CN100341571C - 一种治疗肿瘤的药物及该药物在制备治疗肿瘤药物中应用 - Google Patents
一种治疗肿瘤的药物及该药物在制备治疗肿瘤药物中应用 Download PDFInfo
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Abstract
本发明涉及医药技术领域，具体地说是一种治疗肿瘤的药物及该药物在制备治疗肿瘤病药物中的应用。它以人用狂犬病纯化疫苗为单一成分。本发明药物对肿瘤具有明显的治疗作用的同时无毒副作用。
Description
技术领域
本发明涉及医药技术领域，具体地说是一种治疗肿瘤的药物及该药物(人用狂犬病纯化疫苗)在制备治疗肿瘤药物中应用。
背景技术
恶性肿瘤严重威胁人类的健康与生命，据世界卫生组织统计，每年有近700万人死于癌症，从1996年以来全球每年新确诊的肿瘤病人在1000万人以上，全球肿瘤病人总数已超过4000万。据卫生部的统计资料，目前我国每年新确诊的肿瘤患者约160万人，年死亡130万人，癌症患者总数在200万人以上。随着癌症发病率的上升，抗肿瘤研究已成为国内外医学研究的重要课题。科学届预言，找到癌症的超级抗原，破解癌基因的死亡密码，人类将最终战胜癌症。
到目前为止尽管已有数十种化疗或辅助抗癌药物用于临床治疗。二十一世纪治疗疾病，合成药、中草药、生物制剂各占一个领地。但大多数药物只能使病情缓情，无法达到治愈的目的。近年来，各国都在抗癌药物的研究与发展上投入了大量的人力、物力，希望在不久的将来能有所突破。
肿瘤是人体中正在发育的或成熟的正常细胞，在某些不良因素的长期使用下，某部的细胞群出现的过度增生或异常分化而生成的新生物，在局部形成肿块。但它与正常的组织和细胞不同，不按正常细胞的新陈代谢规律生长，而变得不受约束和控制，不会正常死亡导致了细胞呈现异常的形态、功能和代谢，以致可以破坏正常的组织器官的结构并影响其功能。恶性肿瘤细胞还能向周围浸润蔓延，甚至扩散转移到其他器官组织，继续成几何倍数增生，造成对人体或生命极大的威胁。如：巨噬细胞是机体防御和维持自稳性的重要细胞，当其遇到异物刺激时，细胞表面的各种受体及胞内的多种酶类均被不同程度的激活，分泌各种细胞因子，提呈抗原，通过内吞外排等方式清除异物或衰老细胞。可将该药物和化疗剂均视为来自体外的异物，但这些异物又有所区别，一种是生物制品，与细胞生物膜的结构成分相似，可保护和修复细胞。一种为细胞毒剂，导致细胞处于活化或抑制状态。
癌症是危及人们生命与健康的常见病，目前国内、外没有根治癌症的特效药物。目前用于肿癌治疗的主要手段有手术、放疗、化疗和生物治疗，其他有效手段还包括内分泌治疗、中医中药治疗、热疗和射频消融治疗等。由于现有各种治疗手段各有其最佳适应症，也各有其不足。
现在治疗肿瘤的药物中用于临床的较多的有：烷化剂类，抗代谢类，抗肿瘤抗生素类，抗肿瘤植物药类，这些用于临床的抗肿瘤药物，在杀伤和抑制肿瘤细胞生长等方面，均有较好的疗效，但化疗药物的共同缺点是对人体正常细胞损害较大，如长时间使用，均会给肿瘤患者带来一定的毒副作用，这样就使化疗药物的广乏使用受到了极大限制。生物或免疫调节剂，是生物制品，用于临床治疗疾病，主要可调节人体免疫功能，起到机体免疫增强作用。如干扰素、白介素-II等，对部分肿瘤如肾癌、黑色素瘤等有一定的疗效，但价格较昂贵，许多肿瘤疗效不确切，不宜用作一线治疗。现在人用狂犬病纯化疫苗及其免疫血清球蛋白长期以来是用于预防或治疗狂犬病的唯一有效药物，且效果较好。但其关于对人治疗肿瘤方面的药物研究和应用还尚未见任何报道。
发明内容
本发明的目的是提供一种治疗肿瘤病的药物，该药物对肿瘤具有明显的治疗作用，无毒副作用；并提供一种该药物在制备治疗肿瘤药物中应用。
本发明技术方案是：
治疗肿瘤病的药物：采用人用狂犬病纯化疫苗单一成分(可为液体或冻干型)。
人用狂犬病纯化疫苗在制备治疗肿瘤病药物中的应用：采用人用狂犬病纯化疫苗单一成分(可为液体或冻干型)，人临床用量每日肌肉注射2.5IU～10IU，30天为一个疗程。
本发明为生物制剂，研究发现：作为治疗肿瘤病的药物，人用狂犬病纯化疫苗具有明显的抗肿瘤作用，通过动物肿瘤模型试验和临床观察，均获得满意的有益效果，具体如下：
与对照组相比，本发明在实验组中可产生不同的正向和负向调节，增强了巨噬细胞的吞噬和消化功能。
