脑清喷鼻微乳治疗急性缺血性脑卒中的临床研究
|
摘要
背景
急性缺血性脑卒中是指各种原因引起的供应脑部血液的动脉堵塞,使得该动脉供血区局部脑组织发生不可逆性损害,导致脑组织缺血、缺氧性坏死的一种脑血管疾病。本病具有发病率高、病死率高、致残率高的特点。由于大脑结构精细而重要,血脑屏障(blood-brain barrier,BBB)的存在以及药物药理研究的滞后,现代医学治疗缺乏理想的药物和方法,尤其是在恢复期和后遗症期更是缺乏有效的治疗药物。急性缺血性脑卒中属于祖国医学“中风”范畴,中医药治疗中风已有两千多年历史,疗效肯定。鼻疗法是中医外治法的一种。近年来,鼻疗法(经鼻给药)治疗脑血管疾病已是目前防治脑血管疾病的一个新的课题。将传统中医药结合现代制药技术制成的脑清喷鼻微乳通过鼻腔给药治疗本病,临床疗效确切，使用简便,值得进一步研究。
目的
观察脑清喷鼻微乳喷鼻治疗急性缺血性脑卒中的临床疗效,结合文献研究初步探明其疗效机制,同时确定脑清喷鼻微乳喷的制剂工艺。
方法
共80例急性缺血性脑卒中患者纳入研究,采用随机数字表法分为治疗组与对照组,各40例,两组均给予基础治疗(包括调整血压、控制血糖,口服拜阿司匹林肠溶片、尼莫地平片,必要时予脱水,抗感染等。)治疗组予脑清喷鼻微乳喷鼻,2喷/次,3次/天；对照组予安慰剂喷鼻,2喷/次,3次/天。疗程均为14天。
通过伪三相图优选出脑清喷鼻微乳的最佳处方比例,通过单因素考察选出合适的制备工艺,确定了表面活性剂、助表面活性剂和Km值,确定处方组成与配比比例,并进行有效药物含量检测。
结果
一脑清喷鼻微乳处方与工艺的研究,通过伪三元相图对脑清喷鼻微乳的处方进行筛选,确定了表面活性剂、助表面活性剂和Km值,确定处方组成与配比比例,以及含量与粒径检测,麝香酮浓度为0.060 mg/g。
二治疗组总体疗效优于对照组,p<0.05。治疗组40例,基本治愈12例,显效17例,有效9例,总有效率达95%；对照组基本痊愈7例,显效8例,有效22例,总有效率92.5%。两组总有效率相似,但等级资料分布不同,经Ridit分析,统计量u=2.5126,p=0.0120,p<0.05,提示治疗组优于对照组。
三两组患者治疗7天及治疗14天后NIHSS评分均有明显降低,提示治疗效果较好。两组患者治疗14天后NIHSS评分显著低于治疗7天后,p<0.01；治疗7天后NIHSS评分显著低于治疗前,p<0.01。治疗7天及治疗14天后NIHSS评分组间比较则治疗组优于对照组,p<0.01(0.05)。
四两组患者治疗前后中医症状积分比较。治疗组能明显改善患者中医症候,治疗7天后中风病症状积分显著低于治疗前,p<0.01；治疗14天后中风病症状积分显著低于治疗7天后,p<0.01。对照组中风病症状积分亦有所改善,治疗后7天与治疗后14天中医症状积分均明显低于治疗前,p<0.01。组间比较则治疗组治疗后7天,治疗后14天中医症状积分显著低于对照组,p<0.01。
五两组患者治疗前后空腹血糖,甘油三脂,总胆固醇水平比较,两组患者治疗前空腹血糖,甘油三脂,总胆固醇水平较高。治疗后两组空腹血糖,甘油三脂,总胆固醇均明显下降,与治疗前比较有统计学意义。但组间比较差异无统计学意义。
六两组患者治疗前后D-二聚体,血沉,超敏C反应蛋白水平比较。两组患者治疗前D-二聚体,血沉,超敏C反应蛋白水平均有所增高,其中血沉与超敏C反应蛋白水平均值高于正常值上限。治疗后,D-二聚体,血沉,超敏C反应蛋白水平均明显降低,与治疗前对比,p<0.01。组间比较,治疗组治疗14天后超敏C反应蛋白水平及血沉水平明显低于对照组,p<0.01(0.05)；组间比较,两组治疗14天后D-二聚体水平差异无统计学意义,p>0.05。
七两组患者治疗前后脂质过氧化物(LPO)、超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、同型半胱氨酸水平比较(HCY)。治疗前,两组患者LPO、SOD、GSH-Px、HCY等指标均有异常表现,主要为LPO, HCY水平增高,而SOD与GSH-Px降低。治疗后,两组患者LPO, HCY水平均有所下降,与治疗前对比,p<0.01(0.05)；SOD与GSH-Px水平有所上升,与治疗前对比,p<0.01(0.05)。组间比较,治疗组在降低LPO,提高SOD, GSH-Px水平优于对照组,p<0.01(0.05)；但在降低HCY水平上则与对照组无显著差异,p>0.05。
八不良反应观察结果：两组治疗前后血常规、尿常规、大便常规、肝肾功能、心电图无明显变化。治疗组患者治疗后鼻粘膜情况：7例治疗前3天有鼻痒,喷嚏等现象,但未影响疗程。5例鼻粘膜可见轻度潮红,充血,有少许分泌物附着。对照组患者治疗依从性良好,均能接受全疗程治疗。其中2例治疗前3天有鼻痒,喷嚏等现象,但未影响疗程。1例鼻粘膜可见轻度潮红,充血,有少许分泌物附着。
结论
脑清喷鼻微乳治疗急性缺血性脑卒中疗效较好,优于安慰剂,且安全性较高,其可能的疗效机制,中医方面包括有效发挥麝香、川芎、三七、冰片、石菖蒲、薄荷等药物的活血通络,开窍醒神的作用,以及刺激经络,调节脏腑(包括脑腑)功能；现代医学方面包括改善大脑血液循环,抗氧自由基损伤,抗炎症反应等神经保护机制。
Background
Acute ischemic stroke, also known as cerebral infarction, is a cerebral vascular disease caused by various reasons, the blood supply of the brain artery was blockage, making the local cerebral tissue irreversible damage, leading to cerebral ischemia, hypoxia necrosis. The disease has the characteristics of high incidence, high mortality and high morbidity.As the brain structure is fine and important, blood-brain barrier and trail of drug pharmacological studies, modern medical treatments had no ideal drug and methods on it. Acute ischemic stroke is equivalent to the "stroke" of Chinese medicine, the Chinese medicine treatment of stroke had more than two thousand years of history, and Confirmed more effective. Nasal therapy is one type of External therapy in traditional Chinese medicine。Nasal therapy (Nasal administration) to treat cerebral vascular disease was the current hot topic of cerebrovascular disease. Naoqing penbi weiru was made by traditional Chinese medicine combined with modern pharmaceutical technology, had clinical efficacy and easy using on Acute ischemic stroke, it is worth further study.
