CN108969621A - 一种中药组方用于制备治疗宫颈癌药物的应用 - Google Patents
一种中药组方用于制备治疗宫颈癌药物的应用 Download PDFInfo
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Abstract
本发明公开了一种中药组方用于制备治疗宫颈癌药物的应用,所述中药组方为:当归15质量份、黄柏10质量份、赤芍10质量份、花粉10质量份、川芎10质量份、甘草8质量份、红花5质量份、朱砂5质量份、白矾4质量份、木香4质量份、紫硵砂3.5质量份、枯矾3质量份、白硵砂3质量份、冰片3质量份、苍术3质量份、血竭2质量份、雄黄1质量份、红娘0.5质量份。本发明对宫颈癌有理想的治疗效果。
Description
技术领域
本发明涉及宫颈癌治疗药物,具体涉及一种组方用于制备治疗宫颈癌药物的应用。
背景技术
宫颈癌(HPV)是常见的妇科肿瘤之一,是仅次于乳腺癌的第二个常见肿瘤。其发病率在中国女性生殖道恶性肿瘤中仍位居第一位。世界上每年大约有50万的宫颈癌新发病例,其中80%的病例发生在发展中国家。我国每年有新发病例约约13.15万,占世界宫颈癌新发病例总数的1/3。采用中医治疗是比较温和的治疗手段。
发明内容
本发明提供了中药组方用于制备治疗宫颈癌药物的应用,所述中药组方为:当归15质量份、黄柏10质量份、赤芍10质量份、花粉10质量份、川芎10质量份、甘草8质量份、红花5质量份、朱砂5质量份、白矾4质量份、木香4质量份、紫硵砂3.5质量份、枯矾3质量份、白硵砂3质量份、冰片3质量份、苍术3质量份、血竭2质量份、雄黄1质量份和红娘0.5质量份。
本发明还提供了一种治疗宫颈癌的中药。
本发明所提供的中药包括药体,该药体外包裹有纤维材料,该纤维材料上或外绑扎或固定有绳,所述绳的自由端设有牵引绳;所述药体是将15质量份当归、10质量份黄柏、10质量份赤芍、10质量份花粉、10质量份川芎、8质量份甘草、5质量份红花、5质量份朱砂、4质量份白矾、4质量份木香、3.5质量份紫硵砂、3质量份枯矾、3质量份白硵砂、3质量份冰片、3质量份苍术、2质量份血竭、1质量份雄黄和0.5质量份红娘研末混合、蜜调为丸而成。
进一步,本发明药体为片状、球状、棒状或椎体状,所述纤维材料依附药丸的外形包裹形成片状、球状、棒状或椎体状。
进一步,本发明所用纤维材料为纱布、无纺布、脱脂棉、无菌棉或无菌布。
有一些实施方案中,本发明的中药还包括送药棒。
另一些实施方案中,本发明的中药还包括送药管,所述送药管包括套筒和推送杆,所述套筒上沿轴向开设有第一缝隙,所述推送杆为中空结构,所述推送杆壁上沿轴向开设有第二缝隙,所述推送杆一端伸入套筒中。使用时,本发明的中药放置在套筒内且位于推送杆端部,所述牵引绳穿过推杆内部并且伸出推送杆外。
本发明对宫颈癌有理想的治疗效果。
附图说明
图1为本发明的中药组方对SiHa细胞增殖作用的影响细胞电镜对照结果;其中:(a)为空白组、(b)为低剂量组、(c)为中剂量组、(d)为高剂量组、(e)为对照组;
图2为本发明的中药组方对SiHa细胞凋亡形态(Hoechst 33342/PI染色)影响的细胞电镜对照结构;其中:(a)为空白组、(b)为低剂量组、(c)为中剂量组、(d)为高剂量组、(e)为对照组;
图3为本发明中药的一种药物结构形状;
图4为图3的俯视图;
图5为本发明中药的另一药物结构形状;
图6为本发明中药的又一药物结构形状;
图7为本发明给药管的一种结构形状。
具体实施方式
本发明的中药组方为:当归150质量份、黄柏100质量份、赤芍100质量份、花粉100质量份、川芎100质量份、甘草80质量份、红花50质量份、朱砂50质量份、白矾40质量份、木香40质量份、紫硵砂35质量份、枯矾30质量份、白硵砂30质量份、冰片30质量份、苍术30质量份、血竭20质量份、雄黄10质量份、红娘5质量份。
制备方法为:研细末,过100目筛,蜜调抟丸,每丸1-10克,之后用纤维材料包裹,纤维材料外表面或收口处绑有绳,绳的自由端延伸作为牵引绳。
