CN116407637A - 5-羟色胺3受体拮抗剂和芳香物质的组合物及其制备方法 - Google Patents
5-羟色胺3受体拮抗剂和芳香物质的组合物及其制备方法 Download PDFInfo
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- CN116407637A CN116407637A CN202111649552.1A CN202111649552A CN116407637A CN 116407637 A CN116407637 A CN 116407637A CN 202111649552 A CN202111649552 A CN 202111649552A CN 116407637 A CN116407637 A CN 116407637A
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- hydroxytryptamine
- receptor antagonist
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- aromatic substance
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Abstract
一种包含5‑羟色胺3受体拮抗剂和芳香物质的组合物,以5‑羟色胺3受体拮抗剂和芳香物质作为主要物质,一种或者多种药物能接受的赋形剂和调味剂为辅料制成组合物,用于口服缓解恶心呕吐。根据权利要求1所述的5‑羟色胺3受体拮抗剂为昂丹司琼、格拉司琼、托烷司琼、帕洛诺司琼中的一种,所述的芳香物质包括生姜、留兰香、薄荷、柠檬、薰衣草、佛手柑、甜橙和豆蔻等中的一种或一种以上混合物。根据权利要求1所述的5‑羟色胺3受体拮抗剂和芳香物质的组合物,在不影响药理活性的同时,与芳香物质发生协同作用,用于缓解化疗、放疗或术后恶心呕吐等不良反应,提高5‑羟色胺3受体拮抗剂的治疗效果,提高治疗效果,改善患者情绪。
Description
技术领域
本发明涉及一种5-羟色胺3受体拮抗剂和芳香物质的组合物,以及包含5-羟色胺3受体拮抗剂和芳香物质的组合物的制备方法。以5-羟色胺3受体拮抗剂和芳香物质作为主要成分,发挥协同作用,用于缓解化疗、放疗或术后恶心呕吐等不良反应,改善患者情绪。
背景技术
癌症作为威胁人类健康的重大疾病之一,越来越受到广泛关注。目前对于癌症,化疗、放疗、手术是目前最主要的治疗方法,但由于化疗、放疗引起的一系列副作用影响着患者的生活质量及后续治疗,特别是化疗、放疗、手术后恶心呕吐,是患者中最常见、最令患者担忧的不良反应之一,发生率高达80%~90%,尤其是以顺铂为主的各种方案时,恶心呕吐发生率高达100%。而即使在化疗前给予一定的止吐措施,仍有61%的患者会经历不同程度的恶心呕吐,其中急性期的恶心呕吐占34%,迟发型的恶心呕吐占58%。对患者的生活造成很大的影响,患者容易出现胃部损伤、营养不良等问题,患者对治疗产生焦虑、恐惧,继续治疗时容易出现预期性恶心呕吐。在不同程度上影响着患者的生存质量。
急性恶心呕吐是由于十二指肠释放的5-羟色胺和迷走神经传入的5-羟色胺3受体向大脑的催吐中心产生冲动所致,而迟发型恶心呕吐是P物质作用于神经激肽1受体上产生的,和胃肠动力紊乱及细胞的损伤有关。预期性恶心呕吐的发生机制比较复杂,涉及感觉、精神因素,通过直接刺激大脑皮质通路而产生恶心呕吐。
目前对于化疗、放疗、手术后恶心呕吐的患者主要采用选择性的5-羟色胺3受体拮抗剂治疗。
