CN117442659A - 一种补肾理脾舒肝组合物及其制备方法和应用 - Google Patents
一种补肾理脾舒肝组合物及其制备方法和应用 Download PDFInfo
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Abstract
本发明属于医药治疗领域,具体涉及一种补肾理脾舒肝组合物及其制备方法和应用。本发明的组合物包括如下原料:柴胡,太子参,菟丝子,川续断,白芍,北沙参,茯神,巴戟天,鹿角霜,龟甲,川牛膝,女贞子,桑寄生和甘草。制备方法包括先将龟甲加水煎煮得煎煮液,再煎煮液中倒入其余原料,加水煎煮,过滤,浓缩即得。本发明的组合物不仅可在一定程度上改善POI患者FSH、LH、E2水平;还可改善部分POI患者抗缪勒管激素水平(AMH)及基础窦卵泡计数,并在一定程度上改善患者生活质量。
Description
技术领域
本发明属于医药治疗领域,具体涉及一种补肾理脾舒肝组合物及其制备方法和应用。
背景技术
早发性卵巢功能不全(POI)的特点包括女性在40岁以前出现月经稀少、低雌激素水平和促性腺激素水平升高。目前,对于POI的治疗,现代西医学仍然局限于激素补充疗法。40岁以前女性一旦发生卵巢功能不全甚至衰竭,卵巢功能难以逆转,需长期、持续治疗,而长期应用激素等西药治疗,其改善女性卵巢功能疗效的有效性并不是十分满意。
中医药具有副作用小,靶点多,相比较而言可长期服用的特点,受到了研究者们的青睐。
中医学无“早发性卵巢功能不全”的病名,根据其临床表现,认为本病归属“不孕”“血枯”“血隔”“闭经”和“年未老经水断”等疾病范畴,多为肾水渐枯竭,冲任脉衰闭。
中国发明专利申请CN105213467A公开了及一种治疗卵巢早衰的中药组合物,由下列重量份的原料药制成:牛膝15-35份,当归15-35份,杜仲20-35份,益母草10-25份,熟地黄10-25份,生姜10-30份,肉苁蓉10-30份,瓜蒌皮10-20份,厚朴5-25份,牛蒡子5-25份,秦皮10-35份,党参10-30份,白花蛇舌草5-35份,莪术5-30份,密蒙花5-20份,酸枣仁5-20份,垂盆草5-25份,玉竹5-20份,女贞子15-25份,知母15-25份,茺蔚子10-15份,竹茹10-15份,川楝子5-15份。该中药组合物具有养血调经、温宫散寒、补气养阴、疏肝解郁、补肾益精、健脾益气的功效,可用于治疗女性卵巢早衰,用药安全,无毒副作用,治疗效果显著。
中国发明专利申请CN103405566A公开了一种治疗卵巢功能减退和早衰的中药组合物,所述中药组合物的活性成分按重量份计主要由以下重量的原料药组成:熟地黄9~25份、菟丝子6~25份、杜仲6~20份、当归6~15份、丹参10~20份、北沙参9~18份、党参9~30份、柴胡3~10份、白芍6~15份,提取所述组分的提取液,干燥后粉碎,制成所需中药制剂。该发明所述的治疗卵巢功能减退和早衰的中药组合物具有补益肝肾、疏肝解郁、活血祛瘀、通经止痛等功效,用于治疗卵巢功能减退和卵巢早衰病症。
中国发明专利申请CN114470075A公开了一种治疗卵巢早衰引起的不孕症的中药组合物,所述中药组合物由以下重量份的原料药制成:紫河车25-35份、紫石英25-35份、熟地黄10-20份、白芍10-20份、白术7-12份、菟丝子14-16份、巴戟天14-16份、肉苁蓉14-16份、淫羊藿14-16份、仙茅8-10份、炙甘草5-7份。该发明还提供了中药组合物的用途。该发明改善卵巢早衰引起的不孕症患者的生殖功能,该发明中药组较DHEA组总妊娠率有上升趋势,移植成功率明显提高。
中医药对POI的治疗也进行了一定的探索,并取得了一定的进步,但是其改善指标仍需进一步提高,且除了追求疗效指标改善外,患者的生活质量,如生理功能、躯体症状、情感和精神健康均需要进行关注和治疗。