Objective
To study clinical efficacy of the Naoqing penbi weiru treat Acute ischemic stroke by Nasal administration, combined with literature research initially proved its efficacy mechanism, at the same time, to determine the preparation of Naoqing penbi weiru.
Methods
A total of 80 cases of acute stroke patients were Observed in the study, were randomly divided into treatment group and control group,40 patients of each group, two groups patients were given basic treatment (including the adjustment of blood pressure, control blood sugar, oral Aspirin and Nimodipine tablets, if necessary, to dehydration, anti-infection.) Treatment group were treated with Naoqing penbi weiru by Nasal administration,2 spray each and 3 times a day; the control group were treated with placebo,2 spray each and 3 times a day. Course of treatment was 14 days.
To Screen the best prescription of Naoqing penbi weiru by pseudo-ternary phase diagram, to electe appropriate production process by the single factor test, to determine the surfactant, cosurfactant and Km values, and to determine the composition and proportion of prescriptions Ratio, and effective drug content testing. Results
1 The study of prescription and production process of Naoqing penbi weiru, to Screen the best prescription of Naoqing penbi weiru by pseudo-ternary phase diagram, determining the surfactant, cosurfactant and Km values, and to determine the composition and proportion of prescriptions Ratio, and effective drug content testing, muscone concentration was 0.060 mg/g.
2 Clinical efficacy of treatment group were superior to control group,p <0.05. Treatment group had 40 cases, fully recovered in 12 cases, effective in 17 cases,9 cases of effective, ineffective and worse in 1 case, the total effective rate was 95%;Control group had 40 cases, fully recovered in 7 cases, effective in 8 cases,22 cases of effective,2 cases of ineffective and deteriorated in 1 case, the total effective rate was 92.5%. The total effective rate were similar, but different level of data distribution, the ridit analysis, statistics u=2.5126, p=0.0120, p<0.05, prompt treatment group were superior to the control group.
3 Two groups of patients 7 days and 14 days after treatment NIHSS scores were significantly lower, suggesting that the treatment effect is good. Two groups of patients 14 days after the NIHSS score was significantly lower than for 7 days, p<0.01; NIHSS score of 7 days after treatment was significantly lower than before treatment, p<0.01. The NIHSS score of Treated group were superior to the control group For 7 days and 14 days after treatment, p<0.01 (0.05).
4 Symptom score of traditional Chinese medicine beteen the two groups of before and after treatment. Treated group were significantly improve symptoms of Chinese medicine, symptom scores of 7 days after stroke was significantly lower than before treatment, p<0.01; treatment 14 days after stroke symptom score was significantly lower than for 7 days, p<0.01 (0.05). Control group also had obvious improvement in stroke symptom score of Chinese medicine before treatment and 7 days after treatment,14 days after treatment, Chinese medicine symptom score did not change significantly, p<0.01. Between the two groups after the treatment,7 days,14 days after treatment, Chinese medicine symptom score of Treated group was significantly lower than the control group, p<0.01.
5 The fasting blood glucose, triglycerides, total cholesterol levels in two groups before and after treatment:The fasting blood glucose, triglycerides, total cholesterol levels in two groups before treatment were higher. After treatment, fasting blood glucose, triglycerides, total cholesterol decreased significantly, compared with before treatment were statistically significant. However, differences between groups was not significant.
6 The D-dimer, ESR, hs-Crp level of Two groups before and after treatment: D-dimer, ESR, hs-Crp levels of Two groups before treatment are increased in both, including ESR and hs-Crp level were higher than the average upper limit of normal. After treatment, D-dimer, ESR and hs-Crp level were significantly decreased compared with that before treatment, p<0.01. Between the two groups, 14 days after treatment, hs-Crp level and ESR were significantly lower than the control group, p<0.01 (0.05); between the two groups, the D-dimer levels in 14 days after treatment had no statistically significant.
7 lipid peroxides, superoxide di-smutase, glutathione peroxidase, compared homocysteine levels of The two groups before and after treatment:Before treatment, both groups of lipid peroxides, superoxide dismutase, glutathione peroxidase, homocysteine are abnormal, mainly lipid peroxides and homocysteine levels increased, while superoxide dismutase and glutathione peroxidase decreased. After treatment, both groups of lipid peroxides, homocysteine levels are decreased compared with that before treatment, p<0.01 (0.05);superoxide dismutase and glutathione peroxide increased physical activity levels, compared with that before treatment, p<0.01 (0.05). Between the two groups, the treatment group decreased lipid peroxidation, increased superoxide dismutase and glutathione peroxidase levels were superior to the control group, p<0.01 (0.05); but in the homocysteine levels with the control group had no significant difference, p>0.05.
8 Adverse reaction observation:Before and after treatment, the blood, urine, stool test, liver and kidney function and ECG had no significant changes. After treatment, patients treated with nasal cases:7 cases in the first 3 days of had nasal itching, sneezing and so on, but did not affect the course of treatment.5 cases of nasal mucosa shows mild flushing, congestion, there is a little discharge attachment. After treatment, patients treated with placebo cases:2 cases in the first 3 days of had nasal itching, sneezing and so on, but did not affect the course of treatment.1 cases of nasal mucosa shows mild flushing, congestion, there is a little discharge attachment.
