CN116270943B - 一种用于治疗缺血性脑卒中的中药复方制剂及其制备方法 - Google Patents
一种用于治疗缺血性脑卒中的中药复方制剂及其制备方法 Download PDFInfo
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Abstract
本发明公开了一种用于治疗缺血性脑卒中的中药复方制剂及其制备方法，涉及中药制剂技术领域。中药复方制剂包括以下重量份组分：三桠苦：13份‑18份；红花：7份‑12份；羌活：8份‑12份；姜黄：12份‑18份；熟大黄：2份‑7份；蝉蜕：3份‑6份；炒僵蚕：3份‑8份。本发明中药复方制剂切合缺血性脑卒中的中医病因病机及现代医学的发病机制，可以增强改善血流、抗氧化、降低脑代谢等作用，药效充分作用于脑窍，提高该中药复方制剂对缺血性卒中脑损伤的神经保护作用，可制备成各种剂型的成药，与传统汤剂相比，其质量相对稳定，有利于剂量的控制，也更方便携带和服用。
Description
技术领域
本发明涉及中药制剂技术领域，尤其涉及一种用于治疗缺血性脑卒中的中药复方制剂及其制备方法。
背景技术
缺血性脑卒中是一种常见的神经系统疾病，可造成肢体瘫痪、言语障碍、认知功能下降等多种神经功能缺损症状，是全球最常见的死亡原因以及致残原因之一，已成为人类重要的公共卫生问题。缺血性脑卒中的发生主要是由于脑供血动脉急性闭塞或严重狭窄所致的脑血栓和脑栓塞，以及血流动力学改变导致局部脑组织低灌注，从而造成局部脑组织缺血、缺氧性坏死。缺血性脑卒中导致脑损伤的机制复杂，包括能量代谢障碍、钙超载、兴奋性氨基酸毒性、氧化应激损伤、炎症反应及细胞凋亡等。
目前，缺血性脑卒中主要的有效治疗手段为静脉溶栓和血管介入治疗，能够使血管再通迅速恢复缺血区域的脑灌注，挽救缺血半暗带，避免或减轻原发性脑损伤。此外还有抗血小板聚集剂、抗凝剂、脑保护剂、他汀类药物等药物的使用，也是临床上常用的治疗缺血性脑卒中的手段。
静脉溶栓和血管介入治疗是目前治疗缺血性脑卒中最有效的手段，但有严格的时间窗要求，而且容易造成脑缺血再灌注损伤导致脑组织进一步损害，因此获益的患者并不多。而临床上常用的治疗缺血性脑卒中的药物，由于缺血性脑卒中病理机制复杂，患者的个体差异较大等因素，这些药物的疗效也十分有限。
发明内容
本发明提供了一种用于治疗缺血性脑卒中的中药复方制剂及其制备方法，切合缺血性脑卒中的中医病因病机及现代医学的发病机制，以提供有效治疗缺血性脑卒中的中药复方制剂。
为了解决上述技术问题，本发目的之一提供了一种用于治疗缺血性脑卒中的中药复方制剂，包括以下重量份组分：
三桠苦：13份-18份；
红花：7份-12份；
羌活：8份-12份；
姜黄：12份-18份；
熟大黄：2份-7份；
蝉蜕：3份-6份；
炒僵蚕：3份-8份。
通过采用上述方案，本发明所述的中药复方制剂组成成分中，僵蚕味咸辛,性平,升浮宣透，僵而不腐,有息风止痉、祛风通络之功效；蝉蜕味咸甘性凉,质轻而升，有息风解痉、疏风散邪之效；姜黄味辛苦，性温，辛散苦泄，能破血行气通经；大黄味苦，性寒，有泻下涤痰、逐瘀通经之用，可降浊阴而推陈致新；僵蚕、蝉蜕升阳中之清阳，姜黄、大黄降阴中之浊阴，四药相配，升降相施，内外通达，温寒并用，疏利气机，降浊升清；但该四药组分活血化瘀、清解热毒之力不强，因而加重姜黄用量，配伍红花，增强活血行气之功，加三桠苦增强清热解毒之效，且姜黄、红花辛温，可缓和方中大黄、三桠苦之寒性，顾护脾胃；加用羌活取其在三化汤中之意，具有驱散外风、通经升清、宣窍于上、引诸药直达巅顶、理气机升降之效，使药效充分作用于脑窍；此外，姜黄具有抗炎、抗氧化、调脂、抗凝血的作用，红花具有抗炎、抗氧化、调脂作用，对脑缺血损伤有治疗作用，三桠苦具有较好的抗炎、调脂、降糖作用，羌活具有抗炎、抗血栓形成、改善血液循环的作用，可改善血流、抗氧化、降低脑代谢等作用。