此外,有效中药方剂在临床的推广应用,因存在以下共性的问题往往遭遇“瓶颈”:⑴基于对证候“辨证”的中医治疗方法,如在临床中POI可辨证为肝肾阴虚、肝郁肾虚、脾肾阳虚等多个中医证型,医者对证候的认识或辨证技术存在着差异,故往往导致对同一证候的辨证结论存在差异;⑵中西医结合治疗本病时,西医医生因不掌握中医辨证技术而无法正确在临床中应用中药。
发明内容
针对上述不足,本发明提供了一种补肾理脾舒肝组合物及其制备方法和应用。所述补肾理脾舒肝组合物是基于对POI疾病“共性病机”理论而提出。一旦POI疾病诊断明确,以“补肾理脾舒肝组合物”为方药的POI中医治疗,不再依赖对疾病的辨证分型,“补肾理脾舒肝组合物”可作为一种相对普遍适用的中药方剂,更易于在POI疾病“长期健康管理”治疗时的应用。
本方案不仅关注POI疾病治疗医学指标的有效改善,更关注POI患者在全程治疗期内的“个体”感受—对生活质量及健康质量的感受,以及对患者因POI疾病可能导致未来发生不良预后的风险防范。
为解决上述技术问题,本发明采用的技术方案为:
一种补肾理脾舒肝组合物,所述补肾理脾舒肝组合物的原料包括:柴胡,太子参,菟丝子,川续断,白芍,北沙参,茯神,巴戟天,鹿角霜,龟甲,川牛膝,女贞子,桑寄生和甘草。
优选地,按重量份数计,所述补肾理脾舒肝组合物包括如下原料:柴胡3-6份,太子参10-20份,菟丝子10-20份,川续断10-20份,白芍10-15份,北沙参10-20份,茯神10-15份,巴戟天5-10份,鹿角霜10-15份,龟甲10-20份,川牛膝10-15份,女贞子10-20份,桑寄生10-20份和甘草3-6份。
进一步优选地,按重量份数计,所述补肾理脾舒肝组合物包括如下原料:柴胡5份,太子参15份,菟丝子15份,川续断15份,白芍10份,北沙参15份,茯神10份,巴戟天10份,鹿角霜10份,龟甲15份,川牛膝10份,女贞子15份,桑寄生15份和甘草6份。
优选地,所述白芍为酒白芍,所述龟甲为醋龟甲,所述甘草为生甘草。
本发明再一目的是提供上述补肾理脾舒肝组合物的制备方法,包括如下步骤:
(1)先将龟甲加水煎煮得煎煮液;
(2)将煎煮液中倒入其余原料,加水煎煮,过滤,浓缩即得。
优选地,步骤(1)中水的添加量为龟甲质量的7-9倍,优选为8倍;步骤(1)和(2)中煎煮前均进行浸泡,浸泡的时间均为20-40min;步骤(1)中所述煎煮的时间为20-40min。
优选地,步骤(2)中所述煎煮的次数为1-3次,优选为2次,每次煎煮的时间为20-40min。
优选地,本发明组合物的制备方法包括如下步骤:先煎煮龟甲,大火煮开后小火煎煮30分钟;其他原料倒入药锅中,大火煮开后小火煎煮30分钟,熬制至汤液的浓度为1g生药量/mL,澄出药液,为第一煎;再次药锅内注水约300mL,大火烧开,小火熬制至汤液的浓度为1g生药量/mL,澄出药液,为第二煎;两次煎煮药液混匀后,即得。
上述组合物,早晚分2次温服。
本发明还有一个目的是提供上述补肾理脾舒肝组合物在制备治疗早发性卵巢功能不全药物中的应用。
优选地,所述药物能改善早发性卵巢功能不全患者FSH、LH和/或E2的水平。
优选地,所述药物能提高部分患者AMH水平及基础窦卵泡计数。
优选地,所述药物能改善患者生活质量。
与现有技术相比,本发明的积极和有益效果在于:
(1)与目前及既往更着重于对患者终末医学疗效指标改善的治疗思路相比,以“补肾理脾舒肝组合物”为方药的“补肾理脾舒肝”治法,更关注POI患者在全程治疗期内的“个体”感受—对生活质量及健康质量的感受,以及对患者因POI疾病可能导致未来发生不良预后的风险防范。
