CN117959394A - 参芪通脉制剂在制备防治糖尿病神经病变药物中的用途 - Google Patents
参芪通脉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,具体涉及一种参芪通脉制剂在制备治疗糖尿病神经病变的用途。所述的糖尿病神经病变主要是下肢血管神经病变,本发明参芪通脉制剂含有植物药、动物药各味中药材协同增效,在药理学及临床案例中所述的中药组合物可以降低血糖水平,调节神经传导速率,改善痛性糖尿病神经病变引起的周围神经病变,尤其是糖尿病足,治疗起效快、总有效率高,具有较高的市场价值。
Description
技术领域
本发明涉及参芪通脉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。
糖尿病足的临床表现为神经和血管病变,包括感觉改变(袜套样表现、轻触觉、本体感觉、温度觉和疼痛感知的共同减弱)、足内在肌萎缩;皮肤正常排汗,温度及血运调节功能丧失:局部溃疡、感染、骨髓炎、Charcot关节病等。
近年研究发现,对糖尿病患者应用中医中药,除了能够降低患者血糖意外,最主要是能够改善患者临床症状与防治其慢性的并发症;应用中药进行降糖,其效果大多不如西药,但对糖尿病患者血管并发症的治疗上却具有显著的作用。同时中药对于AGEs-RAGE系统进行的治疗可以有多种途径,比如对AGEs的形成进行抑制,并抑制RAGE的表达与其下游相关的信号转导。
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,对参芪通脉汤进行全面的研究,并进行了全方的革新,由原来的5味变成了12味药物,本发明以科学严谨的态度,通过确切的药理学实验证实,参芪通脉制剂对治疗周围神经病变,尤其是糖尿病足变具有优良的疗效,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参芪通脉制剂的新类型。可以是口服制剂,优选的,所述口服制剂为汤剂、丸剂、片剂、合剂、胶囊剂、颗粒剂、散剂或膏剂,更优选为片剂或丸剂,最优选为片剂。
在临床实验的基础上,汤剂、片剂、丸剂等只要是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。
具体而言,本发明的技术目的是通过以下技术方案实现的:
一种由生黄芪、白术、川牛膝、薏苡仁、当归、丹参、鸡血藤、金银花、党参、地龙、全蝎、生甘草组成的参芪通脉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,所述参芪通脉制剂各组分为:
本发明的第二个目的是提供参芪通脉制剂的制药的用途。所述神经病变为痛性糖尿病周围神经病变、下肢血管神经。
进一步地,所述的糖尿病神经病变主要是下肢血管神经病变,本发明参芪通脉制剂含有植物药、动物药各味中药材协同增效,在药理学及临床个例中本发明中药组合物可以降低血糖水平,调节神经传导速率,改善痛性糖尿病神经病变引起的周围神经病变,尤其是糖尿病足,治疗起效快、总有效率高,具有较高的市场价值。
进一步地,本发明所述糖尿病为1型糖尿病或2型糖尿病。
进一步地,本发明所述下肢血管神经为糖尿病足。
进一步地,本发明所述糖尿病足是指糖尿病患者足部由于神经病变使下肢保护功能减退,大血管和微血管病变使动脉灌注不足致微循环障碍而发生溃疡和坏疽的疾病状态,是糖尿病的一种并发症。
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,所述参芪通脉制剂为口服制剂,优选的,所述口服制剂为汤剂、丸剂、片剂、合剂、胶囊剂、颗粒剂、散剂或膏剂,更优选为片剂。
进一步的,本发明还提供了所述参芪通脉制剂的制备方法:
取地龙、全蝎,粉碎使粒径小于100μm;
生黄芪、白术、川牛膝、薏苡仁、当归、党参加入65-85%的乙醇提取1-2次,每次提取1.5-3.5小时,过滤,滤液回收乙醇、减压浓缩至相对密度为1.05-1.10的浸膏;再取过滤后的药渣加2-5倍水提取1-2次,过滤,水提取液备用;
金银花、丹参、甘草、鸡血藤加水提取挥发油,剩余药液、药渣加1/2处方量的地龙、全蝎加水煎煮1-2次,每次煎煮1.5-3.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达40-50%,常温静置24-48小时,滤液回收乙醇,浓缩至相对密度为1.15-1.20的浸膏,备用;
