CN112516236A - 一种治疗肝癌的中药组合物及其制备方法 - Google Patents
一种治疗肝癌的中药组合物及其制备方法 Download PDFInfo
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Abstract
本发明属于治疗肝癌的药物领域,具体涉及一种治疗肝癌的中药组合物及其制备方法,所述中药组合物的原料药包括生赭石、太子参、生怀山药、天花粉、鳖甲、赤芍药、桃仁、红花、夏枯草、生黄芪、枸杞子、焦山楂、泽泻、猪苓、龙葵、白英、白芍、三七粉、半枝莲、白花蛇舌草、七叶一枝花和焦六曲。本发明的中药组合物化瘀利水,湿利气而调积消,攻补兼施、扶正祛邪、标本兼治,治疗肝癌疗效显著。
Description
技术领域
本发明属于治疗肝癌的药物领域,具体涉及一种治疗肝癌的中药组合物及其制备方法。
背景技术
随着社会的发展,人们的生活节奏、工作负担都加大,人体和精神都承受着巨大的压力。 肝癌是常见癌症之一。临床表现早期起病常颇隐匿,无明显的症状和体征,常通过甲胎蛋白 的检测或普查而发现。常见症状有肝区间歇性或持续性疼痛,上腹胀满,食欲减退,上腹部 肿块呈进行性肿大,全身症状有消瘦、发热、腹泻、黄疸,并发症有消化道出血、肝昏迷、 肝脏结节破裂出血、继发感染等。
目前,国内外对肝癌病的治疗,大致分以下几种:
1、西医药治疗;2、放疗或化疗,以上疗法不但有副作用,效果也不是太好。3、作手术, 存在的不足是:手术后易发(癌细胞扩散、患者死亡)或转移。4、中西药结合治疗,疗效也不 很理想。5、国内有很多用纯中药治疗肝癌,但配伍方药不对症,效果不佳。
中医药治疗肝癌有独特的优势,可有效缓解患者术后不适,提高患者免疫力,改善患者 生活质量等,已成为实验、临床研究热点之一。
原发性肝癌属于中医“痞气”“积聚”“肢胀”等病范畴,其病因病机总的来说不外乎本虚标实,本虚为正气亏虚,标实则为气滞、血瘀、湿热、癌毒;初期多为肝郁脾虚,气滞 血瘀,久之痰热蕴结;晚期因癌毒损伤人体正气,气血津液大伤,多表现为肝肾阴虚,生风 动血。临床实验研究表明,中医药治疗肝癌主要通过抑制肝癌细胞增殖生长、诱导肝癌细胞凋亡及分化、抑制端粒酶活性、调节信号转导通路等途径;在临床治疗中,中医药治疗原发性肝癌不仅在辩证论治、专方专药、中药制剂等方面有着独特优势,同时在中医药联合放化疗、手术、分子靶向药物、TACE等治疗中有不错的临床疗效。
目前,肝癌的中医治疗主要有辩证分型治疗、专方专药治疗、中成药治疗、中药注射治 疗、外治法、中药介入治疗等。其中,在中医药物治疗肝癌的长期临床实践中,诸多医学家 探索出了一些有效的经验配方及多种剂型的药物,显示出良好的临床疗效,众所周知,肿瘤 治疗是世界性难题,其治疗途径及靶点仍在探索之中,因此充分发挥中医药物特长,针对肝 癌开发不同治疗途径及靶点中药制剂,对于改善肝患者生活质量和恶病质、能延长患者生存 期仍具有重要意义。
中国发明专利CN1072940C公开了一种抗癌口服液及其制备方法,它是将中草药生赭石、 太子参、生怀山药、天花粉、天冬、鳖甲、赤芍药、桃仁、红花、夏枯草、生黄芪、枸杞子、焦山楂、泽泻、猪苓、龙葵、白英、白芍、焦六曲、三七粉并加水进行蒸煮,浓缩后,其过 滤后药液配以蜂蜜均质后消毒杀菌即制成本口服液,有湿化解毒、化瘀理气功能,服用后能 增强人体免疫机能,抗拒癌细胞的产生与扩散,适于肝癌、肺癌、胃癌、食道癌、肠癌患者 防治服用。但是该专利的抗癌口服液的治疗效果有待进一步提高。