卵巢功能一旦不全甚至衰竭,难以逆转,需长期、持续治疗。“补肾理脾舒肝组合物”着眼于“长期健康管理”治疗理念,即强调治法疗效的现实意义(治疗前后医学指标如FSH、AMH、AFC改善),更注重治疗全过程中对患者生活质量的改善(如生活质量评价PHQ-9量表评分、改良Kupperman评分)、对未来不良预后的风险评估与防范(如OP、ASCVD风险评估),是中医学“未病先防、既病防变、瘥后防复”理念在现代疾病谱系治疗时的具体发挥与实践。
(2)“补肾理脾舒肝组合物”基于对POI疾病“共性病机”理论而提出。一旦POI疾病诊断明确,以“补肾理脾舒肝组合物”为方药的POI中医治疗,不再依赖对疾病的辨证分型,从而使“补肾理脾舒肝组合物”可作为一种相对普遍适用的中药方剂,更易于在POI疾病“长期健康管理”治疗过程中应用。
(3)本发明组合物以菟丝子、太子参、柴胡为君药。菟丝子味辛、甘,性微温,入肝、肾、脾经,气和性缓,能浮能沉,补肾养肝健脾,阴阳并补,《本草汇言》称其为“补肾养肝,温脾助胃之药也”;太子参味甘润微苦,性平,入脾、肺经,补益脾肺,并偏于补益气阴,为清补之品;柴胡味苦辛,性微寒,微香升散,入肝经,疏肝解郁。以巴戟天、川续断、桑寄生、女贞子、鹿角霜、醋龟甲、酒白芍、茯神为臣药,其中巴戟天《得宜本草》称其“功专温补元阳”;川续断、桑寄生、女贞子补肝肾,滋阴血,调血脉;《临证指南》云“任脉为病,龟甲以静摄,督脉为病,用鹿角以温煦”,鹿角霜、醋龟甲调补肾之阴阳,通补奇经,以上诸药辅助菟丝子补肾益肝,调养冲任,调补胞宫;酒白芍养血柔肝平肝;茯神健脾宁心安神。以川牛膝、生甘草为佐使药,牛膝活血祛瘀,补益肝肾,引血下行;生甘草少量调和诸药。
前期研究中,通过数据挖掘发现滕秀香教授治疗POI的核心治法是补肾理脾舒肝法,其处方核心中药组合为“菟丝子-太子参-柴胡”。菟丝子性平,味辛甘,有补肾温阳,填精益髓之效;太子参味甘、微苦,平,归脾、肺经,具有益气健脾,生津润肺之效;柴胡苦而性微寒,归肝、胆经,功善舒肝解郁。
前期研究中,基于网络药理学方法,初步筛选出滕秀香教授治疗POI处方核心药物“菟丝子-太子参-柴胡”药对的潜在活性化合物及靶点。靶点数量位于前5位的化合物分别为:MOL00098(槲皮素)、MOL00422(山柰酚)、MOL000006(木犀草素)、MOL000354(异鼠李素)、MOL000358(β-谷甾醇)。
槲皮素、山柰酚、木犀草素、异鼠李素为黄酮类物质。槲皮素具有抗氧化、抗凋亡、抗炎作用。动物实验表明,槲皮素可增加卵巢体积和窦卵泡数量,减少颗粒细胞的凋亡,减轻卵巢间质血管充血和水肿;可通过影响衰老大鼠卵巢卵泡储备而发挥积极作用。山奈酚具有抗炎、抗氧化以及抗癌特性。研究表明,山奈酚可以通过降低氧化应激和改善线粒体功能来减缓猪卵母细胞衰老;可维护卵泡生存,增加线粒体活性水平,促进卵母细胞减数分裂恢复,由山奈酚刺激的羊次级卵泡发育是通过PI3K通路介导。木犀草素具有抗炎、抗氧化作用。建立小鼠双酚A卵巢损伤模型,发现在有木犀草素干预的处理组中,卵巢组织过氧化损伤指标丙二醛下降,过氧化氢酶(CAT)、超氧化物歧化酶(SOD)水平改善,提示木犀草素可能有缓解卵巢损伤作用。异鼠李素具有广泛药理作用,包括抗炎、抗氧化和调节细胞凋亡。主要活性化合物中的β-谷甾醇为醇类物质。β-谷甾醇是弱的雌激素受体α(ERα)和雌激素受体β(ERβ)激动剂,可通过ER途径调节下游靶基因的表达而发挥植物雌激素样作用而保护卵巢功能。
前期研究中,基于网络药理学GO富集分析发现,“菟丝子-太子参-柴胡”这组药中的活性成分作用的靶点主要集中在基因表达、RNA转录、细胞凋亡等生物过程中。在分子功能方面,酶结合、蛋白质结合排位靠前;在细胞组分中,细胞外间隙所占比例最大。
前期研究中,基于网络药理学KEEG通路分析可知,“菟丝子-太子参-柴胡”药对主要通过AGE-RAGE信号通路、PI3K-Akt信号通路、IL-17信号通路等发挥治疗作用。