昂丹司琼是(Ondansetron)一种高度选择性的5-羟色胺3(5-HT3)受体拮抗剂,能抑制由化疗和放疗引起的恶心呕吐,有高强度和高度的选择性,能控制小肠及CTZ中受体受刺激而引起的呕吐。对一些强致吐作用的化疗药(如顺铂、环磷酰胺、阿霉素等)引起的呕吐有迅速而强大的抑制作用,还能增强胃排空,有助于减轻恶心;对中枢神经系统还具有抗焦虑和地西泮作用,有利于抑制呕吐中枢的兴奋。适用于治疗由化疗和放疗引起的恶心呕吐,也可用于预防和治疗手术后引起的恶心呕吐。
研究表明芳香物质在缓解患者恶心呕吐方面疗效显著且不良反应少,可用于缓解妊娠、术后、化疗相关的恶心呕吐,还具有催眠、止痛、缓解焦虑症状、提高患者生活质量等作用。呕吐中枢处于第四脑室复测面极后区化学触发带和孤束核上方。可以分为神经反射中枢和化学感受器触发带。神经反射中枢接受皮质(视觉、嗅觉、味觉)、咽喉、胃肠道和内耳前庭迷路、冠状动脉及化学触发带的传入刺激。在患者接触到芳香物质后,触发嗅细胞的兴奋时,芳香物质所具有的化学情报就会变成信号,传达到神经反射中枢,当芳香情报传达至此时,毗邻的脑垂体就会有相应的反应,促进释放神经化学物质,然后大脑中枢神经发出指令,调控平衡自主神经系统,引起身心的变化,调整人体的内外环境,从而产生镇定、放松、愉悦的主观感受,改变人的心情,减轻恶心呕吐的不适。
申请人在研究中发现,芳香物质与昂丹司琼共同应用时,可以发挥协同作用,不仅降低了恶心呕吐的发生率和严重程度,而且减少了止吐药物的使用,最终提高了患者的满意度。
发明内容
本发明提供了一种包含5-羟色胺3受体拮抗剂和芳香物质的组合物,可方便的用于化疗、放疗及手术后的患者,缓解恶心呕吐的效果明显,并能明显改善负性情绪。
本发明是通过以下技术方案实现的:
一种包含5-羟色胺3受体拮抗剂和芳香物质的组合物,5-羟色胺3受体拮抗剂占组合物重量的5-40%,芳香物质占组合物重量的0.5-10%,赋形剂占组合物重量的50-90%,调味剂占组合物1-10%。[00012]所述5-羟色胺3受体拮抗剂选自昂丹司琼、格拉司琼、托烷司琼、帕洛诺司琼中的一种。
优选的,所述5-羟色胺3受体拮抗剂为昂丹司琼。
所述芳香物质选自生姜、留兰香、薄荷、柠檬、薰衣草、佛手柑、甜橙和豆蔻等中的一种或一种以上混合物。
优选的,所述芳香物质为生姜、留兰香、薄荷、柠檬中的一种或两种。
所述赋形剂选自糖醇、明胶、多糖、环糊精、甘氨酸中的一种或一种以上的组合物。
所述调味剂选自阿司帕坦、三氯蔗糖、甜蜜素、枸橼酸、酒石酸、苹果酸中的一种或一种以上的组合物。
所述5-羟色胺3受体拮抗剂和芳香物质组合物的制备方法,步骤如下:
(a)将赋形剂、调味剂加到纯化水中搅拌使其完全溶解:
(b)将5-羟色胺3受体拮抗剂和芳香物质加到赋形剂溶液中,高速剪切使其分散均匀;
(c)将组合物混悬液定量分装到模具中,冷冻干燥。
本发明的再包含5-羟色胺3受体拮抗剂和芳香物质的组合物,有减轻恶心呕吐作用的芳香物质与5-羟色胺3受体拮抗剂发挥协同作用,减轻恶心、呕吐症状,改善不良情绪。
本发明的有益效果为:
本发明提供的组合物有以下优点:1)减轻放疗、化疗、手术患者出现的不同程度恶心、呕吐症状;2)提高了5-羟色胺3受体拮抗剂的治疗效果;3)不影响5-羟色胺3受体拮抗剂主要药理作用的同时,减轻不良反应;4)患者依从性高;5)给药方便,无需大量水送服。
具体实施方式
为了使本发明实现的技术手段、创作特征、达成目的与功效易于明白了解,下面结合具体实施例,进一步阐述本发明。