将剩余1/2处方量的地龙、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。
进一步地,本发明所述参芪通脉制剂的制备方法为:
取地龙、全蝎,粉碎使粒径小于100μm;
生黄芪、白术、川牛膝、薏苡仁、当归、党参加入75%的乙醇提取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1.08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;
金银花、丹参、甘草、鸡血藤加水提取挥发油,剩余药液、药渣加1/2处方量的地龙、全蝎加水煎煮2次,每次煎煮2.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达45%,常温静置48小时,滤液回收乙醇,浓缩至相对密度为1.18的浸膏,备用;
将剩余1/2处方量的地龙、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。
本发明君臣佐使俱全,配伍恰当,切中机理,方中君药为:生黄芪、白术。这些药材是通脉方剂中起到核心作用的主要成分。生黄芪有益气养血、补气固表的功效;白术具有健脾止泻、补脾止血的作用;臣药:川牛膝、鸡血藤、地龙、全蝎。这些药材在通脉方剂中起到辅助治疗和增强效果的作用。佐药:薏苡仁、当归、丹参、金银花、党参,薏苡仁有利尿消肿、清热解毒的功效;当归能够活血调经、补血养血;丹参具有活血化瘀、舒筋活络的作用;鸡血藤可以活血化瘀、消肿止痛;金银花有清热解毒、解毒消肿的功效;党参具有益气健脾、提升免疫力的作用;地龙可以活血通络、祛风除湿;全蝎有活血化瘀、止痛的功效。使:甘草,在通脉方剂中起到调和药性、增加药物稳定性和促进吸收的作用。
与现有技术相比,本发明具有以下优点:
本研究拟采用给予气虚血瘀型糖尿病溃疡患者口服参芪通脉片,检测患者不同时间节点的AGEs-RAGE的下游因子、创面的愈合情况等变化进一步验证参芪通脉片治疗糖尿病溃疡患者的有效性与安全性,进行临床推广。可以看出,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。
附图说明
图1表示的是实施例1以及对比例1-3创面治愈的情况分析。
图2表示的是实施例1以及对比例1-3创面面积的改变情况。
图3表示的是实施例1以及对比例1-3在治疗3周时的创面面积对比。
图4表示的是实施例1以及对比例1-3在治疗4周时的创面面积对比。
图5表示的是实施例1以及对比例1-3的TNF-a改变情况。
图6表示的是是实施例1以及对比例1-3的IL-6改变情况。
图7表示的是是实施例1以及对比例1-3的超敏C反应蛋白改变情况。
具体实施方式
为验证本发明参芪通脉制剂的功效,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。
实施例1:参芪通脉片的制备
组方:
制备方法如下:
A)取地龙、全蝎,粉碎使粒径小于100μm;
B)生黄芪、白术、川牛膝、薏苡仁、当归、党参加入65的乙醇提取1次,提取1.5小时,过滤,滤液回收乙醇、减压浓缩至相对密度为1.05的浸膏;再取过滤后的药渣加2倍水提取1次,过滤,水提取液备用;
C)金银花、丹参、甘草、鸡血藤加水提取挥发油,剩余药液、药渣加1/2处方量的地龙、全蝎加水煎煮1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40%,常温静置24小时,滤液回收乙醇,浓缩至相对密度为1.15的浸膏,备用;
D)将剩余1/2处方量的地龙、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片剂型。
实施例2:参芪通脉片的制备
组方:
制备方法如下:
A)取地龙、全蝎,粉碎使粒径小于100μm;
B)生黄芪、白术、川牛膝、薏苡仁、当归、党参加入85%的乙醇提取2次,每次提取3.5小时,过滤,滤液回收乙醇、减压浓缩至相对密度为1.10的浸膏;再取过滤后的药渣加5倍水提取2次,过滤,水提取液备用;
