CN118059202A - 一种治疗乳腺结节的中药组合物及其制备方法和用途 - Google Patents
一种治疗乳腺结节的中药组合物及其制备方法和用途 Download PDFInfo
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Abstract
本发明提供了一种治疗乳腺结节的中药组合物，它是由下述重量配比的原料药制备而成：醋鳖甲5‑15份、土贝母8‑12份、橘叶3‑6份、青皮8‑12份、香附5‑15份、延胡索5‑15份、没药5‑10份、山慈姑8‑12份、土鳖虫4‑10份、莪术5‑15份、天葵子4‑10份、黄芪5‑15份、当归2‑10份、菟丝子2‑10份、巴戟天2‑10份。本发明还提供了该药物组合物的制备方法和用途。本发明药物安全性高，药效及临床试验证明，治疗乳腺增生，尤其针对乳腺结节，药效显著，为临床治疗乳腺结节、乳腺增生提供了一种新选择。
Description
技术领域
本发明涉及一种治疗乳腺结节的中药组合物，属于中药领域。
背景技术
现代医学认为女性乳腺结节产生的原因通常是雌、孕激素比例失调，内分泌激素紊乱以及性激素紊乱所致。通常和情绪、压力、生活习惯、生活环境也有一定关系。
中医学并无乳腺结节的病名，一般认为本病属于中医的“乳癖”，“乳痞”，“乳粟”等。历代医家对乳腺结节有不同的描述和命名。本病属于中医“乳癖”“乳痞”“乳中结核”“乳粟”“乳栗”等病的范畴。对于本病的病因病机，历代医家都有各自的见解。王肯堂《正治准绳》认为“忧怒郁遏，时日积累，肝气横逆，遂成瘾核”。伤寒论第131条“病发于阳反下之，热人因作结胸。发于阴，而反下之因作痞.....”。痞者癖也，痞是气血运行不畅，在人体的任何部位出现的胀满疼痛，时隐时现，时好时坏，血瘀经闭，这和乳癖的临床表现十分一致。《高氏疡科心得集》“肝气有所停，气不敢舒，肝气不舒，而肿硬之形成”。明代陈实功认为本病“多由思虑伤脾，恼怒伤肝，郁结而成”。阐明了肝郁气滞，情志内伤，淤血阻滞是本病发生的主要病因病机。对本病治疗方面的认识，《黄帝内经》日：百病由气生。《外证医案汇编》指出：“治乳症，肝胆木气郁，则位疽；正气虚，则为癌。痰气凝结，为癖，为痞，为核。各方之中，夹理气舒络之品，使乳络疏通，治肝而肿自消也”的观点。对后世医家影响较大。而余听鸿的“乳中结核，虽云在病，其病在肾”的观点。为本病采用调摄冲任，温补肾阳的治法提供了理论依据。
乳腺结节是一种症状，常见于乳腺增生及乳腺肿瘤性疾病。包括乳腺良性肿瘤。(包括乳腺纤维瘤，分叶状肿瘤等)以及乳腺恶性肿瘤(乳腺癌)。乳腺结节可发生于女性的任何年龄段。目前除了手术治疗以外，尚无更好的药物防治。尤其是B超检查出的结节形态不规则；还有乳腺非典型增生；乳腺腺病等。这些即非良性又没有发展到恶性的程度，这时就非常必要采用药物进行治疗，软化消散结节，控制其疾病进展和恶化。
申请号201310405052.2，发明名称：一种治疗乳癖的中药颗粒剂及其制备方法，公开了一种治疗乳癖的中药颗粒剂及其制备方法，主要取下述重量配比的主要原料制备而成：香附，山慈菇，土贝母，山楂，穿山甲，漏芦，郁金，莪术，皂角刺，鳖甲，栝楼，薤白，西洋参，王不留行，红花，该发明中药颗粒剂能够有效缓解。由乳癖引起的气血不畅，能够舒筋活血，对乳癖有很好的治疗作用。申请号201210219219.1，发明名称：治疗乳腺小叶增生与乳房纤维腺瘤的中药方剂。公开了治疗乳腺小叶增生与乳房纤维腺瘤的中药方剂，其组成成分如下：白芍6-10克、当归6-12克、茯苓6-10克、白术6-12克、柴胡3-6克、香附6-10克、郁金6-9克、青皮6-12克、元胡6-9克、三棱6-9克、莪术6-9克、丹参6-10克、红花3-6克、生山楂6-10克、玉不留行6-10克、路路通9-12克、鳖甲10-15克、生牡蛎10-20克、土贝母6-9克、瓜蒌皮6-9克、白芥子6-12克、天花粉6-10克、生甘草5克。由于“乳癖”的病因病机不同，辩证也有区别，目前公开的组方，还不能满足临床的需求。
