CN117018076A - 一种益肾祛风的中药复方组合物及其制备方法与应用 - Google Patents
一种益肾祛风的中药复方组合物及其制备方法与应用 Download PDFInfo
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Abstract
本发明属于中药领域,涉及一种益肾祛风的中药复方组合物及其制备方法与应用。一种益肾祛风的中药复方组合物,它包括如下重量份数的组分:生黄芪9~30份,酒萸肉6~12份,全蝎3~6份,炒僵蚕5~10份,太子参9~30份,炒白术6~12份,石韦6~30份,红花3~10份,川芎3~10份,白花蛇舌草15~30份,茯苓皮15~30份,车前子9~30份。本发明的中药复方组合物中全蝎使用剂量较一般方子稍大,全蝎属虫类药,用于治疗肾炎蛋白尿较多,服用一日常规剂量为1~3g,发明人传承国医大师邹燕勤用药经验,并结合多年临床心得,突破全蝎等虫类药用于肾炎蛋白尿的使用剂量,经反复临证思考总结,验证临床治疗可加大剂量使用全蝎,疗效较低剂量使用更为显著,且无明显毒副作用。
Description
技术领域
本发明属于中药领域,涉及一种益肾祛风的中药复方组合物及其制备方法与应用。
背景技术
我国成人慢性肾炎的患病率为10%左右,慢性肾炎多数起病隐匿,病情迁延反复,可伴随不同程度的肾功能减退,甚至逐渐进展为慢性肾衰竭。早期患者可无明显症状,容易让人忽视,其基本临床表现是蛋白尿、血尿、高血压和水肿,其中蛋白尿不仅可损伤肾小球滤过膜和肾小管细胞,促进肾小球硬化和小管间质纤维化,是肾功能恶化、病情进展至终末期肾病的一个独立危险因素。因此,降低蛋白尿的治疗非常重要,关乎慢性肾炎患者的预后。
目前西医学对于慢性肾炎、肾病综合征蛋白尿无特异性治疗,研究主要集中在降低尿蛋白及血压控制,而控制蛋白尿的措施主要以ACEI和ARB类药物为主,在临床上效果显著的糖皮质激素、细胞毒药物、免疫抑制剂等,也存在部分患者不敏感、长期服用带来副作用、减量或停药后易于反复、价格昂贵等问题。
鉴于中医药在慢性肾炎治疗中,疗效确切,搭配激素或者免疫抑制剂起到增效减毒的作用,深得广大患者的推崇和信赖。目前市场上降蛋白尿的中成药包括有百令胶囊、至灵菌素(主要成分人工养殖冬虫夏草),黄葵胶囊(主要成分为黄蜀葵花)等,这几种中成药组分相对单一,对复杂难治的蛋白尿往往兼顾不到。因此,临床迫切需要开发一种对慢性肾炎患者高效且方便的中成药制剂,为广大肾病患者谋取更大的福利。
发明内容
本发明所要解决的技术问题是针对现有技术的不足,提供一种益肾祛风的中药复方组合物。
本发明还要提供上述益肾祛风的中药复方组合物的制备方法。
最后本发明还要提供上述益肾祛风的中药复方组合物的应用。
为了解决上述技术问题,本发明采用的技术方案如下:
本发明公开了一种益肾祛风的中药复方组合物,它包括如下重量份数的组分:
生黄芪9~30份,
酒萸肉6~12份,
全蝎3~6份,
炒僵蚕5~10份,
太子参9~30份,
炒白术6~12份,
石韦6~30份,
红花3~10份,
川芎3~10份,
白花蛇舌草15~30份,
茯苓皮15~30份,
车前子9~30份。
在一些实施例中,优选地,它包括如下重量份数的组分:
生黄芪30份,
酒萸肉10份,
全蝎4份,
炒僵蚕10份,
太子参15份,
炒白术10份,
石韦10份,
红花10份,
川芎10份,
白花蛇舌草15份,
茯苓皮30份,
车前子15份。
在一些实施例中,所述的中药复方组合物,其剂型为颗粒剂、液体制剂、胶囊剂、片剂或丸剂。