图3是一种具体的包裹方式,其中药体为球状或椭球状,外包纱布1,纱布外表绑扎绳2,绳的自由端延伸为牵引绳3,从其俯视图4显示,绑好的绳呈梅花状、多瓣面状。图5为另一种包裹方式,将药体装在袋状的纤维材料(如布袋)10中,袋口穿有绳11,袋口沿绳收束和开放。纤维材料可选用医用纤维材料、无菌布、无菌棉、纱布、脱脂棉等。图6为有一种包裹方式,药体被纤维材料4包括为棒状,牵引绳5的一端被固定在纤维材料4内部,另一端伸出实现取药需要。
本发明中药的使用方法:置入阴道宫颈口处(牵引绳外置),三日取出(通过拉动牵引绳取出),温开水冲洗干净即可,属于外用;持续使用时,置入阴道宫颈口处,三日取出,温开水冲洗干净,休三日后再使用。
为方便患者将药送入宫颈口,可配送药棒,其表面光滑圆润,避免划伤皮肤,使用舒适。另一种方便给药的方式是配置如7所示的给药管,包括套筒7和推送杆6,套筒7上沿轴向开设有缝隙9,用于放置或取出牵引绳,推送杆6为中空结构,推送杆壁上沿轴向开设有缝隙8,推送杆一端伸入套筒中,给药时,包裹好并设有牵引绳的中药放置在套筒内且位于推送杆端部,牵引绳穿过推杆内部并且伸出套筒外,通过推动送药棒或推送杆将药物送至阴道宫颈口,药物放置好后,取走送药棒或给药管;取药时,通过拉动牵引绳将药物取出体外。
以下是发明人提供的关于本发明药物的效果支持说明。
实施例1:本发明药物对SiHa细胞增殖作用的影响(抗HPV)
宫颈癌在女性恶性肿瘤的发病率位居第二,近年来其发病率逐年升高并有年轻化趋势,研究发现其与生殖道人乳头瘤病毒(HPV)感染的增加密切相关,统计显示,HPV感染在正常人小于4%,但99.8%宫颈癌患者中检测到HPV的DNA,其中以HPV16最为多见,采用MTT法和细胞凋亡实验,从体外实验细胞水平探索本发明的中药组方治疗宫颈癌效果。
1 材料和仪器
1.1 细胞株
市售人宫颈癌SiHa细胞(HPV16)
1.2 器材
96孔板、血细胞计数板、微量移液器、倒置相差显微镜、CO2培养箱、超净台、酶标仪、十万分之一天平、电热恒温水箱、流式细胞仪。
1.3 药品及试剂
药品:本发明药物、保妇康栓(市售);
含药血清制备:将本发明药物低剂量、中计量、高剂量和保妇康栓(本发明中药各计量组方按480mg/kg大鼠重量、960mg/kg和1920mg/kg,保妇康栓按960mg/kg)制成适合SD大鼠(SPF级)阴部大小的药丸和栓剂。每日给药一次,连续给药5天,取末次给药后1h血清,37℃水浴静置30min,3000r/min离心10分钟取血清,血清置于56℃水浴30min灭活补体,分装于1mL无菌EP管中置于﹣80℃冰箱冷藏备用。用前将各组含药血清用含2.5%胎牛血清的DMEM全培养基稀释为三个梯度浓度,0.22um滤膜过滤除菌,分别得到浓度分别为2%、4%和8%含药血清。
主要试剂:DMEM培养液、胎牛血清、胰酶、噻唑蓝(MTT溶液)、PI、二甲基亚砜、溴乙啶、DMSO、0.25%Trypsin-EDTA液、PBS溶液、RNase溶液、青霉素和链霉素。
0.25%Trypsin-EDTA液:Trypsin0.25g;10×PBS:10mL。
PBS溶液:PBS粉,三蒸水加至1L,充分溶解后0.22um滤膜过滤除菌,pH7.2~7.4,分装备用,4℃冰箱保存。
MTT溶液:用PBS溶液配制MTT溶液,浓度为5mg/mL充分溶解后0.22um滤膜过滤,PH7.2~7.4,4℃避光保存。
PI的配制:取0.5mLPI,溶于2mL重蒸水中,终浓度为250ug/mL,4℃避光保存备用。
RNase溶液的配制:取0.16mgRNaseA,溶于80ul重蒸水中,终浓度为2000ug/mL,﹣20℃保存备用。
2 方法
2.1 对SiHa细胞细胞生长周期的影响(MTT法检测)
(1)接种细胞:取对数生长期的细胞,用含0.25%Trypsin-EDTA液的消化液消化,制成单细胞悬液,计数,调整细胞浓度为2.8×104个细胞/mL,接种于96孔培养板中,每孔100μl(6.8×103个细胞/孔),培养于5%CO2、37℃、饱和湿度的培养箱中培养。培养过夜后,换无血清培养基作用24h。
(2)加受试药物:分别加入已稀释不同比例的本发明药物和保妇康栓含药血清和配制含药血清同等条件培养基,终体积为100ul/孔,每种浓度设立6个平行对照,并设正常对照,置正常培养条件下培养,48h换液1次。