中国发明专利CN1187071C公开了一种治疗肝癌的药物,由Ⅰ、Ⅱ、Ⅲ号系列方药组成, Ⅰ号方药以菟丝子、枸杞子、生黄芪、醋鳖甲、生赭石等为原料,Ⅱ号方药以丹参、当归、熟地、炒白术、白英、蛇莓、五味子等为原料,Ⅲ号方药以太子参、土炒白术、麦芽、谷芽、 枸杞子、酒蒸菟丝子、鸡内金为原料,分别按比例制成汤剂。本发明的药物具有保护肝脏, 促进肝细胞再生,以扩张肝脏血管,增强肝内血液循环和增加肝脏血流量,从而改善肝脏营养及氧气供应,增强免疫功能,防止肝细胞再损,促进肝癌向好的趋势转化的功能。该发明声称效果显著,但是处方涉及药味多,处方较复杂。
因此,利用开发一种能解决上述技术问题的治疗肝癌的中药组合物及其制备方法是非常 必要的。
发明内容
本发明的目的是克服现有技术的不足而提供一种治疗肝癌的中药组合物,该药物调气化 瘀利水,攻补兼施、扶正祛邪、标本兼治。
本发明是通过以下技术方案予以实现的:
一种中药组合物,所述中药组合物由如下重量份的组分组成:
优选地,所述中药组合物由如下重量份的组分组成:
优选地,所述中药组合物由如下重量份的组分组成:
本发明还涉及上述的中药组合物的制备工艺,包括如下步骤:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、部分白花蛇舌草粉碎,加入水煎煮,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1;
(2)将滤渣1、生怀山药、天花粉、赤芍药、红花、夏枯草、生黄芪、枸杞子粉碎,加 溶剂A提取,并收集提取过程中产生的挥发油,过滤,得到滤渣2和滤液2;
(3)将滤渣2、焦山楂、泽泻、猪苓、龙葵、白英、白芍、七叶一枝花、焦六曲、剩余 白花蛇舌草粉碎,加溶剂B提取,并收集提取过程中产生的挥发油,过滤,得到滤液3;
(4)将滤液1、滤液2和滤液3合并,浓缩干燥,与收集的挥发油、三七粉混合,即得。
优选地,步骤(1)中所述粉碎的目数为20-40目。
优选地,步骤(1)中所述水的质量为步骤(1)中药物总质量(即生赭石、太子参、鳖甲、桃仁、半枝莲和部分白花蛇舌草的总质量)的5-10倍。
优选地,步骤(1)中所述煎煮的时间为2-4h。
优选地,步骤(1)中所述部分白花蛇舌草为30-40%白花蛇舌草。
优选地,步骤(1)中在加入水煎煮之前,将步骤(1)的药物采用1-2倍体积的30-40% 乙醇浸润30-40min。即30-40%乙醇与步骤(1)中药物总质量的体积质量比为1-2mL/g。
更优选地,步骤(1)中在加入水的同时添加乙酸和乙酸钠。
更优选地,所述乙酸在水中的质量浓度为20-30%,所述乙酸钠在水中的质量浓度为 3-10%。
更优选地,步骤(1)包括如下步骤:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、30-40%白花蛇舌草粉碎至20-40目,采用1-2倍体积的30-40%乙醇浸润药物30-40min,然后加入5-10倍量的水和20-30%的乙酸以 及3-10%的乙酸钠,煎煮2-4h,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液 1。
优选地,步骤(2)中所述粉碎的目数为40-80目。
优选地,步骤(2)中所述溶剂A为50-70%(体积浓度)乙醇、异丙醇与正丁醇的混合溶剂,三者体积比为3-6:1-4:1。
优选地,步骤(2)中所述溶剂A与步骤(2)中药物总质量的体积质量比为8-15mL/g。
优选地,步骤(2)中提取温度为30-50℃,提取时间为2-4h。
更优选地,步骤(2)包括如下步骤:
将滤渣1、生怀山药、天花粉、赤芍药、红花、夏枯草、生黄芪、枸杞子粉碎至40-80目,加8-15倍量的溶剂A在30-50℃提取2-4h,并收集提取过程中产生的挥发油,过滤,得 到滤渣2和滤液2。
优选地,步骤(3)中所述粉碎的目数为60-100目。