目前对于AGE-RAGE信号通路和IL-17信号通路在POI方面的研究较少,但有研究表明,AGE通过与RAGE和其他受体结合而积聚在卵巢相关细胞表面上,可能在卵巢功能下降的病理改变中发挥作用。
PI3K-Akt信号通路调节原始卵泡的休眠和启动募集、卵母细胞的分裂和成熟、颗粒细胞的增殖和分化,是卵巢功能的调控通道,若该通路异常表达,会致原始卵泡过度激活而提早耗竭,当外界信号分子刺激原始卵泡后,P13K发生磷酸化,进而磷脂酰肌醇-4,5-二磷酸(PIP2)向三磷酸肌醇(PIP3)转化,再加丙酮酸脱氢酶激酶同工酶1(PDK1)参与,与下游AKT结合,使AKT关键位点发生磷酸化,活化后的AKT进一步与下游靶点相结合,发挥其生物学效应。正常情况下,自噬具有细胞保护功能。若自噬被过度激活,可能导致卵巢颗粒细胞凋亡、卵泡闭锁。有研究表明,PI3K/AKT信号通路为调节细胞自噬的经典信号通路,通过激活AKT来加强PI3K/AKT信号通路,使下游靶点mTOR抑制结节性硬化症基因2(TSC2),用来控制自噬发生,进一步调节卵泡的发育、闭锁。
故基于网络药理学研究方法,前期研究得到以下研究结论:
①滕秀香教授治疗POI核心药对“菟丝子-太子参-柴胡”,其发挥作用的潜在主要活性成分包括槲皮素、山柰酚、木犀草素、β-谷甾醇等;
②“菟丝子-太子参-柴胡”核心药对,可能是通过AKT1、TP53、VEGFA、TNF、IL6等靶点,作用于AGE-RAGE、PI3K-Akt、IL-17等信号通路,通过调控基因表达、RNA转录、细胞凋亡等多种途径,达到改善卵巢功能的治疗目的。
(4)本发明组合物的显著效果:⑴可在一定程度上改善POI患者FSH、LH、E2水平;⑵可改善部分POI患者AMH水平及基础窦卵泡计数;⑶可在一定程度上改善POI患者生活质量。
(5)本发明在前期研究中还曾尝试过其他功效类似的药材,如用茯苓来代替本发明的茯神,虽二者均可健脾益气,但茯苓无宁心安神,交通心肾之用,临床对POI引发之睡眠障碍患者治疗改善效果不及茯神;如以旱莲草替代女贞子,临床发现旱莲草最终煎煮得到药液在改善POI患者激素水平和双侧窦卵泡计数方面效果不及女贞子。考虑旱莲草性寒,味咸,滋补肝肾凉血止血;而女贞子性凉,味甘、苦,补益肝肾,明目乌发,二者均为滋补肝肾之品,但旱莲草之寒敛之性不利于本病的治疗。研究表明,本发明药材组合物具有最优的配伍。
具体实施方式
下面结合具体实施例,对本发明作进一步详细的阐述,下述实施例不用于限制本发明,仅用于说明本发明。以下实施例中所使用的实验方法如无特殊说明,实施例中未注明具体条件的实验方法,通常按照常规条件,下述实施例中所使用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1
本实施例补肾理脾舒肝组合物的原料由如下药材组成:
柴胡5g,太子参15g,菟丝子15g,川续断15g,白芍10g,北沙参15g,茯神10g,巴戟天10g,鹿角霜10g,龟甲15g,川牛膝10g,女贞子15g,桑寄生15g和甘草6g。
制备方法如下:
(1)将龟甲加入药锅中,向药锅中加总药材质量8倍量的水,大火煮开后小火煎煮30分钟;
(2)将其他原料倒入药锅中,大火煮开后小火煎煮30分钟;熬制至汤液的浓度为1g生药量/mL,澄出药液,为第一煎;
(3)将第一煎的药渣再次注水约300mL(总药材质量2倍量的水),大火烧开,小火熬制至汤液的浓度为1g生药量/mL,澄出药液,为第二煎;两次煎煮药液混匀后,即得。
实施例2
本实施例补肾理脾舒肝组合物的原料由如下重量份的药材组成:
柴胡3份,太子参10份,菟丝子10份,川续断10份,白芍10份,北沙参10份,茯神10份,巴戟天5份,鹿角霜10份,龟甲10份,川牛膝10份,女贞子10份,桑寄生10份,甘草5份。
制备方法如下:
(1)将龟甲加入药锅中,向药锅中加总药材质量8倍量的水,大火煮开后小火煎煮30分钟;
(2)将其他原料倒入药锅中,大火煮开后小火煎煮30分钟;熬制至汤液的浓度为1g生药量/mL,澄出药液,为第一煎;
(3)将第一煎的药渣再次注水约300mL(总药材质量2倍量的水),大火烧开,小火熬制至汤液的浓度为1g生药量/mL,澄出药液,为第二煎;两次煎煮药液混匀后,即得。
实施例3
本实施例补肾理脾舒肝组合物的原料由如下重量份的药材组成:
柴胡6份,太子参20份,菟丝子20份,川续断20份,白芍15份,北沙参20份,茯神15份,巴戟天15份,鹿角霜15份,龟甲20份,川牛膝15份,女贞子20份,桑寄生20份,甘草3份。
制备方法如下:
(1)将龟甲加入药锅中,向药锅中加总药材质量8倍量的水,大火煮开后小火煎煮30分钟;
(2)将其他原料倒入药锅中,大火煮开后小火煎煮30分钟;熬制至汤液的浓度为1g生药量/mL,澄出药液,为第一煎;
(3)将第一煎的药渣再次注水约300mL(总药材质量2倍量的水),大火烧开,小火熬制至汤液的浓度为1g生药量/mL,澄出药液,为第二煎;两次煎煮药液混匀后,即得。
效果测试
实验一、“补肾理脾舒肝组合物”治疗3个月对POI患者激素水平的影响
1.入组诊断标准
根据《早发性卵巢功能不全的临床诊疗中国专家共识》[陈子江,田秦杰,乔杰,等.早发性卵巢功能不全的临床诊疗中国专家共识[J].中华妇产科杂志,2017,52(09):577-581.]制定。①年龄小于40岁;②月经稀发或停经至少4个月以上;③至少2次血清基础 FSH>25 IU/L(间隔≥4周)。
2.治疗方案
治疗组:实施例1组,入组后给予“补肾理脾舒肝组合物”(柴胡5g,太子参15g,菟丝子15g,川续断15g,白芍10g,北沙参15g,茯神10g,巴戟天10g,鹿角霜10g,龟甲15g,川牛膝10g,女贞子15g,桑寄生15g和甘草6g)水煎服,日2服,连续服用3个月,治疗前后测定血清激素水平(FSH、LH、E2)。
3.疗效评定标准
痊愈:血清FSH值恢复正常(FSH≤10mIU/L);
显效:血清FSH值接近正常,或FSH下降率≥50%;
有效:血清FSH值有所改善,或50%>FSH下降率≥20%;
无效:血清FSH值无改善甚至升高,或FSH下降率<20%。
有效率=(痊愈+显效+有效)/总例数×100%。
4.结果及分析
4.1临床疗效比较
4.2“补肾理脾舒肝组合物”对POI患者激素水平的影响
结果见表1。
表1治疗前及治疗3个月FSH、LH、E2水平比较
注:治疗前、治疗后,FSH、LH、E2变量不符合正态分布,用中位数、四分位间距表示,采用Wilcoxon秩和检验。*P<0.05。
实验二、“补肾理脾舒肝组合物”治疗6个月对POI患者激素水平、AFC的影响
1.入组诊断标准
根据《早发性卵巢功能不全的临床诊疗中国专家共识》[陈子江,田秦杰,乔杰,等.早发性卵巢功能不全的临床诊疗中国专家共识[J].中华妇产科杂志,2017,52(09):577-581.]制定。①年龄小于40岁;②月经稀发或停经至少4个月以上;③至少2次血清基础 FSH>25 IU/L(间隔≥4周)。
2.治疗方案
治疗组:实施例1组
3.结果及分析
3.1采用单臂实验方法,33例POI患者予口服“补肾理脾舒肝组合物”(柴胡5g,太子参15g,菟丝子15g,川续断15g,白芍10g,北沙参15g,茯神10g,巴戟天10g,鹿角霜10g,龟甲15g,川牛膝10g,女贞子15g,桑寄生15g和甘草6g)水煎服,日2服,连续治疗6个月。观察指标:⑴理化指标FSH、LH、E2改变;⑵基础窦卵泡计数改变。结果见表2和表3。
表2治疗组治疗前及治疗6个月FSH、LH、E2水平比较
