CN105497011A - 一种航天员专用茶氨酸及表没食子儿茶素没食子酸酯制剂 - Google Patents
一种航天员专用茶氨酸及表没食子儿茶素没食子酸酯制剂 Download PDFInfo
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- CN105497011A CN105497011A CN201510981137.4A CN201510981137A CN105497011A CN 105497011 A CN105497011 A CN 105497011A CN 201510981137 A CN201510981137 A CN 201510981137A CN 105497011 A CN105497011 A CN 105497011A
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Abstract
本发明涉及一种航天员专用茶氨酸及表没食子儿茶素没食子酸酯制剂，该制剂由下列原料组成：茶氨酸、表没食子儿茶素没食子酸酯、山梨糖醇、木糖醇、硬脂酸镁。本发明提供的制剂便于携带、安全性好、服用方便，具有较好的抗辐射、改善记忆力、镇静、保护脑神经细胞、降血压、提高免疫力、抗氧化作用。可以一定程度上降低空间失重环境对宇航员造成的心理生理应激效应，适合在航天环境下食用。
Description
技术领域
本发明涉及一种制剂配方，特别涉及一种针对航天员在空间飞行期间，由于空间环境引发心理生理应激问题而研发的制剂配方及生产工艺。
背景技术
近些年来，随着航天事业的发展，人们逐渐意识到外太空环境对人体生命活动的影响。宇航员在外太空复杂特殊的环境下会引起一系列适应性生理变化。这些生理变化在短时间或长时间会引起病理改变，从而对宇航员的健康造成严重威胁。为了确保宇航员的身体健康以及太空探索任务的圆满成功，对宇航员在完成任务前后的治疗与保养就成了各国航天医学领域研究的热点。载人飞船远离地球，与社会完全隔绝，飞船座舱环境狭小，航天员的活动受到限制。长期在这样的环境中生活，可能会导致严重的心理障碍，如厌烦、不安、焦虑、睡眠障碍、抑郁、头痛和易激怒等。另外微重力条件下航天员血液系统会发生改变，主要表现在血浆容量、红细胞生成素的减少和红细胞质量的降低。航天员在经过3个月的航天飞行之后，其血液内的红细胞数量会减少大约15%。此外，航天员的免疫系统也会发生变化，在返回地面后，宇航员血液内的白细胞(主要是中性白细胞)增多，而淋巴细胞和嗜酸性白细胞减少。除上述因素外，宇宙射线等空间辐射作用也是太空环境下对航天员身体伤害的重要原因之一。在载人航天活动中，由于没有地球磁场和稠密大气层的保护，宇航员受到的来自外层空间电离辐射及非电离辐射的影响很大。地球磁场的防护也随着飞行轨道远离地球而逐渐减弱。辐射对航天员的伤害主要是免疫系统、中枢神经系统损伤及造血功能障碍，并可诱发癌症。而且航天员是处在失重与辐射双重因素，甚至多重因素复合作用的影响，情况更加复杂。因此尽快找到切实有效的防护措施，成为当前重力生理学和航天医学面临的重要课题之一。本发明品由茶氨酸、表没食子儿茶素没食子酸酯及辅料组成，有便于携带、安全性好、服用方便，具有较好的改善记忆力、镇静、保护脑神经细胞、降血压、提高免疫力、抗氧化作用。可以一定程度上降低空间失重环境对宇航员造成的心理生理应激效应，适合在航天环境下食用。
发明内容
本发明的目的是提供一种航天员专用的茶氨酸及表没食子儿茶素没食子酸酯复合制剂，主要原料由茶氨酸及表没食子儿茶素没食子酸酯组成。