此外，本发明复方制剂经差异代谢物筛选，发现黄酮类化合物、脂质、酚酸类化合物隐绿原酸上调表达显著，黄酮类化合物具有神经保护、降压、改善学习记忆认知、抗炎、抗菌、抗氧化以及降血糖等药理活性，且黄酮类化合物槲皮素具有通过减少氧化应激损伤实现抗凝血、抑制血小板聚集的作用；脂质上调表达以游离不饱和脂肪酸为主，不饱和脂肪酸具有降低血液总胆固醇水平，预防动脉粥样硬化，调节血脂、抗氧化以及体外抑制血小板聚集等功效；隐绿原酸进入体内后产生核心代谢产物咖啡酸和奎宁酸，并在此基础上发生进一步的代谢，产生阿魏酸、异阿魏酸、香豆酸等，它们均具有很好的抗炎的药理作用。
作为优选方案，包括以下重量份组分：三桠苦15份；红花10份；羌活10份；姜黄15份；熟大黄5份；蝉蜕5份；炒僵蚕5份。
作为优选方案，所述中药复方制剂为片剂、丸剂、胶囊、颗粒剂、散剂或口服液。
作为优选方案，所述缺血性脑卒中为短暂性缺血、可逆性神经功能障碍、进展性卒中和完全性卒中中的一种或多种。
作为优选方案，还包括医学上可接受的辅料。
作为优选方案，包括但不限于填充剂、润滑剂、分散剂、润湿剂、粘合剂、抗氧剂或防腐剂。
为了解决上述技术问题，本发目的之一提供了一种用于治疗缺血性脑卒中的中药复方制剂的制备方法，包括以下步骤：
(1)取三桠苦饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得三桠苦提取物；
(2)取红花饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得红花提取物；
(3)取羌活饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得羌活提取物；
(4)取姜黄饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得姜黄提取物；
(5)取熟大黄饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得。
(6)取蝉蜕饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得熟大黄提取物；
(7)取炒僵蚕饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得炒僵蚕提取物；
(8)分别取步骤(1)-(7)的7味提取物，混合使药物均匀，将混合物干法制粒制成颗粒。
作为优选方案，在步骤(1)-(7)中，所述清膏的比重为1-1.2。
作为优选方案，在步骤(8)中，所述颗粒的目数为10-80目。
作为优选方案，在步骤(1)-(7)中，加水煎煮中水占固料的8-10倍质量，加水煎煮的次数为1-3次。
作为优选方案，在步骤(1)中，每次煎煮0.5～2.5小时；在步骤(2)中，每次煎煮0.5～2小时；在步骤(3)中，每次煎煮1～3小时；在步骤(4)中，每次煎煮0.5～2小时；在步骤(5)中，每次煎煮0.5～2小时；在步骤(6)中，每次煎煮0.5～2.5小时；在步骤(7)中，每次煎煮0.5～2.5小时。
相比于现有技术，本发明实施例具有如下有益效果：
本发明所述的中药复方制剂切合缺血性脑卒中的中医病因病机及现代医学的发病机制，可以增强改善血流、抗氧化、降低脑代谢等作用，而且引经“羌活”的使用，使药效充分作用于脑窍，提高该中药复方制剂对缺血性卒中脑损伤的神经保护作用。此外，所述的中药复方制剂可制备成各种剂型的成药，与传统汤剂相比，其质量相对稳定，有利于剂量的控制，也更方便携带和服用。
附图说明
图1：为本发明实施例1和对比例1中样品的代谢火山图(注：绿色表示下调差异代谢物；红色表示上调差异代谢物；灰色表示检测到但差异不显著代谢物)；
