CN110870889B - 一种中药组合物及其制备方法和应用 - Google Patents
一种中药组合物及其制备方法和应用 Download PDFInfo
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- CN110870889B CN110870889B CN201811000257.1A CN201811000257A CN110870889B CN 110870889 B CN110870889 B CN 110870889B CN 201811000257 A CN201811000257 A CN 201811000257A CN 110870889 B CN110870889 B CN 110870889B
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- paeonol
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- cyclodextrin
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Abstract
本发明公开了一种中药组合物,其特征在于,该中药组合物由桂枝、茯苓、牡丹皮、白芍、桃仁按等比例制成,其中,所述中药组合物包含芍药苷、苦杏仁苷、苯甲酰芍药苷、肉桂酸、丹皮酚、桂皮醛。该组合物生产效率高、有效成分含量高、茯苓酸转移率高、吸湿性降低、提高各指标成分的溶出度。
Description
技术领域
本发明涉及包括中草药桂枝(Ramulus cinnamomi)和茯苓(Poria cocos)的组合物、及其制备方法和应用。
背景技术
桂枝茯苓胶囊由桂枝、茯苓、牡丹皮、白芍和桃仁共五味中药组成,具有活血、化瘀、消癥之功效,主治妇人瘀血阻络所致癥块、经闭、痛经、产后恶露不尽;子宫肌瘤,慢性盆腔炎包块,痛经,子宫内膜异位症,卵巢囊肿见上述证候者;也可用于女性乳腺香囊性增生病属瘀血阻络症,症见乳房疼痛、乳房肿块、胸肋胀闷;或用于前列腺增生属瘀阻膀胱证,症见小便不爽、小腹胀痛。
现有技术公开的桂枝茯苓胶囊制备方法主要是通过由桂枝、白芍、茯苓、桃仁和牡丹皮按所需重量比经水蒸汽蒸馏、乙醇提取、浓缩、制粒、干燥等步骤制成胶囊,缺陷在于:该方法制备的药物的有效成分含量相对较低、溶出度较差,生产效率较低,噪音大、对除尘要求高等;因此,有必要改进现有工艺方法,以获得有效成分含量高的原料药或制剂。
发明内容
有鉴于此,本发明提出一种由桂枝、茯苓、牡丹皮、白芍、桃仁按照等比例制成的组合物的制备方法,其特征在于,包括步骤:
(a)茯苓粉中间体的制备:取足量的茯苓70℃干燥至水分≤5.0%,120筛粉碎,取30-49%处方量的茯苓粉,即得茯苓粉中间体;优选,取45%处方量的茯苓,即得;
(b)丹皮酚包合物的制备:牡丹皮直通蒸汽蒸馏提取丹皮酚,收集芳香水,药渣,待用;芳香水静置48-72小时至晶体结晶完全,过滤,阴干,得丹皮酚晶体;取β-环糊精包合制得丹皮酚包合物;