Conclusion
The clinical efficacy of the Naoqing penbi weiru on acute ischemic stroke by Nasal administration were superior to placebo, and safety, the possible effect mechanisms, for Chinese medicine, including effectively Playing drug effects to promot blood circulation, activating blood and dredging meridine, opening orifices and resuscitation, and to stimulate the meridians, regulate internal organs (including brain) function; for modern medicine, including the neuroprotective mechanisms of improve cerebral blood circulation, anti-oxygen free radical damage, anti-inflammatory reaction.
急性缺血性脑卒中是指各种原因引起的供应脑部血液的动脉堵塞,使得该动脉供血区局部脑组织发生不可逆性损害,导致脑组织缺血、缺氧性坏死的一种脑血管疾病。本病具有发病率高、病死率高、致残率高的特点。由于大脑结构精细而重要,血脑屏障(blood-brain barrier,BBB)的存在以及药物药理研究的滞后,现代医学治疗缺乏理想的药物和方法,尤其是在恢复期和后遗症期更是缺乏有效的治疗药物。急性缺血性脑卒中属于祖国医学“中风”范畴,中医药治疗中风已有两千多年历史,疗效肯定。鼻疗法是中医外治法的一种。近年来,鼻疗法(经鼻给药)治疗脑血管疾病已是目前防治脑血管疾病的一个新的课题。将传统中医药结合现代制药技术制成的脑清喷鼻微乳通过鼻腔给药治疗本病,临床疗效确切，使用简便,值得进一步研究。
目的
观察脑清喷鼻微乳喷鼻治疗急性缺血性脑卒中的临床疗效,结合文献研究初步探明其疗效机制,同时确定脑清喷鼻微乳喷的制剂工艺。
方法
共80例急性缺血性脑卒中患者纳入研究,采用随机数字表法分为治疗组与对照组,各40例,两组均给予基础治疗(包括调整血压、控制血糖,口服拜阿司匹林肠溶片、尼莫地平片,必要时予脱水,抗感染等。)治疗组予脑清喷鼻微乳喷鼻,2喷/次,3次/天；对照组予安慰剂喷鼻,2喷/次,3次/天。疗程均为14天。
通过伪三相图优选出脑清喷鼻微乳的最佳处方比例,通过单因素考察选出合适的制备工艺,确定了表面活性剂、助表面活性剂和Km值,确定处方组成与配比比例,并进行有效药物含量检测。
结果
一脑清喷鼻微乳处方与工艺的研究,通过伪三元相图对脑清喷鼻微乳的处方进行筛选,确定了表面活性剂、助表面活性剂和Km值,确定处方组成与配比比例,以及含量与粒径检测,麝香酮浓度为0.060 mg/g。
二治疗组总体疗效优于对照组,p<0.05。治疗组40例,基本治愈12例,显效17例,有效9例,总有效率达95%；对照组基本痊愈7例,显效8例,有效22例,总有效率92.5%。两组总有效率相似,但等级资料分布不同,经Ridit分析,统计量u=2.5126,p=0.0120,p<0.05,提示治疗组优于对照组。
三两组患者治疗7天及治疗14天后NIHSS评分均有明显降低,提示治疗效果较好。两组患者治疗14天后NIHSS评分显著低于治疗7天后,p<0.01；治疗7天后NIHSS评分显著低于治疗前,p<0.01。治疗7天及治疗14天后NIHSS评分组间比较则治疗组优于对照组,p<0.01(0.05)。
四两组患者治疗前后中医症状积分比较。治疗组能明显改善患者中医症候,治疗7天后中风病症状积分显著低于治疗前,p<0.01；治疗14天后中风病症状积分显著低于治疗7天后,p<0.01。对照组中风病症状积分亦有所改善,治疗后7天与治疗后14天中医症状积分均明显低于治疗前,p<0.01。组间比较则治疗组治疗后7天,治疗后14天中医症状积分显著低于对照组,p<0.01。
五两组患者治疗前后空腹血糖,甘油三脂,总胆固醇水平比较,两组患者治疗前空腹血糖,甘油三脂,总胆固醇水平较高。治疗后两组空腹血糖,甘油三脂,总胆固醇均明显下降,与治疗前比较有统计学意义。但组间比较差异无统计学意义。
六两组患者治疗前后D-二聚体,血沉,超敏C反应蛋白水平比较。两组患者治疗前D-二聚体,血沉,超敏C反应蛋白水平均有所增高,其中血沉与超敏C反应蛋白水平均值高于正常值上限。治疗后,D-二聚体,血沉,超敏C反应蛋白水平均明显降低,与治疗前对比,p<0.01。组间比较,治疗组治疗14天后超敏C反应蛋白水平及血沉水平明显低于对照组,p<0.01(0.05)；组间比较,两组治疗14天后D-二聚体水平差异无统计学意义,p>0.05。
七两组患者治疗前后脂质过氧化物(LPO)、超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、同型半胱氨酸水平比较(HCY)。治疗前,两组患者LPO、SOD、GSH-Px、HCY等指标均有异常表现,主要为LPO, HCY水平增高,而SOD与GSH-Px降低。治疗后,两组患者LPO, HCY水平均有所下降,与治疗前对比,p<0.01(0.05)；SOD与GSH-Px水平有所上升,与治疗前对比,p<0.01(0.05)。组间比较,治疗组在降低LPO,提高SOD, GSH-Px水平优于对照组,p<0.01(0.05)；但在降低HCY水平上则与对照组无显著差异,p>0.05。
八不良反应观察结果：两组治疗前后血常规、尿常规、大便常规、肝肾功能、心电图无明显变化。治疗组患者治疗后鼻粘膜情况：7例治疗前3天有鼻痒,喷嚏等现象,但未影响疗程。5例鼻粘膜可见轻度潮红,充血,有少许分泌物附着。对照组患者治疗依从性良好,均能接受全疗程治疗。其中2例治疗前3天有鼻痒,喷嚏等现象,但未影响疗程。1例鼻粘膜可见轻度潮红,充血,有少许分泌物附着。
结论
脑清喷鼻微乳治疗急性缺血性脑卒中疗效较好,优于安慰剂,且安全性较高,其可能的疗效机制,中医方面包括有效发挥麝香、川芎、三七、冰片、石菖蒲、薄荷等药物的活血通络,开窍醒神的作用,以及刺激经络,调节脏腑(包括脑腑)功能；现代医学方面包括改善大脑血液循环,抗氧自由基损伤,抗炎症反应等神经保护机制。
Background
Acute ischemic stroke, also known as cerebral infarction, is a cerebral vascular disease caused by various reasons, the blood supply of the brain artery was blockage, making the local cerebral tissue irreversible damage, leading to cerebral ischemia, hypoxia necrosis. The disease has the characteristics of high incidence, high mortality and high morbidity.As the brain structure is fine and important, blood-brain barrier and trail of drug pharmacological studies, modern medical treatments had no ideal drug and methods on it. Acute ischemic stroke is equivalent to the "stroke" of Chinese medicine, the Chinese medicine treatment of stroke had more than two thousand years of history, and Confirmed more effective. Nasal therapy is one type of External therapy in traditional Chinese medicine。Nasal therapy (Nasal administration) to treat cerebral vascular disease was the current hot topic of cerebrovascular disease. Naoqing penbi weiru was made by traditional Chinese medicine combined with modern pharmaceutical technology, had clinical efficacy and easy using on Acute ischemic stroke, it is worth further study.