C)金银花、丹参、甘草、鸡血藤加水提取挥发油,剩余药液、药渣加1/2处方量的地龙、全蝎加水煎煮2次,每次煎煮3.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达50%,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处方量的地龙、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片剂型。
实施例3:参芪通脉片的制备
制备方法如下:
A)取地龙、全蝎,粉碎使粒径小于100μm;
B)生黄芪、白术、川牛膝、薏苡仁、当归、党参加入75%的乙醇提取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1.08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、丹参、甘草、鸡血藤加水提取挥发油,剩余药液、药渣加1/2处方量的地龙、全蝎加水煎煮2次,每次煎煮2.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达45%,常温静置48小时,滤液回收乙醇,浓缩至相对密度为1.18的浸膏,备用;
D)将剩余1/2处方量的地龙、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片剂型。
实施例4:参芪通脉片的制备
制备方法同实施例3。
实施例5:参芪通脉丸剂的制备
制备方法同实施例3,按常规工艺添加辅料制备成丸剂。
实施例6:参芪通脉外用膏剂的制备
制备方法同实施例3,按常规工艺添加辅料制备成外用。
对比例1:参芪通脉片的制备
制备方法同实施例3。
对比例2:参芪通脉片的制备
制备方法同实施例3。
对比例3:参芪通脉片的制备
制备方法同实施例3。
对比例4:参芪通脉片的制备
制备方法同实施例3。
对比例5:参芪通脉片的制备
制备方法同实施例3。
对比例6:参芪通脉外用乳膏的制备
制备方法如下:
A)取地龙、全蝎,粉碎使粒径小于100μm;
B)生黄芪、白术、川牛膝、薏苡仁、当归、党参加入75%的乙醇提取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1.08的浸膏;备用;
C)金银花、丹参、甘草、鸡血藤加水煎煮2次,每次煎煮2.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达45%,常温静置48小时,滤液回收乙醇,浓缩至相对密度为1.18的浸膏,备用;
D)将地龙、全蝎与步骤B醇浸膏、步骤C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外用乳膏。
对比例7:参芪通脉外用乳膏的制备
制备方法如下:
A)地龙、全蝎、生黄芪、白术、川牛膝、薏苡仁、当归、党参加入75%的乙醇提取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1.08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;
B)金银花、丹参、甘草、鸡血藤加水提取挥发油,剩余药液、药渣加水煎煮2次,每次煎煮2.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达45%,常温静置48小时,滤液回收乙醇,浓缩至相对密度为1.18的浸膏,备用;
C)将水提取液与步骤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外用乳膏。
1.药理实验——本发明制剂对小鼠创伤面上的实验以及结果
1.材料
1.1动物:
SPF级昆明种小鼠若干只,18~22g,实验动物许可证号:SYXK(鲁)20180004,实验前适应性饲养7天。
1.2受试物
1.2.1药物
按照本发明实施例6以及对比例6-7处方及制备方法制得的乳膏剂。
湿润烧伤膏组(国药准字Z20000004)。
1.2.2使用方法
本发明的膏剂:外用。涂于创面或待愈合面(泡沫厚度1-2cm,乳膏剂厚度薄于1mm),每2~4小时更换新药。换药前,先将残留在创面上的泡沫或者液体拭去。暴露创面,然后继续用药。
湿润烧伤膏组:外用。本品涂于烧﹑烫﹑灼伤等创面(厚度薄于1mm),每2~4小时更换新药。换药前,须将残留在创面上的药物及液化物拭去。暴露创面,然后继续用药。