(c)桂枝挥发油包合物的制备;桂枝直通蒸汽蒸馏提取挥发油,过程中加乙酸乙酯萃取,收集乙酸乙酯层芳香水,药渣,待用;芳香水层放置于分液漏斗中,静置,分取上层乙酸乙酯层,下层用等倍量乙酸乙酯再萃取,合并乙酸乙酯层,减压回收,加乙醇继续浓缩,得纯品挥发油;取β-环糊精包合制得桂枝挥发油包合物;
(d)提取物喷干粉中间体的制备:将牡丹皮药渣进行醇提取和水提取,桂枝药渣进行醇提取和水提取,白芍、桃仁及处方量51-70%的茯苓进行醇提取和水提取;将上述醇提液或水提液分别浓缩,合并浓缩液后继续浓缩,喷雾干燥后混合得喷干粉;
(e)总混:将茯苓粉中间体、提取物喷干粉中间体、丹皮酚包合物、桂枝挥发油包合物,混合,即得。总混时间优选≥30min。
进一步地,所述步骤(a)中,将部分茯苓粉碎后,所得粉末过60-200目筛,优选120目筛。茯苓药材干燥灭菌的水分优选<5%;混合后检测样品前后水分差异,所述水分控制在<5%。
具体地,所述步骤(b)中:
所述蒸汽蒸馏过程收集约4-6倍量芳香水,优选5倍量芳香水;具体为牡丹皮饮片投入提取罐中,通蒸汽蒸馏提取丹皮酚,滤布过滤,芳香水流速控制在5kg/min左右,收集约5倍量芳香水;优选地,滤布目数选自100目;
牡丹皮芳香水静置析晶步骤中,将所得丹皮酚芳香水静置至晶体结晶完全,过滤、净化区阴干,即得丹皮酚晶体,备用;优选地,过滤滤布选自200目;
所述β-环糊精包合具体为,取β-环糊精加入其2.7倍量纯化水中搅匀,加热至60℃,取β-环糊精1/6~1/12量的丹皮酚加入其4-6倍量乙醇中,加热使之溶解,趁热倒入β-环糊精溶液中,过胶体磨30min,放料,放置过夜16-24h,抽滤,常压干燥,粉碎,混合15min,即得丹皮酚包合物;优选地,所述粉碎过100目筛,干燥温度选自50℃。
进一步地,所述步骤(c)中:
所述蒸汽蒸馏过程乙酸乙酯的加入量为药材量的3.5%(重量体积比);具体为桂枝饮片投入提取罐中,通蒸汽蒸馏提取挥发油,过程中加入3.5%药材量的乙酸乙酯萃取,收集乙酸乙酯层芳香水;优选地,萃取时间选自5小时;
在桂枝芳香水精制步骤中,乙酸乙酯层芳香水静置后,分取上层乙酸乙酯层,下层用等倍量乙酸乙酯再萃取,合并乙酸乙酯层,浓缩后加入粗品挥发油等倍量的乙醇,再次浓缩,得纯品挥发油,备用;优选地,所述乙酸乙酯初始浓缩温度选自60℃,加乙醇后浓缩温度选自80℃;优选最终浓缩温度为90℃,浓缩20min。
所述β-环糊精包合为,取β-环糊精加入4-6倍量乙醇中,优选5倍量乙醇,搅拌均匀,使成混悬状,取β-环糊精1/6~1/12量的挥发油倒入其中,优选1/10量,搅拌均匀,过胶体磨30min,放料,放置16-24h,抽滤,干燥,粉碎,混合15min,即得桂枝挥发油(肉桂油)包合物,优选地,所述乙醇选自浓度为20%乙醇,粉碎过100目筛,干燥温度选自50℃。
优选地,所述步骤(d)中,
所述白芍、桃仁及处方量51-70%的茯苓的投料顺序为白芍底部、桃仁中部、茯苓上部;
喷干粉制备过程中,设定进风温度165-170℃,控制喷干过程中出风温度90-95℃;冷却至室温,出料,混合,得喷干粉。
优选地,上述制备方法包括对所用药材的前处理过程,如:
茯苓切成规格为0.5-1cm左右的饮片;牡丹皮经冲洗等工序后,再制成饮片;其余药材可以为净药材饮片投料。
本发明提出一种中药组合物,其特征在于,该中药组合物由桂枝、茯苓、牡丹皮、白芍、桃仁按等比例制成,其中,所述中药组合物还包含芍药苷、苦杏仁苷、苯甲酰芍药苷、肉桂酸、丹皮酚、桂皮醛。
