CN108261481A - 一种具有持续降压功能的活性物质及其制备方法和应用 - Google Patents
一种具有持续降压功能的活性物质及其制备方法和应用 Download PDFInfo
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Abstract
本发明属于食品、保健食品及药物制备领域,涉及一种具有持续降压功能的活性物质及其制备方法和应用。该活性物质为香蕉皮,尤其是香蕉皮提取物,该香蕉皮提取物采用香蕉皮烘干,粉碎,加水煎煮或浸泡,过滤取上清液,适当浓缩成浓缩液或浓缩后干燥制成粉末而成。该活性物质具有持续降压功能,在停药后12天内,血压仍保持在较低水平,并且,本发明活性物质以香蕉皮为主要原料,成本低,副作用小,具有很好的临床应用前景。
Description
技术领域
本发明属于食品、保健食品及药物制备领域,涉及一种具有持续降压功能的活性物质及其制备方法和应用,特别是涉及一种以香蕉皮为主要原料的具有持续降压功能的活性物质及其制备方法和应用。
背景技术
高血压是常见病、多发病,据2014年4月3日发表于《美国高血压杂志》的文章,目前我国高血压患病率为29.6%,男性患病率高于女性(31.2%vs28.0%),知晓率、治疗率和控制率分别为42.6%、34.1%与9.3%,接受降压治疗的患者中血压达标率为27.4%。多种生活方式因素与高血压患病相关,包括体育运动不足、习惯性饮酒、非甾体类抗炎药的慢性使用者、较高体重指数和腹型肥胖。
高血压治疗的主要目标是血压达标,降压治疗的最终目的是最大限度地减少高血压患者心、脑血管病的发生率和死亡率。降压治疗应该确立血压控制目标值。另一方面,高血压常常与其他心、脑血管病的危险因素合并存在,例如高胆固醇血症、肥胖、糖尿病等,协同加重心血管疾病危险,治疗措施应该是综合性的。不同人群的降压目标不同,一般患者的降压目标为140/90mmHg以下,对合并糖尿病或肾病等高危患者,应酌情降至更低。
治疗高血压的药物有很多种类型,比如①利尿药、②β受体阻滞剂、③钙通道阻滞剂、④血管紧张素转换酶抑制剂、⑤血管紧张素Ⅱ受体阻滞剂,等等。很多类型的降压药需要长期服用,应根据患者的危险因素、靶器官损害及合并临床疾病的情况,选择单一用药或联合用药。选择降压药物的原则如下:1)使用半衰期24小时以及以上、每日一次服药能够控制24小时的血压药物;2)使用安全、可长期坚持并能够控制每一个24小时血压的药物,提高患者的治疗依从性;3)使用心脑获益临床试验证据充分并可真正降低长期心脑血管事件的药物,减少心脑血管事件,改善高血压患者的生存质量。
但是,很多人存在不能坚持规律服药的情形,并且长期服用降压药有一定的副作用,部分药物停药后还会引起反跳现象。中医养生保健强调药食同源,药补不如食补,很多食物具有一定的药用价值。根据报导指出,香蕉皮富含色氨酸、维生素B6、丰富血清素,能产生舒适、满足、幸福、惬意、和乐观的情绪。网络也有报道说香蕉皮具有软化疣、治皮肤瘙痒症、治口腔溃疡、治痔疮和便血、治高血压、防中风、解酒、使皮肤滋润光滑等功效。但目前并没有文献报道香蕉皮具有持续降压的作用。香荠降压颗粒是中药6类内服新药,主要由香蕉皮、荠菜、葛根组成,具有清肝降压之功,适用于原发性高血压肝火亢盛证的治疗,降压作用明显。但也没有文献报导香荠降压颗粒具有持续降压作用。
发明内容
本发明的目的是根据上述技术问题提出一种以香蕉皮为主要原料的具有持续降压功能的活性物质。
本发明的另一个目的是提供上述以香蕉皮为主要原料的具有持续降压功能的活性物质的制备方法。
本发明还有一个目的是提供上述以香蕉皮为主要原料的具有持续降压功能的活性物质在制备食品、保健食品或药品中的应用。
本发明的目的是通过下列技术方案实现的:
一种具有持续降压功能的活性物质,该活性物质为香蕉皮。
进一步,所述的活性物质为香蕉皮提取物。
更进一步,所述的活性物质为香蕉皮水提物。
所述的活性性质,其中香蕉皮水提物是通过下列方法制备得到的:香蕉皮烘干,粉碎,加水煎煮或浸泡,过滤取上清液,适当浓缩成浓缩液或浓缩后干燥制成粉末即可。
进一步,该香蕉皮水提物是通过下列方法制备得到的:
