CN115475219B - 海龙蛤蚧口服液在制备治疗老年痴呆药物中的应用 - Google Patents
海龙蛤蚧口服液在制备治疗老年痴呆药物中的应用 Download PDFInfo
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- CN115475219B CN115475219B CN202211169639.3A CN202211169639A CN115475219B CN 115475219 B CN115475219 B CN 115475219B CN 202211169639 A CN202211169639 A CN 202211169639A CN 115475219 B CN115475219 B CN 115475219B
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Abstract
本申请公开了海龙蛤蚧口服液在制备治疗老年痴呆药物中的应用,属于中药制备领域,本申请制备的海龙蛤蚧口服液补肾阳而不伤阴,益肾精,补气血,补而不滞,补而不燥,又具补脾益肺之功,能够有效改善记忆功能,治疗老年痴呆。
Description
技术领域
本申请涉及海龙蛤蚧口服液在制备治疗老年痴呆药物中的应用,属于中药技术领域。
背景技术
老年性痴呆是主要在老年人中流行的一种慢性神经变性疾病。其中最常见的是阿尔茨海默氏症(Alzheimer′s disease,AD)。AD是以脑细胞丢失为特征的一种进展性疾病,导致严重痴呆和死亡。虽然每个人AD的病程均有不同,但AD患者有许多共同的症状。最早观察到的症状往往被误以为是与年龄有关的忧虑和紧张;早期阶段最常见的症状是学习、记忆和认知障碍;随着病情的进展,产生的症状包括思维混乱,易怒和攻击性,情绪波动,语言破裂,长期记忆丧失;晚期逐渐发生身体功能丧失,最终导致死亡。
老年痴呆在中医中属“健忘”“呆病”“善忘”范畴,传统中医学认为老年痴呆症的发病机制为肾气肾精亏虚。
发明内容
为了解决上述问题,提供了海龙蛤蚧口服液在制备治疗老年痴呆药物中的应用,本申请制备的海龙蛤蚧口服液补肾阳而不伤阴,益肾精,补气血,补而不滞,补而不燥,又具补脾益肺之功,能够有效改善记忆功能,治疗老年痴呆。
根据本申请的一个方面,提供了海龙蛤蚧口服液在制备治疗老年痴呆药物中的应用。
可选地,所述老年痴呆包括阿尔茨海默病性痴呆和肾精亏虚型老年痴呆。
可选地,所述海龙蛤蚧口服液由中药原料、辅料和水制备而成,所述中药原料由海龙、蛤蚧、人参、羊鞭、羊外肾、黄芩、熟地黄、菟丝子、何首乌、地黄、陈皮、当归、黄芪、阳起石、莲须、甘草、川芎、泽泻、锁阳、豆蔻、沉香、鹿茸、枸杞子、肉苁蓉、淫羊藿、肉桂、韭菜子、蛇床子和花椒组成。
可选地,所述中药原料由海龙39.1g、蛤蚧0.73g、人参4.68g、羊鞭4.68g、羊外肾4.68g、黄芩4.68g、熟地黄3.1g、菟丝子3.1g、何首乌3.1g、地黄3.1g、陈皮3.1g、当归1.56g、黄芪4.68g、阳起石1.56g、莲须1.56g、甘草1.56g、川芎1.56g、泽泻1.56g、锁阳1.56g、豆蔻1.56g、沉香1.56g、鹿茸1.56g、枸杞子1.56g、肉苁蓉0.78g、淫羊藿1.56g、肉桂1.56g、韭菜子1.56g、蛇床子1.56g和花椒0.31g组成。
可选地,所述辅料由蔗糖、苯甲酸和氢氧化钠组成。
可选地,所述辅料由蔗糖300g、苯甲酸1.9g和氢氧化钠组成。
可选地,所述海龙蛤蚧口服液的制备方法包括以下步骤:
(1)将中药原料混合后加水煎煮2次,每次2h,合并两次的煎液,浓缩至相对密度1.04~1.06的清膏,加乙醇,在2±2℃下冷藏12h,滤过,回收乙醇,再次浓缩至相对密度1.09~1.11的清膏,加水,冷藏,滤过;