图2：为本发明实施例1和对比例1中样品的差异代谢物聚类热图(注：红色表示高含量；绿色表示低含量；Phenolicacids：酚酸类；Flavonols：黄酮；Others：其它；Lipids：脂质；Quinones：醌类；Aminoacids and derivatives：氨基酸及其衍生物；Organic acids：有机酸；Lignans and Coumarins：木脂素和香豆素；Terpenoids：萜类；Alkaloids：生物碱；Nucleotides and derivatives：核苷酸及其衍生物；Tannins：鞣质)；
图3：为本发明实施例1和对比例1差异代谢物对比得到的前20个差异表达代谢物样品的差异倍数柱状图(注：Isopimpinellin:异茴芹内酯；Quercetin-3-O-sophoroside(Baimaside):槲皮素-3-O-槐糖苷(白麻苷)；Isorhamnetin-3-O-neohesperidoside:异鼠李素-3-O-新橙皮糖苷；Skimmianine:茵芋碱；5-O-p-Coumaroylquinicacid:5-O-对香豆酰奎宁酸；Hispidulin(5,7,4'-Trihydroxy-6-methoxyflavone):高车前素；Cryptochlorogenic acid(4-O-Caffeoylquinic acid):隐绿原酸(4-O-咖啡酰奎宁酸)；Diosmetin(5,7,3'-Trihydroxy-4'-methoxyflavone):香叶木素；Quercetin-3-O-rutinoside-7-O-glucoside:槲皮素-3-O-芸香糖苷-7-O-葡萄糖苷；Furanodienone:呋喃二烯酮；2'-Deoxyguanosine:2'-脱氧鸟苷；1-O-Galloyl-3-O-p-Coumaroyl-β-D-glucose:1-O-没食子酰-3-O-对香豆酰-β-D-葡萄糖；Cyclic3',5'-Adenylicacid:环-3',5'-腺嘌呤核苷酸；Physcion-8-O-(6-acetyl)-glucoside:大黄素甲醚-8-O-β-D-(6-乙酰基)-葡萄糖苷；1-O-Galloyl-6-O-Cinnamoyl-β-D-glucose:1-O-没食子酰-6-O-肉桂酰-β-D-葡萄糖；Chrysophanol-8-O-(6'-acetyl)-glucoside:大黄酚-8-O-(6'-乙酰基)-吡喃葡萄糖苷；L-Prolyl-L-Leucine:L-脯氨酰-L-亮氨酸；2-Methoxy-4-ethenylphenol:2-甲氧基-4-乙烯基苯酚；Chrysophanol-1-O-(6'-acetyl)-glucoside:大黄酚-1-O-(6-O-乙酰基)-葡萄糖苷；Torachrysone-8-O-(6”-acetyl)glucoside:决明酮-8-O-(6”-乙酰)葡萄糖苷)；
图4：为本发明大鼠缺血性脑卒造模试验中各组大鼠的神经功能评分统计结果(注：sham-假手术组；tMCAO-模型组；SJS-对照组；XNSJS-实验组)；
图5：为本发明大鼠缺血性脑卒造模试验中各组大鼠的TTC染色脑梗死形态图和脑梗死体积比(注：sham-假手术组；tMCAO-模型组；SJS-对照组；XNSJS-实验组)；
图6：为本发明大鼠缺血性脑卒造模试验中各组大鼠组织经Western blot检测的TNF-α的表达水平(注：sham或sh-假手术组；tMCAO或tMC-模型组；SJS或S-对照组；XNSJS或XN-实验组)；
图7：为本发明大鼠缺血性脑卒造模试验中各组大鼠组织经qPCR检测TNF-α的表达水平(注：sham-假手术组；tMCAO-模型组；SJS-对照组；XNSJS-实验组)。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1
一种用于治疗缺血性脑卒中的中药复方制剂，包括以下重量份原料：15份三桠苦、10份红花、10份羌活、15份姜黄、5份熟大黄、5份蝉蜕和5份炒僵蚕。
上述实施例1中一种用于治疗缺血性卒中的中药复方制剂的制备方法，包括以下步骤：