从本发明对药物开展的药理、药效实验中可见：该药物对荷瘤动物的体内实验及对癌细胞的组织细胞病理观察中均可证实药物的抑瘤疗效，相关的实验研究工作也探讨了药物对机体免疫和抗氧化等多种功能的影响。大量的实验研究工作，也为了进一步的开发该药功能提供了可靠的科学理论依据。
附图说明
图1为本发明H22组实验中空白组病理照片。
图2为本发明H22组实验中胸腺五肽对肿瘤细胞杀伤作用病理照片。
图3为本发明H22组实验中环磷酰胺对肿瘤细胞杀伤作用病理照片。
图4为本发明H22组实验中该药对肿瘤细胞杀伤作用病理照片。
图5为本发明S180组实验中空白组病理照片。
图6为本发明S180组实验中胸腺五肽对肿瘤细胞杀伤作用病理照片。
图7为本发明S180组实验中环磷酰胺对肿瘤细胞杀伤作用病理照片。
图8为本发明S180组实验中该药对肿瘤细胞杀伤作用病理照片。
具体实施方式
下面通过实施例对本发明作进一步说明。
实施例1
人临床实验：取人用狂犬病纯化疫苗(Vero细胞)药物(市购产品)。每日肌肉注射2.5IU，30天为一个疗程，本实施例为两个疗程。
李某某：病理诊断：宫颈鳞癌，II期B；经CAF化疗方案2个疗程，局部放射治疗后，临床征状改善，恢复尚可；复查时CEA比值升高；用本发明药物治疗后，病情好转，病理塗片未见异常。
实施例2
人临床实验：取该药物，每日肌肉注射7.5IU，30天为一个疗程，共1个疗程。
应某：病理诊断：食管鳞癌，III期A；局部放射治疗20天后，临床征状改善，饮食尚可；用本发明药物治疗后，病情好转，生理指标尚可。
实施例3
赵某：原发灶不清，脑转移，病理诊断：星形细胞癌；伽玛刀治疗后，出现脑水肿及昏迷现象，家属要示改用该药物进行治疗：以活性单位2.5IU计，每日肌肉注射10IU，30天为一个疗程，现已服用27天，脑水肿部分消失、状态良好。
实施例4(用荷瘤小鼠验证该药物对肿瘤的抑制作用)
考察该药物对小鼠H22肝癌和小鼠S180实体瘤的抑制作用，及提高小鼠艾氏腹水癌的生命延长率作用。
受试药物：本发明药物，市购产品；用生理盐水配成浓度为0.1U/ml的混悬液备用。
实验材料：
1.动物昆明种小鼠，体重20±2g，每实验组20只，由中国医科大学实验动物室提供。实验动物合格证号：辽实动字第521号。
2.小鼠S180肉瘤和H22肝癌瘤株、艾氏腹水癌瘤株，均由北京中国医学科学院药物所提供。
3.饲料小鼠颗粒料，由沈阳实验动物颗粒饲料厂提供。
4.对照药：
1)(化疗药；批号：05060721)，注射用针剂，由江苏恒医药有限公司提供。用生理盐水配制成3mg/ml水溶液。
2)胸腺五肽(生物药，批准文号：20050602)，海南中和药业股份有限公司提供，用生理盐水配成0.04mg/ml液备用。
5.空白对照组：生理盐水。
试验方法：按<新药临床前抗肿瘤药指导原则>和<第三届全国肿瘤药理及化疗会议制定方案>进行。将生长良好的荷瘤小鼠，在无菌条件下抽取瘤液，用生理盐水稀释成103个/ml的细胞悬液。
一、抑瘤试验
取小鼠，每批实验用雌雄各半，将0.2ml瘤液稀释液注入小鼠右腋皮下，次日称体重随机分组，第四天开始给药，每天一次，肿瘤组织注射给药连续5天(空白组：肿瘤组织注射生理盐水0.2ml)。停药15天后处死动物，解剖分离皮下瘤块，称重，瘤组织做病理检查，计算各组平均瘤重和抑制率。
2.生命延长率试验
取小鼠，每批实验用雌雄各半，将0.2ml稀释液注入小鼠的腹腔，次日称体重随机分组，第四天开始给药，每天一次，每天给药一次，腹腔注射给药，连续5天给药(空白组：腹腔注射生理盐水0.2ml)。停药后观察，直至小鼠全部死亡，记录每只鼠的死亡时间，称体重。
实验结果：
H22组，解剖肉眼处理：肿瘤组织包膜较完整，个别呈腐败状。包膜内存大量液体(血性液体居多)，肿瘤组织许多呈腐烂状，病理片见瘤组织中许多坏死变化，核染浅，细胞内许多结构消失或变性，瘤组织缩小，癌细胞核染变浅。从病理片见较环磷酰胺，胸腺五肽对照组坏死性程度大(参见图1，H22空白组病理照片，癌细胞满视野，核深染，胞桨少；参见图2，H22胸腺五肽病理照片，可见少量癌细胞坏死变性，局部还可见大量的癌组织；参见图3，H22环磷酰胺病理照片，癌组织局部分散，坏死变性组织分散在其中；参见图4，H22本发明病理照片，大量癌组织变性坏死，局部液化，核染变浅，癌组织少量居中)。
S180组，解剖肉眼外可见：肿瘤组织包膜较完整，个别局部肉眼可见坏死，变性。包膜内有大量液体，呈半透明淡黄色，少部有半血性液体。