注:治疗前、治疗后,FSH、LH、E2变量不符合正态分布,用中位数、四分位间距表示,采用Wilcoxon秩和检验。#P>0.05,*P<0.05。
表3治疗前及治疗6个月双侧窦卵泡计数改变()
治疗组双侧窦卵泡总数(个) | |
治疗前 | 1(0,3) |
治疗6个月 | 4(1,5) |
Z | -2.38 |
p | 0.017* |
注:治疗前、治疗后,基础窦卵泡计数变量不符合正态分布,采用Wilcoxon秩和检验。*P<0.05。
实验三、“补肾理脾舒肝组合物”对POI患者生活质量的影响
采用单臂实验方法,对上述33例POI患者予口服“补肾理脾舒肝组合物”(柴胡5g,太子参15g,菟丝子15g,川续断15g,白芍10g,北沙参15g,茯神10g,巴戟天10g,鹿角霜10g,龟甲15g,川牛膝10g,女贞子15g,桑寄生15g和甘草6g)水煎服,日2服,连续
服用治疗6个月。采用SF-36生活质量量表评价患者生活质量的改善。
SF-36生活质量量表又叫健康调查简表,是一个本领域公认的普适性测定量表,包含生理功能、生理职能、肌体疼痛、总体健康、活力、社会功能、情感职能和精神健康等8个领域。
本实验治疗前、后SF-36总评分及8个维度评分,见表4。
表4治疗前及治疗6个月SF-36量表评分比较( )
注:变量均符合正态分布,采用两独立样本t检验。*P<0.05。
结果分析:本发明“补肾理脾舒肝组合物”具有以下显著的优势:⑴可在一定程度上改善POI患者FSH、LH、E2水平;⑵可改善POI患者基础窦卵泡计数;⑶可在一定程度上改善POI患者生活质量。
以上所述实施例仅表达了本发明的几种实施方式,其描述较为具体和详细,但并不能因此而理解为对本发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。因此,本发明专利的保护范围应以所附权利要求为准。
Claims (9)
1.一种补肾理脾舒肝组合物,其特征在于,按重量份数计,所述补肾理脾舒肝组合物包括如下原料:柴胡3-6份,太子参10-20份,菟丝子10-20份,川续断10-20份,白芍10-15份,北沙参10-20份,茯神10-15份,巴戟天5-15份,鹿角霜10-15份,龟甲10-20份,川牛膝10-15份,女贞子10-20份,桑寄生10-20份和甘草3-6份。
2.根据权利要求1所述的补肾理脾舒肝组合物,其特征在于,按重量份数计,所述补肾理脾舒肝组合物包括如下原料:柴胡5份,太子参15份,菟丝子15份,川续断15份,白芍10份,北沙参15份,茯神10份,巴戟天10份,鹿角霜10份,龟甲15份,川牛膝10份,女贞子15份,桑寄生15份和甘草6份。
3.根据权利要求1所述的补肾理脾舒肝组合物,其特征在于,所述白芍为酒白芍,所述龟甲为醋龟甲,所述甘草为生甘草。
4.一种如权利要求1-3任一项所述的补肾理脾舒肝组合物的制备方法,其特征在于,包括如下步骤:
(1)先将龟甲加水煎煮得煎煮液;
(2)将煎煮液中倒入其余原料,加水煎煮,过滤,浓缩即得。
5.根据权利要求4所述的制备方法,其特征在于,步骤(1)和(2)中煎煮前均进行浸泡,浸泡的时间均为20-40min;步骤(1)中所述煎煮的时间为20-40min。
6.根据权利要求4所述的制备方法,其特征在于,步骤(2)中所述煎煮的次数为1-3次,每次煎煮的时间为20-40min。
7.一种如权利要求1-3任一项所述的补肾理脾舒肝组合物在制备治疗早发性卵巢功能不全药物中的应用。
8.根据权利要求7所述的应用,其特征在于,所述药物能改善早发性卵巢功能不全患者FSH、LH和/或E2的水平。
9.根据权利要求7所述的应用,其特征在于,所述药物能提高部分患者AMH水平及基础窦卵泡计数。
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