进一步地,本发明公开了上述益肾祛风的中药复方组合物的制备方法,将生黄芪、酒萸肉、全蝎、炒僵蚕、太子参、炒白术、石韦、红花、川芎、白花蛇舌草、茯苓皮和车前子加水煎煮,滤过,滤液减压浓缩,得到浓缩液。
在一些实施例中,所述的加水煎煮,每次煎煮时水的加入重量为中药材总重量的6~10倍,煎煮次数为2~3次,每次煎煮时间为20~40min。
其中,第一次加水煎煮前需要浸泡10~30min。
其中,所述煎煮次数优选为2次;当煎煮次数为2次时,第一次煎煮时间优选为30~40mim,第二次煎煮时间优选为20~30min。
在一些实施例中,所述的减压浓缩,浓缩真空度为-0.08~-0.04MPa,浓缩温度为70~80℃,将煎液浓缩至60℃相对密度为1.02~1.22,得到浓缩液。
在一些实施例中,在制备过程中向浓缩液中加入药学上可接受的辅料。
更进一步地,本发明公开了上述益肾祛风的中药复方组合物在制备治疗肾病药物中的应用。
在一些实施例中,所述肾病为慢性肾炎、肾病综合证或蛋白尿。
上述益肾祛风的中药复方组合物在制备治疗肾病药物中的应用也在本发明的保护范围之内。
上述的益肾祛风的中药复方组合物与雷公藤多苷平组成的组合物也在本发明的保护范围之内。
上述中药复方组合物与雷公藤多苷平组成的组合物在制备治疗肾病药物中的应用也在本发明的保护范围之内。
本发明的中药复方组合物的中药配伍原理为:
中药复方组合物中生黄芪、酒萸肉二药为君,生黄芪补元气益肾气、益气升提固精、补肺实表,为治肾病要药,酒萸肉强阴益精、补益肝肾为其专功,结合张锡纯所言:“敛正气而不敛邪气,与他酸敛之药不同”,故而涩精止泄而不敛邪,二药相伍益肾固肾治本。全蝎、炒僵蚕二药为臣,以“祛风”为要义,风邪伏留难除,非一般祛风药能及能散,日久则伴随肾络瘀滞,取二虫祛风通络以搜剔伏邪,僵蚕轻浮升散,外散风热邪气,利咽祛风,从咽兼顾邪气,因此内外风并解。
太子参,人参之小者,归肺脾二经,补而能清,功用灵活,五脏之虚,随所引而至。五脏之阳,生阴生血,阳自生而阴自长。退虚火,止汗生津,补肺脾元气。
白术:李宗梓认为:“白术味甘性温,得中宫冲和之气,故补脾胃之药,更无出其右者”,中土虚弱,得白术以斡运中气、实脾燥湿,土旺自能复清升浊降本位,自能健运除湿充里,里气充则表气自固,配合生黄芪则充里实表兼而治之。
红花、川芎:血分治疗活血和络贯始终,红花、川芎二味相佐平和缓散瘀血。深入血分以除顽瘀死血,腰痛肾瘀渐畅,血脉自和。
石韦、茯苓皮、车前子、白花蛇舌草:研发者继承国医大师邹燕勤利水喜用淡渗利水、轻药重投法的思想,临证常用茯苓皮、车前子等轻淡渗利之品合而重投,利水不致过伤气阴,慢性肾炎伴随水肿者以利水为先,结合白花蛇舌草、石韦等清利湿热之品,共奏淡渗清利之功。且能引药入肾经,为佐使药。
发明思路:发明人认为无论是原发还是继发肾脏病引起的蛋白尿,病位主要在于肾,以脾肾为关键,涉及肺、肝两脏及三焦、膀胱等。病因不离先天不足、后天失养两面,六淫、药毒、七情、饮食、劳倦等内外因损害是发病之由、也是进展之因,常贯穿疾病发展的始末,临床治疗不容忽视。本病证属本虚标实,以脾肾亏虚为本,尤以肾气不足为根,病变过程中风邪、水湿、湿热、瘀血等病理因素常夹杂为患,以致蛋白尿缠绵难愈。
