CN101353380A - 霞水母来源有免疫增强活性的胶原蛋白肽及制备和应用 - Google Patents
霞水母来源有免疫增强活性的胶原蛋白肽及制备和应用 Download PDFInfo
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Abstract
本发明属天然生物活性物质领域,具体涉及一种霞水母来源的具有免疫增强活性的胶原蛋白肽及其制备工艺和应用。该霞水母来源的胶原蛋白肽含有80~90%的蛋白质,10~20%的糖,该胶原蛋白肽的平均分子量在1,000~3,000之间。所含单糖以葡萄糖为主,所含氨基酸中甘氨酸占16%以上,脯氨酸与羟脯氨酸之和占18%以上。该胶原蛋白肽应用于制备具有免疫增强功能的药品、保健品或护肤美容用品,效果显著,无明显毒副作用。
Description
技术领域
本发明涉及一种霞水母来源有免疫增强活性的胶原蛋白肽及制备和应用,属天然生物活性物质领域。
背景技术
霞水母(Cyanea nozakii),俗称麻蜇,是一种大型海洋浮游生物,属刺胞动物门(Phylum Cnidaria),钵水母纲(Class Scyphomedusae),旗口水母目(Order Phylum cnidaria),霞水母科(Family Cyanea)。我国沿海已发现的有白色霞水母(Cyanea nozaki Kishinouye)、发形霞水母(Cyanea capillata)、棕色霞水母(Cyanea ferrugineaEschscholtz),和紫色霞水母(Cyanea purpurea Kishinouye)4个种,其中以白色霞水母数量最多、分布范围最广。霞水母通常以小型浮游动物为饵,其生殖腺发达,繁殖能力强,生长速度极快,目前我国霞水母的年产量已经高达千万吨,构成了一种新的天然海洋生物资源。
海洋来源的多糖、蛋白聚糖和胶原蛋白肽是十分重要的天然海洋食品资源,常常具有显著的生物活性,如海参多糖、海藻多糖等均有许多的研究报道,证实其具有显著的生物活性。以霞水母为原料,从中分离提取制备胶原蛋白肽的研究报道国内外尚很少见,迄今未见有从中分离提取具有免疫增强活性的胶原蛋白肽的报道。
发明内容
本发明发明了一种霞水母来源的具有免疫增强活性的胶原蛋白肽及其制备工艺和应用。较为独特的是,它以一种新型的天然海洋生物资源-霞水母(Cyanea nozakii)-作为胶原蛋白肽的制备原料进行加工,实现了对霞水母进行开发利用的目的。按照本发明进行操作,能够以极高的产率获得高纯度胶原蛋白肽产品。这对于霞水母这一天然海洋生物资源的综合利用而言是至关重要的。
本发明发明的霞水母活性胶原蛋白肽经初步的研究确认,基本无毒,具有显著的免疫增强活性,将作为新型的生物活性材料和保健食品原料被广泛应用于食品、保健品、护肤美容用品和医药用品等领域。
具体来说,首先,我们发现新鲜的或经过三矾腌制处理的市售麻蜇可以在经过脱盐处理之后用作胶原蛋白肽的制备原料。其中所含的胶原蛋白肽对水浸泡处理是稳定的,在我们所采取的浸泡工艺条件下,既不会因受到浸泡而被降解、被提取到水中流失,也不会因受过浸泡而影响其在后续的水解处理中的分散性,即经过三矾腌制处理的市售麻蜇与刚捕捞上岸的新鲜的霞水母具有同等的可加工性,均可用作制备高纯度高生物活性胶原蛋白肽的原料。由此奠定了以霞水母为原料加工制备高纯度高生物活性胶原蛋白肽的基础。
其次,在对温度、压力等水解条件以及氢氧化钠、盐酸、胶原蛋白酶等各种常用的溶融剂进行了***的考察和对比后,我们发现,在适当的水解条件下,霞水母中所含有的胶原蛋白不经过变性处理,便可直接被水解,分散到水中,得到澄清透明,所含杂质很少的水解分散液。