Objective
To study clinical efficacy of the Naoqing penbi weiru treat Acute ischemic stroke by Nasal administration, combined with literature research initially proved its efficacy mechanism, at the same time, to determine the preparation of Naoqing penbi weiru.
Methods
A total of 80 cases of acute stroke patients were Observed in the study, were randomly divided into treatment group and control group,40 patients of each group, two groups patients were given basic treatment (including the adjustment of blood pressure, control blood sugar, oral Aspirin and Nimodipine tablets, if necessary, to dehydration, anti-infection.) Treatment group were treated with Naoqing penbi weiru by Nasal administration,2 spray each and 3 times a day; the control group were treated with placebo,2 spray each and 3 times a day. Course of treatment was 14 days.
To Screen the best prescription of Naoqing penbi weiru by pseudo-ternary phase diagram, to electe appropriate production process by the single factor test, to determine the surfactant, cosurfactant and Km values, and to determine the composition and proportion of prescriptions Ratio, and effective drug content testing. Results
1 The study of prescription and production process of Naoqing penbi weiru, to Screen the best prescription of Naoqing penbi weiru by pseudo-ternary phase diagram, determining the surfactant, cosurfactant and Km values, and to determine the composition and proportion of prescriptions Ratio, and effective drug content testing, muscone concentration was 0.060 mg/g.
2 Clinical efficacy of treatment group were superior to control group,p <0.05. Treatment group had 40 cases, fully recovered in 12 cases, effective in 17 cases,9 cases of effective, ineffective and worse in 1 case, the total effective rate was 95%;Control group had 40 cases, fully recovered in 7 cases, effective in 8 cases,22 cases of effective,2 cases of ineffective and deteriorated in 1 case, the total effective rate was 92.5%. The total effective rate were similar, but different level of data distribution, the ridit analysis, statistics u=2.5126, p=0.0120, p<0.05, prompt treatment group were superior to the control group.
3 Two groups of patients 7 days and 14 days after treatment NIHSS scores were significantly lower, suggesting that the treatment effect is good. Two groups of patients 14 days after the NIHSS score was significantly lower than for 7 days, p<0.01; NIHSS score of 7 days after treatment was significantly lower than before treatment, p<0.01. The NIHSS score of Treated group were superior to the control group For 7 days and 14 days after treatment, p<0.01 (0.05).
4 Symptom score of traditional Chinese medicine beteen the two groups of before and after treatment. Treated group were significantly improve symptoms of Chinese medicine, symptom scores of 7 days after stroke was significantly lower than before treatment, p<0.01; treatment 14 days after stroke symptom score was significantly lower than for 7 days, p<0.01 (0.05). Control group also had obvious improvement in stroke symptom score of Chinese medicine before treatment and 7 days after treatment,14 days after treatment, Chinese medicine symptom score did not change significantly, p<0.01. Between the two groups after the treatment,7 days,14 days after treatment, Chinese medicine symptom score of Treated group was significantly lower than the control group, p<0.01.
5 The fasting blood glucose, triglycerides, total cholesterol levels in two groups before and after treatment:The fasting blood glucose, triglycerides, total cholesterol levels in two groups before treatment were higher. After treatment, fasting blood glucose, triglycerides, total cholesterol decreased significantly, compared with before treatment were statistically significant. However, differences between groups was not significant.
6 The D-dimer, ESR, hs-Crp level of Two groups before and after treatment: D-dimer, ESR, hs-Crp levels of Two groups before treatment are increased in both, including ESR and hs-Crp level were higher than the average upper limit of normal. After treatment, D-dimer, ESR and hs-Crp level were significantly decreased compared with that before treatment, p<0.01. Between the two groups, 14 days after treatment, hs-Crp level and ESR were significantly lower than the control group, p<0.01 (0.05); between the two groups, the D-dimer levels in 14 days after treatment had no statistically significant.
7 lipid peroxides, superoxide di-smutase, glutathione peroxidase, compared homocysteine levels of The two groups before and after treatment:Before treatment, both groups of lipid peroxides, superoxide dismutase, glutathione peroxidase, homocysteine are abnormal, mainly lipid peroxides and homocysteine levels increased, while superoxide dismutase and glutathione peroxidase decreased. After treatment, both groups of lipid peroxides, homocysteine levels are decreased compared with that before treatment, p<0.01 (0.05);superoxide dismutase and glutathione peroxide increased physical activity levels, compared with that before treatment, p<0.01 (0.05). Between the two groups, the treatment group decreased lipid peroxidation, increased superoxide dismutase and glutathione peroxidase levels were superior to the control group, p<0.01 (0.05); but in the homocysteine levels with the control group had no significant difference, p>0.05.