(2)取蔗糖300g加水溶解与上述步骤(1)得到的滤液合并,混匀,加苯甲酸1.9g,用焦糖约1.25~1.45g调整颜色为淡棕色至红棕色,用氢氧化钠调节pH至4.6~4.8,同时补充纯化水调整总量至1000ml,滤过,分装,流通蒸汽灭菌后即得。
可选地,步骤(1)中浓缩温度为80℃。
可选地,步骤(1)中乙醇加入量为浓缩清膏的二倍。
可选地,步骤(1)乙醇的质量分数为95%。
本申请的有益效果包括但不限于:
1.本申请开发了海龙蛤蚧口服液在制备治疗老年痴呆药物中的新应用。
2.根据本申请的海龙蛤蚧口服液,配方中重用海龙、羊鞭、羊外肾、鹿茸血肉有情之品以填精补髓,温壮元阳;以菟丝子、肉桂、淫羊藿、莲须、锁阳、韭菜子、蛇床子、肉苁蓉、阳起石辅助之药温补命门,以助温肾壮阳之功。
以人参、黄芪、熟地黄、川芎、当归、枸杞子补益气血活血,益肾脏填精;以花椒、豆蔻、陈皮温中行气、理气健脾;何首乌补肝养血;蛤蚧补肺益虚;以地黄养阴生津,益阴摄阳。扶正不忘祛邪,故又用黄芩、泽泻等泻火利湿,以泻湿浊。以沉香引药归经,甘草调和诸药,诸药相合,大补肾阳而不伤阴,益肾精,补气血,补而不滞,补而不燥,又具补脾益肺之功。
具体实施方式
下面结合实施例详述本申请,但本申请并不局限于这些实施例。
除非另行定义,文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。本发明所使用的试剂或原料均可通过常规途径购买获得,如无特殊说明,本发明所使用的试剂或原料均按照本领域常规方式使用或者按照产品说明书使用。此外,任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。本专利中所述的较佳实施方法与材料仅作示范之用。
实施例1海龙蛤蚧口服液1#
中药原料由海龙39.1g、蛤蚧0.73g、人参4.68g、羊鞭4.68g、羊外肾4.68g、黄芩4.68g、熟地黄3.1g、菟丝子3.1g、何首乌3.1g、地黄3.1g、陈皮3.1g、当归1.56g、黄芪4.68g、阳起石1.56g、莲须1.56g、甘草1.56g、川芎1.56g、泽泻1.56g、锁阳1.56g、豆蔻1.56g、沉香1.56g、鹿茸1.56g、枸杞子1.56g、肉苁蓉0.78g、淫羊藿1.56g、肉桂1.56g、韭菜子1.56g、蛇床子1.56g和花椒0.31g组成。
制备方法为将以上29味中药加水煎煮2次,每次2h,合并煎液,浓缩至相对密度1.05的清膏,浓缩温度为80℃,加浓缩清膏二倍量的乙醇,乙醇的质量分数为95%,2℃冷藏12h,滤过,回收乙醇,浓缩至相对密度1.10的清膏,加水,冷藏,滤过;取蔗糖300g加水溶解与上述滤液合并,混匀,加苯甲酸1.9g,用焦糖1.3g调整颜色为淡棕色至红棕色,用氢氧化钠调pH至4.7,加纯化水调整总量至1000ml,滤过,分装,灭菌,即得海龙蛤蚧口服液1#。
实施例2药理实验研究
1.仪器与药品:
旷场实验系统、水迷宫实验、Y迷宫实验系统均购自上海欣软公司。
海龙蛤蚧口服液1#为实施例1制备得到,盐酸多奈哌齐购自卫材(中国)药业有限公司,银杏叶提取物片购自Dr.Willmar Schwabe GmbH&Co.KG(德国)。
2.分组及给药
将60只购自扬州大学的小鼠,随机分为5组:假手术组、模型组、海龙蛤蚧口服液组(3ml/kg)、盐酸多奈哌齐组(1.5mg/kg)、银杏叶提取物片组(0.9片/kg),12只/组。假手术组侧脑室注射生理盐水,其余各组侧脑室注射Aβ25-356μg/只,从造模手术后第4天开始给药,每天一次,连续30天。海龙蛤蚧口服液组使用实施例1制备的海龙蛤蚧口服液1#,盐酸多奈哌齐组、银杏叶提取物片组分别按照上述剂量以灌胃方式给药;假手术组和模型组给予等量的生理盐水。
3.试验过程