我们发现,在浸泡溶剂、浸泡时间、水解剂等水解工艺参数中,水解剂的种类和水解时所采用的温度对于水解得率而言是最为重要的。其中,有效的溶融剂为常见的碱(如钠、钾、钙、钡的氢氧化物或碳酸盐、氨水等)、常见的酸(如盐酸、磷酸、硫酸等无机酸或甲酸、醋酸、苹果酸、乳酸、柠檬酸等有机酸)或各种蛋白酶(如胃蛋白酶、胰蛋白酶、胰糜蛋白酶、酸性蛋白酶、碱性蛋白酶、中性蛋白酶、木瓜蛋白酶、菠萝蛋白酶、胶原蛋白酶、弹性蛋白酶等)中的一种或若干种。当选用氢氧化钠为溶融剂时,pH值应当在7.0-14.0范围之内,当选用盐酸为溶融剂时,pH值应当在0.5-6.8范围之内,当选用蛋白酶类为溶融剂时,pH值应当在所选酶的最适pH范围之内;当选用酸碱为溶融剂时,融溶温度应当在10-120℃范围内,最好是在0-60℃的范围内,当选用蛋白酶类为溶融剂时,应当在蛋白酶类的最适温度下进行水解。其他各项参数,浸泡应在pH调节为2-12范围内某一定值,最好是在6.5~6.8,的水中进行,浸泡温度在0~98℃范围内,最好是在0~15℃的范围内,浸泡操作进行至浸泡水的电导率低于30μScm-1停止。离心分离在0~120℃,最好是在0~10℃条件下进行,离心机的转速在4000~12000rpm之间,最好是在6000~8000rpm之间,离心时间为10~60min。液体的干燥方式,可以是冷冻干燥,也可以是喷雾干燥。
具体实施方式
下面的实例将具体说明本发明的操作方法,但不能作为对本发明的限定。
实例一
取1000g三矾腌制处理的市售麻蜇,沥水后,室温下浸没于2-5倍量的去离子水中浸泡,并每2-3小时换一次水,直至浸泡水中氯化钠的含量低于1.5ppm(氯离子检测呈阴性),浸泡水的电导率低于30μScm-1为止。浸泡后的脱盐霞水母添加活力为4000Units的胰蛋白酶10g,在30-60℃下保温溶融4-24小时,得到一悬浮液。然后离心(4℃,8000rpm,30min),弃去不溶性残渣,得到澄清透明的液体,即为胶原蛋白肽液;胶原蛋白肽液置旋转蒸发仪上,40℃,0.001MPa下浓缩至原体积的1/5后喷雾干燥(进风温度185℃,出风温度85℃),得到20g纯度达到90%以上的具有显著的免疫增强活性的胶原蛋白肽粉固体。
实例二
取100kg新鲜霞水母,3~10℃下浸没于2-5倍量的去离子水中浸泡,并每2-3小时换一次水,直至浸泡水的电导率低于30μScm-1为止。浸泡后的脱盐霞水母添加500g复合酶制剂(由市售胰蛋白酶、木瓜蛋白酶、胶原蛋白酶和中性蛋白酶按照1∶1∶1∶1的配比组成),在35~50℃下保温处理8-16小时,然后在4℃,8000rpm下离心30min。弃去不溶性残渣,得到澄清透明的液体,即为胶原蛋白肽液;胶原蛋白肽液在40℃,0.001MPa下浓缩至原体积的1/2后冷冻干燥,得到1000g纯度达到95%以上的具有显著的免疫增强活性的胶原蛋白肽粉固体。
实例三
对一份胶原蛋白肽粉样品进行了蛋白含量的测定,总糖含量的测定,氨基酸组成的测定以及单糖组成的测定。测定结果表明,该样品中含88%的蛋白质,10.5%的糖,平均分子量为1274。所含单糖以葡萄糖为主,所含氨基酸的组成见表1。
表1供试样品的氨基酸组成
实例四
以健康昆明种小白鼠(雌雄各半,4周龄,体重18-22g,由无锡市惠山江南实验动物场提供【批准号:SCXK(苏)2002-0006】)为实验动物,对所得到的胶原蛋白肽粉进行急性毒性试验,所得结果见表2和表3。
表2供试样品对小鼠体重的影响
表3急性毒性实验结果