发明内容
本发明的技术方案是提供了一种治疗乳腺结节的中药组合物及其制备方法和用途。
本发明提供了一种治疗乳腺结节的中药组合物，它是由下述重量配比的原料药制备而成：
醋鳖甲5-15份、土贝母8-12份、橘叶3-6份、青皮8-12份、香附5-15份、延胡索5-15份、没药5-10份、山慈姑8-12份、土鳖虫4-10份、莪术5-15份、天葵子4-10份、黄芪5-15份、当归2-10份、菟丝子2-10份、巴戟天2-10份。
进一步优选地，它是由下述重量配比的原料药制备而成：醋鳖甲8-12份、土贝母8-12份、橘叶4-6份、青皮4.8-7.2份、香附6.4-9.6份、延胡索6.4-9.6份、没药4-6份、山慈姑4.8-7.2份、土鳖虫4-6份、莪术4.8-7.2份、天葵子4-6份、黄芪6.4-9.6份、当归4.8-7.2份、菟丝子4.8-7.2份、巴戟天4.8-7.2份。
更进一步优选地，它是由下述重量配比的原料药制备而成：
醋鳖甲10份、土贝母10份、橘叶5份、青皮6份、香附8份、延胡索8份、没药5份、山慈姑6份、土鳖虫5份、莪术6份、天葵子5份、黄芪8份、当归6份、菟丝子6份、巴戟天6份。
本发明中药组合物是由所述的中药组合物的原生药粉、水或有机溶剂提取物为活性成分，加入药学上可接受的辅料或辅助性成分制备成药学上常用的制剂。
其中，所述的制剂是口服制剂。
其中，所述的口服制剂是片剂、胶囊剂、丸剂、颗粒剂、口服液。
本发明还提供了一种制备所述的中药组合物的方法，它包括如下步骤：
a、称取各重量配比的原料药；
b、土贝母、橘叶、青皮、香附、延胡索、没药、山慈姑、莪术加60％-90％乙醇，回流提取2-4次，将醇提物回收乙醇；
c、上述乙醇提取后的药渣与天葵子、黄芪、当归、菟丝子、巴戟天混合，加水煎煮，合并水提液，去弃药渣，煎出液与b步骤回收乙醇后的浓缩液合并，浓缩，干燥；
d、取醋鳖甲、土鳖虫打粉，与c步骤的干燥物混合，再加入药学上可接受的辅料或辅助性成分制备成药学上常用的制剂。
本发明还提供了所述的中药组合物在制备治疗乳腺结节的药物中的用途。
本发明还提供了所述的中药组合物在制备治疗乳腺结节或乳腺增生的药物中的用途。
本发明还提供了所述的中药组合物在制备具有疏肝理气，活血化瘀，调理冲任，温补肾阳的药物中的用途。
本发明药物组方以醋鳖甲、土贝母作为君药。醋鳖甲是中药里的“血肉有情”之品，是一种名贵中药。味咸，入肝经，长于软坚散结，善治癥瘕积聚。土贝母微寒，擅长散结消肿。现代医学研究土贝母有治疗结节，肿瘤的功效。土贝母无毒且价廉。臣用橘叶、青皮、香附、延胡索、没药作为臣药。橘叶性平，入肝经。根据研究，橘叶中的植物类黄酮化合物具有抗肿瘤作用。橘叶与青皮可增强疏肝理气的功效，而香附味辛善舒肝郁，延胡索，没药辛温，具有活血止痛作用。佐以山慈姑、土鳖虫、莪术、天葵子。山慈菇味甘辛，归肝经，擅长清热解毒，化痰散结。土鳖虫味咸入肝经，活血散瘀通络。莪术辛散温通，入肝经，破血行气止痛消癥。天葵子增强散结作用。使以黄芪、当归、菟丝子、巴戟天，黄芪当归扶正气，恐活血化瘀过犹。再用菟丝子，巴戟天调理冲任，温补肾阳。
