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happykeren2008捐助贵宾 (正式写手)
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尼莫地平综述中译英（3天内有效）
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尼莫地平（Nimodipine，Nim）又称硝苯吡酯（Nimotop），是第二代吡啶类钙拮抗剂。目前在临床上多用于脑血管病变的治疗，即用于缺血性脑血管病，治疗轻或中度高血压，预防和治疗蛛网膜下腔出血后脑血管痉挛、突发性耳聋、偏头痛等。由于它具有很高的亲脂性特点，易透过血脑屏障。当用于蛛网膜下腔出血的治疗时，脑脊液中的浓度可达12.5ng/ml，与中枢神经的特异受体相结合，该特异性使本品能有效地预防和治疗因脑血管痉挛造成的脑组织缺血性损害。在适宜剂量下选择性扩张血管几乎不影响外周血管，但增加剂量对高血压也有较好的疗效。然而在人体应用该药的作用机制仍不完全清楚。此外尚具有保护和促进记忆、促进智力恢复的作用。 尼莫地平作为临床脑血管药已应用多年，但因其本身理化性质原因存在水溶性差、首过效应明显等缺点，直接影响临床药效的发挥。临床证明，由于尼莫地平制备工艺和剂型的不同，它们的生物利用度和扩张血管效力有着很大差距。普通尼莫地平片剂、胶囊剂因溶出速率和首过效应等原因，其绝对生物利用度仅为20%左右，采用固体分散技术提高尼莫地平的溶出速率是提高其生物利用度的较好方法，文献报道多采用传统的熔融法、溶剂法、或溶剂-熔融法制备，制得的固体分散物粉碎困难，粉碎过程中易造成药物分散状态的改变，本文以水溶性载体材料聚乙烯吡咯烷酮(PVPk30)为载体，采用喷雾干燥工艺制备粉末状尼莫地平固体分散体，通过对不同药物载体比例的固体分散体体外溶出速率比较药物分散状态分析，筛选其最佳处方和制备工艺。水溶性载体材料聚乙烯吡咯烷酮(PVPk30)制备尼莫地平固体分散体载药量大，载体稳定性好，不易老化；喷雾干燥工艺重现性好，分散体颗粒无需粉碎可满足各类固体制剂的制备要求，是一种较理想的尼莫地平固体分散体的制备方法。 尼莫地平片剂、胶囊剂由于经过胃肠道吸收，要经肝脏代谢，进入周围毛细血管或淋巴管，再进入血液循环，中间有较长时间的吸收、分布过程，药物在整个过程中大约损失80%，首过效应非常明显；而尼莫地平注射剂虽然直接进入血液循环而被全部吸收，但存在使用不方便、病人难以接受的缺点。因此我们拟将尼莫地平制备为口腔速溶片。尼莫地平口腔速溶片是运用现代速释技术制备而成的一种新型制剂。本类制剂无需以水送服，通过速释系统，可使药物在口腔内能迅速崩解，口感良好，可避免胃肠道首过作用，以期增加药物溶出度，提高药物生物利用度，提高患者用药的顺应性。 市售尼莫地平片的剂量为30mg，本研究设计的口溶片剂量为20mg，片剂硬度控制在2kg/cm2左右。 由于本类制剂无需以水送服，为达到较好的崩解效果，一般要求主药含量要小，总片重也应较小。从FDA批准产品的规格上可得到证实。因此本类制剂在主成分的选择范围相对较窄。本制剂处方中采用了聚乙烯吡咯烷酮（PVPk30）、交联聚乙烯吡咯烷酮（PVPP）、微晶纤维素（ＭＣＣ）和矫味剂，另加以部分其他辅料。 制剂中所含赋形剂如填充剂、崩解剂、润滑剂、粘合剂等不同，即会影响药片崩解和溶出的速度。微晶纤维素在口溶片中是较为常用的辅料，由于其较好的流动性，压缩后较好的粘合性。不仅有助于压片，而且微晶纤维素还具有一定的崩解作用，有助于口溶片在口中快速崩解。但其溶胀性很差，浓度较高的MCC制得的片剂，在高湿度时片剂变软，并且MCC用量太多时口腔会有一种砂砾感。经过考察，当微晶纤维素与NaHCO3的配比为 60:40 时，片剂崩解时间最短，释药速率为 58%/0.5min。故在本处方中，作为粘合剂和助流剂的MCC与NaHCO3的配比选用60:40。 该类制剂与普通制剂相区别最主要的质控指标为崩解度和溶出度。崩解度检查文献一般采用两种方法：志愿者口服试验法和药典崩解度检查方法改进法。志愿者口服试验法以服药后的主观感觉为依据，无粗糙砂砾感即为崩解完全；而崩解度检查方法改进法采用不加振摇的崩解度测定法，片剂全部通过10目筛即为崩解完全。 根据优化处方制备的口溶片，该片口感良好；崩解时间约为21.5s，符合相关要求。其体外溶出度与普通市售片相比：口溶片T50为0.47min，而普通片为5.4min，溶出速率明显提高。初步确定了尼莫地平口溶片的工艺及处方组成。 建立了尼莫地平口腔速溶片的体外考察方法，体外考察结果表明：口溶片在溶出前15min溶出度显著大于普通市售片，15min后无明显差异。说明该片能达到迅速释药的目的。 对自制的尼莫地平口腔速溶片进行了初步稳定性研究。加速试验结果显示，除6个月内该片除略有片重增加外，其它指标无明显变化，说明该片在考察期内基本稳定。 溶出度检查则一般采取各国通用药典所收载的普通片剂的溶出度检查方法进行。由于本类制剂要求在体内行为与普通片剂一致，故采用普通片剂的溶出度检查方法尚属可行。 Nim片目前已在全国各大医院广泛使用，但由于Nim亲脂性高、水溶性小，口服不易吸收。制剂配方的合理，制剂工艺的好坏将直接影响Nim片的生物利用度，影响Nim的临床疗效。为克服现有剂型不足，进一步改进Nim口服后的吸收性能，提高生物利用度，研制了口溶片。该制剂不仅适用于吞咽困难的病人，而且，对于在工作时不易获得饮用液体的患者也很方便。本实验观察了Nim口溶片在健康志愿者体内的药代动力学和相对生物利用度，并与其市售片进行比较研究，旨在为口溶片的临床应用提供参考依据。 Nim在体内转化后有多种代谢产物，且在人体血液或其它体液中的治疗浓度较低。已经有报道的方法有HPLC，放免法及GC，本试验采用简单、快速、灵敏的HPLC法，测定了6名健康志愿受试者口服自制Nim口溶片和市售普通片后的体内药时过程，进行了人体药代动力学研究。并通过对计算参数的统计学比较，进行了相对生物利用度的探讨。 本文所建立的血浆样品中尼莫地平的HPLC测定方法，方法简便可靠，从色谱峰看血样杂质、样品、内标均得到很好的分离，血浆中内源性物质均不干扰样品峰，尼莫地平在相应的线性范围内，呈良好的线性关系；相对回收率、日内和日间精密度、稳定性、定量限、检测限均符合生物样品分析测定的要求。尼群地平作为内标较理想，其结构、理化性质与Nim相似，色谱行为相似并能完全分离，也不是Nim的代谢产物。本实验所建立的方法，具有灵敏度高，专属性强，定量准确等特点，符合生物样品分析要求。通过HPLC方法测定健康志愿者体内尼莫地平的血药浓度，对尼莫地平在人体内的药代动力学特征进行了研究。单剂量口服给药口腔速溶片和普通片后，人体内尼莫地平的血药浓度个体差异较大。 单剂量口服给药口溶片与普通片，药代动力学参数有明显变化，通过 AUC值可算出自制尼莫地平口溶片相对于普通市售片的生物利用度为177.27%，Nim口溶片的生物利用度显著提高。口溶片达峰时间Tmax比普通片达峰时间快0.63h，口溶片的Cmax与市售片相比有极显著性差异（P<0.01），而体内平均滞留时间MRT有显著性差异（P＜0.01）。说明口溶片速释效果不影响药物在体内的治疗效果。口溶片的吸收速率常数Ka值明显高于市售片，说明口溶片吸收快，其可能的原因为药物在口腔通过唾液迅速溶化而被口腔粘膜所吸收，相应的吸收速率常数较大。 人们患高血压、缺血性脑血管病、痴呆症等服药时，必须用开水送服药。一方面当患者用水服药，特别是老年和妇女儿童患者，常常十分不便；另一方面药物在口腔迅速崩解（通常30秒以下），能大大地提高药效（生物利用度）并迅速发挥作用。因此，药物口腔崩解制剂技术已成为当代医药高科技之一，具有广泛的应用前景。 [ Last edited by happykeren2008 on 2010-3-3 at 00:16 ] |
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xiaoqihu