病理片见：瘤组织存在大量浅染区，核膜消失，核浅染，组织结构变性或消失(参见图1，S180空白组病理照片，癌细胞满视野，核深染，胞桨少；参见图2，S180胸腺五肽病理照片，可见少量癌细胞坏死变性，局部还可见大量的癌组织；参见图3，S180环磷酰胺病理照片，癌组织局部分散，坏死变性组织分散在其中；参见图4，S180本发明病理照片，大量癌组织变性坏死，局部液化，核染变浅，癌组织少量居中)。
艾氏腹水癌组，实验组生存期较对照组与空白组明显延长。
实验结论：实验药物对H22，S180有较强的抑瘤作用，病理片可见对肿瘤细胞有较强大的杀伤破坏作用。实验药物对荷瘤动物生存期延长有明显作用。
试验结论：
通过对荷瘤小鼠连续5天注射给药，实体瘤观察瘤重、抑制率，腹水型质量观察生命延长率，从而验定了药物的疗效。
1.实体瘤疗效评价：抑瘤率均大于30％，连续试验3次，疗效稳定，经统计学处理有显著差异P＜0.05，该药对实体瘤疗效较好。
2.腹水型疗效评价：生命延长率＞50％。实验连续3次，疗效较稳定，统计学处理有显著差异P＜0.05，该药对腹水癌疗效较好。
根据上述试验结果认为：该药对实体瘤及腹水型癌瘤疗效稳定较好，抑瘤作用较强，实验中未发现其它明显毒副作用。
二、免疫功能的调节作用、增效解毒作用，对放化疗损伤修复的调节作用及预防作用。
化疗剂是细胞毒剂，可对免疫功能产生了明显的抑制作用。通过免疫和抗氧化等动物实验，结果提示，用药后对化疗剂的抑制，使抗体的形成有所提高，促进吞噬细胞的趋化、黏附作用，促进细胞内活性物质的释放，进而促进吞噬和消化功能。
本发明研究了药物对荷瘤小鼠放疗损伤修复的调节作用。主要观察了用药后的小鼠体内的肿瘤抑制率、抗辐射、抗氧化、抗疲劳、提高免疫功能的变化。
其研究结果经数据处理具有显著性差异。
1.用药后使小鼠腹腔巨噬细胞吞噬率达35.02％，和化疗药物并用达44.55％，吞噬指数亦明显提高，分别为1.02和1.44，还可增加吞噬细胞消化功能；使血清半数溶血值增加，对化疗后抗体形成有较强的调节作用(免疫功能的调节作用)。
2.可迅速回升外周血白细胞总数达正常水平、使用环磷酰胺大剂量化疗降白细胞，通常要经相当长一段时间才可恢复正常，而用药后可使白细胞在7-10天回升至正常水平(解毒作用)。
3.荷瘤小鼠单用药物抑瘤率为34.02％，如与化疗并用，可达59.53％(增效作用)。
4.用药后可增强小鼠肝脏超氧化物歧化酶(SOD)的活性，SOD水平为662.97ug/ml。化疗时并用为452.69ug/ml，高于对照组，与正常对照组相当(抗氧化作用)。
对辐射损伤的修复也较明显，如照射后动物开始出现死亡较晚，出现头部皮肤及粘膜损伤较轻，而对照组损伤较重，头面部皮肤、粘膜溃疡严重，大部脱毛并伴有腹泻等症状。实验组小鼠骨髓微核率未见明显升高。而且30天存活率为82.07％，平均月生存时间为24.62天，均高于对照组(放化疗损伤修复的调节作用)。
药物可延长小鼠游泳时间达75％，明显增强耐力(预防作用)。
通过上述实验研究发现，该药物具有多种生物调解作用。能改善恶性肿瘤治疗中的不良反应状态。面临肿瘤治疗与康复的庞大市场，应用前景广阔。
Claims (2)
1.一种药物在制备治疗肿瘤病药物中的应用，其特征在于：其活性成分为人用狂犬病纯化疫苗。
2.按权利要求1所述的应用，其特征在于：其中所述人用狂犬病纯化疫苗为液体或冻干型。
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| CNB2005100472200A CN100341571C (zh) | 2005-09-16 | 2005-09-16 | 一种治疗肿瘤的药物及该药物在制备治疗肿瘤药物中应用 |
| PCT/CN2006/001388 WO2007030992A1 (fr) | 2005-09-16 | 2006-06-20 | Medicament de traitement de tumeurs et son utilisation dans la fabrication d'un medicament de traitement de tumeurs |
| EP06775663A EP1944039A4 (en) | 2005-09-16 | 2006-09-14 | ACTIVE AGENT FOR THE TREATMENT OF TUMORS AND ITS USE IN THE MANUFACTURE OF MEDICAMENTS FOR THE TREATMENT OF TUMORS |