8 Adverse reaction observation:Before and after treatment, the blood, urine, stool test, liver and kidney function and ECG had no significant changes. After treatment, patients treated with nasal cases:7 cases in the first 3 days of had nasal itching, sneezing and so on, but did not affect the course of treatment.5 cases of nasal mucosa shows mild flushing, congestion, there is a little discharge attachment. After treatment, patients treated with placebo cases:2 cases in the first 3 days of had nasal itching, sneezing and so on, but did not affect the course of treatment.1 cases of nasal mucosa shows mild flushing, congestion, there is a little discharge attachment.
Conclusion
The clinical efficacy of the Naoqing penbi weiru on acute ischemic stroke by Nasal administration were superior to placebo, and safety, the possible effect mechanisms, for Chinese medicine, including effectively Playing drug effects to promot blood circulation, activating blood and dredging meridine, opening orifices and resuscitation, and to stimulate the meridians, regulate internal organs (including brain) function; for modern medicine, including the neuroprotective mechanisms of improve cerebral blood circulation, anti-oxygen free radical damage, anti-inflammatory reaction.
引文
[1]张云云,张海梅,郭德莹,等.168例缺血生脑卒中患者体质特点研究.上海中医药杂志,2008,42(2)：31-34.
[2]李鹏涛,王永炎,黄启福.“毒损脑络”病机假说的形成及其理论与实践意义.北京中医药大学学报,2001,24(1)：126.
[3]王永炎.关于提高脑血管疾病疗效难点的思考.中国中西医结合杂志,1997,17：195.
[4]祝美珍,胡国恒,肖艳芬,等.淤痰热毒并治抗急性脑缺血损伤的策略探究.时珍国医国药,2009,20(2)：392-393.
[5]梁伟雄,温泽淮,赖世隆,等.中风病中医证候特征与脑病理改变的相关关系研究.新中医,1999,31(7)：41-42.
[6]栗广明,艾伟真,张琦.中医辨证治疗脑梗塞480例.中日友好医院学报,1998,12(3)：220
[7]杨国荣.中医辨证合黄芪血塞通静点治疗脑梗塞80例.天津中医,2000,17(1)：9-10.
[8]王喜芳.从痰瘀论治缺血性中风89例.中医研究,2007,20(8)：53-54.
[9]李琴福.化痰通络汤合星蒌承气汤治疗缺血性中风64例.陕西中医,2006,27(11)：1335-1336.
[10]化痰通脑饮治疗急性缺血性中风30例.中医研究,2008,21(2)：35-37
[11]陈建华,杨秀捷,赵冰.中医辨证合血疗治疗急性脑梗塞60例临床观察.中国中医急症,1998,7(2)：72-73.
[12]张新民,宋永福.川芎嗪治疗急性脑梗塞的临床研究.医学信息,2010,23(8)：118-119.
[13]方征宇,熊亮,黄杰,等.川芎嗪对脑缺血—再灌注大鼠神经功能及神经电生理的影响.山东医药,2010,50(2)：19-20.
[14]汪远金,申国明,王钦茂.川芎嗪对大鼠脑缺血再灌注损伤的保护作用.安徽中医学院学报,2000,19(1)：44-45.
[15]王东吉,尚改萍,连为民,等.川芎嗪对兔脑缺血再灌注损伤的保护作用.长治医学院学报,2003,17(4)：245-247.
[16]孙蓉,张作平,黄伟,等.麝香酮对完全性脑缺血大鼠的保护作用.中药新药药与临床药理,2009,20(3)：197-200.
[17]粱辉,陈虎,高颖,等.麝香酮抗局灶性脑缺血损伤的实验研究.中成药,2003,25(3)：225-227.
[18]刘继生,刘树鹏.刺五加注射液治疗缺血性脑卒中78例临床及血液流变学观察.中西医结合实践杂志,1997,10(4)：322.
[19]寿延红,陈颖,冯加继,等.刺五加对蛛网膜下腔出血患者血浆内皮素含量的影响.中风与神经疾病杂志,2001,18(3)：139.
[20]徐立新,何绘敏,曲云霞,等.新生大鼠缺氧缺血性脑病脑组织酯质过氧化改变及丹参保护作用探讨.新生儿科杂志,2000,15(2)：63-65.
[21]夏利霞,邓红霞,冯娟.注射用血塞通在脑梗死治疗中的应用.中国医药学刊,2006,4(4)：39.
[22]邢燕玲,涂乾,肖清丰,等.红花黄色素注射液治疗缺血性中风60例临床疗效观察.中国医院药学杂志,2008,28(17)：1493-1495.
[23]熊桂华.注射用灯盏细辛酚注射液治疗缺血性中风急性期(脑络瘀阻证)42例临床疗效分析.中国社区医师,2008,24(6)：414.
[24]江莲,戎小平.参麦、乌司他丁对大鼠脑缺血再灌注损伤保护作用的研究.河北医科大学学报,2002,23(3)：144.
[25]杨赶梅,夏娣文,余江健,等.芪蛭胶囊对中风高黏血症患者血液流变学变化的影响.中国中医药科技,2002,9(4)231.
[26]刘艳,罗祖明,冀玲,等.华佗再造丸对大鼠局灶性脑缺血损伤的保护作用.华西药学杂志,2004,19(2)：103.
[27]邓常青,刘志龙,葛金文,等.补阳还五汤抗脑缺血再灌注损伤作用机理的研究.中国中医基础医学杂志,1998,4(8)：32-35.
[28]阎惠霞,张万民,于继州.丹参通脉胶囊治疗脑卒中临床观察.中国医药学刊,2006,4(4)：77-78.
[29]潘国庆,罗清平.脑脉通胶囊治疗缺血性中风60例临床观察.中医药导报,2008,14(9)：31-32.
[30]徐建银,王林.步长脑心通胶囊治疗脑梗死临床观察.药物与临床,2008,16(7)：36-37.
[31]顾卫,谭峰,吴海科,等.清开灵注射液合中风Ⅰ号冲剂治疗脑梗塞及其对t-PA、PAI、GMP-140活性影响的研究.中国中医急症,2002,11(5)：335-336.
[32]赵军,王翔宇,汪香君,等.缺血性脑血管病的危险因素分析.中华现代内科学杂志,2007,4(1)：51-52.