本发明药物所治之疾病，来势顽疾。清代名医王清任主张“治病要快”，“逐瘀活血”。本方采用了软坚散结的醋鳖甲和山慈菇作为君药，利用土鳖虫、莪术、延胡索、没药的活血化瘀作用，再适时的用橘叶、香附、等药梳理肝气，共呈软坚疏肝活血散结之效。同时，还能提高病人的免疫功能。
本发明药物安全性高，单次给药毒性方面：对正常小鼠按单次最大给药量(580.8g/kg)，相当于临床成人日剂量(0.3666g/kg)的1584倍，均未出现明显的急性毒性。重复给药毒性方面：对雌性SD大鼠进行44g/kg剂量(相当于临床成人日剂量的120倍)连续给药13周，大鼠的组织病理学、生化学、血液学等各项指标均未见异常。药效及临床试验证明，本发明药物治疗乳腺增生，尤其针对乳腺结节，药效显著，为临床治疗乳腺结节、乳腺增生提供了一种新选择。
附图说明
图1药物组合物对乳腺增生大鼠乳腺组织形态的改善(A.空白组：镜检乳腺小叶腺泡数少，腺泡和导管内无分泌物；B.模型组：镜检乳腺小叶体积增大，小叶内腺泡数量增多，导管扩张，腔内有多量分泌物；C.他莫昔芬(3mg/kg)组，D-F.药物组合物原料药2.26g/kg、4.52g/kg、9.02g/kg组：与模型组相比，镜检乳腺小叶腺泡数量减少，扩张的导管数量减少。(Bar＝300μm,×100，黑色箭头所指为增生的乳腺小叶或扩张的导管))。
具体实施方法
实施例1本发明药物的制备
称取原料药：醋鳖甲100g、土贝母100g、橘叶50g、青皮60g、香附80g、延胡索80g、没药50g、山慈姑60g、土鳖虫50g、莪术60g、天葵子50g、黄芪80g、当归60g、菟丝子60g、巴戟天60g。
取土贝母、橘叶、青皮、香附、延胡索、没药、山慈姑、莪术加6倍量的75％乙醇，回流提取2-4次，每次1小时，将醇提物回收乙醇；
上述乙醇提取后的药渣与处方中的天葵子、黄芪、当归、菟丝子、巴戟天混合，加6倍量的水，煎煮2-4次，每次2小时，滤过，合并水提液，去弃药渣，煎出液与上述回收乙醇后的浓缩液合并，在-0.015-0.030MPa下，减压浓缩，温度为80℃，浓缩至浸膏相对密度为1.05-1.15时，在70℃下喷雾干燥为干膏粉，再与前述备用的醋鳖甲、土鳖虫灭菌细粉混匀原料药粉，装胶囊，制备成胶囊剂。
实施例2本发明药物片剂的制备
称取原料药：醋鳖甲12g、土贝母12g、橘叶6g、青皮7.2g、香附9.6g、延胡索9.6g、没药6g、山慈姑7.2g、土鳖虫6g、莪术7.2g、天葵子6g、黄芪9.6g、当归7.2g、菟丝子7.2g、巴戟天7.2g，按实施例1的方法制备，混合粉直接压片。
实施例3本发明药物胶囊剂的制备
醋鳖甲8g、土贝母8g、橘叶4g、青皮4.8g、香附6.4g、延胡索6.4g、没药4g、山慈姑4.8g、土鳖虫4g、莪术4.8g、天葵子4g、黄芪6.4g、当归4.8g、菟丝子4.8g、巴戟天4.8g，按实施例1的方法制备成胶囊剂。
以下通过具体药效学试验或临床试验证明本发明的有益效果。
试验例1本发明药物对乳腺增生大鼠模型的治疗作用
1试验药物及试剂制备
造模药物的制备：苯甲酸雌二醇注射液(购自宁波第二激素厂，生产批号：171026，规格：4mg/2ml)临用前用注射用大豆油(购自浙江田雨山药用油有限公司，批号：171212，规格：1000ml)稀释至0.5mg/ml、黄体酮注射液(购自天津金耀药业有限公司，批号：171028，规格：2mg/ml)临用前用注射用大豆油稀释至5mg/ml。注射体积均为1ml/kg，即每只大鼠给药量为苯甲酸雌二醇0.5mg/(kg·d)、黄体酮5mg/(kg·d)。