2.造模及分组、给药
2.1造模方法
第1天,小鼠背部脱毛,脱毛面积约3cm×4cm左右,观察24h,确定脱毛部位无红肿、炎症及破损等异常情况;第2天,室温下,小鼠腹腔麻醉后,至于俯卧位,四肢伸展并固定在操作台上,使背部皮肤平坦,推去小鼠背部毛发,范围约6cm,面积大于预计烧伤面积,将20g的砝码置于容器内加热至沸,保持10min,用75%的乙醇对小鼠实验区皮肤消毒后,迅速将加热的砝码放在小鼠皮肤上,稍加压力,形成约2cm×2cm烫伤面积的浅Ⅱ度烫伤模型。烫伤后的局部皮肤呈瓷白色,表皮皱缩,常见局部皮肤有溃破,正常区域与烫伤部位清晰可辨,烫伤4h内皮下组织水肿明显。随机抽取1只小鼠取其创面组织做病理组织学检查,镜下可见小鼠烫伤区域表皮消失,表皮全层、真皮浅层细胞浸润,符合浅Ⅱ度烫伤。
2.2分组及给药
取造模成功的小鼠50,随机分为模型组、湿润烧伤膏组、实施例6以及对比例6-7组10只。
实验各组:湿润烧伤膏组、实施例6组、以及对比例6-7,涂抹区域按照上述使用方法分别涂抹对应的药物,模型组使用0.9%生理盐水涂抹。连续给药14天。
3.观察指标
3.1皮损愈合率治疗后第7、10、14天采用描记加称重法测定局部皮损面积。先用透明胶片标记皮损范围,后剪下与皮损面积大小相应的透明胶片称其质量,以质量代替面积。
3.2统计方法
采用SPSS17.0软件进行数据处理。所得数据以均数±标准差表示,对各组数据行正态分布检验及方差齐性检验,符合皮尔森检测的要求,组间比较用单因素方差分析。以P<0.05为差异有统计学意义。
4.结果及结论
治疗后第7、10、14天,本发明实施例6以及对比例5-6组以及湿润烧伤膏组皮损均有不同程度的修复,时间越长,愈合越好,其中以本发明实施例6组的愈合效果最好。
与模型组相比,各给药组小鼠治疗第7、10、14天的愈合率较高,差异有统计学意义(P<0.01),进一步说明本发明造模成功;与湿润烧伤膏组相比,本发明实施例6组小鼠皮损愈合率较高,差异有统计学意义(P<0.05)。
表1各组小鼠皮损愈合率比较(n=10)
组别 | 治疗第7天 | 治疗第10天 | 治疗第14天 |
模型组 | 32.34±3.11 | 47.47±5.83 | 58.27±7.11 |
湿润烧伤膏组 | 42.43±5.82& | 57.74±6.14& | 74.92±8.19& |
实施例6 | 44.56±6.11& | 63.09±6.72&# | 84.33±7.75&# |
对比例6 | 39.67±3.40 | 52.36±7.89 | 64.77±8.28 |
对比例7 | 38.33±5.71 | 53.46±5.11 | 65.98±6.42 |
注:与模型组对比,*P<0.05,&P<0.01;
与湿润烧伤膏对比,#P<0.05。
2.本发明的药物组合物的抗菌试验
2.1材料和方法
1)菌种和培养基:沙氏培养基,金黄色葡萄球菌、白色念珠菌、大肠杆菌和绿脓杆
菌(以上菌种通过商业途径购得)。
2)药物:按照本发明实施例3~4,对比例4-5的原料和方法制成的药物组合物(未加辅料之前的原料药)。
3)方法:制备沙氏培养基并装入锥形瓶中,湿热灭菌。用无菌方法分别取本发明实施例3-4,对比例4-5与灭菌生理盐水1∶20稀释液各1ml注入消毒的平皿内,每个剂量组10个平皿(平皿直径为10cm),然后倾入沙氏培养时接种上述四种菌(直径约0.5mm的菌团)。保温(37℃)培养6天。观察菌落生长状态以及有无杂菌生长,测量菌落直径(mm)并与空白组比较。
表2各实施例组的抗菌效果(n=10)
注:与对比例41对比,*P<0.05,&P<0.01;
与对比例44对比,#P<0.05,@P<0.01;
由上表2可知,本发明实施例3-4有明显的抗菌作用,对金黄色葡萄球菌、白色念珠菌、肠杆菌和绿脓杆菌等致病菌有明显的抑制或杀灭作用。
二、药效学实验:
1.临床研究:本研究通过对2021年7月至2023年7月济南市中医医院外科门诊或住院病人中,选择符合标准的气虚血瘀型糖尿病溃疡患者120例,随机分为5组,各组之间性别、年龄以及创伤面积没有显著性差异(P>0.05)。
2.分组以及给药