3.1旷场实验:将动物放于一50×50×25厘米的旷场内,所有动物头均面对同一位置放入旷场,启动轨迹跟踪系统,检测小鼠的运动距离、休息时间及运动时间等指标。
3.2Morris水迷宫实验:采用直径1米的水池,水温21℃-22℃,水中加入牛奶使追踪背景呈白色。实验第1天将鼠放入水池中自由游泳60s以适应环境。定位航行实验:第2天起将平台置于某一象限,进行获得性训练,面向池壁将动物放入4个不同的象限各一次,共训练5天。动物找到平台后一般在平台上休息10~15秒,若规定时间内找不到平台,则由实验者将其引导至平台,在平台休息相同时间。由行为学追踪软件记录动物的游泳的路程、轨迹和寻找平台的时间。空间探索实验:定位航行实验结束24小时后,撤除平台,任选1个入水点将动物面向池壁放入水中,记录动物在60秒内第一次跨越平台的时间和次数等指标。
3.3Y迷宫实验:Y迷宫共3个臂,包括新异臂、起始臂和其他臂。新异臂:在实验的第1阶段用隔板挡住,在第2阶段即测试期时打开;起始臂:小鼠进入迷宫时所在的臂。整个实验过程中起始臂和其他臂一直打开。Y迷宫实验包括两个阶段。第一阶段为训练期,新异臂被挡住,小鼠由起始臂放入,在起始臂和其他臂中自由活动10分钟。1h后进行第2阶段即测试期,抽开新异臂的隔板,小鼠由起始臂放入,在3个臂中自由活动5min。记录5min内每只小鼠在各个臂停留的时间和穿梭次数。
3.4社交实验:用透明隔板将三个空间分隔开,将鼠放入中间,让其自由活动适应环境5min。第一阶段:移开隔板,将一个装有陌生鼠的笼子放入左侧空间,将另一个空笼放入右侧空间。计时10min,记录测试鼠进入两个空间的时间。(以四肢均进入空间为标准)。第二阶段:将右侧空笼也放入陌生鼠,并再次记录小鼠进入右侧笼子里的时间和次数。做完一只鼠后,将箱子用酒精擦拭干净。
3.5筑巢试验:将小鼠分成单笼(每笼1只),让其适应单笼环境48h后,在每笼中换入厚度1cm的刨花垫料,夜节律钱2h均匀平铺放入大小一致的棉花一片(长4.5cm,宽4.5cm,厚1cm),18h后用5分法对筑巢质量进行评分:1分,棉花杂乱的散步在笼子各处,没有撕咬,2分,棉花被聚到笼子的一侧,但较松散,没有成型的筑巢,没有明显的撕咬或者折叠;3分,棉花聚拢折叠呈成型但较平的巢,没有明显的撕咬;4分,棉花撕成球状,已经筑成窝的形状,但高度未高过小鼠;5分,棉花聚拢折叠成较深的巢,并被撕咬成小块。
4.试验结果
4.1旷场试验:与假手术组比较,模型组运动总路程和运动总时间明显减少,其差异具有统计学意义;与模型组比较,海龙蛤蚧口服液组的运动总路程、运动总时间有明显改善(P<0.05),与盐酸多奈哌齐片组比较,运动总路程、总时间有增大趋势,与银杏叶提取物片比较,运动总路程显著增加(P<0.05),运动总时间有增加趋势。结果详见表1。
表1海龙蛤蚧口服液对小鼠自主活动的影响
注:a与模型组比较P<0.05;b与阳性对照组(盐酸多奈哌齐)比较P<0.05;c与阳性对照组(银杏叶提取物片)比较P<0.05。
4.2水迷宫试验:Morris水迷宫定位航行实验中,随着训练时间的延长,潜伏期逐渐降低,但模型组游出率的上升幅度和潜伏期的下降幅度明显小于假手术组,与模型组相比海龙蛤蚧口服液组小鼠逃避潜伏期明显降低(P<0.05),与阳性对照组比较,海龙蛤蚧口服液组同时间段潜伏期也明显降低(P<0.05)。结果详见表2。空间探索实验中,模型组小鼠与假手术组相比空间探索能力明显减弱,而海龙蛤蚧口服液可改善小鼠空间探索能力。海龙蛤蚧口服液组与对照组比较,目标象限时间更显著增加(P<0.05),目标象限穿台次数有增加趋势。结果详见表3。
表2海龙蛤蚧口服液对小鼠水迷宫定位导航试验潜伏期的影响
组别 | 第1天 | 第2天 | 第3天 | 第4天 |
假手术组 | 47.28±8.33 | 30.53±6.62 | 24.08±3.63 | 17.94±3.24 |