进一步地,所述芍药苷含量占所述中药组合物的15mg/g以上,所述苦杏仁苷含量占所述中药组合物的10mg/g以上,所述丹皮酚含量占所述中药组合物的10mg/g以上。
优选地,所述中药组合物中茯苓酸的转移率大于90%。
本发明提供一种包含桂枝和茯苓组合物或制剂的制备方法,以中草药材桂枝、茯苓、牡丹皮、白芍和桃仁为原料,所述方法包括步骤:
(a)制备茯苓(Poria)粉中间体;
(b)制备牡丹皮(Cortex moutan)的提取物丹皮酚包合物;
(c)制备桂枝的提取物桂枝挥发油包合物;
(d)制备提取物喷干粉中间体;
(e)总混;和
(f)制粒得产品;
其特征在于,所述步骤(d)中还包括白芍、桃仁及处方量55%的茯苓提取的步骤;
所述步骤(e)包括将茯苓粉中间体、喷干粉中间体、丹皮酚包合物、肉桂油包合物进行混合。
优选地,所述步骤(a)之前所用药材进行前处理,其中,
药材切成规格为0.5-1cm左右的饮片;
称取55%茯苓饮片,供提取用;
其余药材均为净药材饮片投料。
进一步地,所述前处理还包括将牡丹皮经冲洗、晾干后,再制成饮片。
优选地,所述步骤(a)中,取45%茯苓药材进行干燥灭菌后,粉碎打粉,混合均匀,即得茯苓粉中间体;
优选地,其中,
粉碎所得粉末过60-200目筛,优选120目筛。
优选地,所述步骤(b)还包括丹皮酚芳香水提取、牡丹皮芳香水精制及制备丹皮酚包合物;
在丹皮酚芳香水提取步骤中,牡丹皮饮片投入提取罐中,通蒸汽蒸馏提取丹皮酚,滤布过滤,收集约4-6倍量芳香水,优选5倍量芳香水;药渣,待用;所述滤布目数选自80-200目,优选100目;
在牡丹皮芳香水精制步骤中,将所得丹皮酚芳香水静置至晶体结晶完全,过滤、净化区阴干,即得丹皮酚晶体,备用;所述过滤滤布选自80-200目,优选200目;
在制备丹皮酚包合物步骤中,取β制环糊精加入其2.7倍量纯化水中搅匀,加热,取β量环糊精1/6~1/12量的丹皮酚加入其4-6倍量乙醇中,加热使之溶解,趁热倒入β量环糊精溶液中,过胶体磨,放料,放置过夜,抽滤,常压干燥,粉碎,混合,即得丹皮酚包合物;所述丹皮酚加入量优选β糊环糊精的1/10,所述乙醇加入量优选5倍量,所述粉碎过60-200目筛,优选100目;所述常压干燥温度选自40-90℃,优选50℃。
优选地,所述步骤(c)还包括桂枝芳香水提取、桂枝芳香水精制及制备肉桂油包合物;
在桂枝芳香水提取步骤中,桂枝饮片投入提取罐中,通蒸汽蒸馏提取挥发油,过程中加入3.5%药材量的乙酸乙酯萃取,收集乙酸乙酯层芳香水;所述萃取时间选自4-8小时,优选5小时;
在桂枝芳香水精制步骤中,乙酸乙酯层芳香水静置后,分取上层乙酸乙酯层,下层用等倍量乙酸乙酯再萃取,合并乙酸乙酯层,浓缩后加入粗品挥发油等倍量的乙醇,再次浓缩,得纯品挥发油,备用;优选地,所述乙酸乙酯浓缩温度选自51-70℃,优选60℃,乙醇浓缩温度选自70-95℃,优选80℃;
在制备肉桂油包合物步骤中,取β制环糊精加入4-6倍量乙醇中,优选5倍量乙醇,搅拌均匀,使成混悬状,取β量环糊精1/6~1/12量的肉桂油倒入其中,优选1/10量,搅拌均匀,过胶体磨,放料,放置过夜,抽滤,常压干燥,粉碎,混合,即得肉桂油包合物;所述乙醇选自浓度为10-50%乙醇,优选20%乙醇,粉碎过60-200目筛,优选100目,所述常压干燥温度选自40-90℃,优选50℃。