铁杆木虫 (著名写手)
- 翻译EPI: 88
- 应助: 1 (幼儿园)
- 贵宾: 0.005
- 金币: 9724.8
- 散金: 7
- 红花: 4
- 帖子: 1337
- 在线: 105.6小时
- 虫号: 590066
- 注册: 2008-08-31
- 专业: 有机合成
错误肯定比较多，没仔细检查，你得自己好好看啊
★ ★
phyweiw(金币+2):积极应助，奖励一下 2010-03-03 13:19
happykeren2008(金币+1000):谢谢，高手！You deserve the golds！ 2010-03-03 23:15
phyweiw(金币+2):积极应助，奖励一下 2010-03-03 13:19
happykeren2008(金币+1000):谢谢，高手！You deserve the golds！ 2010-03-03 23:15
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Nimodipine (Nimotop), a second generation pharmacological agent, is known as a dihydropyridine calcium channel blocker which is used clinically for prevention and treatment of cerebrovascular dysfunction, ischemic cerebrovascular disease, hypertension, cerebrovascular spasm after subarachnoid hemorrhage, sudden sensorineural hearing loss, migraine, etc. Due to its high lipophilicity, nimodipine is easy to cross blood-brain barrier, and the concentrations of nimodipine as high as 12.5 ng/mL have been detected in the cerebrospinal fluid of nimodipine-treated subarachnoid hemorrhage patients. The characteristics of binding with specific receptors of nervuscentralis make Nimodipine a potential drug for prevention and treatment of ischemic brain damage resulting from cerebrovascular spasm. It leads to dilate blood vessel without interfering peripheral vessel under the appropriate dosage. It also has preferably medicinal effect when increasing dosage properly. However, it is unclear how the pharmacology.However, the precise mechanism of action of nimodipine in humans is unknown. It shows that nimodipine has positive effect on protecting memory and recovering intelligence. Have been introduced to cerebrovascular drug in clinically for several years, the drug effect of nimodipine is limited because of its low solubility in water and the evident first-pass metabolism. Clinically, the bioavailability and vasodilatability of nimodipine result extremely different due to the difference from preparation and dosageform. By the reason of intrinsic dissolution rate and first pass effect of tablets and capsules, the available bioavailability is only maximum 20%. But it seems that the better way to increase the bioavailability is to improve the first pass effect by employing the solid dispersion technique for making tablet and capsules. Previous reports showed that the traditional preparation of solid dispersion utilizing melting method, solvent method or melting-solvent method was difficult in crush and easiness of change when crushing. In our report, the way of preparation of solid dispersion is using spray drying technique that is based on carrier of water soluble materials, Polyvinylpyrrolidone (PVPk30). The best recipes and preparations were screened after careful analysis of intrinsic dissolution rate from different solid dispersion samples with different ratio of carriers. Preparation of nimodipine solid dispersion based on water soluble materials (PVPk30) is highly loaded, stable and endurable. Spray drying technique is reliable for preparation of nimodipine solid dispersion, and its good reproducibility and the dispersion is fulfilled in demands of all kinds of solid preparation. Nimodipine tablets and capsules absorbed in gastrointestinal tract entered peritubular capillary or lymphatic vessel, and then blood circulation until metabolized by liver, in that of relatively long time of abortion