分为实验组A组、实验组B组、实验组C组、实验组D组、阳性对照组,每组24例,分别服用实施例1、对比例1-3的片剂,各组每日6片,二次早晚空腹温服。1周为一个疗程,连续4个疗程,阳性对照组(国药准字Z32020535通塞脉片,按照说明书服用),根据患者血糖水平和患者实际情况选择合适的降糖药物,口服降糖药物或皮下注射胰岛素治疗,使空腹血糖维持在8.0mmol/L以下。如需要各组进行局部正常盐水护理。
诊断标准
3.1根据中华中医药学会《中国糖尿病足诊治指南》(2020版)诊断标准:
(1)2型糖尿病患者出现肢体血管和(或)神经病变和(或)出现感染者;
(2)2型糖尿病患者肢体有湿性坏疽或干性坏疽的临床表现和体征,并符合1~5级坏疽标准;
(3)静息时ABI指数<0.9以下者;
(4)超声彩色多普勒检查,提示肢体血管狭窄,肢体血供减少而导致缺血或者坏疽者;
(5)血管造影证实,CTA、MRA提示血管腔狭窄或阻塞,并有临床表现者;
(6)电生理检查,可见周围神经传导速度减慢或肌电图、体感诱发电位异常改变者;
(7)X线检查,可见骨质疏松脱钙、骨质破坏、骨髓炎或关节病变、手足畸形及夏科关节等改变者;
同时符合以上(1)、(2)两条,加上(3)-(7)条中任意1条即可明确诊断。
3.2中医诊断标准
参考2017年国家中医药管理局发布的《中医病证诊断疗效标准》中脱疽诊断标准:
(1)多发于下肢一侧或两侧。患者有多年糖尿病病史、受冷冻、外伤、长期大量吸烟等病史。初起趾、指冷痛,下肢酸麻胀痛,行走多时加重,休息时减轻,呈间歇性跛行,趺阳脉减弱。继之疼痛呈持续性,肢端皮肤发凉,皮肤暗红、青紫,皮肤干燥,毫毛脱落,趾甲变形增厚,肌肉萎缩,趺阳脉消失。进而发生坏死,疼痛剧烈,彻夜不眠,抱膝而坐。溃烂染毒时,出现湿性坏死,肢端红肿热痛,全身发热;
(2)血脉瘀阻型:患趾喜暖怕冷,麻木酸胀疼痛,遇冷剧痛,步履不利,沉重乏力,多走则疼痛加剧,肤色暗红、青紫,破溃者疼痛持续加剧,彻夜不能入寐。舌质暗红或有瘀斑,苔白,脉弦或涩,趺阳脉消失。
3.3分级标准
采用最为经典的糖尿病足分级——Wagner分级。
0级有发生足溃疡的危险因素,但目前无溃疡
1级足部表浅溃疡,无感染征象,突出表现为神经性溃疡
2级较深溃疡,常合并软组织感染,无骨髓炎或深部脓肿
3级深部溃疡,有脓肿或骨髓炎
4级局限性坏疽(趾、足跟或前足背),其特征为缺血性坏疽,通常合并神经病变
5级全足坏疽
3.4纳入标准
(1)符合2型糖尿病的诊断标准;(2)符合糖尿病足溃疡的西医诊断标准;
(3)符合中医血脉瘀阻型诊断标准;(4)Wagner分级属1-3级者;
(5)踝肱指数(ABI)≥0.4;(6)年龄18-80岁,不限性别;
3.5排除标准
(1)肢体严重缺血,需要紧急行血管搭桥或介入治疗者;
(2)肢体局部坏死或感染严重,需进行截肢者;
(3)踝肱指数(ABI)<0.4者;
(4)癌性、结核性及其它特异性的溃疡;
(5)病情严重,生命体征不平稳者;
(6)重度营养不良者;
(7)合并精神疾病、酗酒或吸毒者;
(8)患有甲亢、低血压、低血钙、低血糖、臭氧过敏、柑橘过敏(使用柠檬酸钠者)、凝血机制障碍(如血友病)、蚕豆病等臭氧治疗禁忌症者;
(9)同时参加其他试验患者;
3.6剔除及脱落标准
(1)误纳,不符合纳入标准;
(2)依从性差,不能按规定接受治疗方案者;
(3)资料缺失,不能进行有效性和安全性判断者;
(4)有对药物产生严重不良反应,必须中止试验者;
(5)病情加重或产生死亡病例,导致研究终止;
4.临床观察指标
分别于治疗0周、治疗1周、治疗2周、治疗3周、治疗4周时观察创面面积;在治疗4周时检测血清(TNF-a、IL-6、超敏C反应蛋白(hs-CRP))情况。
5.疗效评定标准
参照《中药新药临床研究指导原则(2022)》中制定的临床研究指导原则,结合糖尿病足溃疡临床特点,制定临床疗效评价标准如下:
痊愈:创面基本愈合,临床症状、体征基本消失。创面证候积分指数≥90%。
显效:创面面积(深度)明显缩小,创面局部疼痛消失或明显减轻,分泌物明显减少,肉芽新鲜,周围无红肿。60%≤创面证候积分指数<90%。
有效:创面面积(深度)有所缩小,创面局部疼痛有所减轻,分泌物减少,肉芽新鲜,周围红肿消减。30%≤创面证候积分指数<60%。
无效:创面面积(深度)无缩小或有所增大,创面局部疼痛无减轻或加重,分泌物未见减少,创面情况无改善。创面证候积分指数<30%。
结果分析
图1表示的是实施例1以及对比例1-3创面治愈的情况分析,可以看出,实施例1的治疗效果最佳,治愈和显效个体远大于其他实施例。