[33]Schllinger PD, Fiebach JB, MohrA, et al. Thrrmbolytic therapy for ischem is therapy for ischem is smoke review Part 1. Intravenous thrrmbolysis Crit Care Med,2001,29 (9):1812-1820.
[34]Mayer To, Biller J. Antiplatetprescrbing patterns for TIA and schemic stroke.the Ind ana Vniversity experience J NeurolSci,2003,20(2):5-15.
[35]急性缺血性脑卒中临床试验(CAST)协作中心、急性缺血性脑卒中临床试验(CAST)全国协作组.全国2万例急性缺血性脑卒中早期抗血小板治疗临床对照研究结果(CAST临床试验),中国循证杂志,1999,14：34.
[36]Bednar MM. Combining antiplatelet and thrombolytic therapies for strokd Expert opin Phamacother,2002,3(4):401.
[37]Counsell C, Sandetcock P lonmolecular weight heparins or heparinoids veisus standard unfractionated heparin for acute ischaem is stroke (COCH RANER eview).In The Cochrane library Issue oxford Update software 2003:1223.
[38]Ooboshi H, Tbayashi S, Takada J, et al. Brain ischem ia as a potential target of gene therapy Exp Gerontol,2003,38(1-2):183.
[39]吴家华,罗焕敏.神经干细胞移植治疗中枢神经系统疾病可行性研究.中国老年学杂志,2005,25(1)：110.
[40]Phatouros CC, Franzer MBBS, Hiaashida RT, el al. carotidartery stent placement for atherosclerotic disease:rationale, techinique and current status. Radiology 2000,217(1):26-41.
[41]Graziadei PP, DeHan RS. Neuronal regeneration in frog olfactory system. J Cell Biol,1993,59:525-530.
[42]Mackay-Sim A, Kittel P. Cell dynamics in the adult mouseolfactory epithelium:a quantitative autoradiographic study. J Neurosci,1998,11:979-984.
[43]张朝佑.人体解剖学.第2版.北京：人民卫生出版社,1998.1845-1846.
[44]纪荣明,周晓平,许家军,等.嗅神经、嗅球和嗅束的应用解剖.解剖学杂志,2001,24(2)：179-181.
[45]赵红梅,刘新峰.经鼻给药-有效避开血脑屏障的中枢用药途径.中国临床神经科学,2003,11(3)：320-322.
[46]Chou KJ, Donovan MD. The distribution of local anesthetics into the CSF following intranasal ladministration. IntJPharm,1998,168(2):137.
[47]Gozes I, Bardea A, Reshef A, et al. Neuroprotective strategy for Alzheimer disease:intranasal administration of a fatty neuropeptide. Proc Natl Acad Sci USA,1996,93(1):427-432.
[48]Yajima T, Juni K, Saneyoshi M, et al.Direct transport of 2,3-didehydro-3-deoxythymidine(D4T) and its ester derivatives to the cerebrospinal fluid via the nasal mucous membrane in rats. BiolPharmBull,1998,21(3):272-277.
[49]Thorne RG, Emory CR, Ala TA, et al. Quamtitative analysis of the oltactir pathway for drug delivery to the brain. BrainRes,1995,692:278-282.
[50]Shipley MT. Transport of molecules from nose to brain:transneurona anterograde and retrograde labeling in the ratolfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain ResBull,1995,15:129-142.
[51]Frey WH, Liu J, Chen X, et al. Delivery of 125I-NGF to the brain via the olfactory route. DrugDelivery,1997,4:82-92.
[52]Mathison S, Nagilla R, Kompella UB. Nasal route for direct delivery of solutes to the central nervous system:factorfiction. J Drug Target, 1998,5:415-441.
[53]王宝庆,丁伟娇,孟兆凯,等.多肽类药物鼻黏膜吸收的研究进展.牡丹江医学院学报,2002,23(3)：57-58.
[54]Wang J, Sakai S, Deguchi Y, et al. Aminated gelatin as a nasal alsorptio nenhancer for peptide drugs:evaluation of absorption enhancing effect and nasal mucosa perturbation in rats. J Pharm Pharmacol,2002,54(2):181-188.
[55]侯铁宁,辛伟红.氮酮促进胰岛素经鼻吸收的功能和病理研究.中华耳鼻咽喉科杂志,2002,37(4)：271-273.
[56]许卫华,王晖,许卫铭.川芎嗪的鼻腔吸收及冰片的促进作用.中国临床药理学与治疗学,2002,7(5)：434-436.
[57]陆彬,张正全.用三角相图法研究药用微乳的形成条件.药学学报,2001,36(1)：58-59.
[58]Yun Seok Rhee, Jung Gyo Choi, Eun Seok Park, Sang Cheol Chi. Transdermal delivery, of ketoprofen using nanoemulsions. Int J Pharm.2001,228:61-63.
[59]Trotta M, Gallarate M, Carlotti ME,Morel S. Preparation of griseofu.lvin nanoparticles from water dilutable nanoemulsions. Int J Pharm.2003,254: 235-238.
[60]Hsiu-o Ho, Chih-chuan Hsiao, Ming-thau Sheu. Preparation of microemulsions using polyglycerol acid esters as suefactant for the delivery of protein drugs. J Pharm Sci,1996,85:138-143.
[61]刘亚敏,张赐安,彭胜权.开窍法治疗中风的临床再认识.新中医,2002,34(8)：7-8
[62]巩海涛,王雁群,贺广彬,等.麝香药理及代用品的研究近况.山东医药工业,2002,21(1)：26-28.
[63]季宇彬.中药有效成分药理与应用.哈尔滨：黑龙江科学技术出版社,1995：313-315.
[64]粱辉,陈虎,高颖,等.麝香酮抗局灶性脑缺血损伤的实验研究.中成药, 2003,25(3)：225-227.
[65]孙蓉,张作平,黄伟,等.麝香酮对完全性脑缺血大鼠的保护作用.中药新药与临床药理,2009,20(3)：197-199.
[66]沈强,刘亚敏.麝香在神经系统疾病中的临床运用及其药理作用.中西医结合心脑血管病杂志,2003,1(4)：217-219.