阳性对照药物：枸橼酸他莫昔芬片，扬子江药业集团有限公司，规格(按他莫昔芬计)：10mg/片，生产批号：18030211，批准文号：国药准字H32021472。临用前研末，用蒸馏水配制成浓度为0.38mg/ml的药液，每只大鼠给药体积为8ml/(kg·d)，即每只大鼠给药量为3mg/(kg·d)。
雌二醇(E2)、孕酮(P)、泌乳素(PRL)ELISA酶联免疫分析试剂盒(上海优选生物科技有限公司，批号：201809)；其他试剂均为国产分析纯。
2试验动物及仪器
雌性清洁级SD大鼠，155-165g，未孕，购自重庆市中药研究院试验动物研究所，许可证号SCXK(渝)2017-0003。试验动物质量合格证号0001542。饲养于西南大学药学院试验动物中心，试验动物使用许可证号SYXK(渝)2014-0002。温度20～25℃，相对湿度：40％～60％，12h/12h明暗交替。
MNT-150游标卡尺(上海美耐特实业有限公司)、EL204电子天平(梅特勒托利多仪器有限公司)、R134A低温高速离心机(Eppendorf)、ELX800酶标仪(基因有限公司)、CM1900石蜡切片机(徕卡显微系统贸易有限公司)、DM4000电子显微镜(德国Leica仪器有限公司)。
3试验设计
3.1大鼠乳腺增生模型的复制
模型复制方法：取雌性未孕清洁级SD大鼠66只，适应性饲养一周，随机分为空白组(n＝10)和造模组(n＝56)，根据预试验确定的方法造模。具体操作如下：造模组大鼠在后肢内侧肌肉交替注射苯甲酸雌二醇0.5mg/kg，每天一次，连续25天；然后肌肉注射黄体酮5mg/kg，每天一次，连续5天，共计30天。自31天起，每3天肌肉注射一次苯甲酸雌二醇0.5mg/kg。空白组肌肉注射等体积大豆油(苯甲酸雌二醇和黄体酮注射液的稀释溶剂)。
模型成功判定标准：造模30天后，随机选取6只造模组大鼠。以造模组大鼠第二对乳头高度和直径均显著高于空白组(P<0.01)，病理切片观察造模组大鼠乳头的腺导管、腺泡、腺小叶等出现相应的病理变化，判定造模成功。
3.2药物剂量的设置
本实施采用的样品为中药组合物的提取原料药粉，每1g粉末相当于6.6g生药。本中药组合物每日临床推荐用量为生药22g/60kg。取临床用量的1倍、2倍、4倍为试验剂量，折算至大鼠，依次设生药含量2.26g/kg为低剂量组，生药含量4.52g/kg为中剂量组，生药含量9.04g/kg为高剂量组。
3.3分组与给药
分组及组间均衡性检验：造模30天后，将符合造模成功标准的大鼠按随机数字表随机分为5组，即模型组，他莫昔芬组，中药组合物原料药粉低、中、高剂量组，每组10只。对经过造模的5组动物进行组间乳头高度和直径均值统计学处理，以P>0.05为无显著性差异，方可纳入下一步试验。
给药剂量及周期：各组按照下表给予相应药物，给药体积为0.8ml/100g，空白组及模型组灌胃给予等体积的蒸馏水。一天一次，给药90天。(见表1)
表1药物组合物对大鼠乳腺增生的治疗作用试验分组与剂量
3.4乳房直径与乳头高度的测量
采用精密游标卡尺于造模前、给药前后测定大鼠胸部的第2对乳头高度和乳房直径。
3.5脏器系数的测定
于末次给药24h后处死大鼠，测定体重、胸腺、脾脏、子宫和卵巢的重量，并按以下公式计算脏器系数。脏器系数＝脏器质量(g)/体重(g)×100％。
3.6血清激素水平的检测