模型组 | 48.30±10.46 | 46.81±9.26 | 39.13±6.52 | 31.84±5.16 |
海龙蛤蚧口服液组 | 46.79±7.17 | 34.77±4.55abc | 26.53±4.06abc | 19.34±2.16abc |
阳性对照组(盐酸多奈哌齐) | 48.92±9.29 | 41.52±5.93 | 32.43±4.61 | 24.81±3.72 |
阳性对照组(银杏叶提取物片) | 47.02±8.79 | 40.51±5.37 | 33.87±5.04 | 23.26±2.94 |
注:a与模型组比较P<0.05;b与阳性对照组(盐酸多奈哌齐)比较P<0.05;c与阳性对照组(银杏叶提取物片)比较P<0.05。
表3海龙蛤蚧口服液对小鼠水迷宫空间探索的影响
组别 | 目标象限时间(s) | 目标象限穿台次数(次) |
假手术组 | 21.29±4.26 | 5.33±2.05 |
模型组 | 13.78±3.48 | 2.69±0.52 |
海龙蛤蚧口服液组 | 20.43±2.83abc | 4.72±1.41a |
阳性对照组(盐酸多奈哌齐) | 16.25±2.85 | 3.82±1.71 |
阳性对照组(银杏叶提取物片) | 16.16±2.19 | 3.71±1.61 |
注:a与模型组比较P<0.05;b与阳性对照组(盐酸多奈哌齐)比较P<0.05;c与阳性对照组(银杏叶提取物片)比较P<0.05。
4.3Y迷宫试验:Y迷宫试验中,模型组小鼠,正确循环的比例数和运行步数明显下降,给药组小鼠正确的循环比例和运行的步数明显增加,表明小鼠记忆功能提高。结果见表4。
表4海龙蛤蚧口服液对小鼠Y迷宫试验影响
注:a与模型组比较P<0.05;b与阳性对照组(盐酸多奈哌齐)比较P<0.05;c与阳性对照组(银杏叶提取物片)比较P<0.05。
4.4社交试验:社交试验中,第一阶段,模型组小鼠与陌生鼠接触时间较假手术组明显降低,给药组小鼠与模型组、阳性对照组比,与陌生鼠接触时间均明显增加。第二阶段,模型组小鼠与新放入的陌生鼠接触时间较假手术组明显降低,给药组小鼠与模型组相比,与新放入的陌生鼠接触时间明显增加,给药组小鼠与阳性对照组比,与新放入的陌生鼠接触时间有增加趋势。说明,海龙蛤蚧口服液可以显著提高小鼠的记忆功能。结果见表5。
表5海龙蛤蚧口服液对小鼠社交影响
注:a与模型组比较P<0.05;b与阳性对照组(盐酸多奈哌齐)比较P<0.05;c与阳性对照组(银杏叶提取物片)比较P<0.05。
4.5筑巢试验结果:筑巢试验结果见表6和图1。结果表明,模型组小鼠筑巢能力与假手术组比明显降低,海龙蛤蚧口服液组小鼠筑巢试验得分与模型组、阳性对照组比均显著提高(P<0.05),说明海龙蛤蚧口服液可以提高小鼠记忆功能和手部运动功能。
表6小鼠筑巢试验得分
组别 | 筑巢试验得分 |
假手术组 | 4.41±0.31 |
模型组 | 2.84±0.25 |
海龙蛤蚧口服液组 | 4.88±0.38abc |
阳性对照组(盐酸多奈哌齐) | 4.06±0.33a |
阳性对照组(银杏叶提取物片) | 3.85±0.31a |
注:a与模型组比较P<0.05;b与阳性对照组(盐酸多奈哌齐)比较P<0.05;c与阳性对照组(银杏叶提取物片)比较P<0.05。
实施例3临床实验
1.诊断标准:
阿尔茨海默性痴呆诊断标准:1984年由美国国立神经病语言障碍卒中研究所和阿尔兹海默病相关协会制定阿尔茨海默病的诊断标准,该标准于2011年由美国国立老化研究所和阿尔茨海默协会进行修改。采用修改后的标准作为诊断标准。