(1)取三桠苦饮片，加10倍水煎煮二次，每次煎煮2小时，过滤，滤液浓缩至比重为1.02～1.06的清膏，喷雾干燥，过筛，混合，即得三桠苦提取物；
(2)取红花饮片，加10倍水煎煮二次，每次煎煮1.5小时，过滤，滤液浓缩至比重为1.05～1.09的清膏，喷雾干燥，过筛，混合，即得红花提取物；
(3)取羌活饮片，加10倍水煎煮一次，煎煮2小时，过滤，滤液浓缩至比重为1.09～1.13的清膏，喷雾干燥，过筛，混合，即得羌活提取物；
(4)取姜黄饮片，加10倍水煎煮二次，每次煎煮1.5小时，过滤，滤液浓缩至比重为1.02～1.06的清膏，喷雾干燥，过筛，混合，即得姜黄提取物；
(5)取熟大黄饮片，加10倍水煎煮二次，每次煎煮1.5小时，过滤，滤液浓缩至比重为1.07～1.11的清膏，喷雾干燥，过筛，混合，即得熟大黄提取物；
(6)取蝉蜕饮片，加10倍水煎煮二次，每次煎煮2小时，过滤，滤液浓缩至比重为1.00～1.04的清膏，喷雾干燥，过筛，混合，即得蝉蜕提取物；
(7)取炒僵蚕饮片，加10倍水煎煮二次，每次煎煮2小时，过滤，滤液浓缩至比重为1.03～1.07的清膏，喷雾干燥，过筛，混合，即得炒僵蚕提取物；
(8)分别取步骤(1)-(7)的7味提取物，混合30分钟使药物均匀，将混合物干法制粒制成12-40目颗粒。
对比例1
一种用于治疗缺血性脑卒中的中药方剂，包括以下重量份原料：3份蝉蜕、6份僵蚕、9份姜黄、12份酒大黄。
上述对比例1中一种用于治疗缺血性卒中的中药复方制剂的制备方法，包括以下步骤：
(1)取蝉蜕饮片，加10倍水煎煮二次，每次煎煮2小时，过滤，滤液浓缩至比重为1.00～1.04的清膏，喷雾干燥，过筛，混合，即得蝉蜕提取物；
(2)取僵蚕饮片，加10倍水煎煮二次，每次煎煮2小时，过滤，滤液浓缩至比重为1.03～1.07的清膏，喷雾干燥，过筛，混合，即得僵蚕提取物；
(3)取姜黄饮片，加10倍水煎煮二次，每次煎煮1.5小时，过滤，滤液浓缩至比重为1.02～1.06的清膏，喷雾干燥，过筛，混合，即得姜黄提取物；
(4)取酒大黄饮片，加10倍水煎煮二次，每次煎煮1.5小时，过滤，滤液浓缩至比重为1.07～1.11的清膏，喷雾干燥，过筛，混合，即得酒大黄提取物；
(5)分别取步骤(1)-(4)的4味提取物，混合30分钟使药物均匀，将混合物干法制粒制成12-40目颗粒。
性能检测试验
1、将实施例1和对比例1的药物进行差异代谢物筛选试验，试验分为对应实施例1的实验组N组和对应对比例1的对照组O组，使用超高效液相色谱和串联质谱进行代谢物的定性定量分析，并筛选差异代谢物。
1)代谢成分总体分析
基于UPLC-MS/MS检测平台和迈维自建数据库对两组样品进行检测，共检测到922个代谢物，共有12种，包括酚酸类233个、其它类140个、脂质139个、黄酮80个、氨基酸及其衍生物79个、有机酸63个、核苷酸及其衍生物51个、醌类46个、生物碱34个、萜类26个、木脂素和香豆素23个，鞣质8个。
2)差异代谢物结果
根据VIP≥1和fold change≥2或fold change＜0.5的标准筛选代谢物，代谢物在对照组和实验组中差异为2倍以上或0.5倍以下,当fold change≥2表示差异上调，foldchange≤0.5则表示差异下调。实验组(N)样品和对照组(O)样品一共筛选出488个差异代谢物，其中有204个代谢物上调表达，有284个代谢物下调表达。火山图直观展示出两组样品代谢物的相对含量差异以及统计学上差异的显著性，结果如图1所示。
为方便观察代谢物变化规律，对差异显著的代谢物进行归一化处理，实验组N组与对照组O组的样品均为3个生物学重复(实验组N组标记为N1、N2、N3，对照组O组标记为O1、O2、O3)，并绘制聚类热图，结果如图2所示，该图简单、直观地反映出差异代谢物的变化情况。在488个差异代谢物成分中，酚酸类146个(上调52个，下调94个)，黄酮62个(上调38个，下调24个)，其它类55个(上调20个，下调35个)，脂质50个(上调37个，下调13个)，醌类45个(上调4个，下调41个)，氨基酸及其衍生物25个(上调15个，下调10个)，有机酸24个(上调11个，下调13个)，木脂素和香豆素21个(上调17个，下调4个)，萜类21个(上调9个，下调12个)，生物碱16个(上调7个，下调9个)，核苷酸及其衍生物15个(上调8个，下调7个)，鞣质8个(均为下调)。