优选地,所述步骤(d)还包括提取过程、浓缩、喷雾干燥步骤;其中,提取过程进一步包括牡丹皮药渣提取,桂枝药渣提取,白芍、桃仁及处方量55%的茯苓提取;浓缩进一步包括醇提液浓缩、水提液浓缩及合并浓缩的步骤;喷雾干燥进一步包括合并浸膏进行喷雾干燥得喷干粉粗品、喷干粉粗品粉碎后混合得到提取物喷干粉。
进一步地,所述牡丹皮药渣提取步骤中,将牡丹皮提取芳香水后所得的药渣按照体积重量比分批次加入90%乙醇提取,过滤,合并滤液得A1,备用;所述分批次加入乙醇的量为先加入3-5倍量,优选4倍量,再加入2-4倍量,优选3倍量;
将牡丹皮药渣再按照体积重量比分批次加入水提取,过滤,合并滤液得B1,备用;药渣弃之;所述分批次加入水的量为先加入5-8倍量,优选6倍量,再加入2-6倍量,优选4倍量;
优选地,所述乙醇提取次数选自1-4次,优选2次,所述水提取次数选自1-4次,优选2次,乙醇和水每次提取时间选自2小时。
进一步地,所述桂枝药渣提取步骤中,桂枝提取芳香水后的药渣按照体积重量比分批次加入90%乙醇提取,过滤,合并滤液得A2,备用;所述分批次加入乙醇的量为先加入3-5倍量,优选4倍量,再加入2-4倍量,优选3倍量;
将桂枝药渣再按照体积重量比分批次加入水提取,过滤,合并滤液得B2,备用;药渣弃之;所述分批次加入水的量为先加入5-8倍量,优选6倍量,再加入2-6倍量,优选4倍量;
优选地,所述乙醇提取次数选自1-4次,优选2次,所述水提取次数选自1-4次,优选2次,乙醇和水每次提取时间选自2小时。
进一步地,所述白芍、桃仁及处方量55%的茯苓提取步骤中,将白芍、桃仁、55%茯苓按照投料顺序投入提取罐中,按照药材体积重量比分批次加入90%乙醇提取,过滤;合并滤液得A3,备用;所述分批次加入乙醇的量为先加入3-5倍量,优选4倍量,再加入2-4倍量,优选3倍量;
将药渣再按照体积重量比分批次加入水提取,过滤,合并滤液得B3,备用;药渣弃之;所述分批次加入水的量为先加入5-8倍量,优选6倍量,再加入2-6倍量,优选4倍量。
优选地,所述投料顺序为白芍底部、桃仁中部、茯苓上部;所述乙醇提取次数选自1-4次,优选2次,所述水提取次数选自1-4次,优选2次,乙醇和水每次提取时间选自2小时。
进一步地,所述醇提液浓缩步骤中,合并A1、A2、A3醇提液、减压浓缩至相对密度1.00-1.10,优选1.02-1.05,称重,得醇提浸膏;
所述水提液浓缩步骤中,合并B1、B2、B3水提液、减压浓缩至相对密度1.02-1.20,优选1.05-1.10,称重,得水提浸膏;
所述合并浓缩的步骤中,合并醇提液及水提液的浓缩液、继续浓缩至相对密度1.05-1.30,优选1.15,过60-200目筛,优选80-100目,得浸膏,冷藏保存或直接喷雾干燥。
进一步地,所述合并浸膏进行喷雾干燥得喷干粉粗品步骤中,取合并浸膏进行喷雾干燥,设定进风温度120-200℃,优选165-170℃,控制喷干过程中出风温80-110℃,优选90-95℃;冷却至室温,出料,得喷干粉;
所述喷干粉粗品粉碎步骤中,将所得全部喷干粉粗品进行60-200目粉碎,优选100目,得粉碎后喷干粉。