[67]方永奇,邹衍衍,李羚,等.芳香开窍药和祛痰药对中枢神经兴奋性的影响.中医药研究,2002,18(3)：40.
[68]魏楚蓉.冰片的药理作用及其机制研究进展.国际病理科学与临床杂志,2010,30(5)：45-47.
[69]徐冬英,余昭胜,杨意兰.三七总皂苷治疗脑出血的药理和临床研究进展.广西中医学院学报,2008,11(3)：106-108.
[70]杨雪梅.川芎嗪药理作用研究进展.中国生化药物杂志,20.10,31(3)：183-185.
[2]李鹏涛,王永炎,黄启福.“毒损脑络”病机假说的形成及其理论与实践意义.北京中医药大学学报,2001,24(1)：126.
[3]王永炎.关于提高脑血管疾病疗效难点的思考.中国中西医结合杂志,1997,17：195.
[4]祝美珍,胡国恒,肖艳芬,等.淤痰热毒并治抗急性脑缺血损伤的策略探究.时珍国医国药,2009,20(2)：392-393.
[5]梁伟雄,温泽淮,赖世隆,等.中风病中医证候特征与脑病理改变的相关关系研究.新中医,1999,31(7)：41-42.
[6]栗广明,艾伟真,张琦.中医辨证治疗脑梗塞480例.中日友好医院学报,1998,12(3)：220
[7]杨国荣.中医辨证合黄芪血塞通静点治疗脑梗塞80例.天津中医,2000,17(1)：9-10.
[8]王喜芳.从痰瘀论治缺血性中风89例.中医研究,2007,20(8)：53-54.
[9]李琴福.化痰通络汤合星蒌承气汤治疗缺血性中风64例.陕西中医,2006,27(11)：1335-1336.
[10]化痰通脑饮治疗急性缺血性中风30例.中医研究,2008,21(2)：35-37
[11]陈建华,杨秀捷,赵冰.中医辨证合血疗治疗急性脑梗塞60例临床观察.中国中医急症,1998,7(2)：72-73.
[12]张新民,宋永福.川芎嗪治疗急性脑梗塞的临床研究.医学信息,2010,23(8)：118-119.
[13]方征宇,熊亮,黄杰,等.川芎嗪对脑缺血—再灌注大鼠神经功能及神经电生理的影响.山东医药,2010,50(2)：19-20.
[14]汪远金,申国明,王钦茂.川芎嗪对大鼠脑缺血再灌注损伤的保护作用.安徽中医学院学报,2000,19(1)：44-45.
[15]王东吉,尚改萍,连为民,等.川芎嗪对兔脑缺血再灌注损伤的保护作用.长治医学院学报,2003,17(4)：245-247.
[16]孙蓉,张作平,黄伟,等.麝香酮对完全性脑缺血大鼠的保护作用.中药新药药与临床药理,2009,20(3)：197-200.
[17]粱辉,陈虎,高颖,等.麝香酮抗局灶性脑缺血损伤的实验研究.中成药,2003,25(3)：225-227.
[18]刘继生,刘树鹏.刺五加注射液治疗缺血性脑卒中78例临床及血液流变学观察.中西医结合实践杂志,1997,10(4)：322.
[19]寿延红,陈颖,冯加继,等.刺五加对蛛网膜下腔出血患者血浆内皮素含量的影响.中风与神经疾病杂志,2001,18(3)：139.
[20]徐立新,何绘敏,曲云霞,等.新生大鼠缺氧缺血性脑病脑组织酯质过氧化改变及丹参保护作用探讨.新生儿科杂志,2000,15(2)：63-65.
[21]夏利霞,邓红霞,冯娟.注射用血塞通在脑梗死治疗中的应用.中国医药学刊,2006,4(4)：39.
[22]邢燕玲,涂乾,肖清丰,等.红花黄色素注射液治疗缺血性中风60例临床疗效观察.中国医院药学杂志,2008,28(17)：1493-1495.
[23]熊桂华.注射用灯盏细辛酚注射液治疗缺血性中风急性期(脑络瘀阻证)42例临床疗效分析.中国社区医师,2008,24(6)：414.
[24]江莲,戎小平.参麦、乌司他丁对大鼠脑缺血再灌注损伤保护作用的研究.河北医科大学学报,2002,23(3)：144.
[25]杨赶梅,夏娣文,余江健,等.芪蛭胶囊对中风高黏血症患者血液流变学变化的影响.中国中医药科技,2002,9(4)231.
[26]刘艳,罗祖明,冀玲,等.华佗再造丸对大鼠局灶性脑缺血损伤的保护作用.华西药学杂志,2004,19(2)：103.
[27]邓常青,刘志龙,葛金文,等.补阳还五汤抗脑缺血再灌注损伤作用机理的研究.中国中医基础医学杂志,1998,4(8)：32-35.
[28]阎惠霞,张万民,于继州.丹参通脉胶囊治疗脑卒中临床观察.中国医药学刊,2006,4(4)：77-78.
[29]潘国庆,罗清平.脑脉通胶囊治疗缺血性中风60例临床观察.中医药导报,2008,14(9)：31-32.
[30]徐建银,王林.步长脑心通胶囊治疗脑梗死临床观察.药物与临床,2008,16(7)：36-37.
[31]顾卫,谭峰,吴海科,等.清开灵注射液合中风Ⅰ号冲剂治疗脑梗塞及其对t-PA、PAI、GMP-140活性影响的研究.中国中医急症,2002,11(5)：335-336.
[32]赵军,王翔宇,汪香君,等.缺血性脑血管病的危险因素分析.中华现代内科学杂志,2007,4(1)：51-52.
[33]Schllinger PD, Fiebach JB, MohrA, et al. Thrrmbolytic therapy for ischem is therapy for ischem is smoke review Part 1. Intravenous thrrmbolysis Crit Care Med,2001,29 (9):1812-1820.
[34]Mayer To, Biller J. Antiplatetprescrbing patterns for TIA and schemic stroke.the Ind ana Vniversity experience J NeurolSci,2003,20(2):5-15.
[35]急性缺血性脑卒中临床试验(CAST)协作中心、急性缺血性脑卒中临床试验(CAST)全国协作组.全国2万例急性缺血性脑卒中早期抗血小板治疗临床对照研究结果(CAST临床试验),中国循证杂志,1999,14：34.