于末次给药24h后，用3.5％水合氯醛麻醉大鼠，腹主动脉取血，在4℃下3000r/min离心15分钟，分离血清，-80℃冷冻保存。按照试剂盒说明，采用酶联免疫分析法测定雌二醇(E2)、孕酮(P)、泌乳素(PRL)含量。
3.7乳腺组织病理学检查
取血后，无菌取下大鼠第二对完整的乳房，用4％多聚甲醛溶液固定。4℃过夜后，乙醇逐级脱水，石蜡包埋，切片，HE染色，在光镜下观察大鼠乳腺组织增生情况。具体操作如下(见表2)。
表2石蜡切片HE染色实验步骤
封片完成后，在显微镜下进行镜检，图像采集分析。3.8乳腺组织ER和PR表达的检测
具体操作如下(见表3)。
表3石蜡切片免疫组化实验步骤
结果判断：以细胞质和(或)细胞核内出现棕黄色颗粒作为阳性细胞，每例标本选取5个高倍镜视野进行统计。用Image-Pro Plus测量棕黄色区域的积分光密度值(IOD)和有效面积(area)，计算光密度平均值(IOD/area)。
3.9统计学处理
采用SPSS22.0统计软件分析，试验数据用表示，组间比较采用单因素方差分析(One-way ANOVA)，t检验进行显著性分析，P<0.05为差异有统计学意义。
4试验结果
4.1药物组合物显著减低乳腺增生大鼠乳房直径、乳头高度
空白组大鼠隔毛看不见乳头位置，将毛分开后，可见乳头呈小颗粒状，贴在皮肤上，柔软，个别稍隆起。与空白组相比，模型组大鼠乳房直径和乳头高度显著增大(P<0.01)，乳头红肿或增大。各给药组乳头肿胀程度有所减轻，乳房直径和乳头高度均小于模型组(P<0.01)，见表4。
4.2药物组合物显著增加乳腺增生大鼠胸腺系数、减小子宫系数
与空白组相比，模型组胸腺系数极显著降低(P<0.01)，子宫系数极显著增大(P<0.01)，说明大鼠在性激素的刺激下免疫力下降，胸腺萎缩，子宫囊肿。与模型组相比，他莫昔芬和药物组合物原料药各剂量组胸腺系数显著升高(P<0.05)，子宫系数极显著下降(P<0.01)，见表5。结果表明，药物组合物原料药有改善子宫囊肿，提高免疫力的作用。
表4药物组合物显著减低乳腺增生大鼠乳房直径、乳头高度
注：与空白组相比，1)P<0.01；与模型组相比，2)P<0.01
表5药物组合物显著增加乳腺增生大鼠胸腺系数、减小子宫系数
注：与空白组相比，1)P<0.01；与模型组相比，2)P<0.05，3)P<0.01
4.3药物组合物对乳腺增生大鼠血清激素含量具有显著调节作用
与空白组相比，模型组大鼠血清E2、PRL含量显著增加(P<0.01)，P含量显著降低(P<0.01)。他莫昔芬和药物组合物原料药低、中、高剂量组均能不同程度降低大鼠血清E2、PRL含量，并能显著升高模型组大鼠血清P含量(P<0.01)。见表6。
表6药物组合物对乳腺增生大鼠血清激素含量具有显著调节作用
注：与空白组相比，1)P<0.01；与模型组相比，2)P<0.01
4.4药物组合物显著降低乳腺增生大鼠乳腺组织ER和PR表达
与空白对照组比较，模型组大鼠乳腺组织ER和PR的表达明显增强(P＜0.01)。给药组大鼠乳腺组织ER和PR表达降低，与模型组比较具有显著差异(P＜0.01)。见表7。
表7药物组合物显著降低乳腺增生大鼠乳腺组织ER和PR表达
注：与空白组相比，1)P<0.01；与模型组相比，2)P<0.01
4.5药物组合物对乳腺增生大鼠乳腺组织形态学具有显著改善作用
HE结果显示空白组大鼠乳腺小叶腺泡数少，腺泡和导管内无分泌物；模型组大鼠乳腺小叶体积增大，小叶内腺泡数量增多，导管扩张，腔内有多量分泌物；与模型组相比，他莫昔芬组大鼠乳腺小叶腺泡数明显减少，扩张的导管数量和分泌物减少；药物组合物原料药高、中、低剂量组大鼠乳腺小叶腺泡数减少，导管直径明显减小。见图1。