通过观察,给药后1h内小鼠活动均减少,4h后逐渐恢复正常活动。试验组7d内进食量逐渐增加,且小鼠食欲、精神、毛色均正常;7d后,脱颈处死,肉眼尸检未见心、肝、脾、肺、肾等主要脏器病变和中毒现象。观察期7d内每天称重,试验组小鼠的体重不断增加。研究结果表明,在供试样品大剂量灌胃的情况下,未出现小鼠死亡,也未有明显毒性反应。说明其无毒性或毒性很小,其最大安全剂量在7500mg/Kg以上。
实例五
以健康昆明种小白鼠(雌雄各半,4周龄,体重18-22g,由无锡市惠山江南实验动物场提供【批准号:SCXK(苏)2002-0006】)为实验动物,对所得到的胶原蛋白肽进行免疫增强测试,所得结果见表4~6。
1小鼠血清溶血素测定
表4供试样品对小鼠血清溶血素的影响
方差分析,P<0.05;与对照组比较*P<0.05
溶血素(IgM)是反映体液免疫功能状况的一种方法,如果用药后溶血素生成增多,则出现红细胞溶血时的吸光度值增高,表明用药后机体的体液免疫作用增强。由表4结果可知,高剂量组与空白对照組比较,差异有显著性(P<0.05),低剂量组、中剂量组与对照组比较无差异性(P>0.05),这说明,高剂量供试样品对血清溶血素(IgM)的生成有十分明显的影响,表现出较好的体液免疫增强作用。
2小鼠迟发型超敏反应(DTH)测定
表5供试样品对小鼠迟发型超敏反应的影响
方差分析,P<0.01;与对照组比较**P<0.01
迟发型超敏反应是反映细胞免疫功能状况的一种方法,由表5可知,试验组的小鼠左右耳廓片重量之差与对照组比较均有增加,中剂量组与空白对照組比较差异有高度显著性(P<0.01),其中低剂量组和高剂量组与对照组比较无显著性差异(P>0.05)。表明供试样品在一定浓度范围内能显著提高小鼠细胞免疫功能。
3小鼠吞噬细胞吞噬功能测定
表6供试样品对小鼠吞噬细胞吞噬功能的影响
方差分析,P<0.01;与对照组比较*P<0.05;**P<0.01
吞噬细胞吞噬功能是反映非特异性免疫功能状况的一种方法,由表6可知,中剂量组与高剂量组与对照组比较吞噬百分率有显著性差异(P<0.05),中剂量组与高剂量组与对照组比较吞噬指数有高度显著性差异(P<0.01),低剂量组与对照组比较无差异(P>0.05),说明一定剂量的供试样品能激活吞噬活性,提高单核吞噬细胞***的吞噬功能。
免疫增强实验结果表明一定剂量的供试样品对小鼠体液免疫功能,细胞免疫功能和单核-巨噬细胞功能都有一定的增强作用。
根据功能学评价检验方法,在细胞免疫功能、体液免疫功能、单核-巨噬细胞功能、NK细胞活性四个方面任两个方面结果阳性,可判定该受试样品具有增强免疫力功能作用。本实验在实验小鼠细胞免疫功能、体液免疫功能、单核-巨噬细胞功能三个方面结果阳性,因此可判定供试样品具有免疫增强作用。
Claims (9)
1.一种霞水母来源的具有免疫增强活性的胶原蛋白肽,其特征在于外观为白色或淡黄色,无嗅,略带苦味的粉末,自霞水母科海洋生物白色霞水母(Cyanea nozaki Kishinouye)、发形霞水母(Cyanea capillata)、棕色霞水母(Cyanea ferruginea Eschscholtz)或紫色霞水母(Cyanea purpurea Kishinouye)的新鲜捕捞品或其经过三矾腌制的腌制品中分离提取得到,无毒,具有显著的免疫增强活性,其中含有80~90%的蛋白质,10~20%的糖,平均分子量在1,000~3,000之间。所含单糖以葡萄糖为主,所含氨基酸中甘氨酸占16%以上,脯氨酸与羟脯氨酸之和占18%以上。
2.权利要求1所述的胶原蛋白肽的制备工艺。该工艺由下列步骤组成:
(1)将霞水母用水浸泡;