优选地,步骤(3)中所述溶剂B为乙酸乙酯与无水乙醇的混合溶剂,两者体积比为1:2-4。
优选地,步骤(3)中所述溶剂B与步骤(3)中药物总质量的体积质量比为15-20mL/g。
优选地,步骤(3)中提取温度为30-50℃,提取时间为2-4h。
更优选地,步骤(3)包括如下步骤:
将滤渣2、焦山楂、泽泻、猪苓、龙葵、白英、白芍、七叶一枝花、焦六曲、剩余白花 蛇舌草粉碎至60-100目,加15-20倍量的溶剂B在30-50℃提取2-4h,并收集提取过程中产 生的挥发油,过滤,得到滤液3。
本发明还涉及一种药物制剂,包括上述的中药组合物或上述的制备工艺制备得到的药物 组合物。
本发明还涉及上述的中药组合物或上述的制备工艺制备得到的药物组合物或上述的药物 制剂在制备治疗肝癌药物中的应用。
本发明的有益效果是:
本发明提供了一种中药组合物,优化了其原料组成与各组分的用量配比,治疗肝癌的效 果显著,无副作用。
本发明优化了中药组合物的制备工艺,比如优化了各组分的提取顺序,分步提取各中药 原料,制备得到的中药组合物的治疗效果进一步提高。
本发明中药组合物在制备过程中,对于不同的中药原料采用不同的制备工艺,并对不同 原料的制备工艺分别进行了优化,显著提高了治疗肝癌的效果。
具体实施方式
下面结合具体实施例来进一步描述本发明,本发明的优点和特点将会随着描述而更为清 楚。但这些实施例仅是范例性的,并不对本发明的范围构成任何限制。本领域技术人员应该 理解的是,在不偏离本发明的精神和范围下可以对本发明技术方案的细节和形式进行修改或 替换,但这些修改和替换均落入本发明的保护范围内。
实施例1
一种中药组合物,包括生赭石15份、太子参10份、生怀山药10份、天花粉10份、鳖甲10份、赤芍药5份、桃仁10份、红花5份、夏枯草10份、生黄芪20份、枸杞子20份、 焦山楂20份、泽泻10份、猪苓10份、龙葵10份、白英10份、白芍10份、焦六曲20份、 三七粉3份、半枝莲10份、白花蛇舌草10份、七叶一枝花5份。
中药组合物的制备工艺如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、30%白花蛇舌草粉碎至20目,采用1 倍体积的30%乙醇浸润药物30min,然后加入5倍量的水煎煮2h,并收集煎煮过程中产生的 挥发油,过滤,得到滤渣1和滤液1;
(2)将滤渣1、生怀山药、天花粉、赤芍药、红花、夏枯草、生黄芪、枸杞子粉碎至40目,加8倍量的溶剂A在30℃提取2h,并收集提取过程中产生的挥发油,过滤,得到滤渣2 和滤液2;所述溶剂A为50%乙醇、异丙醇与正丁醇的混合溶剂,三者体积比为3:1:1;
(3)将滤渣2、焦山楂、泽泻、猪苓、龙葵、白英、白芍、七叶一枝花、焦六曲、剩余 白花蛇舌草粉碎至60目,加15倍量的溶剂B在30℃提取2h,并收集提取过程中产生的挥 发油,过滤,得到滤液3;所述溶剂B为乙酸乙酯与无水乙醇的混合溶剂,两者体积比为1:2;
(4)将滤液1、滤液2和滤液3合并,浓缩干燥,与收集的挥发油、三七粉混合,即得。
实施例2
一种中药组合物,包括生赭石25份、太子参15份、生怀山药20份、天花粉20份、鳖甲20份、赤芍药15份、桃仁20份、红花15份、夏枯草20份、生黄芪30份、枸杞子30份、 焦山楂30份、泽泻20份、猪苓20份、龙葵20份、白英20份、白芍20份、焦六曲30份、 三七粉5份、半枝莲20份、白花蛇舌草20份、七叶一枝花15份。
中药组合物的制备工艺如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、40%白花蛇舌草粉碎至40目,采用2 倍体积的40%乙醇浸润药物40min,然后加入10倍量的水煎煮4h,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1;