为了实现本发明的目的，一种航天员专用茶氨酸及表没食子儿茶素没食子酸酯制剂，该制剂由下列原料组成：茶氨酸、表没食子儿茶素没食子酸酯、山梨糖醇、木糖醇、硬脂酸镁。该制剂的组分原料重量比如下：
茶氨酸30%～50%
表没食子儿茶素没食子酸酯20%～30%
山梨糖醇15%～38%
木糖醇10%～20%
硬脂酸镁0.1%～1.5%
优选的为：
茶氨酸40%
表没食子儿茶素没食子酸酯25%
山梨糖醇24%
木糖醇10%
硬脂酸镁1%
具体生产工艺如下：
将茶氨酸、表没食子儿茶素没食子酸酯按一定原料比例置入搅拌机混匀，在混合过程中，用40～80％的食用乙醇以细雾状喷洒造粒，过10～60目筛，60～90℃下烘干，然后按比例加入山梨糖醇、木糖醇、硬脂酸镁充分混匀，压成一定规格的片剂。
本发明提供的一种航天员专用的茶氨酸及表没食子儿茶素没食子酸酯复合制剂，主要成分茶氨酸的生理功能如下：
1）神经保护
茶含有具有兴奋作用的咖啡因，然而，茶氨酸是咖啡因的拮抗物，可用于抑制咖啡因引起的兴奋作用。以大脑中动脉堵塞模型的小鼠进行实验表明：腹腔内注射茶氨酸(1mg/kg)/d后，可以使脑梗塞体积显著缩小，但脑血流、脑温度，血氧分压、二氧化碳分压和血球密度不受影响。
2）镇静、提高记忆力
L-茶氨酸能够显著提高D-半乳糖诱导的亚急性衰老小鼠机体组织SOD活性和乙酰胆碱酯酶活性，降低MDA含量，从而降低脂质过氧化，促进中枢胆碱系统的功能，达到提高记忆力，延缓衰老的目的。动物实验表明：茶氨酸对记忆力和学习能力产生正面的影响。研究发现老鼠服用茶氨酸3～4个月后，学习能力提高，能在较短时间内掌握要领，对危险环境的记忆力比对照群强。目前很多研究证明茶氨酸的这种提高学习和记忆能力的作用是来自活化中枢神经递质的结果。经期综合症(PMS)是女性在月经前3～10d中出现的精神及身体上不舒适症状，研究人员让24名女性每日服用茶氨酸200mg两个月后，经期综合症（PMS）症状如头痛、腰痛、胸部胀痛、无力、易疲劳、精神无法集中、烦躁等症状得到改善。
3）降血压
茶氨酸可通过调节脑中神经递质的浓度来发挥降血压作用。降低血压的调节主要依靠儿茶酚胺和5-羟色胺，茶氨酸可以降低5-羟色胺的含量。以自发性高血压大鼠试验表明：注射谷氨酸(2.0g／kg)对血压没有明显影响，但注射谷酰胺甲胺和茶氨酸(谷酰胺乙胺)则有明显的降低血压作用。将茶氨酸溶解在生理盐水中，投饲给高血压鼠群，一小时后可见对高血压鼠群血压有明显降低作用，对正常血压鼠群无影响。同时实验也证明：茶氨酸对大脑血清素的合成和分解也能产生影响，能够降低血清素的合成及增加其分解，或抑制其释放，服用茶氨酸后，大脑中的血清素含量明显降低。
4）抗肿瘤
茶氨酸被广泛用于抗肿瘤，它能提高多种抗肿瘤药物疗效。茶氨酸能够提高树突状细胞刺激T淋巴细胞增殖的能力。茶氨酸可以显著抑制肝细胞瘤性腹水细胞系中AH109A细胞侵入小鼠单层肠系膜间皮细胞的能力，但是茶氨酸并不能抑制AH109A细胞增殖。茶氨酸不仅可以抑制肝癌细胞的浸润，对其他癌细胞同样也具有抑制浸润的作用。茶氨酸的直接抗癌活性使得它在癌症治疗中的应用更加广泛。
5）抗疲劳
茶氨酸具有延缓运动性疲劳作用，其机制与茶氨酸增加脑组织中多巴胺含量，抑制5-羟色胺的合成和释放等效应有关。茶氨酸能明显延长小鼠负重游泳时间，减少肝糖原的消耗，降低运动时血清尿素氮水平，对小鼠运动后血乳酸升高有明显的抑制作用，能促进运动后血乳酸的消除。
主要成分表没食子儿茶素没食子酸酯的生理功能如下：
1）抗氧化活性作用