and distribution the drug effect lost 80% approximately. First pass effect is extremely obvious. Nimodipine injection, however, was absorbed completely after injected directly into blood circulation system, the inconvenience and unacceptability resulted limitation in wide utilization. In order to escape from above reasons, we expected to prepare nimodipine tablets in orally rapid dissolving tablets, a novel preparation of drugs based on modern rapid releasing technique. The tablets we introduced was fast dissolved in mouth without aid of water, convenient, tasty, avoiding from first pass effect, and improving dissolution rate, bioavailability and adaptability of drug. Commercially available nimodipine tablets is 30 mg per table, the tablets used in our research is 20 mg per tablet, and the hardness is 2 kg cm-2 Because the analogies we used is tablet without aid of water, it needed to keep main effective contents and weight of tablet small for obtaining better disintegration. According to regulation of FDA, the selection of main effective contents is limited. The tablets is made from PVPk30, PVPP, MCC, corrigent and other excipients The rate of disintegration and dissolution depended on different composition of excipients such as stuffings, disintegrants, Lubricants and adhesives. MMC, a common excipient for oral drugs, is not only used for help of tabletting, but also used for help of improving rapid dissolution in mouth due to good fluidity, disintegration and adhesivity after compression. For the MMC’s poor resistance to swelling, the tablets containing too much MMC became soft and tasted grittiness. Research indicated that the best time of disintegration is the ratio of MMC and Na2CO3 is 3:2, the dissolution is 58% / 0.5 min. Therefore, the best recipe of MMC and Na2CO3 for our tablets is MMC :Na2CO3 = 3:2. The difference for quality control between common tablet and self-made tablet is disintegration and dissolution. The reported methods for testing disintegration include oral testing by volunteers and modification of pharmacopoeial disintegration testing methods. Determination by volunteers depends on subjective description, taste of no grittiness representing complete disintegration. Moreover, modification of pharmacopoeial disintegration testing methods depends on disintegration without shake, the suspension passing through 10 Å sieve representing complete disintegration. The disintegration of oral dissolution tablets based on the preparation of modified recipe was dramatically improved to 21.5 s and tasted good, which is fulfilled with the demands. Comparing with dissolution of commercially available tablets 5.4 min, our tablets is 0.47 min, the rate of dissolution is highly increased. Preliminarily, the composition of nimodipine oral dissolution was confirmed. In vitro, the rate of dissolution is extremely faster than marketed tablets before first 15 min, no difference after first 15 min, which indicated intention of rapid release of drug. Preliminary research for self-made nimodipine tablets demonstrated that there was no change in other indexes except for gaining weight in 6 months, which meant it was basically stable in probation. The testing of dissolution rate was determined from popular phrarmacopeial method accordingly. Requirement for the agreement of behavior in vivo, the method used in common tablets was suitable for