①脾肾亏虚为本:慢性肾炎蛋白尿属西医病名,历代典籍中无直接相关内容,中医研究可从“水肿、腰痛、癃闭、虚劳、眩晕”等病中去探寻。结合中医古籍、邹氏肾科传承及多年临床经验,发明人认为本病脾肾亏虚为本,肾气不足为病根。脾肾两脏是人体先后天的代表,肾为先天之本,受于父母充于后天,肾中精气、阳气能够滋养、温煦五脏六腑;若肾气虚弱,势必影响五脏六腑的充养和功能状态;同时肾气不足,正气衰惫、气化无力,邪气侵犯下可直伤肾脏;肾为水脏、封藏之本,若功能失调水液代谢、精微物质的蛰藏、废物的排泄则会出现问题,引发水肿、蛋白尿等一系列表现。脾属后天之本,主运化水谷精微和水液,能以后天充养先天,先天不足后天得充则有望恢复,若先天不足再后天不济则难有生机,因此脾肾同调为治肾关键;同时脾胃又为气机升降之枢纽,升输精微为其所主,清阳得升则精微得固,浊阴得降,气机和调,溲便不变。
②风邪作崇贯始终:临床对于肾病蛋白尿病理因素的辨治尤其重视风邪,其认为风邪伤肾贯穿蛋白尿发生、发展的始末,同时也是蛋白尿时隐时现、迁延难愈的主要原因,正如国医大师颜德馨所言:“水无风则平静而澄,遇风则波起浊泛,慢性肾炎蛋白尿缠绵不解,祸根往往为风邪作祟。”对于风邪的辨治需要考虑外风、内风及内外风夹杂三面,其中外风主要为外感风邪,多为风寒、风热邪气犯表所致,临床伴随表证即为提示;咽喉症状临床多见,咽痒咽痛甚至出现乳蛾红肿等当考虑风热邪毒搏结咽喉,此为外风夹杂热毒为患,因咽喉循经入肾邪气可直犯肾脏;部分患者伴随皮肤瘙痒甚至出现皮疹证属风邪为患也是外风的一种表现形式,可作为辨证抓手。至于内风,一方面由于外风扰肾,风邪潜伏肾络,成为伏邪,伏留难除且易伴随它邪同扰;另一方面结合部分慢性肾炎患者伴有血压高、眩晕甚至头痛等表现,证属肝风内动,多由素体肝肾不足、肾中阴精缺乏所致。内外风夹杂临床也易见,且发作时蛋白尿常升高明显,证属表里同病,外风侵扰,伏留之内风引动,内外风邪同流合污;内风不除,正气不充,外风同气相求也会时时侵犯。
③水湿、湿热、瘀血夹杂:肾病多脾肾虚弱,或伴随肺气不足,水液代谢失常,水湿之邪为主要病理因素之一,湿性重浊,临床病人多见下肢水肿,以水湿邪气的轻重对应肿势的低高;一部分患者眼睑面目浮肿为主,则是风邪夹杂水湿为患;大便不成形或者便溏黏腻、倦怠乏力亦多见,多由脾肾气虚、水湿困脾所致。湿热多由水湿久蕴化热而成,湿与热郁而互阻,合而难分,胶黏难解,表现在症状上也难以消除;二者两邪之中谁多谁少,谁主谁辅,病机复杂难辨,也为临床处方用药增添了很大难度;三者湿热弥漫之性,常致弥漫三焦,蛋白尿的形成与下焦关联最大,但不可忽视上中二焦;四者湿属阴邪,伤气又伤阳,热属阳邪,耗阴伤液,病程日久,气阴暗耗,正气虚损,虚实夹杂更为明显;五者湿热居内,外邪居外,易由外引动加剧内里之势,致病情感时即发、起伏不定。邹氏肾科自邹云翔老先生治疗肾病水肿考虑血分水病起,即将瘀血这个病理因素考虑在内,国医大师邹燕勤在此基础上提出肾病皆有血气瘀滞,络脉运行不畅、肾络闭塞不通的病理。发明人传承邹氏经验并结合多年临证心得,认为慢性肾炎蛋白尿瘀血和风邪同样贯穿疾病的始终,辨证时瘀血或可见或难以捕捉,有轻有重,常兼夹其他病理因素,以致风湿热瘀诸邪合而为患,加剧了病机的复杂性、疾病的顽固性。
依据其病因病机及病理因素,发明人创立治疗肾病蛋白尿基本方法“益气祛风化瘀清利”治疗大法,并自拟益肾祛风方,方药组成主要包括生黄芪、太子参、酒萸肉、炒白术、全蝎、炒僵蚕、石韦、红花、川芎、白花蛇舌草、茯苓皮、车前子。益肾祛风方主治肺、脾、肾三脏,祛水湿、湿热、血瘀、风邪等,虚实兼顾,表里同治,在临床运用已颇有成效。临床迫切需要对慢性肾炎患者推出高效且方便的中成药制剂,为广大肾病患者谋取更大的福利。