肾精亏虚型老年痴呆诊断标准:参照2002年《中药新药治疗老年痴呆的临床研究指导原则》,拟定本项研究的观察证型的症候诊断标准。主症:智能减退,腰膝酸软,倦怠思卧。次症:表情呆板,思维迟钝,易于惊怒,眩晕耳鸣,行走艰难,大便自遗,小便失禁,面色晦暗,舌淡苔少,脉沉细弱。以上主症具备2项(智能减退必备),次症至少具备3项以上者即可确诊。
2.纳入标准:年龄50~80岁,性别不限;符合上述西医阿尔茨海默性痴呆诊断标准;符合中医肾精亏虚型老年痴呆诊断标准;在本研究前1个月内未服用任何治疗该病的药物;自愿参加本研究,签署知情同意书,依从性较好者。
3.排除标准:血管性痴呆或其他病因所致痴呆者;有焦虑、抑郁等精神及意识障碍者;老年良性健忘症者;合并严重的原发性疾病,影响疗效评定者;对本次试验用药过敏者。
4.治疗方法:对照组:予盐酸多奈哌齐口服,10mg/次,1片/次,每晚服用。治疗组1:在对照组基础上联合使用海龙蛤蚧口服液1#,海龙蛤蚧口服液1#每次1只,每日2次,餐后服用。治疗组2:在对照组基础上联合使用对比例口服液,每次1只,每日2次,餐后服用。3组均服药6个月。对比例口服液与实施例1的区别为处方中不含羊鞭及羊外肾。
5.观察指标:治疗前及治疗6个月后采用简易精神智能量表(MMSE)、蒙特利尔认知评估量表(MOCA)、日常生活量表(ADL)分别对3组患者记忆力、定向力、注意力、计算力、语言和视空间等认知功能及日常生活能力进行评估。
6.疗效评定标准:
痊愈:主要症状基本恢复,神志清醒,定位健全,回答问题正确,反应灵敏,生活自理,能进行一般社会活动;
有效:主要精神症状有所减轻或部分消失,生活基本自理,回答问题基本正确,但反应迟钝,智力、人格有障碍;
无效:主要症状无改变,或病情有所发展,生活不能自理,回答问题不正确,神志痴呆。
7.临床试验结果:盐酸多奈哌齐能够降低乙酰胆碱的水解,提高脑内乙酰胆碱的浓度,达到改善记忆力,缓解病情的作用,是老年痴呆症的对症治疗药。本研究结果显示治疗6个月后,治疗组1的简易精神智能量表(MMSE)、蒙特利尔认知评估量表(MOCA)、日常生活量表(ADL)评分高于对照组(P<0.05),具有统计学差异、临床总有效率高于对照组。表明长期联合应用海龙蛤蚧口服液和多奈哌齐治疗老年痴呆症能够明显改善患者的认知功能及生活质量,提高临床疗效。治疗组2的MMSE、MOCA和ADL评分均高于对照组(P<0.05),具有统计学差异,但低于治疗组1(海龙蛤蚧口服液组);临床总有效率也高于对照组,低于治疗组1。以上数据说明,在临床试验中海龙蛤蚧口服液比对比例口服液疗效更优,对老年痴呆具有更好的治疗效果。各数据结果详见表7-表10。
表7治疗组与对照组治疗前后MMSE评分比较
组别 | 例数 | 治疗前 | 治疗后 |
对照组 | 28 | 16.32±3.27 | 22.17±2.56a |
治疗组1 | 30 | 17.27±3.03 | 25.72±2.35abc |
治疗组2 | 28 | 16.99±2.09 | 23.86±2.06ab |
注:a与本组治疗前比P<0.05;b与对照组治疗后同时期比较P<0.05,c与对照组2治疗后同时期比较P<0.05。
表8治疗组与对照组治疗前后MOCA评分比较
组别 | 例数 | 治疗前 | 治疗后 |
对照组 | 28 | 11.30±3.44 | 15.73±3.11a |
治疗组1 | 30 | 11.05±3.99 | 20.84±3.24abc |
治疗组2 | 28 | 11.85±3.95 | 19.00±3.17ab |
注:a与本组治疗前比P<0.05;b与对照组治疗后同时期比较P<0.05;c与对照组2治疗后同时期比较P<0.05。
表9治疗组与对照组治疗前后ADL评分比较
组别 | 例数 | 治疗前 | 治疗后 |
对照组 | 28 | 39.75±3.00 | 50.26±2.96a |