以下实施例仅用于说明本发明,但不限制本发明的保护范围。
实施例一:昂丹司琼和芳香物质组合物的制备
(1)处方:
(2)制备方法:
将甘露醇、明胶、阿司帕坦加纯化水搅拌使完全溶解;
加入昂丹司琼、生姜油高速剪切使分散均匀;
将药液分装于压制好的模具中,0.1g孔,冷冻干燥除去水分后,密封包装。
实施例二:昂丹司琼和芳香物质组合物的制备
(1)处方:
(2)制备方法:
将环糊精、三氯蔗糖、枸橼酸加纯化水搅拌使完全溶解;
加入昂丹司琼、薄荷醇高速剪切使分散均匀;
将药液分装于压制好的模具中,0.2g孔,冷冻干燥除去水分后,密封包装。
实施例三:帕洛诺司琼和芳香物质组合物的制备
(1)处方:
(2)制备方法:
将可溶性淀粉、甘氨酸、阿司帕坦加纯化水搅拌使完全溶解;
加入帕洛诺司琼、留兰香油高速剪切使分散均匀;
将药液分装于压制好的模具中,0.2g/孔,冷冻干燥除去水分后,密封包装。
实施例四:格拉司琼和芳香物质组合物的制备
(2)制备方法:
将木糖醇、环糊精、甜蜜素加纯化水搅拌使完全溶解;
加入格拉司琼、甜橙粉高速剪切使分散均匀;
将药液分装于压制好的模具中,0.15g/孔,冷冻干燥除去水分后,密封包装。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
以上显示和描述了本发明的基本原理、主要特征和本发明的优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的仪为本发明的优选例,并不用来限制本发明,在不脱离本发明精神和范围的前提下,本发明还会有各种变化和改进,这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。
Claims (8)
1.一种包含5-羟色胺3受体拮抗剂和芳香物质的组合物,特征在于以5-羟色胺3受体拮抗剂和芳香物质作为主要物质,一种或者多种药物能接受的赋形剂和调味剂为辅料,制成组合物。
2.根据权利要求1所述的5-羟色胺3受体拮抗剂和芳香物质的组合物,其特征在于所述的5-羟色胺3受体拮抗剂为昂丹司琼、格拉司琼、托烷司琼、帕洛诺司琼中的一种。
3.根据权利要求1所述的5-羟色胺3受体拮抗剂和芳香物质的组合物,其特征在于所述的芳香物质包括生姜、留兰香、薄荷、柠檬、薰衣草、佛手柑、甜橙和豆蔻等中的一种或一种以上的组合物。
4.根据权利要求1所述的5-羟色胺3受体拮抗剂和芳香物质的组合物,其特征在于所述赋形剂为糖醇、明胶、多糖、环糊精、甘氨酸中的一种或一种以上的组合物。
5.根据权利要求1所述的5-羟色胺3受体拮抗剂和芳香物质的组合物,其特征在于所述调味剂为阿司帕坦、三氯蔗糖、甜蜜素、枸橼酸、酒石酸、苹果酸中的一种或一种以上的组合物。
6.根据权利要求1所述的5-羟色胺3受体拮抗剂和芳香物质的组合物,其特征在于5-羟色胺3受体拮抗剂占组合物重量的5-40%,芳香物质占组合物重量的0.5-10%,赋形剂占组合物重量的50-90%,调味剂占组合物1-10%。
7.根据权利要求1-6中任一项所述的5-羟色胺3受体拮抗剂和芳香物质的组合物的制备方法,其特征在于,步骤为:
(a)将赋形剂、调味剂加到纯化水中搅拌使其完全溶解;
(b)将5-羟色胺3受体拮抗剂和芳香物质加到赋形剂溶液中,高速剪切使其分散均匀;
(c)将组合物混悬液定量分装到模具中,冷冻干燥。
8.根据权利要求1-6所述的5-羟色胺3受体拮抗剂和芳香物质的组合物用于口服缓解恶心呕吐。
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