项目的开发具有广泛的临床和市场开发前景,仅发明人单人门诊量计算,大约40%~60%肾病患者存在蛋白尿,仅发明人的患者需求量已达2000人次/年,而江苏省中医院肾科年门诊量约15万次,预计其中至少50000人次/年有降尿蛋白的需求,具有很大的经济效益,且能帮助患者延缓肾功能的进展,降低昂贵的免疫抑制剂使用费,给个人、家庭和社会减轻经济负担。今后可在医院制剂的临床使用基础上,进一步开发研制出作用机理清楚、有效成分明确、质量稳定可控、生产工艺先进、疗效确切、安全可靠的降蛋白尿新药,预期可创造巨大的经济效益和社会效益,同时也是弘扬中医药文化,促进中药现代化的重要组成部分。
有益效果:
(1)与现有技术中药味较多、用方较大、兼顾偏多相比,本发明的中药复方组合物以“益肾祛风”为治疗大法,处方精当、药力专一,紧扣肾炎蛋白尿核心病机与主要矛盾:肾气不足、风邪作祟,选方用药积多年临床心得,避免面面俱到、相互牵制之弊,药少用精而疗效显著。
(2)与现有技术相比,本发明中药复方组合物的治疗病种更有针对性,对于多种病理类型肾炎、轻中重度蛋白尿均有显著疗效,总有效率明确,不良反应较低,能够更好推广治疗。
(3)本发明的中药复方组合物中全蝎使用剂量较一般方子稍大,全蝎属虫类药,用于治疗肾炎蛋白尿较多,服用一日常规剂量为1~3g,发明人传承国医大师邹燕勤用药经验,并结合多年临床心得,突破全蝎等虫类药用于肾炎蛋白尿的使用剂量,经反复临证思考总结,验证临床治疗可加大剂量使用全蝎,疗效较低剂量使用更为显著,且无明显毒副作用。
附图说明
下面结合附图和具体实施方式对本发明做更进一步的具体说明,本发明的上述和/或其他方面的优点将会变得更加清楚。
图1为益肾祛风方对大鼠第8周末次24h-UTP(mg/d)的影响结果统计图;其中,Con为空白组,Hem为模型组,YSQF-L为低剂量益肾祛风方煎剂组,YSQF-M为中剂量益肾祛风方煎剂组,YSQF-H为高剂量益肾祛风方煎剂组。。
图2为模型组大鼠肾脏组织Masson染色图。
图3为高剂量益肾祛风方煎剂治疗组大鼠肾脏组织Masson染色图。
图4为模型组大鼠肾脏组织PASM染色图。
图5为高剂量益肾祛风方煎剂治疗组大鼠肾脏组织PASM染色图。
具体实施方式
根据下述实施例,可以更好地理解本发明。然而,本领域的技术人员容易理解,实施例所描述的内容仅用于说明本发明,而不应当也不会限制权利要求书中所详细描述的本发明。
实施例1:益肾祛风方煎剂的制备
将30质量份生黄芪、10质量份酒萸肉、4质量份全蝎、10质量份炒僵蚕、15质量份太子参、10质量份炒白术、10质量份石韦、10质量份红花、10质量份川芎、15质量份白花蛇舌草、30质量份茯苓皮和15质量份车前子加水(水的加入重量为中药材总重量的8倍)浸泡煎煮30min;浸泡完毕后将煎液进行第一次煎煮,武火煮沸后文火煎30min,煎煮结束后滤过,保留滤液;将滤渣加水(水的加入重量为中药材总重量的6倍)进行第二次煎煮,武火煮沸后文火煎煮30min,煎煮结束后滤过,合并两次滤液;将滤液进行减压浓缩得到浓缩液。
实施例2:动物实验
本发明所有研究均符合南京中医药大学附属医院动物研究伦理。
1、动物的选择
SPF级5周龄SD雄性大鼠,体重180±20g。
2、建立SD雄性大鼠被动型海曼肾炎膜性肾病模型
(1)造模方法
选取40只SD雄性大鼠,无特定病原体(Specific pathogen free,SPF)级实验动物房饲养。造模组大鼠尾静脉一次性注射羊抗Fx1A抗血清,剂量为0.5mL/100g,正常对照组尾静脉一次性注射等量生理盐水,于第1周末开始测定大鼠24小时尿蛋白定量,金属代谢笼收集24h尿液,尿蛋白试剂盒测定24h尿蛋白,当24h尿蛋白定量>10mg/d时认为造模成功。
(2)分组及给药