治疗组1 | 30 | 41.37±2.91 | 56.68±2.51abc |
治疗组2 | 28 | 40.36±2.83 | 53.82±3.45ab |
注:a与本组治疗前比P<0.05;b与对照组治疗后同时期比较P<0.05;c与对照组2治疗后同时期比较P<0.05。
表10治疗组与对照组临床疗效比较[n(%)]
组别 | 例数 | 痊愈 | 有效 | 无效 | 总有效率 |
对照组 | 28 | 1(3.6) | 15(53.6) | 12(42.9) | 16(57.1) |
治疗组1 | 30 | 3(10.0) | 19(63.3) | 8(26.7) | 22(73.3) |
治疗组2 | 28 | 2(7.1) | 17(60.7) | 9(32.1) | 19(67.8) |
注:a与本组治疗前比P<0.05;b与对照组治疗后同时期比较P<0.05;c与对照组2治疗后同时期比较P<0.05。
以上所述,仅为本申请的实施例而已,本申请的保护范围并不受这些具体实施例的限制,而是由本申请的权利要求书来确定。对于本领域技术人员来说,本申请可以有各种更改和变化。凡在本申请的技术思想和原理之内所作的任何修改、等同替换、改进等,均应包含在本申请的保护范围之内。
Claims (8)
1.海龙蛤蚧口服液在制备治疗老年痴呆药物中的应用;
所述海龙蛤蚧口服液由中药原料、辅料和水制备而成,所述中药原料由海龙39.1g、蛤蚧0.73g、人参4.68g、羊鞭4.68g、羊外肾4.68g、黄芩4.68g、熟地黄3.1g、菟丝子3.1g、何首乌3.1g、地黄3.1g、陈皮3.1g、当归1.56g、黄芪4.68g、阳起石1.56g、莲须1.56g、甘草1.56g、川芎1.56g、泽泻1.56g、锁阳1.56g、豆蔻1.56g、沉香1.56g、鹿茸1.56g、枸杞子1.56g、肉苁蓉0.78g、淫羊藿1.56g、肉桂1.56g、韭菜子1.56g、蛇床子1.56g和花椒0.31g组成。
2.根据权利要求1所述的应用,其特征在于,所述老年痴呆包括阿尔茨海默病性痴呆和肾精亏虚型老年痴呆。
3.根据权利要求1所述的应用,其特征在于,所述辅料由蔗糖、苯甲酸和氢氧化钠组成。
4.根据权利要求1所述的应用,其特征在于,所述辅料由蔗糖300g、苯甲酸1.9g和氢氧化钠组成。
5.根据权利要求4所述的应用,其特征在于,所述海龙蛤蚧口服液的制备方法包括以下步骤:
(1)将中药原料混合后加水煎煮2次,每次2h,合并两次的煎液,浓缩至相对密度1.04~1.06的清膏,加乙醇,在2±2℃下冷藏12h,滤过,回收乙醇,再次浓缩至相对密度1.09~1.11的清膏,加水,冷藏,滤过;
(2)取蔗糖300g加水溶解与上述步骤(1)得到的滤液合并,混匀,加苯甲酸1.9g,用焦糖约1.25~1.45g调整颜色为淡棕色至红棕色,用氢氧化钠调节pH至4.6~4.8,同时补充纯化水调整总量至1000ml,滤过,分装,流通蒸汽灭菌后即得。
6.根据权利要求5所述的应用,其特征在于,步骤(1)中浓缩温度为80℃。
7.根据权利要求5所述的应用,其特征在于,步骤(1)中乙醇加入量为浓缩清膏的二倍。
8.根据权利要求5所述的应用,其特征在于,步骤(1)乙醇的质量分数为95%。
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我国海龙的研究进展;许东晖, 谢江海, 梅雪婷, 许实波;中国海洋药物(第02期);51-56 * |
海龙健脑胶囊治疗老年性痴呆148例;门艳丽, 曹金梅;中医研究(第04期);30-31 * |
海龙蛤蚧精的药理效应研究;曲钧庆等;《泰山医学院学报》;第第11卷卷(第第1期期);1-8 * |
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