CN116173152B - 脉络舒通制剂在制备防治糖尿病神经病变药物中的用途 - Google Patents
脉络舒通制剂在制备防治糖尿病神经病变药物中的用途 Download PDFInfo
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Abstract
本发明属于中药领域,具体涉及脉络舒通制剂在制备治疗糖尿病神经病变的用途。本发明脉络舒通制剂各味中药材协同增效,药理学及临床个例表明本发明中药组合物可以降低血糖水平,调节神经传导速度,改善痛性糖尿病神经病变引起的周围神经病变,治疗起效快、总有效率高、不良反应小,且无成瘾性。
Description
技术领域
本发明涉及脉络舒通制剂在制备防治糖尿病神经病变的药物中的用途,属于中药领域。
背景技术
糖尿病引发的周围神经病变(DPN)为糖尿病常见并发症之一。据统计,全球患者中,糖尿病引发的DPN致病率可达24.4%-78.8%;中国患者中,糖尿病引发的DPN约有80%,其中约25%的患者临床表现为痛性糖尿病神经病变。由于疾病侵犯感觉神经,典型的糖尿病痛性神经病变患者以自发痛、痛觉过敏和异常性疼痛为特征,可表现为蚂蚁爬行、烧灼、针刺、刺伤、跳跃、刀割、撕裂等,伴随肌肉无力,直接累及周围神经、中枢神经,夜间疼痛明显,严重影响日常生活质量、限制日常活动,并且可能导致患者情绪抑郁、影响社交。
目前,常规治疗多以改善疾病临床表现为主,主要采用控制血糖、缓解疼痛症状等手段。但由于糖尿病、神经病变的病因及发病原因均不明确,虽然α-硫辛酸等抗氧化药物阻断氧化应激、甲钴胺等外源性神经营养因子减轻神经损害以及普瑞巴林、加巴喷丁以及丙戊酸钠等抗惊厥药物或者三环类抗抑郁药被临床认可,但治疗效果不稳定,副作用大,且不宜长期用药、无法达到根治。DPN至今仍缺乏特异性治疗。
鉴于此,临床上迫切需要提供一种副作用小、疗效显著、复发率低的糖尿病痛性神经病变治疗药物。
发明内容
针对现有技术的不足,以上市产品“脉络舒通”的临床应用反馈为依据,本发明以科学严谨的态度,提供脉络舒通制剂的新用途。通过确切的药理学实验证实,脉络舒通制剂对治疗周围神经病变,尤其是糖尿病痛性神经病变具有优良的疗效,副作用小且复发率低,具有较大的商业价值。
本发明的目的之一是提供一种脉络舒通制剂的新用途。本发明所述的用途是在已上市产品“脉络舒通丸”及“脉络舒通颗粒”的临床应用上进行的反馈,但是本发明的用途不限于上述产品,采用本发明如下的技术方案所得到的制剂均能实现达到相同或相似的治疗效果。
本发明的技术目的是通过以下技术方案实现的:
一种由黄芪、金银花、黄柏、苍术、玄参、当归、白芍、甘草、蜈蚣和全蝎组成的脉络舒通制剂在制备防治糖尿病神经病变药物中的用途。
所述中药组合物各组分为:
优选的,所述脉络舒通制剂各组分为:
本发明的第二个目的是提供脉络舒通制剂的制药用途。本发明脉络舒通制剂各味中药材协同增效,药理学及临床个例表明本发明中药组合物可以降低血糖水平,调节神经传导速度,改善周围神经病变,治疗起效快、总有效率高,不良反应小、复发率低。
具体的,脉络舒通制剂具有治疗或改善周围神经病变的作用,尤其是,脉络舒通制剂具有治疗或改善神经痛的作用。
进一步的,所述周围神经病变伴有蚂蚁爬行、烧灼、针刺、刺伤、跳跃、刀割、撕裂的任一异常感觉症状。
所述周围神经病变为糖尿病引发。
此外,所述的脉络舒通制剂具有降糖作用,可用于制备或治疗糖尿病药物中的用途。优选的,所述糖尿病为1型糖尿病或2型糖尿病,优选为2型糖尿病。
本发明的第三个目的是提供一种上述中药组合物的制剂,所述中药组合物为由所述中药组分制备成中药口服制剂或外用制剂,优选的,所述中药口服制剂为汤剂、丸剂、片剂、合剂、胶囊剂、颗粒剂、散剂或膏剂。