40只SD大鼠,适应性喂养1周后,随机分为5组,每组8只:
①空白组(健康大鼠,大鼠标准饲料饮食);
②PHN模型组(造模+生理盐水灌胃);
③低剂量益肾祛风方煎剂组(造模+9.27g/kg/d灌胃);
④中剂量益肾祛风方煎剂组(造模+18.54g/kg/d灌胃);
⑤高剂量益肾祛风方煎剂组(造模+37.08g/kg/d灌胃);
以上给药均在造模成功后进行。
上述益肾祛风方煎剂由实施例1制备,用药剂量以总药材的质量为基准。
3、标本处理
(1)适应性喂养最后一日统一测量24h尿蛋白定量,剔除24h-UTP>10mg/d的大鼠(剔除自发性肾病的大鼠),造模开始后每周1次留取尿标本,测量24h尿蛋白定量,每2周留取血清标本,第8周禁食12h后处死留取肾脏组织标本。
(2)尿液收集:大鼠代谢笼收集24小时尿。
(3)麻醉:4wt%戊巴比妥钠,0.15mL/100g腹腔注射将大鼠麻醉。
(4)肾组织取样:腹腔注射麻醉实验大鼠(4wt%戊巴比妥钠,0.15mL/100g),麻醉成功后,采用心脏取血的方法收集血液样本,心脏取血结束,在大鼠还有微弱心跳时立即进行心脏灌流,首先固定取血针,接入生理盐水,缓慢推进,观察脏器饱满情况,当脏器逐渐鼓起,剪开右心耳,约2-3分钟后,肾脏开始变白,肾脏完全变白后立即停止灌流,除去包膜及周围脂肪,将肾脏组织分为3份,分别用于病理、免疫组化、western blot,样本放于-80℃的冰箱保存。
4、指标检测
(1)尿液:双缩脲法检测尿蛋白定量;
(2)肾脏组织染色:将肾脏组织制成3μm石蜡切片,按常规方法行Masson、PASM染色。
5、实验结果
(1)益肾祛风方对大鼠(每组随机检测3只大鼠)第8周24h-UTP(mg/d)的影响结果,结果见表1。
表1大鼠第8周24h-UTP(mg/d)结果
注:Con为空白组,Hem为模型组,YSQF-L为低剂量益肾祛风方煎剂组,YSQF-M为中剂量益肾祛风方煎剂组,YSQF-H为高剂量益肾祛风方煎剂组。
图1为大鼠第8周末次24h-UTP(mg/d)平均结果统计图。从图1中可知,治疗8周后高剂量益肾祛风方煎剂组(造模+37.08g/kg/d灌胃)较模型组具有显著差异(*P<0.05)。
(2)肾脏组织Masson染色
如图2所示,根据随机选择的模型组MASSON(200X视野)的切片显示,模型组大鼠GBM增厚,见上皮嗜复红蛋白(免疫复合物)沉积,蛋白管型明显,同时肾小球出现了较为显著的胶原沉积。
如图3所示,根据随机选择的治疗组MASSON(200X视野)的切片显示,高剂量益肾祛风方煎剂治疗组的大鼠GBM区域厚度较模型组减轻,上皮嗜复红蛋白(免疫复合物)沉积减少,未见明显蛋白管型,肾小球胶原沉积较少,肾小球结构清晰,小管细胞排列有序,未见明显系膜细胞、内皮细胞和基质增生。
(3)肾脏组织PASM染色
如图4所示,根据随机选择的模型组PASM(200X视野)的切片显示,肾小球系膜区见部分增生,基底膜弥漫增厚伴部分带状空泡变性,钉突样结构形成。
如图5所示,根据随机选择的高剂量益肾祛风方煎剂治疗组PASM(200X视野)的切片显示,肾小球系膜区未见明显增生,基底膜恢复正常,可见清晰的肾小球结构,小管细胞排列有序,无内皮细胞和基质增生。
实施例3:临床试验
1、汤剂的制备