(3)呈色:连续培养,分别于含药血清作用24h、48h、72h、96h后,换为无血清DMEM基础培养基,以消除血清对MTT作用的影响,每孔加入MTT液(5mg/mL)15μl,再培养4hr,小心吸弃上清,加DMSO100μl/孔显色,振荡摇匀,室温静置20~30分钟,使之充分溶解。
(4)比色:全自动酶标仪,选择492nm波长,空白孔调零,测定各孔吸光度(OD)值。记录含药血清作用于SiHa细胞的浓度效应数据和时间效应数据,用下列公式计算含药血清对细胞生长的抑制率。抑制率%=(空白血清组测定的平均OD值-含药血清组测定的平均OD值)/空白血清组测定的平均OD值×100%。
2.2 对SiHa细胞细胞凋亡的影响
(1)接种细胞:取对数生长期的细胞,用含1%的胰酶及1%EDTA的消化液消化,制成单细胞悬液,计数,调整细胞浓度为5×104个细胞/mL,接种于6孔培养板中,每孔2mL(1×105/孔),培养于5%CO2、37℃、饱和湿度的培养箱中培养。培养过夜后,换无血清培养基。
(2)加受试药物:小心吸净原培养液,然后分别加入已稀释为8%浓度的本发明药物和保妇康栓含药血清,终体积为3mL/孔,每种含药血清设立3个平行对照,设配制含药血清同等条件培养基为正常对照,培养于5%、37℃、饱和湿度的培养箱中培养。每24h换液一次。换液时吸净原培养液,再用无血清DMEM培养基小心清洗2次,再加入含药血清及对照培养基。
(3)流式细胞仪测定的步骤:加入不同浓度受试含药血清培养后,用含0.25%胰蛋白酶和0.02%EDTA进行消化,配成单细胞悬液。细胞计数后,取1~2×105个细胞收集于离心管中。1000r/min,离心5min,再用PBS洗涤2次。加入70%冷乙醇固定过夜,取固定的细胞1000r/min,离心5min。再用PBS洗涤2次,留200μlPBS,吹打制悬,加2μlRNaseA(终浓度20ug/mL)在37℃消化30min,30min后加PI50μl(终浓度为50ug/mL),4℃避光染色1小时,1小时后,过200目尼龙网,上机检测。
2.3 统计分析
检测结果SPSS23.0软件进行处理采用单因素方差分析,所测数据以表示,P<0.05认为差异有显著性。
3 结果
3.1 对SiHa细胞细胞生长周期的影响(MTT法检测)
表1 本发明药物各组血清对宫颈癌SiHa细胞增殖作用的影响(OD值, )
与空白组比较,*P<0.05,**P<0.01.
由上表1可知,剂量不同,本发明药物血清对SiHa细胞增殖作用的抑制作用也不同,48h、96h抑制作用最明显,空白对照组与其他四组差异显著(P<0.05),而在药物作用SiHa细胞24h、72h时本发明药物各组间均无显著差异(P>0.05)。
倒置显微镜下观察,空白对照组Siha细胞贴壁生长,细胞扁平状,细胞质均匀透明细胞核及细胞膜轮廓明显,细胞间结构连接紧密,生长旺盛。而本发明药物在高、中、低剂量组及对照组作用后,细胞间质变松,细胞质颗粒增多,染色质凝聚,分块,胞质浓缩。细胞形态对照结果如图1所示。3.2对SiHa细胞细胞凋亡的影响
表1-2 本发明药物阴道给药各组血清作用48h细胞凋亡率比较(%,)
与空白组比较,*P<0.05,**P<0.01;
由上表可知,本发明药物在高、中、低剂量对SiHa细胞都具有一定促进细胞凋亡作用,空白组与保妇康栓组和本发明药丸低、中、高剂量组差异显著(P<0.05)。
经过Hoechst 33342/PI染色后,荧光显微镜下见凋亡细胞形态不规则,早期凋亡细胞发出较明亮的蓝色荧光,部分凋亡细胞碎裂呈点状,大小不一,出现明显的凋亡。说明本发明药物对人宫颈鳞癌SiHa细胞体外增殖有直接的抑制作用,也可促进人宫颈癌SiHa细胞的凋亡。细胞凋亡对照如图2所示。
实施例2:临床效果
病例1:
某女,38岁,曾经做过几次流产。妇科问题折磨十几年。中西医各种治疗反反复复不见好转,04年左侧卵巢囊肿摘除手术;2008年左侧输卵管切除手术,之后身体一直不好,整天离不开药物,导致低血压,贫血,后来宫颈糜烂,宫颈肥大,盆腔积液;宫寒严重,月经量越来越少,一直用氨基酸维持体力。
2016年9月15日诊断hpv高危58阳性~59阳性,低危42阳性。
使用本发明中药组方阴道给药6个月后,HPV全部为阴性。
病例2:
某女,45岁。PCP法检测HPV16 18高危型HPVDNA检测阳性(9.97),慢性宫颈炎(宫颈3+6+9+12点),腺体鳞化显著;(ECC)腺性息肉,腺体不成熟磷化;在医院治疗一年多复查无好转。