[36]Bednar MM. Combining antiplatelet and thrombolytic therapies for strokd Expert opin Phamacother,2002,3(4):401.
[37]Counsell C, Sandetcock P lonmolecular weight heparins or heparinoids veisus standard unfractionated heparin for acute ischaem is stroke (COCH RANER eview).In The Cochrane library Issue oxford Update software 2003:1223.
[38]Ooboshi H, Tbayashi S, Takada J, et al. Brain ischem ia as a potential target of gene therapy Exp Gerontol,2003,38(1-2):183.
[39]吴家华,罗焕敏.神经干细胞移植治疗中枢神经系统疾病可行性研究.中国老年学杂志,2005,25(1)：110.
[40]Phatouros CC, Franzer MBBS, Hiaashida RT, el al. carotidartery stent placement for atherosclerotic disease:rationale, techinique and current status. Radiology 2000,217(1):26-41.
[41]Graziadei PP, DeHan RS. Neuronal regeneration in frog olfactory system. J Cell Biol,1993,59:525-530.
[42]Mackay-Sim A, Kittel P. Cell dynamics in the adult mouseolfactory epithelium:a quantitative autoradiographic study. J Neurosci,1998,11:979-984.
[43]张朝佑.人体解剖学.第2版.北京：人民卫生出版社,1998.1845-1846.
[44]纪荣明,周晓平,许家军,等.嗅神经、嗅球和嗅束的应用解剖.解剖学杂志,2001,24(2)：179-181.
[45]赵红梅,刘新峰.经鼻给药-有效避开血脑屏障的中枢用药途径.中国临床神经科学,2003,11(3)：320-322.
[46]Chou KJ, Donovan MD. The distribution of local anesthetics into the CSF following intranasal ladministration. IntJPharm,1998,168(2):137.
[47]Gozes I, Bardea A, Reshef A, et al. Neuroprotective strategy for Alzheimer disease:intranasal administration of a fatty neuropeptide. Proc Natl Acad Sci USA,1996,93(1):427-432.
[48]Yajima T, Juni K, Saneyoshi M, et al.Direct transport of 2,3-didehydro-3-deoxythymidine(D4T) and its ester derivatives to the cerebrospinal fluid via the nasal mucous membrane in rats. BiolPharmBull,1998,21(3):272-277.
[49]Thorne RG, Emory CR, Ala TA, et al. Quamtitative analysis of the oltactir pathway for drug delivery to the brain. BrainRes,1995,692:278-282.
[50]Shipley MT. Transport of molecules from nose to brain:transneurona anterograde and retrograde labeling in the ratolfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain ResBull,1995,15:129-142.
[51]Frey WH, Liu J, Chen X, et al. Delivery of 125I-NGF to the brain via the olfactory route. DrugDelivery,1997,4:82-92.
[52]Mathison S, Nagilla R, Kompella UB. Nasal route for direct delivery of solutes to the central nervous system:factorfiction. J Drug Target, 1998,5:415-441.
[53]王宝庆,丁伟娇,孟兆凯,等.多肽类药物鼻黏膜吸收的研究进展.牡丹江医学院学报,2002,23(3)：57-58.
[54]Wang J, Sakai S, Deguchi Y, et al. Aminated gelatin as a nasal alsorptio nenhancer for peptide drugs:evaluation of absorption enhancing effect and nasal mucosa perturbation in rats. J Pharm Pharmacol,2002,54(2):181-188.
[55]侯铁宁,辛伟红.氮酮促进胰岛素经鼻吸收的功能和病理研究.中华耳鼻咽喉科杂志,2002,37(4)：271-273.
[56]许卫华,王晖,许卫铭.川芎嗪的鼻腔吸收及冰片的促进作用.中国临床药理学与治疗学,2002,7(5)：434-436.
[57]陆彬,张正全.用三角相图法研究药用微乳的形成条件.药学学报,2001,36(1)：58-59.
[58]Yun Seok Rhee, Jung Gyo Choi, Eun Seok Park, Sang Cheol Chi. Transdermal delivery, of ketoprofen using nanoemulsions. Int J Pharm.2001,228:61-63.
[59]Trotta M, Gallarate M, Carlotti ME,Morel S. Preparation of griseofu.lvin nanoparticles from water dilutable nanoemulsions. Int J Pharm.2003,254: 235-238.
[60]Hsiu-o Ho, Chih-chuan Hsiao, Ming-thau Sheu. Preparation of microemulsions using polyglycerol acid esters as suefactant for the delivery of protein drugs. J Pharm Sci,1996,85:138-143.
[61]刘亚敏,张赐安,彭胜权.开窍法治疗中风的临床再认识.新中医,2002,34(8)：7-8
[62]巩海涛,王雁群,贺广彬,等.麝香药理及代用品的研究近况.山东医药工业,2002,21(1)：26-28.
[63]季宇彬.中药有效成分药理与应用.哈尔滨：黑龙江科学技术出版社,1995：313-315.
[64]粱辉,陈虎,高颖,等.麝香酮抗局灶性脑缺血损伤的实验研究.中成药, 2003,25(3)：225-227.
[65]孙蓉,张作平,黄伟,等.麝香酮对完全性脑缺血大鼠的保护作用.中药新药与临床药理,2009,20(3)：197-199.
[66]沈强,刘亚敏.麝香在神经系统疾病中的临床运用及其药理作用.中西医结合心脑血管病杂志,2003,1(4)：217-219.
[67]方永奇,邹衍衍,李羚,等.芳香开窍药和祛痰药对中枢神经兴奋性的影响.中医药研究,2002,18(3)：40.
[68]魏楚蓉.冰片的药理作用及其机制研究进展.国际病理科学与临床杂志,2010,30(5)：45-47.
[69]徐冬英,余昭胜,杨意兰.三七总皂苷治疗脑出血的药理和临床研究进展.广西中医学院学报,2008,11(3)：106-108.
[70]杨雪梅.川芎嗪药理作用研究进展.中国生化药物杂志,20.10,31(3)：183-185.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |