pharmacokinetic model of colon-specific drug delivery and the therapeutic effects of chitosan capsules containing 5-aminosalicylic acid on 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats

A pharmacokinetic model of colon-specific drug delivery developed in a previous study has been validated by use of 5-aminosalicylic acid (5-ASA) as a model anti-inflammatory drug. The simulation curves obtained from the pharmacokinetic model were in good agreement with experimental data obtained after oral administration of 5-ASA-containing chitosan capsules. The concentrations of 5-ASA in the large intestinal mucosa after drug administration were higher than after administration of the drug in carmellose suspension. We then attempted colon-specific delivery of an anti-ulcerative colitis drug, in chitosan capsules, to accelerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-induced colitis in rats. To confirm this therapeutic model, salazosulphapyridine (SASP), a commercially available 5-ASA prodrug, was used as positive control. Colonic injury and inflammation were assessed by measuring myeloperoxidase activity and visual assessment (damage score), respectively. Because SASP is effective against TNBS-induced colitis in rats, use of the SASP-sensitive TNBS-induced colitis model validated the therapeutic effects of 5-ASA-containing chitosan capsules, which were significantly better than those of a suspension of the drug in carmellose. These findings suggest that our pharmacokinetic model of colon-specific drug delivery can accurately evaluate this colon-specific delivery system and that 5-ASA-containing chitosan capsules are more effective than other 5-ASA formulations for treatment of TNBS-induced colitis in rats.