抗氧化作用是茶多酚类物质所具有的重要功能之一，作为食品添加剂被广泛使用，表没食子儿茶素没食子酸酯是几茶素中抗氧化作用最强的一种成分，大量动物实验和临床实践己证明表没食子儿茶素没食子酸酯具有多种作用。表没食子儿茶素没食子酸酯属非酶抗氧化剂，其很强的抗氧化能力可以清除体内自由基，延缓机体的衰老。生物体内许多氧化酶与自由基的生成有关，如黄嘌呤氧化酶系、髓过氧化酶、脂氧化酶和环氧酶。研究表明：表没食子儿茶素没食子酸酯对上述氧化酶均有抑制作用。
2）抗肿瘤活性作用
肿瘤是当今世界危害人类健康最常见且最严重的疾病，细胞由于癌变进行恶性增殖产生肿瘤。表没食子儿茶素没食子酸酯对多种肿瘤癌细胞增殖的抑制均有明显的效果。已有研究表明，表没食子儿茶素没食子酸酯能够直接强烈地下调端粒酶活性，诱导肿瘤细胞凋亡。端粒酶是一种由RNA和蛋白质构成的一种特殊的逆转录酶，与细胞衰老、永生化和肿瘤发生发展的关系密切，是肿瘤治疗的较理想靶点。且研究发现只需要表没食子儿茶素没食子酸酯在较低浓度(非细胞毒性浓度)时即会对端粒酶活性有很强的抑制作用。除此之外，表没食子儿茶素没食子酸酯对肿瘤癌细胞的抑制还可以通过以下几个途径来实现：干扰细胞的信号通路系统和影响细胞周期、与细胞内的蛋白质分子的结合。
3）抗病毒和抗毒性的活性作用
表没食子儿茶素没食子酸酯具有抗病毒以及抗毒性的功效。
4）保护神经系统机制的活性作用
近年来，由于环境污染加剧、生活节奏加快和社会竞争日益剧烈，导致人们精神状态紧张而致使神经性疾病的呈上升趋势发生。而许多研究表明，表没食子儿茶素没食子酸酯在保护和治疗神经性疾病方面有较好的作用。脑组织中一种重要酶类单胺氧化酶B，能够引起脑组织脂质过氧化加剧，而表没食子儿茶素没食子酸酯能够组织特异性的抑制该酶的活性。目前大量研究表明表没食子儿茶素没食子酸酯能够保护神经退行性疾病(阿尔茨海默病、帕金森病症等)中神经元免受损伤。中枢神经系统疾病发生时，表没食子儿茶素没食子酸酯能够通过降低细胞活性氧和调节凋亡信号分子表达起到抑制细胞凋亡的目的，从而保护神经系统。
5）保护心脑血管的活性作用
脑的短暂性血液供应不足并出现症状就叫做短暂性脑缺血发作，是一种常见的急性脑血管病。缺血性中风以其高发病率、高致残率、高死亡率对人类危害极大。表没食子儿茶素没食子酸酯能够降低小肠中胆固醇的溶解度及小肠吸收胆固醇的程度，阻碍胆固醇进入血液循环，降低血液中胆固醇的浓度，从而预防心脑血管系统疾病的发生。通过实验可知，缺血组大鼠脑组织兴奋性氨基酸及钙离子含量明显增加，表没食子儿茶素没食子酸酯保护机制与抑制兴奋性氨基酸的产生及通过钙抗作用有关，从而阻止钙超载引起的一系列损伤神经元的生化反应、基因表达等级联反应，对神经元起到保护。
本发明运用茶氨酸及表没食子儿茶素没食子酸酯两种有效成分组合，相互协同，可以一定程度上降低空间失重环境对宇航员造成的心理生理应激效应，适合在航天环境下食用。本制剂便于携带、安全性好、服用方便。
具体实施方式：
本实施例片剂的原料如下：
茶氨酸40%
表没食子儿茶素没食子酸酯25%
山梨糖醇24%
木糖醇10%
硬脂酸镁1%
将茶氨酸及表没食子儿茶素没食子酸酯按一定原料比例置入搅拌机混匀，在混合过程中，用60%的食用乙醇以细雾状喷洒造粒，过20目筛，80℃下烘干，然后按比例加入山梨糖醇、木糖醇、硬脂酸镁充分混匀，压成重1克的片剂，每日1-2片。
用该制剂进行动物试验：
试验1
试验目的：研究航天茶氨酸EGCG复合片对小鼠H22肝癌生长及抗氧化作用的影响。