| PCT/CN2006/002404 WO2007031030A1 (en) | 2005-09-16 | 2006-09-14 | Drug for treating tumor and use thereof in the manufature of medicaments for treating tumor |
| CNA2006800311150A CN101247828A (zh) | 2005-09-16 | 2006-09-14 | 一种治疗肿瘤的药物及该药物在制备治疗肿瘤药物中应用 |
| US12/042,367 US20080187556A1 (en) | 2005-09-16 | 2008-03-05 | Medicine for Treating Tumor and Use Therefor in Preparation of the Medicaments for Treating Tumor |
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| CNA2006800311150A Pending CN101247828A (zh) | 2005-09-16 | 2006-09-14 | 一种治疗肿瘤的药物及该药物在制备治疗肿瘤药物中应用 |
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| WO2017171653A1 (en) | 2016-04-01 | 2017-10-05 | Yisheng Biopharma (Singapore) Pte Ltd | A composition comprising pic for treatment of cancer |
| US11218634B2 (en) | 2018-04-28 | 2022-01-04 | Guangdong Oppo Mobile Telecommunications Corp., Ltd. | Data processing method and apparatus, computer-readable storage medium, and electronic device |
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| JP2012526149A (ja) * | 2009-05-08 | 2012-10-25 | サイクローン・ファーマシューティカルズ・インコーポレイテッド | ワクチン増強剤としてのαチモシンペプチド |
| CN102166353B (zh) * | 2010-02-26 | 2015-05-20 | 孙介光 | 一种用于治疗人乳头瘤病毒感染引起的疾病的喷剂及制备 |
| CN102416175A (zh) * | 2011-01-18 | 2012-04-18 | 辽宁成大生物股份有限公司 | 一种治疗hpv感染的药物以及该药物在制备治疗hpv感染药物中的应用 |
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| NZ531025A (en) * | 2001-07-20 | 2005-08-26 | Univ Georgia Res Found | Vaccine comprising a mutant rabies virus N protein which has an amino acid other than serine at position 389 and possibly one or more other mutations within the N protein |
| MXPA05010260A (es) * | 2003-03-27 | 2006-03-17 | Ottawa Health Research Inst | Virus de estomatitis vesicular mutantes y usos de los mismos. |