将生黄芪30g、酒萸肉10g、全蝎5g、炒僵蚕10g、太子参15g、炒白术10g、石韦15g、红花10g、川芎10g、白花蛇舌草30g、茯苓皮30g和车前子30g第一次加水(水的加入重量为中药材总重量的8倍)浸泡煎煮30min;浸泡完毕后将煎液进行第一次煎煮,武火煮沸后文火煎30min,煎煮结束后滤过,保留药液;将滤渣加水(水的加入重量为中药材总重量的6倍)进行第二次煎煮,武火煮沸后文火煎煮30min,煎煮结束后滤过,合并两次药液;将合并的药液均匀分成两份(1剂早晚分服),常温保存待用。
2、用药时间以及用药剂量
用药方式:口服汤剂,每日一剂。
病人用药剂量:2.93g/kg,即205g中药复方对应于70kg体重病人。
治疗组中药复方组合物中全蝎用量为5g。
3、中医疗效判定标准及西医疗效判定标准
3.1、中医疗效标准
参照2002版《中药新药临床研究指导原则》慢性肾小球肾炎的证候疗效判定标准:
采用尼莫地平法计算疗效指数,证候疗效指数=(疗前积分-疗后积分)/疗前积分×100%;
(1)临床痊愈:临床症状、体征减少或者完全消失,且减少证候积分≥95%;
(2)显效:临床症状、体征较为明显改善,且减少证候积分≥70%;
(3)有效:临床症状、体征均有明显好转,且减少证候积分≥30%;
(4)无效:临床症状、体征均未见明显改善甚或恶化,且减少证候积分<30%。
表2中医症状分级量化表
3.2、西医疗效标准
参照2002版《中药新药临床研究指导原则》慢性肾小球肾炎尿蛋白疗效评价:
(1)临床控制:24小时尿蛋白定量正常;
(2)显效:24小时尿蛋白定量减少≥40%;
(3)有效:24小时尿蛋白定量减少<40%;
(4)无效:24小时尿蛋白定量无减少或增加。
4、分组及实验结果
收集2018年9月至2021年1月期间就诊于江苏省中医院门诊及病房的慢性肾炎蛋白尿患者55例,治疗组28例,对照组27例,均符合本研究制定的纳入标准((1)年龄在20岁至75岁之间,性别不限;(2)符合慢性肾小球肾炎西医诊断标准,临床表现以蛋白尿为主;(3)中医辨证为脾肾气虚,兼风邪伤肾证;(4)24小时尿蛋白定量在0.5~3.5g/d;(5)血肌酐<110μmol/L;(6)感染、高血压、高血脂能够有效控制)。
治疗组在基础治疗(控制血压、血糖、血脂,纠正电解质酸碱平衡紊乱,利尿,雷公藤多苷平1mg/kg/d等)上加用中药复方组合物治疗,对照组仅给予基础治疗。观察时间3个月,观察两组患者治疗前后24小时尿蛋白定量、尿素氮、血肌酐、血清白蛋白等指标及中医症候评分的变化,并记录不良反应的发生情况,评价中药复方组合物的临床疗效和安全性。
4.1、治疗后两组患者西医疗效的比较
两组西医疗效组间比较,经秩和检验,Z=-2.183,P=0.033(P<0.05),差异有统计学意义,其中治疗组总有效率为92.86%,对照组总有效率为81.48%,见表3。实验结果表明:治疗组西医疗效高于对照组。
表3治疗后两组患者西医疗效的比较
4.2、治疗后两组患者中医疗效的比较
两组间中医疗效比较,经秩和检验,Z=-4.124,P=0(P<0.01),差异有显著统计学意义,其中治疗组总有效率为89.29%,对照组总有效率为37.04%,见表4。实验数据表明:治疗组中医疗效显著高于对照组。
表4治疗后两组患者中医疗效的比较
4.3、治疗前后两组患者3个月后24小时尿蛋白定量(UTP(g/d))的比较
与治疗前对比,两组患者治疗3个月后24小时尿蛋白定量均有明显改善,具有显著统计学差异(P<0.01)。两组治疗后组间比较,P=0.021<0.05,差异有统计学意义,实验数据结果表明:治疗组尿蛋白定量较对照组下降更明显,见表5。
表5治疗前后两组患者3个月后24小时尿蛋白定量(g/d)的比较
4.4、治疗前后两组患者1月、2月、3月后24小时尿蛋白定量(UTP(g/d))的比较