(2)将滤渣1、生怀山药、天花粉、赤芍药、红花、夏枯草、生黄芪、枸杞子粉碎至80目,加15倍量的溶剂A在50℃提取4h,并收集提取过程中产生的挥发油,过滤,得到滤渣 2和滤液2;所述溶剂A为70%乙醇、异丙醇与正丁醇的混合溶剂,三者体积比为6:4:1;
(3)将滤渣2、焦山楂、泽泻、猪苓、龙葵、白英、白芍、七叶一枝花、焦六曲、剩余 白花蛇舌草粉碎至100目,加20倍量的溶剂B在50℃提取4h,并收集提取过程中产生的挥 发油,过滤,得到滤液3;所述溶剂B为乙酸乙酯与无水乙醇的混合溶剂,两者体积比为1:4;
(4)将滤液1、滤液2和滤液3合并,浓缩干燥,与收集的挥发油、三七粉混合,即得。
实施例3
一种中药组合物,包括生赭石20份、太子参12份、生怀山药15份、天花粉15份、鳖甲15份、赤芍药10份、桃仁15份、红花10份、夏枯草15份、生黄芪25份、枸杞子25份、 焦山楂25份、泽泻15份、猪苓15份、龙葵15份、白英15份、白芍15份、焦六曲25份、 三七粉4份、半枝莲15份、白花蛇舌草15份、七叶一枝花10份。
中药组合物的制备工艺如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、35%白花蛇舌草粉碎至30目,采用1.5倍体积的35%乙醇浸润药物35min,然后加入8倍量的水煎煮3h,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1;
(2)将滤渣1、生怀山药、天花粉、赤芍药、红花、夏枯草、生黄芪、枸杞子粉碎至60目,加12倍量的溶剂A在40℃提取3h,并收集提取过程中产生的挥发油,过滤,得到滤渣 2和滤液2;所述溶剂A为60%乙醇、异丙醇与正丁醇的混合溶剂,三者体积比为4:3:1;
(3)将滤渣2、焦山楂、泽泻、猪苓、龙葵、白英、白芍、七叶一枝花、焦六曲、剩余 白花蛇舌草粉碎至80目,加18倍量的溶剂B在40℃提取3h,并收集提取过程中产生的挥 发油,过滤,得到滤液3;所述溶剂B为乙酸乙酯与无水乙醇的混合溶剂,两者体积比为1:3;
(4)将滤液1、滤液2和滤液3合并,浓缩干燥,与收集的挥发油、三七粉混合,即得。
实施例4
与实施例3的区别仅在于步骤(1)不同,其余条件均相同,具体如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、35%白花蛇舌草粉碎至30目,采用1.5倍体积的35%乙醇浸润药物35min,然后加入8倍量的水和25%的乙酸以及6%的乙酸钠,煎煮3h,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1。
对比例1
与实施例4的区别仅在于中药组合物的组成不同,将半枝莲15份、白花蛇舌草15份和 七叶一枝花10份替换为天冬40份。
对比例2
与实施例4的区别仅在于步骤(1)和(2)原料的提取顺序不同,其余条件均相同,具体如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、35%白花蛇舌草、生怀山药、天花粉、赤芍药、红花、夏枯草、生黄芪、枸杞子粉碎至30目,采用1.5倍体积的35%乙醇浸润药物35min,然后加入8倍量的水和25%的乙酸以及6%的乙酸钠,煎煮3h,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1;
(2)将滤渣1粉碎至60目,加12倍量的溶剂A在40℃提取3h,并收集提取过程中产生的挥发油,过滤,得到滤渣2和滤液2;所述溶剂A为60%乙醇、异丙醇与正丁醇的混合 溶剂,三者体积比为4:3:1;