进一步的,本发明提供的脉络舒通制剂依托于已上市品种“脉络舒通丸”及“脉络舒通颗粒”进行的临床反馈,因此,产品优选为脉络舒通丸或脉络舒通颗粒,但本发明产品不限于该品种。
进一步的,本发明还提供了所述脉络舒通制剂的制备方法:
A、取水蛭、蜈蚣、全蝎,粉碎使粒径小于100μm;
B、黄柏、薏苡仁、玄参、白芍加入乙醇提取,再用水提取,醇提液回收乙醇后,浓缩成醇提浸膏,水提液过滤备用;
C、金银花、苍术、当归、黄芪、甘草加水提取挥发油,剩余药液、药渣加1/2处方量的水蛭、蜈蚣、全蝎以水煎煮,过滤,滤液与步骤B中的水提液浓缩成浸膏;
D、将剩余1/2处方量的水蛭、蜈蚣、全蝎与步骤B醇提浸膏、步骤C水提浸膏混匀,经常规工序直接或加入药学上可接受的赋形剂制成临床可接受的剂型。
具体的,本发明制备方法如下:
A、取水蛭、蜈蚣、全蝎,粉碎使粒径小于100μm;
B、黄柏、薏苡仁、玄参、白芍先醇提后水提,即先加入50-65%乙醇提取2次,每次提取2.5小时,过滤,滤液回收乙醇、减压浓缩至相对密度为1.17-1.23的浸膏;再取过滤后的药渣加3倍水提取2次,过滤,水提取液备用;
C、金银花、苍术、当归、黄芪、甘草提取挥发油备用,剩余药液、药渣加1/2处方量的水蛭、蜈蚣、全蝎加水煎煮三次,每次煎煮1.5-2小时,滤液与步骤B中的水提液加入乙醇使含醇量达55-62%,常温静置24-48小时,滤液回收乙醇,浓缩至相对密度为1.13-1.25的浸膏,备用;
D、将剩余1/2处方量的水蛭、蜈蚣、全蝎与步骤B、步骤C所得浸膏混匀,经常规工序直接或加入药学上可接受的赋形剂制成临床可接受的剂型。
本发明具有以下优点:
(1)本发明中药组合物配方合理,对神经性疼痛具有显著的疗效。
(2)针对临床上用于治疗神经性疼痛尚无特效药的现状,本发明中药组合物的研发为患者进一步提供了的临床选择。采用本发明的中药组合物制剂,对改善运动神经传及感觉神经传导速度、降低痛阈值、降低致痛物质水平有显著作用,可有效缓解症状并改善患者生活质量。
附图说明
图1是本发明实施例1中各组间运动神经传导速度比较结果(与空白对照组比较**P<0.01,*P<0.05;与模型组比较##P<0.01,#P<0.05)。
图2是本发明实施例1中各组间感觉神经传导速度比较结果(与空白对照组比较**P<0.01,*P<0.05;与模型组比较##P<0.01,#P<0.05)。
图3是本发明实施例2中各组间血糖值比较结果(将治疗第6周的各组值进行数据分析,其中,与对照组比较**P<0.01,*P<0.05;与模型组比较##P<0.01,#P<0.05)。
图4是本发明实施例2中各组间痛阀值比较结果(将治疗第6周的各组值进行数据分析,其中,与对照组比较**P<0.01,*P<0.05;与模型组比较##P<0.01,#P<0.05;与阳性对照药组比较@@P<0.01,@P<0.05)。
图5是本发明实施例2中5-HT值比较结果。
图6是本发明实施例2中各组间E2值比较结果(将治疗第6周的各组值进行数据分析,其中,与对照组比较**P<0.01,*P<0.05;与模型组比较##P<0.01,#P<0.05;与阳性对照药组比较@@P<0.01,@P<0.05)。
具体实施方式
为验证本发明脉络舒通制剂的功效,发明人开展了药效学试验研究。需要说明的是,本发明药效学试验研究所选取的药品为本发明具有代表性的配方及其制备方法所得的药品。本发明所包含的其它配方及制备方法所得药品所涉及的试验及其结果,限于篇幅,在此不一一穷举。
实验例1脉络舒通制剂对大鼠糖尿病周围神经病变的影响
1材料
1.1实验动物
常规适应性饲养2周后,取健康雄性8周龄SPF级Wistar大鼠,体重180-200g,动物许可证号:SYXK(鲁)2018-0008。
