【作者】 刘一玄；

【导师】 董梦久；

【作者基本信息】 湖北中医学院 ， 中医内科学， 2009， 硕士

【摘要】 目的本课题拟通过临床研究,初步观察益智胶囊对老年性痴呆的临床疗效及安全性,探讨其治疗老年性痴呆的作用机理,为进一步研究打下基础。对减轻患者痛苦,提高临床疗效及防治老年痴呆都具有重要意义。方法1.病例入选对象(1)年龄≥50和≤80岁。(2)男女均可。(3)符合DSM-Ⅳ痴呆诊断标准、NINCDS-ADRDA老年性痴呆诊断标准,以及中医辩证为脾肾两虚、痰浊血瘀证者。(4)简易智能状态检查量表(MMSE)评分在>10分和≤24分之间,并根据文化程度进行调整(文盲不纳入,小学程度≤20,中学以上程度≤24)。(5)全面衰退量表(GDS)在3期到5期,为轻、中度痴呆。(6)海金斯基缺血指数量表里(HIS)≤4分,或无卒中病史或中风后3个月以上而HIS为5分、6分者,亦可纳入。(7)汉密尔顿抑郁量表(HAMD)≤10分。(8)体重在50-90Kg之间。(9)受试者自愿并有受试者或监护人员签署知情同意书。(10)对药物研究意义有正确认识,对研究人员的观察和评价有良好的依从性。(11)有一定文化程度,能写简单句子。凡符合以上各项的住院病人或门诊病人均可纳入临床试验病例。2.病例排除对象(1)重度痴呆,即MMSE评分≤10分,或GDS评分>5期者。(2)患有血管性痴呆(HIS≥7分)或有其它原因所致的痴呆者。(3)HAMD≥11分。(4)体质过敏者,对茴拉西坦过敏或其它吡咯烷酮类药物不能耐受者。(5)在4周内参加或正在参加其它临床研究者。3.全部病例系2008年2月-2009年2月湖北省中医院神经内科门诊及住院患者,共56例,按入院先后次序,采用随机双盲的原则,分为治疗组和对照组,其中治疗组28例,对照组28例。4.试验组:益智胶囊,日三次,每次2粒,早中晚饭后0.5-1小时温开水送服;对照组:茴拉西坦日三次,每次2粒早中晚饭后0.5-1小时温开水送服。疗程:3个月为一疗程,共服2个疗程。显效病例随访至第9月。5.合并用药要求:(1)试验期间禁止使用治疗老年痴呆(AD)的其它药物与疗法。(2)研究期间禁用神经营养剂、其它促智药和中药滋补剂。6.安全性观测(1)一般体格检查:呼吸、心率、血压、脉搏、体温等。(2)血、尿、粪常规化验。(3)心电图、肝功能(ALT、AST)、肾功能(BUN、Cr)检查。以上检查试验前、试验期3月、6月各检查一次,以确定益智胶囊是否有毒副作用。7.两个疗程结束后,由同一医生复查各种量表,经统计学处理,比较治疗前后各组的总有效率、痊愈率。8.疗效与安全性评定标准8.1疗效评定标准8.1.1智能疗效评定标准评定标准:以MMSE、ADAS-cog评分为主要参考指标,采用尼莫地平法计算疗效指数。8.1.2中医证候疗效评定依据中华人民共和国卫生部颁布的《中药新药临床研究指导原则》相关部分采用尼莫地平方法:[(治疗前-治疗后积分)÷治疗前积分]×100%,以百分数表示。8.2安全性评价标准1级:安全,无任何不良反应。2级:比较安全,如有不良反应,不需要做任何处理可继续给药。3级:有安全性问题,有中等程度的不良反应,做处理可继续给药。4级:因不良反应中止试验。结果1.两组临床疗效比较:治疗组基本痊愈2例,显效14例,有效6例,无退步3例,无效3例。治愈率和显效率之和57.15%,总有效率89.29%。对照组基本痊愈0例,显效7例,有效8例,无退步8例,无效5例。治愈率和显效率之和25.0%,总有效率82.14%,低于治疗组,经统计学分析,治疗组与对照组治愈率和显效率之和有非常显著性差异(P<0.01),总有效率有显著性差异(P<0.01)2.两组日常生活能力量表(ADL)比较:治疗组28例:治疗前28.81±6.60,治疗后21.56±4.35*#;对照组2 8例:治疗前28.42±6.47,治疗后26.74±5.42*。与本组治疗前比较,*P<0.01;与对照组同时段比较,#P<0.01;经配对t检验,两组治疗后与治疗前证候积分比较差异有显著性(P<0.01),治疗组改善明显优于对照组(P<0.01).3.两组MMSE量表积分积分改变比较:治疗组28例:治疗前14.11±2.50,治疗后21.69±2.91**##;对照组28例:治疗前14.69±3.16,治疗后17.88±3.51**。与本组治疗前比较,**P<0.01;与对照组治疗后比较,##P<0.01;经配对t检验,治疗组治疗后较治疗前MMSE量表积分改善差异均有显著性(P<0.01),且组间比较差异亦有显著性(P<0.05,或P<0.01).4.两组治疗前后ADAS-cog量表积分改变情况比较均有改善,治疗组28例:治疗前29.18±6.28,治疗后19.96±6.32*▲;对照组28例:治疗前30.44±7.22,治疗后25.88±7.78*。与本组治疗前比较*P<0.01;与对照组同时段比较▲P<0.01,经配对t检验,两组治疗后与治疗前ADAs-cog积分比较差异有显著性(P<0.01),治疗组改善明显优于对照组(P<0.01)。5.不良反应及毒副作用:治疗组和对照组在临床试验期间,均未出现明显不良反应及毒副作用。两组实验室检查结果(三大常规、肝肾功能)在治疗前后均未出现与治疗相关的异常改变。结论本次研究结果表明,益智胶囊治疗老年性痴呆(AD)(脾肾两虚,痰浊血瘀证),疗效显著且优于茴拉西坦,且未出现明显不良反应及毒副作用,结果表明,益智胶囊能明显改善老年性痴呆(AD)患者的学习记忆功能,减轻老年性痴呆临床症状,提高患者的生活质量。更多还原