成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉,在容器中取上述粉末800-1200g加水4000-6000ml,加热至沸,保持微沸30-40分钟,过滤,取上清液,浓缩到适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可;
或者,成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉,在容器中取上述粉末800-1200g加入4000-6000ml沸水,保温浸泡20-40分钟,过滤,取上清液;在滤渣中再加入4000-6000ml沸水同样方法二次提取,合并两次提取液浓缩至适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可。
更进一步,该香蕉皮水提物是通过下列方法制备得到的:
成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉。在容器中取上述粉末1050g加水5000ml,加热至沸,保持微沸30-40分钟,过滤,取上清液,浓缩到适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可。
或者,成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉。在容器中取上述粉末1050g加入5000ml沸水,保温浸泡30分钟,过滤,取上清液;在滤渣中再加入5000ml沸水同样方法二次提取。合并两次提取液浓缩至适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可。
含有上述任意一种所述活性物质的组合物。
所述的组合物以香蕉皮水提物为主要活性成分,添加适当辅料。
上述任意一种所述活性物质在制备具有持续降压功能的食品、保健食品或药品中的应用。
上述组合物在制备具有持续降压功能的食品、保健食品或药品中的应用。
所述的制备方法,其中所述的液体制剂包括口服液;所述的固体制剂包括颗粒剂、片剂、胶囊剂;所述的食品包括饼干;保健品包括固体饮料等。
辅料可根据剂型的需要选择,常见的辅料有:
填充剂,如微晶纤维素,乳糖,蔗糖,甘露糖醇,麦芽糊精,葡萄糖,小麦或玉米或木薯淀粉,木糖醇,预胶化淀粉,环糊精等,
黏合剂,如单糖浆,黄原胶水溶液,聚乙烯醇水溶液,明胶水溶液,羧甲基纤维素钠水溶液等,
崩解剂,如羧甲基淀粉钠、交联羧甲基纤维素钠、交联聚维酮、羟丙纤维素、可溶性淀粉等
矫味剂,如葡萄糖、蔗糖、乳糖、甘露糖、山梨醇、三氯蔗糖,甜菊糖苷,柠檬酸,酒石酸,各种芳香剂等,
润滑剂,如硬脂酸,硬脂酸镁,滑石粉等,
防腐剂,如山梨酸及其盐,苯甲酸及其盐等,
改善吸湿性的辅料,如亮氨酸等,
制备成饼干所需的常规材料,如面粉、蛋清,大豆油,黄油,白糖,鸡蛋等。
辅料选择及制剂的常规工艺为本领域技术人员公知的技术,这里不再赘述。
本发明有效效果:
本发明提供的活性物质具有持续降压功能,与市场上绝大多数长效降压药每日一次服药仅能够控制24小时相比,本发明活性物质停药后不会出现反跳现象,仍能够持续降压,在停药后12天内,血压仍保持在较低水平,并且,本发明活性物质以香蕉皮为主要原料,成本低,副作用小,具有很好的临床应用前景。
实验采用肾性高血压大鼠模型和自发性高血压大鼠(SHR)模型评价了香蕉皮水提物对实验性高血压大鼠的降压和维持作用。实验结果显示,香蕉皮水提物对两种高血压动物模型同样具有良好的降压活性,降压幅度较大且具有长效性的特点,连续给药10天后,高、中剂量组实验动物血压下降明显,并且停药后12天内,血压仍保持在较低水平。
本发明提供的活性物质对实验性高血压大鼠具有较为明显的降压作用,并且停药后,具有较好的维持作用,而阳性药卡托普利仅具有较好的降压作用,而未发现停药后对血压的维持作用。
附图说明
图1:香蕉皮水提物对肾性高血压大鼠的治疗性降压作用。
图2:香蕉皮水提物对SHR大鼠的治疗性降压作用。
图3:香蕉皮水提物对肾性高血压大鼠的治疗性降压作用实验结果。
图4:香蕉皮水提物对SHR大鼠的治疗性降压作用实验结果。
注:1.*:P<0.05,**:P<0.01;与对照组比较
2.平均动脉压=(收缩压+2*舒张压)/3
具体实施方式
以下通过实施例对本发明作进一步的阐述。
一、制备实施例
实施例1:
配方:干香蕉皮1050g,加适量辅料。
制备工艺:
1、成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉。在容器中取上述粉末1050g加水5000ml,加热至沸,保持微沸30-40分钟,过滤,取上清液,浓缩到100ml,备用;或者上清液适当浓缩后经喷雾干燥/冷冻干燥,得到干粉。
2、取上述香蕉皮浓缩液或浓缩液干燥后粉末(相当于干香蕉皮1050g,以人每天30克计,可食用35天)加辅料,经过筛、混合、制粒、干燥、压片制成片剂(280片,每天早、晚各1次,每次4片);或者经过筛、混合、制粒、干燥、制成胶囊(280粒,每天早、晚各1次,每次4粒),或者经过筛、混合、制粒、干燥制成颗粒剂(70袋,每袋15克生药,每天早晚各1袋),即可。或者,包装成袋泡茶或散装茶,早、晚各1袋,开水冲泡后即可饮用。10天一个疗程。
实施例2:
配方:干香蕉皮1050g,加适量辅料。
制备工艺:
1、成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉。在容器中取上述粉末1050g放在容器中,加入5000ml沸水,保温浸泡30-40分钟,过滤,取上清液;滤渣再加入5000ml沸水,同样方法二次提取,再次过滤,取上清液。合并两次提取液并浓缩至500ml;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可。
2、取上述香蕉皮浓缩液(相当于干香蕉皮1050g,以人每天30克计,可食用35天),加入蜂蜜2g,黄原胶0.16g,单硬脂酸甘油酯0.16g,卡拉胶0.16g,柠檬酸0.4g,加水至700ml,搅拌混合均匀,灌装成10ml/瓶口服液,密塞、压盖、灭菌,即得(70瓶,每天早、晚各一瓶)。10天一个疗程。
实施例3
配方:干香蕉皮1050g,加适量辅料
制备工艺:
1、成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉。在容器中取上述粉末1050g加水5000ml,加热至沸,保持微沸30-40分钟,过滤,取上清液,适当浓缩后经喷雾干燥/冷冻干燥,得到干粉。
2、取浓缩液干燥后粉末(相当于干香蕉皮1050g,以人每天30克计,可食用35天),取适量茶叶粉碎成茶粉,加入适量奶粉,将干燥后的粉末与茶粉及奶粉混合均匀,包装即得香蕉皮固体饮料(70袋,每袋15g生药,早晚各一袋)。
实施例4
配方:干香蕉皮1050g,加适量辅料。
制备工艺:
1、成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉。在容器中取上述粉末1050g放在容器中,加入5000ml沸水,保温浸泡30-40分钟,过滤,取上清液;滤渣再加入5000ml沸水,同样方法二次提取,再次过滤,取上清液。合并两次提取液并浓缩至适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可。
2、取上述香蕉皮浓缩液干燥后粉末(相当于干香蕉皮1050g,以人每天30克计,可食用35天),与小麦粉、淀粉、辅料混合均匀;或直接用浓缩液与小麦粉、淀粉混合搅拌制面团;静置发酵2到4小时后,将面团放入辊轧机中切成符合要求的面带;并将面带通过冲印成型机印成饼坯。将饼坯在200到300℃条件下烘烤3到5分钟,自然冷却,即得饼干(280块,每天早、晚各4块)。
二、效果实施例
实施例、香蕉皮水提物对实验性高血压大鼠的降压作用
1.实验目的
检测香蕉皮水提物对实验性高血压大鼠的降压作用。
2.实验材料
2.1实验药物
2.1.1受试药物
名称:香蕉皮水提物(按实施例1制备)
2.1.2对照药物
名称:卡托普利(片剂)
生产厂家:江苏镇江生宝药业有限责任公司
规格:25mg/片
2.1.3对照药物
名称:山绿茶降压片(片剂)
生产厂家:广西桂林永福制药厂
规格:350mg/片
2.2剂量设置
香蕉皮水提物高剂量为10g(生药量)/kg
香蕉皮水提物低剂量为5g(生药量)/kg
山绿茶降压片为189mg/kg
卡托普利为10mg/kg(肾性高血压)
卡托普利为15mg/kg(SHR)
2.3实验仪器
BPM-II型生理压力监测仪HY-6020A/D-D/A板
HX-II型小动物血压测量器
2.4实验动物
2.4.1SD大鼠