3)主要差异代谢物成分分析
比较两组样品中代谢成分定量信息发生的差异倍数变化，将差异倍数进行处理(log2FC)，上调和下调变化排在前的20个差异表达代谢成分如图3所示。与O组相比，N组中相对含量显著增加的代谢物成分有5种黄酮(槲皮素-3-O-槐糖苷(白麻苷)，异鼠李素-3-O-新橙皮糖苷，高车前素，香叶木素，槲皮素-3-O-芸香糖苷-7-O-葡萄糖苷)、2种酚酸类(5-O-对香豆酰奎宁酸，隐绿原酸(4-O-咖啡酰奎宁酸))、1种萜类(呋喃二烯酮)、1种生物碱(茵芋碱)、1种木脂素和香豆素(异茴芹内酯)；同时N组相比于O组中相对含量显著降低的代谢物有4种酚酸类(1-O-没食子酰-3-O-对香豆酰-β-D-葡萄糖，1-O-没食子酰-6-O-肉桂酰-β-D-葡萄糖，2-甲氧基-4-乙烯基苯酚，决明酮-8-O-(6”-乙酰)葡萄糖苷)、3种蒽醌类(大黄素甲醚-8-O-β-D-(6-乙酰基)-葡萄糖苷，大黄酚-8-O-(6'-乙酰基)-吡喃葡萄糖苷，大黄酚-1-O-(6-O-乙酰基)-葡萄糖苷)、2种核苷酸及其衍生物(2'-脱氧鸟苷，环-3',5'-腺嘌呤核苷酸)及1种氨基酸及其衍生物(L-脯氨酰-L-亮氨酸)。
结论：本试验采用广泛靶向代谢组学技术，对两组样品的代谢物进行对比分析，根据VIP值和Fold_Change值筛选出的差异代谢物中，相比于O组，N组的黄酮类化合物、脂质上调表达显著，黄酮类化合物具有神经保护、降压、改善学习记忆认知、抗炎、抗菌、抗氧化以及降血糖等药理活性，且黄酮类化合物槲皮素具有通过减少氧化应激损伤实现抗凝血、抑制血小板聚集的作用。脂质上调表达以游离不饱和脂肪酸为主，不饱和脂肪酸具有降低血液总胆固醇水平，预防动脉粥样硬化，调节血脂、抗氧化以及体外抑制血小板聚集等功效。N组相比于O组的酚酸类化合物隐绿原酸也显著上调表达，隐绿原酸进入体内后产生核心代谢产物咖啡酸和奎宁酸，并在此基础上发生进一步的代谢，产生阿魏酸、异阿魏酸、香豆酸等，它们均具有很好的抗炎的药理作用。综上所述，本试验表明中药复方制剂N组相比于O组具有较好的抗血栓、改善血流、抗氧化、抗炎、降低脑代谢的作用。
2、通过大鼠缺血性脑卒造模试验中药复方制剂对缺血性脑卒中的防治效果的影响：
1)实验将SFP等级的SD大鼠按随机数字表分为假手术组(sham)、模型组(tMCAO)、对应对比例1的对照组(SJS)、对应实施例1的实验组(XNSJS)，每组7只，根据人与大鼠体表面积药物剂量换算，确定大鼠的给药剂量为：中药复方制剂实验组剂量为1g/kg，对照组剂量为1g/kg，模型组和假手术组给予等体积溶剂，造模前7天灌胃给药，每天1次。
2)灌胃第7天后，对模型组、对照组、实验组SD大鼠按大脑中动脉闭塞法制备缺血性脑卒中模型：将SD大鼠全身麻醉后，分离出右侧颈总动脉(CCA)、颈外动脉(ECA)和颈内动脉(ICA)，将颈外动脉远心端和近心端分别结扎，然后剪断；血管夹夹闭颈内动脉和颈总动脉，将颈外动脉游离端拉至与颈内动脉成一直线，在颈外动脉游离端上剪一小口，将拴线插入，顺着颈内动脉方向延伸，至线栓标记处附近，阻断大脑中动脉血流供应。缺血2h后抽出线栓，结扎ECA伤口，缝合手术切口，再灌注24h。假手术组SD大鼠仅分离颈内外动脉，不闭塞大脑中动脉，其余步骤同模型组。缺血再灌注24小时后进行神经功能评分、脑梗死体积评估及检测梗死脑组织中炎症因子TNF-α的表达水平。
3)按照Zea Longa 5分制评分标准进行神经功能评分：无神经系统损伤症状：0分；不能完全伸展对侧前爪：1分；向左侧转圈：2分；向对侧倾倒：3分；不能自发行走且意识丧失：4分，统计结果如图4所示(n＝7，**P＜0.01vs sham；#＜0.05，##＜0.01 vs tMCAO；&＜0.05 vs SJS)。