self-made tablets. Nowadays, Nim tablet is widely used in hospitals all over the country in spite of high lipophilicity, low solubility and low oral absorption. The bioavailability and clinical effects of Nim depended on rational recipe and techniques, the development of oral dissolution tablet secured shortage of currently available tablets, and improved the absorbability of Nim after orally ingested. It is very convenient for patients who have difficulty to obtain water and patients who have problem with dysphagia. This research investigated pharmacokinetics and relative bioavailability of Nim in healthy group, and comparatively studied the marketed tablets for reference of the clinical applications of Nim Nim metabolized to various products in vivo, and the therapeutic level in human blood and other body fluid is relatively low. It is reported that HPLC， GC and RIA could be used for measurement. In our pharmkenetic study, the comparison testing between Nim and marketed tablets was measured for 6 different healthy volunteers using the simple, fast and sensitive mehod is HPLC, and the relative bioavailability from the statistical comparison of calculated parttens was discussed. The HPLC method reported in this article for measuring the concentration of NiM samples in plasm is convenient and reliable. The signals of impurities, samples and interior labels were fully separated without any interference from endogenous components in plasm, nimodiping was in linear agreement with a range of relative linearity. The relative recovery, precision of intraday and interday, stability, limit of quantitation and detectability were fullfilled with the requirements of determination of biological sample analysis. Nimodipine as an ideal internal label, not metabolites, was fully separated due to its similar chromatographic behaviors in structural, physical and chemical properties.The method in this experiment has high sensitivity, specificity, and accurate characteristics, consistently with requirements of biological sample analysis. In vivo the concentration of nimodipine in healthy volunteers’ plasma was determined by HPLC, and characteristics of pharmacokinetics in hum body were studied. After comparing between ingestion of single dose oral fast dissolving tablets and common tablets, concentration of nimodipine in human plasma was great difference individually. Single dose oral fast dissolving tablets was significantly different from common tablets in partner of pharmacokinetics, it can be calculated through the value of AUC that the relative bioavailability of self-made oral dissolving tablets was 177.27% than that of common commercially available tablets. Nim oral dissolving tablets increased bioavailability significantly.The time to reach peak value Tmax for oral dissolving tablets was 0.63h faster than common tablets, whereas comparing with common tablets the Cmax of oral dissolving tablets was significantly different (P <0.01), so did the residence time MRT in vivo ( P <0.01). Results indicated that release effect of oral dissolving tablets does not affect the therapeutic effect of drugs in the body.The constant of absorption rate Ka was significantly higher than the commercially availables, which demonstrated that the faster absorption of oral dissolving tablets, the bigger constant of absorption rate was, a consequence of dissolution by saliva