经t检验,两组患者治疗1月、2月、3月后24小时尿蛋白定量与治疗前相比均明显降低(P<0.01),有显著差异,见表6。
表6两组患者治疗前与治疗1月、2月、3月后24小时UTP(g/d)组内比较
4.5、治疗前后两组患者白蛋白、尿素氮、血肌酐的比较
经t检验,治疗组治疗前后白蛋白、尿素氮无统计学差异(P>0.05),治疗组血肌酐治疗后较治疗前有所下降,有显著统计学差异(P=0.006<0.01);对照组治疗前后白蛋白、尿素氮、血肌酐均无统计学差异(P>0.05);经配对样本t检验,组间比较发现治疗后两组患者白蛋白、尿素氮、血肌酐均无统计学差异(P>0.05),见表7。
表7治疗前后两组患者白蛋白(g/L)、血尿素氮(mmol/L)、血肌酐(μmol/L)的比较
本发明临床研究慢性肾炎蛋白尿患者的纳入标准为血肌酐<110μmol/L,收集的临床病例血肌酐、白蛋白及尿素氮整体数值本身就处于正常范围,因此治疗前后两组患者白蛋白、尿素氮、血肌酐的组内或组间几乎都是无统计学差异(治疗组血肌酐组内比较除外)。
本发明临床研究的慢性肾小球肾炎,临床表现以蛋白尿为主,治疗也以降蛋白尿为核心,而白蛋白、血肌酐和尿素氮反映的是肝肾功能,这三项指标不是慢性肾小球肾炎治疗的核心,更多是作为长期疗效观察和安全性评估的指标。
本发明提供了一种益肾祛风的中药复方组合物及其制备方法与应用的思路及方法,具体实现该技术方案的方法和途径很多,以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。本实施例中未明确的各组成部分均可用现有技术加以实现。
Claims (10)
1.一种益肾祛风的中药复方组合物,其特征在于,它包括如下重量份数的组分:
生黄芪9~30份,
酒萸肉6~12份,
全蝎3~6份,
炒僵蚕5~10份,
太子参9~30份,
炒白术6~12份,
石韦6~30份,
红花3~10份,
川芎3~10份,
白花蛇舌草15~30份,
茯苓皮15~30份,
车前子9~30份。
2.根据权利要求1所述的益肾祛风的中药复方组合物,其特征在于,它包括如下重量份数的组分:
生黄芪30份,
酒萸肉10份,
全蝎4份,
炒僵蚕10份,
太子参15份,
炒白术10份,
石韦10份,
红花10份,
川芎10份,
白花蛇舌草15份,
茯苓皮30份,
车前子15份。
3.根据权利要求1或2所述的益肾祛风的中药复方组合物,其特征在于,所述的中药复方组合物,其剂型为颗粒剂、液体制剂、胶囊剂、片剂或丸剂。
4.权利要求1或2所述的益肾祛风的中药复方组合物的制备方法,其特征在于,将生黄芪、酒萸肉、全蝎、炒僵蚕、太子参、炒白术、石韦、红花、川芎、白花蛇舌草、茯苓皮和车前子加水煎煮,滤过,滤液减压浓缩,得到浓缩液。
5.根据权利要求4所述的制备方法,其特征在于,所述的加水煎煮,每次煎煮时水的加入重量为中药材总重量的6~10倍,煎煮次数为2~3次,每次煎煮时间为20~40min。
6.根据权利要求4所述的制备方法,其特征在于,在制备过程中向浓缩液中加入药学上可接受的辅料。
7.权利要求1或2所述的益肾祛风的中药复方组合物在制备治疗肾病药物中的应用。
8.根据权利要求7所述的应用,其特征在于,所述肾病为慢性肾炎、肾病综合证或蛋白尿。
9.权利要求1或2所述的益肾祛风的中药复方组合物与雷公藤多苷平组成的组合物。
10.权利要求9所述的组合物在制备治疗肾病药物中的应用。
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