来源、品系:中国药科大学动物饲养中心,SD大鼠
合格证:苏动(质)97004
体重:170~220g
性别:以雄性为主,兼用少量雌性
2.4.2自发性高血压大鼠(SHR)
来源、种属、品系:上海高血压病研究所,种属Wister大鼠,品系SHR
合格证:医动字第0237-1号
体重:200~270g
性别:以雄性为主,兼用少量雌性
2.4.3各组动物数:8只
2.5实验动物分组
3、实验方法
3.1二肾一夹型肾性高血压大鼠模型的制备
取健康雄性SD大鼠,体重170~220g,在乙醚麻醉下,背位固定于一泡沫塑料板上,手术器械及沙布棉花等经煮沸或105℃烘箱消毒。于动物左侧背部肾脏位置纵向剪去长2.5~3.5cm宽1.5~2cm皮肤部位毛,用碘酒及78%酒精消毒皮肤,纵向切开长2~2.5cm切口,用止血钳钝性分离肌肉暴露肾脏。然后用沙氏镊夹住肾脏并拉出体外,小心用玻璃分针找出肾动脉并分离之,在肾动脉上套一内径0.30~0.33mm的圆形铝皮小环以狭窄肾动脉,小环口用线扎住,修饰小环剪去环把,将肾脏放回体内。小心缝合肌肉和皮肤,伤口用碘酒棉球消毒并用消毒沙布包扎。术后连续三天腹腔注射青霉素2~3万单位/只·天,每天一次,以防止感染。手术后动物喂以1%盐水,连续3周,再喂0.5%盐水缓冲一周后停止喂饲盐水,约3~5天后即可测血压。首先连续测压2~3次,凡是收缩压高于170mmHg(22.7kPa)即认为已形成肾性高血压,否则淘汰动物。
3.2清醒大鼠血压测量方法
血压记录采用常用的尾动脉测压法:通过检测在不同外加压力的作用下尾动脉脉搏信号的变化,来测量清醒大鼠的收缩压(SAP)、舒张压(DAP)。使用HX-II型小动物血压测量器测血压,但由于该设备只提供加压装置(加压尾套、加压球及连接管道)及脉搏信号传感器,压力记录仪器及脉搏信号记录仪器需用户自己配置。因此,使用BPM-II型生理压力监测仪记录压力并将压力信号通过A/D卡输入计算机,脉搏信号直接经A/D卡输入计算机观察记录,脉搏及压力数据直接在计算机屏幕上测量及读数。测压时保持环境温度为20~25℃,尾部加温采用100W白炽灯定时、等距离加温,并同时监视脉搏信号的变化以便及时测压。
3.3动物给药前后反应记录
测量给药前后血压的变化,以给药前后SAP、DAP的变化作为药物对血压及心率影响的定量指标。给药前血压至少测5天以上,测压次数不少于5次。慢性治疗性给药实验,以给药前数次测压结果SAP、DAP的平均值作为给药前血压数据,然后在给药期间的1、3、5、7、10天分别记录血压,及停药后1、3、5、7、9、12天记录血压,记录给药期间及停药后血压的变化情况。血压记录时刻选择在给药后4~10小时,具体根据相应药物急性降压实验结果而定,在该药物给药后已出现明显降压并达到稳定的降压效果时记录血压。每组动物每次记录血压均尽量在相同时刻,时间差别不超过2小时。
3.4给药方法
采用灌胃(p.o.)给药方法,每天给药一次,连续给药10天。
4、实验结果
实验结果(见图1~4)显示,香蕉皮水提物给药1天后血压即明显下降,给药5天后血压已降至最低水平并处于平稳,10g/kg、5g/kg组与对照组比较有明显差异(P<0.01)。连续给药10天后停药,继续观察12天,发现停药后3天香蕉皮水提物10g/kg、5g/kg剂量组血压仍维持较低水平,与对照组相比具有极显著性差异(P<0.01)。香蕉皮水提物对SHR具有良好的降压作用,第一天给药后血压即明显下降,在自发性高血压模型中,停药后9天,10g/kg、5g/kg剂量组血压与对照组仍有明显差异(P<0.05)。阳性药卡托普利仅具有较好的降压作用,而未发现停药后对血压的维持作用。
参考文献:
[1].《中药新药研究指南》,中华人民共和国卫生部药政管理局,1999,P:65
[2].徐叔云、卞如濂、陈修主编,《药理实验方法学》(第二版),人民卫生出版社,1991:809
[3].徐叔云、卞如濂、陈修主编,《药理实验方法学》(第二版),人民卫生出版社,1991:1535
[4].BBC news:Two bananas a day keep blood pressure at bay.1999,1,28.From internet:
http://news.bbc.co.uk/hi/english/health/newsid_264000/264552.stm.