【Abstract】 Purpose:This topic plans through the clinic research,the first step observes YI ZHI capsules to the senile dementia clinical curative effect and the security,inquirying into it to cure stupid function mechanism of old age,laying the foundation for the further research,to raise clinical curative effect and prevent and cure senile dementias to all have important meaning towards easing a sufferer pain and sufferings,.Method:1.Case of illness being selected object(1)The age >=50 and <=80 years old.(2)The men and women may(3)Conforms to DSM-Ⅳstupid diagnosi standard,the NINCDS-ADRDA old age is stupid to examine a patient standard, as well as Chinese medicine dialectical for the spleen kidney two falsely,the phlegm muddy blood jam-up certificate.(4)The simple intelligence appearance check meter(MMSE) grades point in >10 minute with <=24 minute between,and carries on adjustment according to the cultural degree,(the illiteracy bring into line with,the primary school degree less than 20,above degree less than in middle school 24)(5)Completely the decline quantity form(GDS) at in 3 expect to 5 periods,for is light,in the degree is stupid.(6)The Hachinski less than 4 cent,or have no the disease history or CVD behind more than 3 months but HIS is 5 divide,6 cent,may also bring into.(7)The HAMD less than 10 centses.(8)The weight is between the 50-90 Kg(9)Test-receiver voluntarily also test-receiver or serve as guardian a personnel to sign to know what happened an approval a book.(10)Have right understanding to the medicine research meaning, have to the researcher’s observation and evaluation to obey sex goodly.(11)There is certain cultural degree,can write simple sentence.Any match above various inpatients or outpatient and all can bring into a clinical trial case.2.The case expels object(1)The heavy degree is stupid,namely the MMSE grade point less than 10 cent,or the GDS grade point>5 period.(2)Get blood vessel stupid(the HIS more than 7 cent) or there is other reason with the result that of stupid.(3)The HAMD more than 11 cents.(4)The physical endowment allergy,pulling the Aniracetan Capsules or other Pyrrolidone medicine to the Aniracetan Capsules can’t bear to be subjected to.(5)Other researchers attends or is attending the Clinical within 4 weeks. 3.All cases is in November,2004 to December 2005 year Hubei Province Chinese medicine hospital nerve internal medicine department outpatient service and is hospitalized the patient,total the altogether 56 example,press to hospitalize to is divided into a treatment the set and matched control order of sequence and random,cure a set among them 28 examples,matched control is 28.Is divided into random two sets of basic balanced was learn by covariance in the age,sex,course of illness,and the condition degree examination,do not show the prominence difference(P>0.05), has the commeasurability.4.Experimental group:YI ZHI capsules,day three times,each time 5 grains,win supper an empress early 0.5-1 hour,the boiled water sends;Matched control group:The Aniracetan Capsules for day three times,each time 2 grains(add to imitate 3 grains of total 5 grains of),win the empress of the supper early 0.5-1 hour,the boiled water sends,period of treatment:It is one period of treatment for 3 months,take period of treatment totally.Shows the effect case with visit to the 9 monthses.Conclusio:This result of research indicated that YI ZHI capsules cure dementia(AD)(the spleen kidney two falsely,the phlegm muddy blood jam-up certificate),the curative effect shows the prominence and better than Aniracetan Capsules,three black capsules can improve a Dementia(AD) sufferer obviously of the study memory function.Ease stupid clinical symptom of old age, raise the sufferer’s living quality.更多还原