1.2实验药品
脉络舒通颗粒(国药准字Z19991025),由鲁南厚普制药有限公司生产;实施例2颗粒剂、对比实施例2颗粒剂;甲钴胺片。所用药材、制剂均为普通市售,产品质量均符合国家规定。
2方法
2.1造模
大鼠禁食不禁水12h后造模:取链脲佐菌素溶于0.1mol/L柠檬酸-柠檬酸钠缓冲液(pH4.2)配制成浓度为1%的溶液,60mg/kg剂量单次腹腔注射。首次注射链脲佐菌素72h后尾静脉采血,连续2周检测血糖值,以血糖高于16.7mmol/L的大鼠作为造模成功。
2.2分组给药
将造模成功的大鼠随机分为模型组、实施例2小剂量组、实施例2大剂量组、脉络舒通组、阳性对照药甲钴胺组、对比实施例2组,每组8只;随机取8只健康大鼠作为空白对照组。
2.3实验方法
(1)药物干预:实施例2小剂量组、实施例2大剂量组、脉络舒通组、对比实施例2组每日分别给予剂量为6.25、12.50、12.50、12.50g/kg,1次/d;阳性对照药以甲钴胺0.030g/kg水溶液灌胃,1次/d;组模型组与空白对照组灌胃等量生理盐水,各组连续给药5天。
(2)运动神经传导速度测定:末次灌胃给药24h后,以刺激强度(3~6mA)的电极刺激大鼠尾神经,按照公式计算运动神经传导速度。计算公式如下:
运动神经传导速度(m/s)=记录电极与刺激电极阴极间距离(14cm)×10/潜伏期(ms)。
(3)感觉神经传导速度测定:末次灌胃给药24h后,将运动神经传导速度测定时的记录电极与刺激电极互换,刺激强度固定于1.2mA,按照公式计算感觉神经传导速度。计算公式如下:
感觉神经传导速度(m/s)=记录电极与刺激电极阴极间距离(14cm)×10/潜伏期(ms)。
2.4统计学分析
实验数据采用SPSS 22.0进行统计学处理。
3结果
3.1大鼠行为学观察
经实验过程中记录各组大鼠的行为学。空白对照组活跃,精神状态好,毛发光泽度好。模型组、对比实施例2组的大鼠与空白对照组相比,大鼠尿量与摄食量明显增多,活跃性差,弓背趴卧,且毛色凌乱、光泽度差。其他治疗组大鼠均表现出不同程度的上述症状,但均较模型组程度轻。
3.2各组大鼠运动神经传导速度数值比较
各组大鼠运动神经传导速度数值如图1所示。由图中数据可见,与空白对照组比较,模型组大鼠运动神经传导速度显著降低。与模型组比较,各给药组大鼠运动神经传导速度均有不同程度的增加。其中,实施例2大剂量组、脉络舒通组、阳性对照药组增加幅度明显,与空白组无显著性差异,对比实施例2组与模型组无显著性差异。
3.3各组大鼠感觉神经传导速度数值比较
各组大鼠感觉神经传导速度数值如图2所示。如图2所示,与空白对照组比较,模型组感觉神经传导潜伏期延长,传导速度减慢,具有显著性差异(P<0.01)。与模型组比较,实施例2大剂量组、脉络舒通组、阳性对照药组传导潜伏期增加幅度小,传导速度大(P<0.01);而实施例2小剂量组、对比实施例2组的传导潜伏期、传导速度与模型组无显著性差异(P>0.05)。
实验例2脉络舒通制剂对大鼠痛性糖尿病周围神经病变的作用
1材料
1.1动物:
SD大鼠,雄性,10周龄,体重(200±20)g,实验动物许可证号:SYXK(鲁)20180008,实验前适应性饲养一周。
1.2药物、试剂
1.2.1药物
脉络舒通颗粒(国药准字Z19991025),由鲁南厚普制药有限公司生产;实施例3颗粒剂;醋酸泼尼松片。所用药材、制剂均为普通市售,产品质量均符合国家规定。
1.2.3大鼠用药剂量
实施例3组:6.25g/kg(小剂量)、12.50g/kg(大剂量),1次/d;
对比实施例2组:12.50g/kg,1次/d;
脉络舒通组:12.50g/kg,1次/d;