图2表示的是实施例1以及对比例1-3创面面积的改变情况,可以看出,在第0-2周,各组之间并咩有显著的变化,在治疗3周开始治疗效果开始出现显著的分层,实施例1的治疗效果显著优于对比例1-3。
图3表示的是实施例1以及对比例1-3在治疗3周时的创面面积对比,可以看出,实施例与其他对比例之间具有显著性差异。
图4表示的是实施例1以及对比例1-3在治疗4周时的创面面积对比,可以看出,实施例与其他对比例之间具有显著性差异,治疗效果的差距明显拉大。
图5表示的是实施例1以及对比例1-3的TNF-a改变情况。
图6表示的是是实施例1以及对比例1-3的IL-6改变情况。
图7表示的是是实施例1以及对比例1-3的超敏C反应蛋白改变情况。
Claims (10)
1.参芪通脉制剂在制备防治糖尿病神经病变药物中的用途,所述参芪通脉制剂由生黄芪、白术、川牛膝、薏苡仁、当归、丹参、鸡血藤、金银花、党参、地龙、全蝎、生甘草制备而成。
2.如权利要求1所述用途,其特征在于,所述参芪通脉制剂各组分为:
生黄芪10-70重量份白术5-30重量份川牛膝8-40重量份
薏苡仁10-60重量份当归10-50重量份丹参5-30重量份
鸡血藤5-30重量份金银花5-30重量份党参10-50重量份
地龙5-30重量份全蝎1-6重量份生甘草5-20重量份。
3.如权利要求2所述用途,其特征在于,所述参芪通脉制剂各组分为:
生黄芪30重量份白术15重量份川牛膝18重量份
薏苡仁30重量份当归20重量份丹参15重量份
鸡血藤15重量份金银花15重量份党参30重量份
地龙15重量份全蝎3重量份生甘草10重量份。
4.如权利要求1-3中任意一项所述用途,其特征在于,所述糖尿病为1型糖尿病或2型糖尿病。
5.如权利要求4所述用途,其特征在于,所述神经病变为痛性糖尿病周围神经病变、下肢血管神经。
6.如权利要求5所述用途,其特征在于,所述下肢血管神经为糖尿病足。
7.如权利要求6所述用途,其特征在于,所述糖尿病足是指糖尿病患者足部由于神经病变使下肢保护功能减退,大血管和微血管病变使动脉灌注不足致微循环障碍而发生溃疡和坏疽的疾病状态,是糖尿病的一种并发症。
8.如权利要求6所述用途,其特征在于,所述参芪通脉制剂为口服制剂,优选的,所述口服制剂为汤剂、丸剂、片剂、合剂、胶囊剂、颗粒剂、散剂或膏剂,更优选为片剂。
9.如权利要求8的用途,其特征在于,所述参芪通脉制剂的制备方法为:
A.取地龙、全蝎,粉碎使粒径小于100μm;
B.生黄芪、白术、川牛膝、薏苡仁、当归、党参加入65-85%的乙醇提取1-2次,每次提取1.5-3.5小时,过滤,滤液回收乙醇、减压浓缩至相对密度为1.05-1.10的浸膏;再取过滤后的药渣加2-5倍水提取1-2次,过滤,水提取液备用;
C.金银花、丹参、甘草、鸡血藤加水提取挥发油,剩余药液、药渣加1/2处方量的地龙、全蝎加水煎煮1-2次,每次煎煮1.5-3.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达40-50%,常温静置24-48小时,滤液回收乙醇,浓缩至相对密度为1.15-1.20的浸膏,备用;
D.将剩余1/2处方量的地龙、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。
10.如权利要求8的用途,其特征在于,所述参芪通脉制剂的制备方法为:
A.取地龙、全蝎,粉碎使粒径小于100μm;
B.生黄芪、白术、川牛膝、薏苡仁、当归、党参加入75%的乙醇提取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1.08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、丹参、甘草、鸡血藤加水提取挥发油,剩余药液、药渣加1/2处方量的地龙、全蝎加水煎煮2次,每次煎煮2.5小时,滤液与步骤B中的水提液加入乙醇使含醇量达45%,常温静置48小时,滤液回收乙醇,浓缩至相对密度为1.18的浸膏,备用;
D.将剩余1/2处方量的地龙、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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