and rapid absorption by oral mucosa People suffering from hypertension, ischemic cerebrovascular disease and dementia etc, the drugs must be used with the aid of water. On the one hand patients, particularly elder people, women and children, often feel inconvenient when using drugs with aid of water; on the other hand, the fast disintegration in mouth (usually 30 seconds or less) can rapidly play a role to greatly enhance the bioavailability. Thus, the technology of oral disintegrating agent has become one of the contemporary prosperous medical technologies with broad prospect . [ Last edited by xiaoqihu on 2010-3-3 at 15:22 ] |
2楼2010-03-03 02:09:27
xiaoqihu
铁杆木虫 (著名写手)
- 翻译EPI: 88
- 应助: 1 (幼儿园)
- 贵宾: 0.005
- 金币: 9724.8
- 散金: 7
- 红花: 4
- 帖子: 1337
- 在线: 105.6小时
- 虫号: 590066
- 注册: 2008-08-31
- 专业: 有机合成
| Have been introduced to cerebrovascular drug in clinically for several years, the drug effect of nimodipine is limited because of its low solubility in water and the evident first-pass metabolism. Clinically, the bioavailability and vasodilatability of nimodipine result extremely different due to the difference from preparation and dosageform. By the reason of intrinsic dissolution rate and first pass effect of tablets and capsules, the available bioavailability is only maximum 20%. But it seems that the better way to increase the bioavailability is to improve the first pass effect by employing the solid dispersion technique for making tablet and capsules. Previous reports showed that the traditional preparation of solid dispersion utilizing melting method, solvent method or melting-solvent method was difficult in crush and easiness of change when crushing. In our report, the way of preparation of solid dispersion is using spray drying technique that is based on carrier of water soluble materials, Polyvinylpyrrolidone (PVPk30). The best recipes and preparations were screened after careful analysis of intrinsic dissolution rate from different solid dispersion samples with different ratio of carriers. Preparation of nimodipine solid dispersion based on water soluble materials (PVPk30) is highly loaded, stable and endurable. Spray drying technique is reliable for preparation of nimodipine solid dispersion, and its good reproducibility and the dispersion is fulfilled in demands of all kinds of solid preparation. |
3楼2010-03-03 06:52:48
xiaoqihu
铁杆木虫 (著名写手)
- 翻译EPI: 88
- 应助: 1 (幼儿园)
- 贵宾: 0.005
- 金币: 9724.8
- 散金: 7
- 红花: 4
- 帖子: 1337
- 在线: 105.6小时
- 虫号: 590066
- 注册: 2008-08-31
- 专业: 有机合成
| Nimodipine tablets and capsules absorbed in gastrointestinal tract entered peritubular capillary or lymphatic vessel, and then blood circulation until metabolized by liver, in that of relatively long time of abortion and distribution the drug effect lost 80% approximately. First pass effect is extremely obvious. Nimodipine injection, however, was absorbed completely after injected directly into blood circulation system, the inconvenience and unacceptability resulted limitation in wide utilization. In order to escape from above reasons, we expected to prepare nimodipine tablets in orally rapid dissolving tablets, a novel preparation of drugs based on modern rapid releasing technique. The tablets we introduced was fast dissolved in mouth without aid of water, convenient, tasty, avoiding from first pass effect, and improving dissolution rate, bioavailability and adaptability of drug. |