醋酸泼尼松片组:1.35mg/kg,1次/d。
2.实验方式
2.1分组、建模及给药
取健康大鼠10组作为空白组。另取10只健康大鼠禁食不禁水12小时后,一次性腹腔注射相等容积的PH为4.2的0.1mol/L枸椽酸缓冲液,作为对照组。
随机挑选大鼠禁食不禁水12小时,腹腔注射2%链脲佐菌素溶液53mg/kg(以PH为4.2的0.1mol/L枸椽酸缓冲液配制)以制备大鼠糖尿病模型。72h后测定大鼠静脉血血糖,以血糖大于16.7mmol/L的大鼠作为造模成功。取造模成功的大鼠,随机分为实施例3组小剂量组、实施例3组大剂量组、脉络舒通组、醋酸泼尼松片组、对比实施例2组,每组10只,对应进行药物干预。
2.2实验方法
(1)分别于实验开始后的24h、1周、2周、4周、6周取大鼠静脉血进行检测空腹血糖。
(2)痛阈值测定
实验开始后的24h、1周、2周、4周、6周,调控热板仪温度55±0.5℃,记录平均痛觉反应时间(痛阈值)。
(3)Elisa法检测各组大鼠血清中致痛因子5-羟色胺、前列腺素E2值。
2.3实验数据统计处理
采用SPSS 22.0软件对所得数据进行统计分析,以P<0.05为差异有统计学意义。
3.结果及结论
3.1大鼠空腹血糖变化情况
与图3所示,造模后,发现大鼠的空腹血糖水平与正常组大鼠相比,有明显升高(P<0.01)。经给药治疗后,治疗组各时期血糖水平均有不同程度的降低。其中,具体给药后6周的空腹血糖水平,发现,与空白组相比,模型组空腹血糖水平明显升高(P<
0.01),与模型组相比,实施例3组小剂量组、实施例3组大剂量组、脉络舒通组、阳性对照药组空腹血糖水平显著降低(P<0.01),而对比实施例2组空腹血糖水平与模型组无显著性差异(P>0.05)。
3.2大鼠痛阈值测定情况
经观察,大鼠痛阈值测定结果如图4所示。数据结果显示,模型组、给药组大鼠的痛阈与正常组大鼠相比均明显升高(P<0.01)。药物干预后的1周,实施例3组大剂量组、实施例3组小剂量组、脉络舒通颗粒组、阳性对照药组、对比实施例2组与模型组相比,大鼠的痛阈均有不同程度的降低;2周、4周、6周后,各治疗组大鼠痛阈值均呈现降低趋势。以给药6周后的结果进行SPSS数据分析,发现,实施例3组大剂量组、实施例3组小剂量组、脉络舒通颗粒组、阳性对照药组与模型组相比,痛阀值均有显著下降(P<0.01);对比实施例2组与模型组相比,痛阀值下降不明显(P>0.05)。进一步的,与阳性对照药相比,发现对比实施例2组痛阀值P>0.05,提示实施例3组组合物、脉络舒通颗粒、阳性对照药均能降低大鼠痛阈值,而对比实施例2组虽也可以降低痛阀值,但治疗效果显著差于其他各治疗组。
3.3Elisa法检测各组大鼠血清中致痛因子5-羟色胺、前列腺素E2值的结果分别如图5、图6所示。
如图显示,经给药干预后的24h、1周、2周、4周、6周,5-羟色胺、前列腺素E2值都呈下降趋势,尤其是,脉络舒通大剂量组的下降值更接近与空白组。以第6周前列腺素E2值进行统计学分析,发现,实施例3组大剂量组、实施例3组小剂量组、脉络舒通颗粒组、阳性对照药组与模型组相比,前列腺素E2值都有显著下降(P<0.01);对比实施例2组与模型组相比,前列腺素E2值下降不明显(P>0.05)。进一步的,与阳性对照药相比,发现对比实施例2组前列腺素E2值P>0.05,提示实施例3组组合物、脉络舒通颗粒、阳性对照药均能降低大鼠前列腺素E2值。
临床典型病例举例:
患者孙XX,女,60岁。主诉:口渴、多饮、多尿12年余。近1月自觉口渴、多饮、多尿加重,伴头晕、咳嗽,无咳痰,测空腹血糖19.6mnol/L,偶有肢体麻木、疼痛,饮食正常,睡眠尚可,大便1次/日,每日活动少,近期体重无明显变化。经相关检查,诊断为2型糖尿病、2型糖尿病性周围血管病变。入院治疗8天,采用常规降糖以及脉络舒通丸治疗,头晕、咳嗽症状消失,腹软,无压痛,双下肢无水肿,麻木、疼痛消失。