4)神经功能评分结束后处死大鼠，分离大鼠大脑并置于-20℃条件下冷冻保存，将冷冻后的大鼠大脑组织均匀切成五片，脑片置于2，3，5－氯化三苯基四氮唑(TTC)溶液中，37℃恒温避光孵育15分钟，正常组织染成红色，缺血梗死灶染成白色，统计结果如图5所示(n＝7，**P＜0.01vs sham；##＜0.01,ns为无统计学意义vs tMCAO；&＜0.01 vs SJS)。
5)Western blot检测各组大鼠脑组织中TNF-α的表达水平，根据制造商的说明，使用RIPA裂解缓冲液适量大鼠脑缺血组织提取总蛋白，裂解完之后12000r/min离心15min，取上清于另外一个干净的EP管，用超微量紫外/可见分光光度计测量蛋白浓度之后，5×蛋白上样缓冲液与蛋白按照1∶4的比例混匀，95℃5min进行蛋白灭活之后，-20℃保存待用；SDS-PAGE凝胶电泳：80V低压跑胶至样品到压缩胶与分离胶交界处，然后改用120V恒压跑胶到能够分离各个目的条带；转膜：恒流200mA转膜2h；封闭：5％脱脂牛奶摇床封闭1h，封闭之后用TBST配置的一抗在4℃条件下孵育过夜，第2天，用TBST配制的二抗室温孵育1h，化学发光成像系统显影拍照，统计结果如图6所示(n＝4，**P＜0.01，ns为无统计学意义vs sham；#＜0.05vs tMCAO；&＜0.05 vs SJS)。
6)qPCR检测各组脑缺血组织中TNF-α的表达，取适量脑组织按照trizol试剂盒操作说明提取总RNA，根据PrimeScriptTM RT reagent kit说明书操作反转录cDNA，根据按照实时荧光定量试剂盒添加试剂，置PCR仪进行扩增，最后使用2-ΔΔCt方法分析Ct值，引物序列如下表1所示，统计结果如图7所示(n＝7，**P＜0.01，ns为无统计学意义vs tMCAO或SJS；##＜0.01 vs tMCAO)。
表1-qPCR检测中引物序列
| 序列名称 | 序列 |
| TNF-α上游 | 5'-TACACTGGCCCGAGGCAACA-3' |
| TNF-α下游 | 5'-GGGCAAGGGCTCTTGATGGC-3' |
| 内参为β-actin上游 | 5'-CGGTCAGGTCATCACTATC-3' |
| 内参为β-actin下游 | 5'-CAGGGCAGTAATCTCCTTC-3' |
结论：
如图4所示，与假手术组相比，模型组、对照组、实验组均出现神经功能缺损症状，其中模型组神经功能评分显著高于其他组；与对照组比较，实验组神经功能评分明显降低。
如图5所示，与假手术组相比，模型组、对照组、实验组均出现脑梗死灶，其中模型组脑梗死灶面积较其他组显著增大，脑梗死体积比也显著高于其他组；与对照组比较，实验组脑梗死体积比明显降低。
如图6所示，与假手术组相比，模型组、对照组、实验组脑组织中TNF-α的表达水平升高，其中模型组TNF-α的表达水平升高显著；与模型组相比，对照组、实验组脑组织中TNF-α的表达水平明显降低，以实验组降低显著；与对照组相比，实验组脑组织中TNF-α的表达水平降低。
如图7所示，与假手术组相比，模型组、对照组、实验组脑组织中TNF-α的表达水平升高，其中模型组的表达水平升高显著；与模型组相比，实验组脑组织中TNF-α的表达水平明显降低，而对照组脑组织中TNF-α表达水平无统计学意义。
实验组可减少缺血性卒中发作后脑梗死体积及减少神经功能损害，并且可以抑制缺血性卒中后脑组织中炎症因子TNF-α的表达，由此可见，该中药复方制剂可以有效防治缺血性卒中。
以上所述的具体实施例，对本发明的目的、技术方案和有益效果进行了进一步的详细说明，应当理解，以上所述仅为本发明的具体实施例而已，并不用于限定本发明的保护范围。特别指出，对于本领域技术人员来说，凡在本发明的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (9)