4楼2010-03-03 07:55:33
xiaoqihu
铁杆木虫 (著名写手)
- 翻译EPI: 88
- 应助: 1 (幼儿园)
- 贵宾: 0.005
- 金币: 9724.8
- 散金: 7
- 红花: 4
- 帖子: 1337
- 在线: 105.6小时
- 虫号: 590066
- 注册: 2008-08-31
- 专业: 有机合成
5楼2010-03-03 08:00:32
xiaoqihu
铁杆木虫 (著名写手)
- 翻译EPI: 88
- 应助: 1 (幼儿园)
- 贵宾: 0.005
- 金币: 9724.8
- 散金: 7
- 红花: 4
- 帖子: 1337
- 在线: 105.6小时
- 虫号: 590066
- 注册: 2008-08-31
- 专业: 有机合成
| Because the analogies we used is tablet without aid of water, it needed to keep main effective contents and weight of tablet small for obtaining better disintegration. According to regulation of FDA, the selection of main effective contents is limited. The tablets is made from PVPk30, PVPP, MCC, corrigent and other excipients |
6楼2010-03-03 08:17:51
xiaoqihu
铁杆木虫 (著名写手)
- 翻译EPI: 88
- 应助: 1 (幼儿园)
- 贵宾: 0.005
- 金币: 9724.8
- 散金: 7
- 红花: 4
- 帖子: 1337
- 在线: 105.6小时
- 虫号: 590066
- 注册: 2008-08-31
- 专业: 有机合成
| The rate of disintegration and dissolution depended on different composition of excipients such as stuffings, disintegrants, Lubricants and adhesives. MMC, a common excipient for oral drugs, is not only used for help of tabletting, but also used for help of improving rapid dissolution in mouth due to good fluidity, disintegration and adhesivity after compression. For the MMC’s poor resistance to swelling, the tablets containing too much MMC became soft and tasted grittiness. Research indicated that the best time of disintegration is the ratio of MMC and Na2CO3 is 3:2, the dissolution is 58% / 0.5 min. Therefore, the best recipe of MMC and Na2CO3 for our tablets is MMC :Na2CO3 = 3:2. |
7楼2010-03-03 09:02:53
xiaoqihu
铁杆木虫 (著名写手)
- 翻译EPI: 88
- 应助: 1 (幼儿园)
- 贵宾: 0.005
- 金币: 9724.8
- 散金: 7
- 红花: 4
- 帖子: 1337
- 在线: 105.6小时
- 虫号: 590066
- 注册: 2008-08-31
- 专业: 有机合成
|
The difference for quality control between common tablet and self-made tablet is disintegration and dissolution. The reported methods for testing disintegration include oral testing by volunteers and modification of pharmacopoeial disintegration testing methods. Determination by volunteers depends on subjective description, taste of no grittiness representing complete disintegration. Moreover, modification of pharmacopoeial disintegration testing methods depends on disintegration without shake, the suspension passing through 10 Å sieve representing complete disintegration. [ Last edited by xiaoqihu on 2010-3-3 at 09:31 ] |
8楼2010-03-03 09:27:25
xiaoqihu
铁杆木虫 (著名写手)
- 翻译EPI: 88
- 应助: 1 (幼儿园)
- 贵宾: 0.005
- 金币: 9724.8
- 散金: 7
- 红花: 4
- 帖子: 1337
- 在线: 105.6小时
- 虫号: 590066
- 注册: 2008-08-31
- 专业: 有机合成
| The disintegration of oral dissolution tablets based on the preparation of modified recipe was dramatically improved to 21.5 s and tasted good, which is fulfilled with the demands. Comparing with dissolution of commercially available tablets 5.4 min, our tablets is 0.47 min, the rate of dissolution is highly increased. Preliminarily, the composition of nimodipine oral dissolution was confirmed. In vitro, the rate of dissolution is extremely faster than marketed tablets before first 15 min, no difference after first 15 min, which indicated intention of rapid release of drug. Preliminary research for self-made nimodipine tablets demonstrated that there was no change in other indexes except for gaining weight in 6 months, which meant it was basically stable in probation. |
9楼2010-03-03 11:24:35
10楼2010-03-03 11:24:41