患者许XX,男,56岁。主诉:口渴、多饮、多尿10余年,诊断为“2型糖尿病”,采用口服降糖药治疗。近20余日自觉口渴、多饮、多尿加重,咳嗽,无咳痰,测空腹血糖10.0-12.0mmo1/L,餐后2小时血糖6.0-9.0mol/L,伴有肢体麻木、疼痛。入院诊断为2型糖尿病、2型糖尿病性周围血管病变,采用常规降糖以及脉络舒通丸治疗8天,患者血糖控制平稳,神志清楚,语言流利,双下肢无水肿,咳嗽、肢体麻木、疼痛消失。
患者于XX,男,62岁。20余年前无明显诱因出现口渴、多饮症状,诊断为“糖尿病”,患者近1年患者自觉双下肢麻木伴有灼热感,视力减退、视物模糊,胸闷、气短、心悸,睡眠欠佳,测空腹血糖12.0mmo1/L。入院诊断为2型糖尿病、2型糖尿病性周围血管病变,采用常规降糖以及脉络舒通丸治疗15天,患者血糖较前明显下降、自诉双下肢麻木较前减轻,无明显恶心、上腹部不适等症状。双下肢无水肿。
患者李XX,男,42岁。糖尿病病程12年,6个月前出现四肢持续性烧灼痛,双下肢为重,伴麻木。入院诊断为2型糖尿病、2型糖尿病痛性周围血管病变。采用常规降糖以及脉络舒通丸治疗15天,症状明显减轻,患者血糖控制平稳,神志清楚。
患者刘XX,男,69岁。糖尿病病程17年,3个月前出现四肢端感觉异常,麻木,咳嗽,无咳痰,测空腹血糖12.0mmo1/L,入院后确诊为痛性糖尿病周围神经病变。采用常规降糖以及脉络舒通丸治疗15天,患者血糖控制平稳,症状明显减轻。
以下通过具体实施例进一步说明本发明,但本领域相关技术人员理应知晓,此所述实施例并不以任何方式限制本发明。
实施例1脉络舒通颗粒的制备
组方:
黄芪780g | 金银花780g | 黄柏500g |
苍术400g | 玄参780g | 当归500g |
白芍400g | 甘草120g | 蜈蚣15g |
全蝎150g | 薏苡仁780g | 水蛭400g |
制备方法:
A、取水蛭、蜈蚣、全蝎,粉碎使粒径小于100μm;
B、黄柏、薏苡仁、玄参、白芍先醇提后水提,即先加入65%乙醇提取2次,每次提取2.5小时,过滤,滤液回收乙醇、减压浓缩至相对密度为1.17的浸膏;再取过滤后的药渣加3倍水提取2次,过滤,水提取液备用;
C、金银花、苍术、当归、黄芪、甘草提取挥发油备用,剩余药液、药渣加1/2处方量的水蛭、蜈蚣、全蝎加水煎煮三次,每次煎煮2小时,滤液与步骤B中的水提液加入乙醇使含醇量达60%,常温静置30小时,滤液回收乙醇,浓缩至相对密度为1.17的浸膏,备用;
D、将剩余1/2处方量的水蛭、蜈蚣、全蝎与步骤B、步骤C所得浸膏混匀,经常规工序直接或加入药学上可接受的赋形剂制成颗粒剂。
实施例2脉络舒通颗粒的制备
组方:
黄芪900g | 金银花900g | 黄柏420g |
苍术450g | 玄参750g | 当归420g |
白芍450g | 甘草100g | 蜈蚣30g |
全蝎100g | 薏苡仁700g | 水蛭420g |
制备方法同实施例1。
实施例3脉络舒通颗粒的制备
组方:
制备方法同实施例1。
实施例4脉络舒通颗粒的制备
黄芪680g | 金银花680g | 黄柏450g |
苍术450g | 玄参630g | 当归450g |
白芍450g | 甘草100g | 蜈蚣40g |
全蝎50g | 薏苡仁650g | 水蛭300g |
制备方法同实施例1。
实施例5脉络舒通颗粒的制备
黄芪900g | 金银花900g | 黄柏450g |
苍术300g | 玄参600g | 当归350g |