| WO2005051330A2 (en) * | 2003-11-25 | 2005-06-09 | United Cancer Research Institute | METHOD FOR TREATING HUMAN TUMOR CELLS WITH A NEWCASTLE DISEASE VIRUS STRAIN HAVING A p53 INDEPENDENT ONCOLYTIC EFFECT |
| DE102005007690A1 (de) * | 2004-06-18 | 2006-01-12 | Institut für Molekular- und Systemmedizin | Mittel zur Erhöhung der Tumorrestistenz des Organismus |
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| New approaches to the treatment of hepatic malignanciesviral oncolysis for malignant liver tumors Annals of Surgical Oncology,Vol.10 No.6 2003 * |
| 冻干人用狂犬病纯化疫苗的研制 微生物学免疫学进展，第32卷第4期 2004 * |
| 溶瘤病毒应用于肿瘤治疗的研究进展 国外医学·生理、病理科学与临床分册，第24卷第5期 2004 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2017171653A1 (en) | 2016-04-01 | 2017-10-05 | Yisheng Biopharma (Singapore) Pte Ltd | A composition comprising pic for treatment of cancer |
| US11218634B2 (en) | 2018-04-28 | 2022-01-04 | Guangdong Oppo Mobile Telecommunications Corp., Ltd. | Data processing method and apparatus, computer-readable storage medium, and electronic device |
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| WO2007031030A1 (en) | 2007-03-22 |
| EP1944039A1 (en) | 2008-07-16 |
| EP1944039A4 (en) | 2010-03-10 |
| CN101247828A (zh) | 2008-08-20 |
| CN1778389A (zh) | 2006-05-31 |
| WO2007030992A1 (fr) | 2007-03-22 |
| US20080187556A1 (en) | 2008-08-07 |
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Effective date of registration: 20161008 Address after: Xi'an Luyuan District in Jilin province Changchun 130062 Road No. 150, room 208, district 108 golden Waltz Patentee after: Changchun Bailong Bioengineering Co., Ltd. Address before: Heping District, Liaoning city in Shenyang Province, 110001 North Road No. 92 two Department of pharmacy China Medical University Meng Fanhao. Patentee before: Sun Jieguang Patentee before: Sun Xueran |
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Addressee: Lu Yang Document name: Notification of eligibility |