CN111388665B - 一种治疗肿瘤的复合物及其制剂和用途 - Google Patents
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Abstract
本发明提供一种治疗肿瘤的复合物及其制剂和用途，所述复合物包括光辉霉素和PD‑1抗体；所述复合物内光辉霉素和PD‑1抗体具有非常显著的协同作用，两药联用可以用于治疗结肠癌等肿瘤，有效提高对肿瘤的治疗效果，减少患者并发症的发生及发展。
Description
技术领域
本发明属于含有机有效成分的医药配制品领域，特别涉及一种治疗肿瘤的复合物及其制剂和用途。
背景技术
肿瘤是威胁人类健康最重要的疾病之一，其发病率呈逐年上升的趋势。结肠癌是由于结肠粘膜上皮或腺体上失去正常生长机制的恶性细胞不断增殖而产生的恶性肿瘤，好发于直肠与乙状结肠交界处。结肠癌的主要治疗手段包括手术治疗、放化疗等。化疗方案中，国际上公认的标准疗法是5-FU+甲酰四氢叶酸(LV)为基础的化疗方案，经典方案主要包括FOLFOX(奥沙利铂+5-FU+亚叶酸钙)和FOLFIRI(伊立替康+5-FU+亚叶酸钙)方案。
光辉霉素(mithramycin A，MIT)属于抗肿瘤抗生素类药物，曾经广泛用于治疗恶性高钙血症、睾丸精原细胞瘤和白血病等疾病，其在高剂量下虽显示出抗肿瘤的效果，但同时具有严重副作用，因此限制了其在临床上的广泛应用。
PD-1是人体免疫系统T细胞上的一个药物靶点，针对这一靶点设计的药物可以激活T细胞对肿瘤细胞的免疫作用，从而唤醒患者自身的抗肿瘤效应。因此，PD-1抗体药物可用于治疗肿瘤。有数据显示，PD-1抗体能使四分之一至五分之一的非小细胞肺癌患者，黑色素瘤患者，或肾细胞癌患者产生客观反应，显示出良好的临床应用价值。
但是现有技术并没有公开过由光辉霉素和PD-1抗体组成的复合物，也没未公开过该复合物的治疗用途。
发明内容
为了解决现有技术存在的问题，本发明提供一种由光辉霉素和PD-1抗体组成的治疗肿瘤的复合物及其制剂和用途。
本发明其中一个技术方案提供一种治疗肿瘤的复合物，所述复合物包括光辉霉素和PD-1抗体。
其中光辉霉素为低剂量，PD-1抗体为抑瘤率达到20-30％的有效剂量。
进一步改进的方案中，所述光辉霉素和PD-1抗体的质量比为1-10：10-1。
进一步改进的方案中，光辉霉素和PD-1抗体的质量比为2：3。
本发明另一个技术方案提供一种制剂，所述制剂包括复合物和药用载体。
本文中所述“药用载体”是指用于治疗及给药的载体，包括各种赋形剂和稀释剂，并且是本领域普通技术人员所熟知的。
本发明另一个技术方案提供一种所述复合物在制备用于治疗肿瘤的药物中的应用。
进一步改进的方案中，所述肿瘤为结肠癌。
进一步改进的方案中，所述复合物中光辉霉素和PD-1抗体可以先后使用也可以同时使用。
本发明的有益效果在于，本发明提供一种由青光辉霉素和PD-1抗体组成的复合物，复合物内光辉霉素和PD-1抗体具有非常显著的协同作用，两药联用可以用于治疗结肠癌等肿瘤，有效提高对肿瘤的治疗效果，减少患者并发症的发生及发展。
附图说明
图1为本发明提供的复合物对结肠癌MC38小鼠体重的影响；
图2为本发明提供的复合物对结肠癌MC38肿瘤体积的影响；
图3为本发明提供的复合物对结肠癌MC38瘤重的影响。
具体实施例方式
试验例1光辉霉素和PD-1抗体联合的动物试验
运用小鼠结肠癌MC38皮下移植瘤模型评价光辉霉素和PD-1抗体联合的体内疗效。
取MC38细胞，按50×106/0.2mL/只接种于C57BL6小鼠腋窝皮下。第9天将荷瘤鼠按瘤块大小分组，每组5只，使每组动物的瘤块大小平均值接近。实验共分4组，给药方式均为腹腔给药，隔日给药一次，共给药4次。4组分别为：对照组(生理盐水)，给药剂量为0.2mL/只；光辉霉素组(本实验室自制)，给药剂量为2mg/kg；PD-1抗体组(Bioxcell InVivoPlusanti-mouse PD-1)，给药剂量为3mg/kg；光辉霉素和PD-1抗体联合组，同时给予光辉霉素(给药剂量为2mg/kg)和PD-1抗体(给药剂量为3mg/kg)。实验期间每2-3天测量一次肿瘤长径a和短径b，并记录动物体重。各组对小鼠体重的影响结果见图1。以公式V＝1/2ab2计算瘤体积和抑瘤率，抑瘤率(％)＝(对照组瘤体积-实验组瘤体积)/对照组瘤体积×100％，抑瘤率的结果见表1。各组MC38瘤体积的结果见图2；当瘤体积达到1000mm3时为实验终点，处死动物并剥取肿瘤称重，各组MC38瘤重的结果见图3。
计算两药相互作用系数CDI，结果见表1。CDI＝AB/(A×B)。AB为两药联用组与对照组瘤重比值；A或B为各药物单独使用组与对照组瘤重比值。
表1各组的抑瘤率和CDI结果
结果表明，两药联合后的CDI<0.7，因此两药联合的协同作用非常显著。采用光辉霉素和PD-1抗体联合作用于MC38皮下移植瘤模型时，两药体现出明显的协同增效作用。
Claims (1)
1.一种复合物在制备用于治疗结肠癌的药物中的应用，其特征在于，所述复合物由光辉霉素和PD-1抗体组成，所述光辉霉素和PD-1抗体的质量比为2：3。
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| CN104974253A (zh) * | 2014-04-01 | 2015-10-14 | 上海中信国健药业股份有限公司 | 抗ctla-4/pd-1双特异性抗体、其制备方法及应用 |
| CN109970857A (zh) * | 2017-12-27 | 2019-07-05 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
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| CN104974253A (zh) * | 2014-04-01 | 2015-10-14 | 上海中信国健药业股份有限公司 | 抗ctla-4/pd-1双特异性抗体、其制备方法及应用 |
| CN109970857A (zh) * | 2017-12-27 | 2019-07-05 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
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| Title |
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| A Bis-Indole-Derived NR4A1 Antagonist Induces PD-L1 Degradation and Enhances Antitumor Immunity;Keshav Karki等;《Molecular Cell Biology》;20200302;第80卷(第5期);第1011-1023页 * |
| Mithramycin suppresses tumor growth by regulating CD47 and PD-L1 expression;Jianhua Gong等;《Biochemical Pharmacology》;20211227;第197卷;第1-13页 * |
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