1.一种治疗缺血性脑卒中的中药复方制剂，其特征在于，由以下重量份组分组成：三桠苦13份-18份、红花7份-12份、羌活8份-12份、姜黄12份-18份、熟大黄2份-7份、蝉蜕3份-6份、炒僵蚕3份-8份。
2.如权利要求1所述的一种治疗缺血性脑卒中的中药复方制剂，其特征在于，由以下重量份组分组成：三桠苦15份、红花10份、羌活10份、姜黄15份、熟大黄5份、蝉蜕5份、炒僵蚕5份。
3.如权利要求1所述的一种治疗缺血性脑卒中的中药复方制剂，其特征在于，所述中药复方制剂为片剂、丸剂、胶囊、颗粒剂、散剂或口服液。
4.如权利要求1所述一种治疗缺血性脑卒中的中药复方制剂，其特征在于，还包括医学上可接受的辅料。
5.一种如权利要求1-4任一所述的治疗缺血性脑卒中的中药复方制剂的制备方法，其特征在于，包括以下步骤：
（1）取三桠苦饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得三桠苦提取物；
（2）取红花饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得红花提取物；
（3）取羌活饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛， 混合，即得羌活提取物；
（4）取姜黄饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得姜黄提取物；
（5）取熟大黄饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得熟大黄提取物；
（6）取蝉蜕饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得蝉蜕提取物；
（7）取炒僵蚕饮片，加水煎煮，过滤，滤液浓缩为清膏，喷雾干燥，过筛，混合，即得炒僵蚕提取物；
（8）分别取步骤（1）-（7）的7味提取物，混合使药物均匀，将混合物干法制粒制成颗粒。
6.如权利要求5所述的一种治疗缺血性脑卒中的中药复方制剂的制备方法，其特征在于，在步骤（1）-（7）中，所述清膏的比重为1-1.2。
7.如权利要求5所述的一种治疗缺血性脑卒中的中药复方制剂的制备方法，其特征在于，在步骤（8）中，所述颗粒的目数为10-80目。
8.如权利要求5所述的一种治疗缺血性脑卒中的中药复方制剂的制备方法，其特征在于，在步骤（1）-（7）中，加水煎煮中水用量为固料的8-10倍质量，加水煎煮的次数为1-3次。
9.如权利要求5所述的一种治疗缺血性脑卒中的中药复方制剂的制备方法，其特征在于，在步骤（1）中，每次煎煮0.5～2.5 小时；在步骤（2）中，每次煎煮 0.5～2 小时；在步骤（3）中，每次煎煮 1～3 小时；在步骤（4）中，每次煎煮 0.5～2 小时；在步骤（5）中，每次煎煮 0.5～2 小时；在步骤（6）中，每次煎煮 0.5～2.5 小时；在步骤（7）中，每次煎煮 0.5～2.5 小时。
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2160418Y (zh) * | 1993-06-18 | 1994-04-06 | 杨恒裕 | 治疗慢性荨麻疹和白癜风的脐疗带 |
| CN101590210A (zh) * | 2009-06-16 | 2009-12-02 | 周辉 | 治疗脑水肿的中药组合物及其制备方法 |
| CN102028910A (zh) * | 2009-09-29 | 2011-04-27 | 丁仁松 | 一种治疗老年痴呆的中药制剂及其制备方法 |
| CN103989941A (zh) * | 2014-06-09 | 2014-08-20 | 强红枫 | 一种用于缺血性脑卒中后神经再生的药物组合物及其制备方法和用途 |