白芍450g | 甘草100g | 蜈蚣30g |
全蝎80g | 薏苡仁900g | 水蛭300g |
制备方法同实施例1。
实施例6脉络舒通颗粒的制备
黄芪600g | 金银花900g | 黄柏450g |
苍术450g | 玄参600g | 当归300g |
白芍300g | 甘草150g | 蜈蚣40g |
全蝎50g | 薏苡仁600g | 水蛭450g |
制备方法同实施例1。
实施例7脉络舒通颗粒的制备
黄芪600g | 金银花900g | 黄柏300g |
苍术300g | 玄参900g | 当归450g |
白芍450g | 甘草150g | 蜈蚣15g |
全蝎150g | 薏苡仁900g | 水蛭450g |
制备方法同实施例1。
对比实施例1脉络舒通颗粒的制备组方:
制备方法:
A、取上述组方量金银花、苍术、玄参、当归、白芍进行水蒸汽蒸馏,得药渣、药液和挥发油粗品;将挥发油粗品重蒸馏,得精制挥发油;
B、将步骤A所得精制挥发油加无水乙醇,混合均匀,得乙醇挥发油溶液,置密闭容器内贮存;
C、取上述组方量黄芪、黄柏、薏苡仁、甘草及1/2处方量的水蛭、蜈蚣、全蝎以及步骤A所得药渣加水煎煮2次,时间分别为1.5小时和1小时,合并煎液,过滤,取步骤A所得药液与之合并浓缩,冷却后加乙醇静置12小时以上,使之充分沉淀,将醇沉后的上清液过滤,回收乙醇,减压浓缩成浸膏;
D、将另1/2处方量的水蛭、蜈蚣、全蝎粉碎成细粉,将细粉、步骤B所得浸膏以及糖粉和糊精等药用辅料按一定比例混匀,加入乙醇作润湿剂制成软材,入沸腾式干燥床干燥,喷入乙醇挥发油溶液,经常规工序直接或加入药学上可接受的赋形剂制成颗粒剂。
对比实施例2脉络舒通颗粒的制备
组方:
黄芪900g | 金银花600g | 黄柏400g |
苍术450g | 玄参600g | 当归360g |
白芍360g | 甘草150g | 蜈蚣30g |
全蝎80g | 薏苡仁650g | 水蛭350g |
制备方法:
A、取金银花、苍术、玄参、当归、白芍进行水蒸汽蒸馏,得药渣、药液和挥发油粗品;将挥发油粗品重蒸馏,得精制挥发油;
B、将步骤A所得精制挥发油加无水乙醇,混合均匀,得乙醇挥发油溶液;
C、取上述组方量的黄芪、黄柏、薏苡仁、甘草及上述1/2处方量的水蛭、蜈蚣、全蝎以及步骤A所得药渣加水煎煮2次,时间分别为1.5小时和1小时,合并煎液,过滤,取步骤A所得药液与之合并浓缩,冷却后加乙醇静置12小时以上,使之充分沉淀,将醇沉后的上清液过滤,回收乙醇,减压浓缩成浸膏;
D、将剩余1/2量的水蛭、蜈蚣、全蝎粉碎成细粉,将细粉、步骤B所得浸膏按一定比例混匀,加入乙醇作润湿剂制成软材,入沸腾式干燥床干燥,喷入乙醇挥发油溶液,经常规工序直接或加入药学上可接受的赋形剂制成颗粒剂。
对比实施例3脉络舒通颗粒的制备
组方:
黄芪960g | 金银花960g | 黄柏200g |
苍术150g | 玄参600g | 当归150g |
白芍360g | 甘草150g | 蜈蚣15g |
全蝎80g | 薏苡仁350g | 水蛭350g |
制备方法:
A、取1/2处方量的水蛭、蜈蚣、全蝎,粉碎成细粉,备用;
B、取处方量金银花、苍术、玄参、当归、白芍,加水浸泡后蒸馏提取,收集挥发油,备用;蒸馏后药液及药渣,备用;
C、取处方量黄芪、黄柏、薏苡仁、甘草、剩余1/2处方量的水蛭、蜈蚣、全蝎以及步骤B所得蒸馏后药渣混合均匀,加水煎煮2次,每次1.5小时,合并煎煮液,备用;
D、取步骤B所得蒸馏后的药液、步骤C所得煎煮液混合,过滤,滤液浓缩至相对密度为1.10的清膏,加乙醇使含醇量达60%,静置24小时,取上清液过滤,回收乙醇,浓缩至相对密度为1.10-1.18的清膏或1.30-1.35的稠膏,干燥,粉碎,得干膏粉,备用;