试验方法：给予荷瘤鼠喂饲2O、40、80mg/kg/d航天茶氨酸EGCG复合片，阳性对照组小鼠腹腔注射20mg/kg/d5-氟尿嘧啶(5-Fu)，并设空白及模型对照组，2周后处死动物，无菌条件下取肿瘤、脾和胸腺，称重，计算抑瘤率及脏器指数。以试剂盒测定各组小鼠血浆中丙二醛(MDA)含量及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH—Px)的活力，进行统计学分析。
试验结果：航天茶氨酸EGCG复合片各剂量组小鼠H肿瘤生长速度较模型组缓慢(p＜0.05)，在一定范围内与剂量呈正相关，低、中、高三剂量组的抑瘤率分别为25.572%、35.367%、44.52%；航天茶氨酸EGCG复合片各剂量组的胸腺指数上升，与模型组及5-Fu对照组均有显著性差异(p＜0.05)；航天茶氨酸EGCG复合片各剂量组的脾指数上升，与模型组之间显著性差异(p＜0.05)，中、高剂量航天茶氨酸EGCG复合片组与5-Fu组之间脾指数有显著性差异(p＜0.05)；与模型组比较，航天茶氨酸EGCG复合片各剂量组及5-Fu组对照组小鼠血浆中MDA的含量明显降低，S0D、GSH—Px活力明显升高，差异有统计学意义(p＜0.05)。
试验结论：航天茶氨酸EGCG复合片各剂量组能较好的抑制H22小鼠肿瘤增长，具有较高的体内抑瘤活性；航天茶氨酸EGCG复合片具有良好的抗氧化作用。
试验2
试验目的：从对自由基代谢影响方面探讨航天茶氨酸EGCG复合片对脑缺血损伤的保护作用机制。
试验方法：选用30只SD雄性大鼠，线栓阻塞大鼠大脑中动脉制备局灶性脑缺血模型，观察脑缺血损伤大鼠神经症状改变，测定脑组织含水量、脑组织病理及钙离子含量；观察其血清和脑组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量变化以及航天茶氨酸EGCG复合片对上述变化的影响。
试验结果：脑缺血组大鼠的神经症状评分、脑组织含水量及钙离子含量均显著增高．病理损伤明显，正常神经元细胞数目减少；航天茶氨酸EGCG复合片可显著降低神经症状评分、脑组织含水量及钙离子含量。增加正常神经元细胞数目。脑缺血组大鼠的血清、脑组织SOD活性显著降低，航天茶氨酸EGCG复合片组大鼠血清、脑组织SOD活性较脑缺血组显著增高；脑缺血组大鼠的血清、脑组织MDA含量显著增高，航天茶氨酸EGCG复合片组脑组织MDA含量较脑缺血组下降明显。
试验结论：航天茶氨酸EGCG复合片对大鼠脑缺血损伤具有显著的保护作用。
试验3
试验目的：观察航天茶氨酸EGCG复合片对血管性痴呆（VD）小鼠学习记忆力及脑内淀粉样前体蛋白（APP）、β-分泌酶（BACE）及tau蛋白表达的影响。
试验方法：60只健康小鼠,随机分成6组,每组10只。除对照组外,其余5组小鼠给予高脂食物灌胃、颈动脉局部缺血及再灌注手术,建立VD小鼠模型,随后分别灌胃生理盐水（模型组）、0.3g/kg脑复康（脑复康组）和20、40和80mg/（kg·d）的航天茶氨酸EGCG复合片（低、中及高剂量航天茶氨酸EGCG复合片组）,1次/d,共15d。用跳台试验检测小鼠的学习和记忆能力,免疫组化法测定脑组织APP、BACE及tau蛋白的表达。
试验结果：6组小鼠学习能力跳台实验错误次数及受电击时间、记忆能力跳台实验错误次数及受电击时间及脑组织APP、BACE及tau蛋白表达差异均有统计学意义（F分别为6.544、2.991、11.179、6.100、484.218、59.317和40.448,P均＜0.01）。与模型组相比,低、中剂量航天茶氨酸EGCG复合片组小鼠学习及记忆能力提高（P＜0.05）。3个航天茶氨酸EGCG复合片组APP及BACE表达水平降低（P＜0.05）,低、中剂量航天茶氨酸EGCG复合片组与对照组比较,tau蛋白表达水平差异无统计学意义（P＞0.05）。