进一步地,所述总混时间≥5min,优选≥30min,即得最终原料药。
本发明还涉及一种桂枝茯苓胶囊的制备方法,其特征在于,所述方法包括将桂枝、茯苓、牡丹皮、白芍、桃仁按等比例制得的原料药进行干法制粒、整粒、混合均匀、得颗粒,充填入胶囊壳中,得成品;优选地,所述干法制粒过16-30目筛,优选24目。
优选地,所述方法还包括将原料药与环糊精混合的步骤。
本发明还涉及一种药物组合物,所述药物组合物包括本发明所述的组合物和药用载体。
进一步地,其中所述组合物被配制成制剂产品,所述制剂选自丸剂、胶囊、颗粒剂、片剂、混悬剂或糖浆剂。
本发明还提出了一种治疗或预防原发性痛经、继发性痛经、功能障碍性子宫出血、慢性盆腔炎或小的壁内子宫肌瘤的药物,其特征在于,该药物为任一前述组合物和药学上可接受的赋型剂制成临床可接受的剂型。如汤剂、颗粒剂、胶囊剂、片剂、口服液、丸剂、酊剂、混悬剂、糖浆剂、栓剂、栓剂、凝胶剂、喷雾剂、注射液等。
具体地,所述胶囊的制备方法,包括前述组合物或原料药进行干法制粒、整粒、混合均匀、得颗粒,颗粒水分控制在5%以内,充填入胶囊壳中,得成品;优选地,所述干法制粒过24目筛。
本发明还提出了任一前述组合物在制备治疗或预防下列任一疾病或病症的药物中的应用:原发性痛经、继发性痛经、功能障碍性子宫出血、慢性盆腔炎或小的壁内子宫肌瘤。具体地,所述应用为前述任一组合物以口服、直肠、肠胃外、阴道内、腹膜内、局部、或作为口或鼻喷雾剂而施用。
本发明的组合物有效成分含量高、生产效率高、茯苓酸转移率高、吸湿性降低、提高各指标成分的溶出度。其制备方法具有如下优点:
(1)减少了浸膏拌茯苓粉干燥、粉碎、湿法制粒干燥等过程,生产效率提高了30%以上;
(2)减少了茯苓拌浸膏干燥粉碎过程,茯苓酸转移率高于90%;
(3)由于茯苓粉在制剂时混合其他三个中间体进行干法制粒,产品吸湿性明显优于原工艺,吸湿性降低60%以上;
(4)制剂中各指标成分含量明显高于原工艺制剂中的含量;
(5)由于浸膏直接喷雾干燥并合并其他中间体直接制剂,各指标成分的溶出度明显优于现有制备方法的溶出度;
(6)本发明改进后的工艺合理性明显优于现有技术。
(7)由于减少了茯苓拌浸膏干燥粉碎过程,生产强度低、噪音小、产尘率低等。
具体实施方式
本发明公开了一种包含中草药桂枝和茯苓的组合物、及其制备方法和应用,本领域技术人员可以借鉴本文内容,适当改进工艺参数实现。特别需要指出的是,所有类似的替换和改动对本领域技术人员来说是显而易见的,它们都被视为包括在本发明。
除特别指出,本发明提供的技术方案中所用药品、试剂、仪器均可由常规渠道或市场购得。
实施例1 本发明组合物胶囊的制备
1、胶囊标准处方
桂枝 | 360g |
茯苓 | 360g |
牡丹皮 | 360g |
白芍 | 360g |
桃仁 | 360g |
制成1000粒(规格为0.465g/粒) |
2、生产组方(400处方量)
桂枝 | 144kg |
茯苓 | 144kg |
牡丹皮 | 144kg |
白芍 | 144kg |
桃仁 | 144kg |
制成40万粒(规格为0.465g/粒) |
3、具体制备方法
前处理
前处理1:
以上五味药中的牡丹皮,水冲洗2分钟,晾干,切成规格为0.5-1cm的饮片,备投料;