E、取步骤B所得挥发油加环糊精制成包含物、与步骤D所得干膏粉、步骤A所得水蛭、蜈蚣、全蝎细粉及淀粉混合均匀,制丸,干燥,得颗粒剂。
对比实施例4脉络舒通颗粒的制备
组方:
黄芪950g | 金银花950g | 黄柏220g |
苍术250g | 玄参200g | 当归260g |
白芍100g | 甘草30g | 蜈蚣100g |
全蝎50g | 薏苡仁200g | 水蛭100g |
制备方法:
A、取水蛭、蜈蚣、全蝎,粉碎使粒径小于100μm;
B、黄柏、薏苡仁、玄参、白芍先醇提后水提,即先加入55%乙醇提取2次,每次提取2.5小时,过滤,滤液回收乙醇、减压浓缩至相对密度为1.20的浸膏;再取过滤后的药渣加3倍水提取2次,过滤,水提取液备用;
C、金银花、苍术、当归、黄芪、甘草提取挥发油备用,剩余药液、药渣加1/2处方量的水蛭、蜈蚣、全蝎加水煎煮三次,每次煎煮1.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达58%,常温静置48小时,滤液回收乙醇,浓缩至相对密度为1.20的浸膏,备用;
D、将剩余1/2处方量的水蛭、蜈蚣、全蝎与步骤B、步骤C所得浸膏混匀,经常规工序直接或加入药学上可接受的赋形剂制成颗粒型。
本发明制备得到的脉络舒通制剂经检测,小檗碱、芍药苷显著优于对比实施例组、市售脉络舒通制剂。
Claims (8)
1.脉络舒通制剂在制备防治糖尿病神经病变药物中的用途,所述脉络舒通制剂由黄芪400-900重量份 金银花400-900重量份 黄柏200-500重量份 苍术200-500重量份 玄参400-900重量份 当归200-500重量份 白芍200-500重量份 甘草50-150重量份 蜈蚣15-40重量份 全蝎50-150重量份 薏苡仁400-900重量份 水蛭100-500重量份制备而成,所述神经病变伴有蚂蚁爬行、烧灼、针刺、刺伤、跳跃、刀割、撕裂的任一异常感觉症状。
2.如权利要求1所述的用途,其特征在于,所述脉络舒通制剂由黄芪600-900重量份 金银花600-900重量份 黄柏300-450重量份 苍术300-450重量份 玄参600-900重量份 当归300-450重量份 白芍300-450重量份 甘草100-150重量份 蜈蚣15-40重量份 全蝎50-150重量份 薏苡仁600-900重量份 水蛭300-450重量份制备而成。
3.如权利要求1或2所述的用途,其特征在于,所述糖尿病为1型糖尿病或2型糖尿病。
4.如权利要求1或2所述的用途,其特征在于,所述神经病变为痛性糖尿病周围神经病变。
5.如权利要求1或2所述的用途,其特征在于,所述脉络舒通制剂为口服制剂。
6.如权利要求5所述的用途,其特征在于,所述脉络舒通制剂为汤剂、丸剂、片剂、合剂、胶囊剂、颗粒剂、散剂或膏剂。
7.如权利要求6所述的用途,其特征在于,所述脉络舒通制剂为脉络舒通颗粒或脉络舒通丸。
8.如权利要求1或2所述的用途,其特征在于,所述脉络舒通制剂的制备方法为:
A、取水蛭、蜈蚣、全蝎,粉碎使粒径小于100μm;
B、黄柏、薏苡仁、玄参、白芍加入乙醇提取,再用水提取,醇提液回收乙醇后,浓缩成醇提浸膏,水提液过滤备用;
C、金银花、苍术、当归、黄芪、甘草加水提取挥发油,剩余药液、药渣加1/2处方量的水蛭、蜈蚣、全蝎以水煎煮,过滤,滤液与步骤B中的水提液浓缩成浸膏;
D、将剩余1/2处方量的水蛭、蜈蚣、全蝎与步骤B醇提浸膏、步骤C水提浸膏混匀,经常规工序直接或加入药学上可接受的赋形剂制成临床可接受的剂型。
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