| TW201505645A (zh) * | 2013-05-15 | 2015-02-16 | wei-quan Li | 降脂護肝中藥組合物及其製備方法和應用 |
| CN108392600A (zh) * | 2018-05-29 | 2018-08-14 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | 一种用于治疗中风的中药方剂 |
| CN114716503A (zh) * | 2022-03-23 | 2022-07-08 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | 一种雷公藤氯内酯醇的制备方法 |
-
2023
- 2023-03-21 CN CN202310282407.7A patent/CN116270943B/zh active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2160418Y (zh) * | 1993-06-18 | 1994-04-06 | 杨恒裕 | 治疗慢性荨麻疹和白癜风的脐疗带 |
| CN101590210A (zh) * | 2009-06-16 | 2009-12-02 | 周辉 | 治疗脑水肿的中药组合物及其制备方法 |
| CN102028910A (zh) * | 2009-09-29 | 2011-04-27 | 丁仁松 | 一种治疗老年痴呆的中药制剂及其制备方法 |
| TW201505645A (zh) * | 2013-05-15 | 2015-02-16 | wei-quan Li | 降脂護肝中藥組合物及其製備方法和應用 |
| CN103989941A (zh) * | 2014-06-09 | 2014-08-20 | 强红枫 | 一种用于缺血性脑卒中后神经再生的药物组合物及其制备方法和用途 |
| CN108392600A (zh) * | 2018-05-29 | 2018-08-14 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | 一种用于治疗中风的中药方剂 |
| CN114716503A (zh) * | 2022-03-23 | 2022-07-08 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | 一种雷公藤氯内酯醇的制备方法 |
Non-Patent Citations (6)
| Title |
|---|
| 中医综合治疗方案对急性缺血性中风中医症征影响的研究;蔡业峰，等;陕西中医;第28卷(第08期);第1037-1041页 * |
| 中西医结合治疗老年缺血性中风临床疗效观察;王红霞;四川中医;-;第29卷(第03期);第82-83页 * |
| 中风祖方治疗溶栓窗外急性缺血性中风血瘀证患者的临床研究;文龙龙, 等;广州中医药大学学报;第35卷(第06期);第981-986页 * |
| 升降散的抗炎作用;瞿融，等;中成药;-(第04期);第28-30页 * |
| 缺血性脑卒中的病理机制研究进展及中医药防治;张艾嘉, 等;中国实验方剂学杂志;第26卷(第05期);第227-240页 * |
| 补阳还五汤合升降散治疗中风的临床观察;耿昌明，等;深圳中西医结合杂志;-;第23卷(第06期);第373-374、379页 * |
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| Publication number | Publication date |
|---|---|
| CN116270943A (zh) | 2023-06-23 |
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