其余药材均为净药材饮片投料;
称取55%茯苓饮片,供提取用。或者,
前处理2:
以上五味药材均为净药材饮片投料;
称取55%处方量的茯苓饮片,供提取用。
(a)茯苓粉中间体制备
取足量的茯苓70℃干燥至水分≤5.0%,120筛粉碎,取30-49%处方量的茯苓粉,即得茯苓粉中间体;优选取45%处方量的茯苓,即得;
(b)丹皮酚包合物制备
(1)丹皮酚芳香水提取
牡丹皮饮片投入多功能提取罐中,直通蒸汽蒸馏提取丹皮酚,滤布目数约100目左右,收集约5倍量(720kg)芳香水;药渣,待用。
(2)牡丹皮芳香水精制
静置48-72小时至晶体结晶完全,200目过滤,净化区阴干,即得丹皮酚晶体1.8-2.4kg,备用。
(3)丹皮酚包合
取β-环糊精加入其2.7倍量纯化水中搅匀,加热至60℃;取β-环糊精1/10量的丹皮酚加入其5倍量95%乙醇中,加热使之溶解,趁热倒入β-环糊精溶液中;过胶体磨30min,放料,放置16-24h;抽滤,50℃常压干燥,100目粉碎,混合,即得丹皮酚包合物16.0-22.0kg。
(c)枝挥发油包合物制备
(1)桂枝芳香水提取
桂枝饮片投入多功能提取罐中,直通蒸汽蒸馏提取挥发油,过程中加入3.5%药材量的乙酸乙酯萃取,提取时间5小时,收集乙酸乙酯层芳香水。
(2)桂枝芳香水精制
乙酸乙酯层芳香水放置于分液漏斗中,静置,分取上层乙酸乙酯层,下层用等倍量乙酸乙酯再萃取,合并乙酸乙酯层,60℃减压回收至无明显液滴回流,加约粗品挥发油等倍量乙醇,80℃浓缩至无明显液滴回流,90℃浓缩20min,得纯品挥发油0.50-0.90L,备用。
(3)肉桂油包合
取β-环糊精加入5倍量20%乙醇中,搅拌均匀,使成混悬状;取β-环糊精1/10量的肉桂油倒入其中,搅拌均匀,过胶体磨30min,放料,放置16-24h,抽滤,50℃常压干燥,100目粉碎,混合,即得肉桂油包合物5.0-9.0kg。
(d)提取物喷干粉中间体制备
(1)提取过程
1)牡丹皮药渣提取
牡丹皮提取芳香水后的药渣加入4+3(体积重量比,576L+432L)倍量90%乙醇提取两次,每次提取2小时(每次提取沸腾后打循环5分钟),滤过,合并滤液得A1,备用。
牡丹皮药渣再加入6+4(864L+576L)倍量水提取两次,每次提取2小时(每次提取沸腾后打循环5分钟),合并滤液得B1,备用;药渣弃之。
2)桂枝药渣提取
桂枝提取芳香水后的药渣加入4+3(体积重量比,576L+432L)倍量90%乙醇提取两次,每次提取2小时(每次提取沸腾后打循环5分钟),合并滤液得A2,备用。
桂枝药渣再加入6+4(864L+576L)倍量水提取两次,每次提取2小时(每次提取沸腾后打循环5分钟),合并滤液得B2,备用;药渣弃之。
3)白芍、桃仁及处方量55%的茯苓提取
白芍、桃仁及55%茯苓投入多功能提取罐中,投料顺序为白芍底部、桃仁中部、茯苓上部,加入药材4+3倍量(体积重量比,1468.8L+1101.6L)90%乙醇提取两次,每次提取2小时(每次提取沸腾后打循环5分钟),并滤液得A3,备用。
药渣再加6+4(2203.2L+1468.8L)倍量水提取两次,每次提取2小时(每次提取沸腾后打循环5分钟),合并滤液得B3,备用;药渣弃之。
(2)浓缩
1)醇提液浓缩