(2)对浸泡后的霞水母进行溶融处理,然后离心分离,得到无色或淡黄色的上清液;
(3)将上清液直接干燥或经过均质、脱色、脱盐处理后干燥,得到白色或浅黄色的粉末,即为胶原蛋白肽。
3.如权利要求2所述的胶原蛋白肽的制备工艺,其特征在于将霞水母在pH调节为2-12范围内某一定值的水中浸泡至浸泡水的电导率低于30μScm-1为止,浸泡温度在0~98℃范围内。
4.如权利要求2所述的胶原蛋白肽的制备工艺,其特征在于所述的溶融处理指采用溶融剂将霞水母融化于水中形成液体。
5.如权利要求4所述的胶原蛋白肽的制备工艺,其特征在于所述的溶融剂为碱、酸或各种蛋白酶中的一种或几种混合。
6.如权利要求5所述的胶原蛋白肽的制备工艺,其特征在于所述的碱为钠、钾、钙、钡的氢氧化物或碳酸盐、氨水,浓度为0.1~10molL-1;所述的酸为盐酸、磷酸、硫酸、甲酸、醋酸、苹果酸、乳酸或柠檬酸,浓度为0.1~10molL-1;所述的蛋白酶为胃蛋白酶、胰蛋白酶、胰糜蛋白酶、酸性蛋白酶、碱性蛋白酶、中性蛋白酶、木瓜蛋白酶、菠萝蛋白酶、胶原蛋白酶或弹性蛋白酶。
7.如权利要求4所述的胶原蛋白肽的制备工艺,其特征在于所述的溶融处理在pH 0.5~14.0,温度10~120℃,操作压力0.0001~0.5MPa条件下进行。
8.如权利要求2所述的胶原蛋白肽的制备工艺,其特征在于所述的干燥为冷冻干燥或喷雾干燥。
9.权利要求1所述的胶原蛋白肽在具有免疫增强功能的药品、保健品、护肤美容用品的制备中的应用。
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US12/993,819 US8450100B2 (en) | 2008-05-20 | 2008-09-17 | Collagen peptide having immune-enhancing activity from Cyanea nozakii and preparation method and uses thereof |
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JP2011509839A JP2011520927A (ja) | 2008-05-20 | 2008-09-17 | ユウレイクラゲ由来で免疫増強活性を有するコラーゲンペプチド及びその調製と使用 |
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CN111995671A (zh) * | 2020-09-07 | 2020-11-27 | 青海瑞肽生物科技有限公司 | 一种胶原蛋白肽及其应用 |
CN111995671B (zh) * | 2020-09-07 | 2023-06-20 | 青海瑞肽生物科技有限公司 | 一种胶原蛋白肽及其应用 |
CN113318003A (zh) * | 2021-04-08 | 2021-08-31 | 海臻(上海)生物科技有限公司 | 一种水母多肽及其应用 |
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US8450100B2 (en) | 2013-05-28 |
US20110077382A1 (en) | 2011-03-31 |
WO2009140833A1 (zh) | 2009-11-26 |
JP2011520927A (ja) | 2011-07-21 |
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