(3)将滤渣2、焦山楂、泽泻、猪苓、龙葵、白英、白芍、七叶一枝花、焦六曲、剩余 白花蛇舌草粉碎至80目,加18倍量的溶剂B在40℃提取3h,并收集提取过程中产生的挥 发油,过滤,得到滤液3;所述溶剂B为乙酸乙酯与无水乙醇的混合溶剂,两者体积比为1:3;
(4)将滤液1、滤液2和滤液3合并,浓缩干燥,与收集的挥发油、三七粉混合,即得。
对比例3
与实施例4的区别仅在于白花蛇舌草一步添加,其余条件均相同,具体如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、白花蛇舌草粉碎至30目,采用1.5倍 体积的35%乙醇浸润药物35min,然后加入8倍量的水和25%的乙酸以及6%的乙酸钠,煎煮3h,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1;
(2)将滤渣1、生怀山药、天花粉、赤芍药、红花、夏枯草、生黄芪、枸杞子粉碎至60目,加12倍量的溶剂A在40℃提取3h,并收集提取过程中产生的挥发油,过滤,得到滤渣2和滤液2;所述溶剂A为60%乙醇、异丙醇与正丁醇的混合溶剂,三者体积比为4:3:1;
(3)将滤渣2、焦山楂、泽泻、猪苓、龙葵、白英、白芍、七叶一枝花、焦六曲粉碎至 80目,加18倍量的溶剂B在40℃提取3h,并收集提取过程中产生的挥发油,过滤,得到滤 液3;所述溶剂B为乙酸乙酯与无水乙醇的混合溶剂,两者体积比为1:3;
(4)将滤液1、滤液2和滤液3合并,浓缩干燥,与收集的挥发油、三七粉混合,即得。
对比例4
与实施例4的区别仅在于步骤(1)中不采用乙醇对药物进行预处理,其余条件均相同, 具体如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、35%白花蛇舌草粉碎至30目,然后加入8倍量的水和25%的乙酸以及6%的乙酸钠,煎煮215min,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1。
对比例5
与实施例4的区别仅在于步骤(1)中仅添加乙酸,其余条件均相同,具体如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、35%白花蛇舌草粉碎至30目,采用1.5倍体积的35%乙醇浸润药物35min,然后加入8倍量的水和25%的乙酸,煎煮3h,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1。
对比例6
与实施例4的区别仅在于步骤(1)中仅添加乙酸钠,其余条件均相同,具体如下:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、35%白花蛇舌草粉碎至30目,采用1.5倍体积的35%乙醇浸润药物35min,然后加入8倍量的水和6%的乙酸钠,煎煮3h,并收集 煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1。
对比例7
与实施例4的区别仅在于溶剂A的组成不同,具体为60%乙醇、异丙醇与正丁醇的混合 溶剂,三者体积比为1:3:4,其余条件均相同。
测试例1
1.受试物:将实施例1-4和对比例1-7制备得到的组合物用生理盐水溶解,配成5mg/mL 的溶液。
2.试剂:PBS缓冲液:pH 7.4。
3.动物及瘤株:雄性昆明种小鼠,体重20±2g。鼠源性H22肉瘤细胞:购自上海细胞库。
4.实验方法:
取冻存的H22小鼠肝癌细胞,置于37℃恒温水浴中解冻,离心,收集细胞,用PBS缓冲液洗涤两次,再用PBS液重悬细胞,经小鼠腹腔传3代以上,腹水长出后,在无菌条件下 抽取瘤液,瘤液与生理盐水按体积比1:1的比例稀释并充分混合得到细胞悬液。用台盼兰染色,然后在血细胞计数器上计数,其中活细胞数大于95%,用生理盐水调整细胞悬液的浓度为1×107个瘤细胞/mL。然后将调整好浓度的细胞悬液按0.2mL/只接种于小鼠右前肢腋窝皮 下,构建实体瘤动物模型,得到H22荷瘤小鼠。
接种后次日随机分组,每组5只,分为模型组(灌胃生理盐水)、实验组(分别灌胃实施例1-4的组合物)和对照组(分别灌胃对比例1-7的组合物),每天一次,剂量均为0.01mL/g(给药体积/小鼠体重),连续给药14天,第15天脱颈椎处死小鼠,剥离肿瘤并称重,按下 式计算肿瘤抑制率:
肿瘤抑制率(%)=(1-实验组或对照组平均瘤重/模型组平均瘤重)×100%。
结果如表1所示。
表1各组小鼠的肿瘤抑制率结果
组别 | 肿瘤抑制率(%) |
实施例1 | 76.39 |
实施例2 | 75.45 |
实施例3 | 76.81 |
实施例4 | 81.23 |
对比例1 | 69.74 |
对比例2 | 72.16 |
对比例3 | 74.58 |
对比例4 | 75.37 |
对比例5 | 78.29 |
对比例6 | 77.32 |
对比例7 | 74.57 |
上述详细说明是针对本发明其中之一可行实施例的具体说明,该实施例并非用以限制本 发明的专利范围,凡未脱离本发明所为的等效实施或变更,均应包含于本发明技术方案的范 围内。
Claims (10)
4.一种权利要求1-3任一所述的中药组合物的制备工艺,其特征在于,包括如下步骤:
(1)将生赭石、太子参、鳖甲、桃仁、半枝莲、部分白花蛇舌草粉碎,加入水煎煮,并收集煎煮过程中产生的挥发油,过滤,得到滤渣1和滤液1;
(2)将滤渣1、生怀山药、天花粉、赤芍药、红花、夏枯草、生黄芪、枸杞子粉碎,加溶剂A提取,并收集提取过程中产生的挥发油,过滤,得到滤渣2和滤液2;
(3)将滤渣2、焦山楂、泽泻、猪苓、龙葵、白英、白芍、七叶一枝花、焦六曲、剩余白花蛇舌草粉碎,加溶剂B提取,并收集提取过程中产生的挥发油,过滤,得到滤液3;
(4)将滤液1、滤液2和滤液3合并,浓缩干燥,与收集的挥发油、三七粉混合,即得。
5.根据权利要求4所述的制备工艺,其特征在于,步骤(1)中所述粉碎的目数为20-40目,步骤(2)中所述粉碎的目数为40-80目;步骤(3)中所述粉碎的目数为60-100目。
6.根据权利要求4所述的制备工艺,其特征在于,步骤(1)中所述水的质量为步骤(1)中药物总质量的5-10倍,煎煮时间为2-4h;所述部分白花蛇舌草为30-40%白花蛇舌草;在加入水煎煮之前,将步骤(1)的药物采用1-2倍体积30-40%乙醇浸润30-40min。
7.根据权利要求4所述的制备工艺,其特征在于,步骤(2)中所述溶剂A为50-70%乙醇、异丙醇与正丁醇的混合溶剂,三者体积比为3-6:1-4:1;步骤(2)中所述溶剂A与步骤(2)中药物总质量的体积质量比为8-15mL/g,提取温度为30-50℃,提取时间为2-4h。
8.根据权利要求4所述的制备工艺,其特征在于,步骤(3)中所述溶剂B为乙酸乙酯与无水乙醇的混合溶剂,两者体积比为1:2-4;所述溶剂B与步骤(3)中药物总质量的体积质量比为15-20mL/g,提取温度为30-50℃,提取时间为2-4h。
9.一种药物制剂,其特征在于,包括权利要求1-3任一所述的中药组合物或权利要求4-8任一所述的制备工艺制备得到的药物组合物。
10.权利要求1-3任一所述的中药组合物或权利要求4-8任一所述的制备工艺制备得到的药物组合物或权利要求9所述的药物制剂在制备治疗肝癌药物中的应用。
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