试验结论：适宜剂量的航天茶氨酸EGCG复合片可通过降低VD小鼠脑内APP和BACE的水平,改善其学习记忆力。
试验4
试验目的：观察航天茶氨酸EGCG复合片对小鼠的镇静催眠作用。
试验方法：将小鼠随机分为空白对照组、地西泮组、航天茶氨酸EGCG复合片高、低剂量组。连续灌胃14d后，以自发活动测试仪测定小鼠的自发活动，并进行睡眠功能性评价试验。
试验结果：与空白组相比，高剂量、低剂量航天茶氨酸EGCG复合片均可极显著减少小鼠的自发活动次数(P＜0.01)，但未出现睡眠现象；高剂量、低剂量航天茶氨酸EGCG复合片能延长注射戊巴比妥钠小鼠的睡眠时间，但与空白组相比无显著性差异；高剂量、低剂量航天茶氨酸EGCG复合片均能显著增加戊巴比妥钠阈下剂量作用下小鼠的入睡率，入睡小鼠的睡眠时间也有所延长，但与空白组入睡小鼠的睡眠时间比较，没有显著性差异；高剂量、低剂量航天茶氨酸EGCG复合片均能缩短巴比妥钠催眠下小鼠的睡眠潜伏期，并且高剂量组与空白组相比差异显著(P＜0.05)。
试验结论：航天茶氨酸EGCG复合片有明显的镇静催眠作用。
Claims (2)
1.一种航天员专用的茶氨酸及表没食子儿茶素没食子酸酯复合制剂，其特征在于：是以茶氨酸及表没食子儿茶素没食子酸酯为主要原料，辅以山梨糖醇、木糖醇、硬脂酸镁制成的口服片剂。
2.根据权利要求1的一种航天员专用的茶氨酸及表没食子儿茶素没食子酸酯复合制剂，其特征在于：该制剂的组分原料重量比如下：
茶氨酸30%～50%
表没食子儿茶素没食子酸酯20%～30%
微晶纤维素15%～30%
山梨糖醇15%～38%
木糖醇10%～20%
硬脂酸镁0.1%～1.5%。
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| CN107252112A (zh) * | 2017-06-08 | 2017-10-17 | 杭州茗朗生物科技有限公司 | 一种含egcg的片剂 |
| CN108743728A (zh) * | 2018-08-20 | 2018-11-06 | 江西佳家易购实业有限公司 | Egcg茶氨酸三七片及其制备工艺 |
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| CN107252112A (zh) * | 2017-06-08 | 2017-10-17 | 杭州茗朗生物科技有限公司 | 一种含egcg的片剂 |
| CN108743728A (zh) * | 2018-08-20 | 2018-11-06 | 江西佳家易购实业有限公司 | Egcg茶氨酸三七片及其制备工艺 |
| CN113499449A (zh) * | 2021-08-24 | 2021-10-15 | 湖南农业大学 | 具协同增效作用的EGCG+L-茶氨酸/β-环糊精包合物及其制备方法与应用 |
| CN113499449B (zh) * | 2021-08-24 | 2022-05-27 | 湖南农业大学 | 具协同增效作用的EGCG+L-茶氨酸/β-环糊精包合物及其制备方法与应用 |
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| CN115778940A (zh) * | 2022-07-12 | 2023-03-14 | 湖南农业大学 | 用于促进神经细胞修复与再生的egcg与l-茶氨酸组合剂及其应用 |
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