试验例2本发明药物治疗乳腺结节患者临床观察100例
1临床患者入组情况
观察门诊就诊患者100例，90％的患者均在大医院接受过多种中西药治疗，但病情未见明显减轻，有的甚至加重。100例均为女性。患者年龄13—74岁，平均年龄35岁。
| 年龄 | 13—25岁 | 26—35岁 | 36—45岁 | 46—52岁 | 74岁 |
| 数量 | 8例 | 16例 | 46例 | 25例 | 5例 |
2诊断标准及临床分型
诊断标准及临床分型：根据1996年国家中医药管理床表现主要是乳房刺痛或胀痛并伴有肿块。有的患者同时伴有月经不调、心情烦躁，有的伴乳头溢液。乳腺癌家族史5例。患者有的疼痛在经前加重，有的生气后加重。临床触诊乳房内可触及单个或多个大小不等的不规则肿块，结节。质地韧，边界清楚，形态规则的72例。边界不清，形态不规则，肿块质地韧硬，活动度差28例。全部病例均经过彩超检查或钼钯检查或细胞学检查，除1例乳腺癌手术3+年后复发的以外，排除其他病变。诊断为乳腺结节病。
3治疗方法
治疗方法：上述患者均仅接受本发明药物(实施例1制备的胶囊)治疗，连续治疗20天，经期停服，服药期间停止服用其他药物。
疗效标准：参照《中药新药临床研究指导原则》中的相关内容和《乳腺增生病诊断标准》制定：
临床治愈：肿块及乳房疼痛消失，B超诊断分类为：1类，停药半年至3年无复发。
显效：肿块最大直径缩小二分之一，疼痛消失，B超诊断分类：4类改变为3类或2类。
有效：肿块最大直径缩小三分之一，乳房疼痛消失，B超之前诊断为3类的改变为2类。
无效：疼痛减轻，肿块未见明显软化缩小，B超诊断无改变。
4治疗结果
本发明药物治疗20天，100例受试者中，临床治愈85例，显效7例，有效6例，无效2例。本发明药物临床治疗结果为治愈率85％，总有率92.3％。
临床典型病例1：
1、姓名：喻xx,性别：女，年龄：48岁，职业：农民，婚姻：已婚。
就诊时间：2018年2月16日
3+年在泸州某医院做了右侧乳腺癌保乳术，2017年12月5日体检时发现癌症复发，医院让患者再次住院手术，化疗。因患者惧怕手术和化疗，于2018年2月16日来门诊求治。B超显示：右侧乳腺11点钟方向腺体层内查见大小约0.73*0.49cm减弱回声团，形态欠规则，边界欠清，其内见片状稍强回声,CDFl:团块周边见少许星点状血流信号。右侧乳腺腺体6点钟方向腺体层内查见大小约0.86*0.46cm，形态欠规则，边界尚清。右侧腋窝查见多个低回声，最大约1.15*0.48cm
超声提示：右侧乳腺实性占位，Bl-RADS-3-4类
观患者面黄憔悴，神色焦虑，舌红苔腻，脉弦涩。
触诊：右侧乳腺11点钟方向查见大小约0.9*0.7cm肿块一个，质硬，欠活动，边界欠清。
诊断：乳岩(乳腺癌术后复发)
处理：给予本发明药物治疗4个疗程(80天)，一日3次
嘱咐患者忌食腥辣食品。服药期间，停服其它药物。
2018年7月16日经西南医科大附属医院B超检查：
诊断意见：右侧乳腺保乳术后；双侧乳腺US-Bl-RADS1类
随访4+年，未见复发。
临床典型病例2：
姓名：杨xx，性别：女，年龄：37岁，职业：经商，婚姻：已婚。
就诊时间：2019年11月23日