2017年9月24号开始使用本发明药丸,连用不休,使用一疗程(12粒,3g/粒,带3天,休3天)在11月23号去医院检查,人乳头瘤病毒(HPV)PCR法检测阴性HPV16 18两项高危阴性;腺性息肉消失,子宫及双侧附件未见明显异常。
病例3:
某女,37岁。2014年查出CIN2癌前病变,在医院进行了LEEP刀手术,2015年11月复查,HPV58型阳性,宫颈薄层液基细胞学检查(TCT)结果提示:异常,活检病理异常。
2016年7月份,开始用本发明药物,使用期间出现少许阴道排液,持续月余消失。连续使用两个疗程后2016年9月20复查,检查结果:宫颈光滑,脓性白带,Ⅲ度,BV阳性,子宫后位,经产大小,附件未见异常,HPV高危型全部为阴性。
2017年年9月复查,宫颈光滑,HPV高危全部阴性;2018年8月再次复查,HPV高危全部阴性。
Claims (7)
1.一种中药组方用于制备治疗宫颈癌药物的应用,所述中药组方为:当归15质量份、黄柏10质量份、赤芍10质量份、花粉10质量份、川芎10质量份、甘草8质量份、红花5质量份、朱砂5质量份、白矾4质量份、木香4质量份、紫硵砂3.5质量份、枯矾3质量份、白硵砂3质量份、冰片3质量份、苍术3质量份、血竭2质量份、雄黄1质量份和红娘0.5质量份。
2.一种治疗宫颈癌的中药,包括药体,该药体外包裹有纤维材料,该纤维材料上或外绑扎有绳,所述绳的自由端设有牵引绳;所述药体是将15质量份当归、10质量份黄柏、10质量份赤芍、10质量份花粉、10质量份川芎、8质量份甘草、5质量份红花、5质量份朱砂、4质量份白矾、4质量份木香、3.5质量份紫硵砂、3质量份枯矾、3质量份白硵砂、3质量份冰片、3质量份苍术、2质量份血竭、1质量份雄黄和0.5质量份红娘研末混合、蜜调为丸而成。
3.如权利要求2所述的治疗宫颈癌的中药,其特征在于,所述药体为片状、球状、棒状或椎体状,所述纤维材料依附药丸的外形包裹形成片状、球状、棒状或椎体状。
4.如权利要求2所述的治疗宫颈癌的中药,其特征在于,所述纤维材料为纱布、无纺布、脱脂棉、无菌棉或无菌布。
5.如权利要求2所述的治疗宫颈癌的中药,其特征在于,还包括送药棒。
6.如权利要求2所述的治疗宫颈癌的中药,其特征在于,还包括送药管,所述送药管包括套筒和推送杆,所述套筒上沿轴向开设有第一缝隙,所述推送杆为中空结构,且推送杆壁上沿轴向开设有第二缝隙,所述推送杆一端伸入套筒中。
7.如权利要求6所述的治疗宫颈癌的中药,其特征在于,所述权利要求2、3或4所述中药放置在套筒内且位于推送杆端部,所述牵引绳穿过推杆内部并且伸出推送杆外。
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1140079A (zh) * | 1996-02-13 | 1997-01-15 | 徐万奇 | 治疗宫颈癌、妇科炎症的方剂及泡制方法 |
CN105560877A (zh) * | 2016-02-22 | 2016-05-11 | 常培兰 | 一种治疗宫颈疾病的中药组合物 |
CN107638511A (zh) * | 2017-11-06 | 2018-01-30 | 黄青春 | 一种治疗宫颈疾病的药物 |
-
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1140079A (zh) * | 1996-02-13 | 1997-01-15 | 徐万奇 | 治疗宫颈癌、妇科炎症的方剂及泡制方法 |
CN105560877A (zh) * | 2016-02-22 | 2016-05-11 | 常培兰 | 一种治疗宫颈疾病的中药组合物 |
CN107638511A (zh) * | 2017-11-06 | 2018-01-30 | 黄青春 | 一种治疗宫颈疾病的药物 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111276048A (zh) * | 2019-06-14 | 2020-06-12 | 华为技术有限公司 | 一种显示屏和电子设备 |
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