合并A1、A2、A3醇提液减压浓缩,醇提液回收至相对密度1.02-1.05(70±5℃),称重,得醇提浸膏。
2)水提液浓缩
合并B1、B2、B3水提液减压浓缩,水提液浓缩至相对密度1.05-1.10(80±5℃),称重,得水提浸膏。
3)合并浓缩
合并二浓缩液继续浓缩至相对密度1.15(80±5℃),过80~100目筛,得浸膏;冷藏保存或直接喷雾干燥。
(3)喷雾干燥过程
1)喷雾干燥
取合并浸膏进行喷雾干燥,设定进风温度165-170℃,控制喷干过程中出风温度90-95℃;冷却至室温,出料,得喷干粉。
2)喷干粉混合
将粉碎后喷干粉进行混合,混合≥15min,最终得提取物喷干粉,备用。
(e)总混
将茯苓粉、喷干粉、丹皮酚包合物、肉桂油包合物,混合在一起,进行总混,时间≥30min,即得最终原料药。
(f)制剂
将原料药进行干法制粒(24目),整粒,混合均匀,得颗粒,以0.465g/粒,充填入0号绿色胶囊壳中,得成品。
4、本发明制备方法与现有技术CN200780027994.4公开的方法比较
表1生产效率的比较
工序耗时 不同工艺 | 茯苓粉碎 | 提取 | 浓缩 | 干燥过程 | 粉碎 | 包合 | 制粒 | 合计(h) |
现有技术方法 | 8h | 12h | 8h | 茯苓粉混合浸膏,常压干燥20h | 10h | 24h | (软材粉+2个包合物)湿法制粒干燥,整粒过程16h | 98h |
本发明方法 | 5h | 12h | 8.5h | 浸膏直接喷雾干燥8h | — | 24h | (浸膏粉+2个包合物+茯苓粉)干法制粒10h | 67.5h |
改进方面 | -3 | 0 | 0.5 | -12 | -10 | 0 | -6 | -30.5h |
由表1可知,本发明合并浸膏直接喷雾干燥得药粉,并直接合并丹皮酚包合物、桂枝挥发油包合物、茯苓粉进行干法制粒,与现有技术比较减少了浸膏拌茯苓粉干燥、粉碎、湿法制粒干燥等过程,本发明制备方法的生产效率提高了30%以上。
表2各指标成分含量比较
由表2数据可判断,本发明制剂中,有效成分明显增加,且各指标成分含量明显高于现有技术方法中的含量。
表3、茯苓酸转移率比较
由表3数据可判断,本发明由于减少了茯苓拌浸膏干燥粉碎过程,湿法制粒干燥过程,茯苓酸转移率达90%以上,远高于现有技术所用方法中茯苓酸的转移率。
表4、产品吸湿率比较
由表4数据可判断,本发明由于茯苓粉在制剂时混合其他三个中间体直接干法制粒(无外加溶剂),产品吸湿率明显比现有技术所用方法降低60%以上。
表5、制剂中各指标成分的溶出度比较
由表5数据可判断,本发明由于浸膏直接喷雾干燥并合并其他中间体直接制剂,各指标成分的溶出度明显优于现有技术所用方法的溶出度。
表6、制剂工艺合理性比较
由表6可判断,本发明制剂工艺合理性明显优于现有技术所用方法。
可见,本发明组合物有效成分含量、溶出度、吸湿率、茯苓酸转移率、生产效率等,以及各项工艺参数均明显优于现有技术。
需要指出的是,本领域技术人员可以借鉴本文内容,适当改进工艺参数实现,所有类似的替换和改动对本领域技术人员来说是显而易见的,它们都被视为包括在本发明。
Claims (8)
1.一种由桂枝、茯苓、牡丹皮、白芍、桃仁按照等比例制成的中药组合物的制备方法,其特征在于,包括步骤:
(a) 茯苓粉中间体的制备:先将茯苓70℃干燥至水分≤5.0%,120目筛粉碎,再取30-49%处方量的茯苓粉,即得茯苓粉中间体;
(b) 丹皮酚包合物的制备:牡丹皮直通蒸汽蒸馏提取丹皮酚,收集芳香水,药渣,待用;芳香水静置48-72小时至晶体结晶完全,过滤,阴干,得丹皮酚晶体;取β-环糊精包合制得丹皮酚包合物;
(c) 桂枝挥发油包合物的制备;桂枝直通蒸汽蒸馏提取挥发油,过程中加乙酸乙酯萃取,收集乙酸乙酯层芳香水,药渣,待用;芳香水层放置于分液漏斗中,静置,分取上层乙酸乙酯层,下层用等倍量乙酸乙酯再萃取,合并乙酸乙酯层,减压回收,最后加乙醇继续浓缩,得纯品挥发油;取β-环糊精包合制得桂枝挥发油包合物;
(d) 提取物喷干粉中间体的制备:将牡丹皮药渣进行醇提取和水提取,桂枝药渣进行醇提取和水提取,白芍、桃仁及处方量51-70%的茯苓进行醇提取和水提取,其中,所述白芍、桃仁及茯苓的投料顺序为白芍底部、桃仁中部、茯苓上部;
(e) 将步骤(d)中获得的醇提液或水提液分别浓缩,合并浓缩液后继续浓缩得浸膏,喷雾干燥后混合得喷干粉;
(f) 总混:将茯苓粉中间体、提取物喷干粉中间体、丹皮酚包合物、桂枝挥发油包合物,混合后,即得。
2.根据权利要求1所述的制备方法,其特征在于,所述步骤(a)中,取45%处方量的茯苓粉。
3.根据权利要求1所述的制备方法,其特征在于,所述步骤(b)中,
所述蒸汽蒸馏过程收集4-6倍药材量的芳香水;
所述β-环糊精包合制备丹皮酚包合物的过程为,取β-环糊精加入其2.7倍量纯化水中搅匀,加热至60℃,得β-环糊精溶液,取β-环糊精1/6~1/12量的丹皮酚加入其4-6倍量乙醇中,加热使之溶解,趁热倒入β-环糊精溶液中,过胶体磨30min,放料,放置16-24h,抽滤,50℃干燥,100目筛粉碎,混合,即得所述丹皮酚包合物。
4.根据权利要求1所述的制备方法,其特征在于,所述步骤(c)中,
所述蒸汽蒸馏过程乙酸乙酯的加入量为药材量的3.5%;
所述β-环糊精包合制备桂枝挥发油包合物的过程为,取β-环糊精加入4-6倍量乙醇中,搅拌均匀,使成混悬状,取β-环糊精1/6~1/12量的挥发油倒入其中,搅拌均匀,过胶体磨30min,放料,放置16-24h,抽滤,50℃干燥,100目筛粉碎,混合,即得桂枝挥发油包合物。
5.一种根据权利要求1-4任一方法制备的中药组合物,其特征在于,该中药组合物由桂枝、茯苓、牡丹皮、白芍、桃仁按等比例制成,所述中药组合物包含芍药苷、苦杏仁苷、苯甲酰芍药苷、肉桂酸、丹皮酚、桂皮醛;其中,所述中药组合物中茯苓酸的转移率大于90%。
6.根据权利要求5所述的中药组合物,其特征在于,所述芍药苷含量占所述中药组合物的15mg/g以上,所述苦杏仁苷含量占所述中药组合物的10 mg/g 以上,所述丹皮酚含量占所述中药组合物的10 mg/g 以上。
7.一种药物,其特征在于,该药物为权利要求5或6所述组合物和药学上可接受的赋型剂制成临床可接受的剂型。
8.根据权利要求5或6所述的中药组合物在制备治疗或预防下列任一疾病的药物中的应用:原发性痛经、继发性痛经、功能障碍性子宫出血、慢性盆腔炎或小的壁内子宫肌瘤。
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