患者自觉双侧乳腺胀痛2+月，加重1+周。经四川大学华西医院B超检查，提示：右乳10点钟处查见大小约13*6*7的囊实混合回声结节，边界较清楚，形态欠规则，内可见多数分隔，周边可见多数点片状强回声。未见明显血流信号。另于左右乳各查见2-5mm,3-9mm的无回声结节，部分透声差，部分囊壁查见斑片状强回声，未见血流信号。
诊断提示：
右乳10点钟囊实性结节伴钙化。(Bl—RADS 4A类)
双乳囊肿，部分囊液粘稠。(Bl—RADS 3类)
触诊：右侧10点钟方向触摸到一个肿块，大小约1.4cm3左右，表面欠光滑，质韧硬，欠活动。
诊断：乳癖(双侧乳腺结节)右侧为甚。
观患者面白无华，眼神忧虑，舌红苔黄，脉弦无力。
处理：给予本发明药物治疗3个疗程(60天)，一日3次。服药期间，停服其他药物。忌食腥辣食品。
2020年经成都市第一人民医院B超检查：双侧乳腺
(Bl—RADS2类)
随访3年，未见复发。
Claims (10)
1.一种治疗乳腺结节的中药组合物，其特征在于：它是由下述重量配比的原料药制备而成：
醋鳖甲5-15份、土贝母8-12份、橘叶3-6份、青皮8-12份、香附5-15份、延胡索5-15份、没药5-10份、山慈姑8-12份、土鳖虫4-10份、莪术5-15份、天葵子4-10份、黄芪5-15份、当归2-10份、菟丝子2-10份、巴戟天2-10份。
2.根据权利要求1所述的治疗乳腺结节的中药组合物，其特征在于：它是由下述重量配比的原料药制备而成：
醋鳖甲8-12份、土贝母8-12份、橘叶4-6份、青皮4.8-7.2份、香附6.4-9.6份、延胡索6.4-9.6份、没药4-6份、山慈姑4.8-7.2份、土鳖虫4-6份、莪术4.8-7.2份、天葵子4-6份、黄芪6.4-9.6份、当归4.8-7.2份、菟丝子4.8-7.2份、巴戟天4.8-7.2份。
3.根据权利要求2所述的治疗乳腺结节的中药组合物，其特征在于：它是由下述重量配比的原料药制备而成：
醋鳖甲10份、土贝母10份、橘叶5份、青皮6份、香附8份、延胡索8份、没药5份、山慈姑6份、土鳖虫5份、莪术6份、天葵子5份、黄芪8份、当归6份、菟丝子6份、巴戟天6份。
4.根据权利要求1-3任意一项所述的治疗乳腺结节的中药组合物，其特征在于：它是由所述的中药组合物的原生药粉、水或有机溶剂提取物为活性组分，加入药学上可接受的辅料或辅助性成分制备成药学上常用的制剂。
5.根据权利要求4所述的治疗乳腺结节的中药组合物，其特征在于：所述的制剂是口服制剂。
6.根据权利要求5所述的治疗乳腺结节的中药组合物，其特征在于：所述的口服制剂是片剂、胶囊剂、丸剂、颗粒剂、口服液。
7.一种制备权利要求1-6任意一项所述的中药组合物的方法，其特征在于：它包括如下步骤：
a、称取各重量配比的原料药；
b、土贝母、橘叶、青皮、香附、延胡索、没药、山慈姑、莪术加60％-90％乙醇，回流提取2-4次，将醇提物回收乙醇；
c、上述乙醇提取后的药渣与天葵子、黄芪、当归、菟丝子、巴戟天混合，加水煎煮，合并水提液，去弃药渣，煎出液与b步骤回收乙醇后的浓缩液合并，浓缩，干燥；
d、取醋鳖甲、土鳖虫打粉，与c步骤的干燥物混合，再加入药学上可接受的辅料或辅助性成分制备成药学上常用的制剂。
8.权利要求1-6任意一项所述的中药组合物在制备治疗乳腺结节的药物中的用途。
9.权利要求1-6任意一项所述的中药组合物在制备治疗乳腺包块或乳腺增生的药物中的用途。
10.权利要求1-6任意一项所述的中药组合物在制备具有疏肝理气、活血化瘀、调理冲任、温补肾阳的药物中的用途。
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