[5].《中华本草》(精选本,上册),国家中医药管理局《中华本草》编委会,上海科学出版社,1996,P:896(葛根)
[6].李定格、王世军、李以菊等,葛根素对小鼠脑微循环血流量的影响,微循环学杂志,1998(2)
[7].王世军、姬广臣、毛海燕等,葛根素、丹参注射液、川芎嗪对MCAO大鼠血浆6-keto-PGF1、TXB2、NO、ET的影响,中药药理与临床,1999,Vol.15,No.4
[8].《中华本草》(精选本,上册),国家中医药管理局《中华本草》编委会,上海科学出版社,1996,P:696(荠菜)
[9].陈奇,主编中药药理研究方法学,人民卫生出版社,1993,P:422-424
[10].同[3],P:854-859
[11].陈修黄倩霞周铁军等,枳实及其升压有效成分与多巴胺、多巴丁胺对心脏功能和血液动力学的影响的对比研究,药学学报,1980,15(2),P:71
[12].冯国鸣冯高闳周前贵,甲基橙皮甙对犬冠脉、肾、脑循环的作用,中国药理学报1988,9(6),P:548-550
[13].同[9],P:540-543
Claims (10)
1.一种具有持续降压功能的活性物质,其特征在于该活性物质为香蕉皮。
2.根据权利要求1所述的活性物质,其特征在于该活性物质为香蕉皮提取物。
3.根据权利要求2所述的活性物质,其特征在于该活性物质为香蕉皮水提物。
4.根据权利要求3所述的活性性质,其特征在于香蕉皮水提物是通过下列方法制备得到的:香蕉皮烘干,粉碎,加水煎煮或浸泡,过滤取上清液,适当浓缩成浓缩液或浓缩后干燥制成粉末即可。
5.根据权利要求4所述的活性物质,其特征在于香蕉皮水提物是通过下列方法制备得到的:
成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉,在容器中取上述粉末800-1200g加水4000-6000ml,加热至沸,保持微沸30-40分钟,过滤,取上清液,浓缩到适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可;
或者,成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉,在容器中取上述粉末800-1200g加入4000-6000ml沸水,保温浸泡20-40分钟,过滤,取上清液;在滤渣中再加入4000-6000ml沸水同样方法二次提取,合并两次提取液浓缩至适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可。
6.根据权利要求5所述的活性物质,其特征在于香蕉皮水提物是通过下列方法制备得到的:
成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉,在容器中取上述粉末1050g加水5000ml,加热至沸,保持微沸30-40分钟,过滤,取上清液,浓缩到适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可;
或者,成熟的带麻点的香蕉取皮,皮在60-80度烘箱中烘干,粉碎成粗粉,在容器中取上述粉末1050g加入5000ml沸水,保温浸泡30-40分钟,过滤,取上清液;在滤渣中再加入5000ml沸水同样方法二次提取,合并两次提取液浓缩至适宜体积;或者上清液适当浓缩后经喷雾干燥/冷冻干燥制成粉末即可。
7.含有权利要求1~6任意一种所述活性物质的组合物。
8.根据权利要求7所述的组合物,其特征在于该组合物以香蕉皮水提物为主要活性成分,添加适当辅料。
9.权利要求1~6任意一种所述活性物质在制备具有持续降压功能的食品、保健食品或药品中的应用。
10.权利要求7所述组合物在制备具有持续降压功能的食品、保健食品或药品中的应用。
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