CN108553508B - 一种防治化疗后口腔黏膜炎的三草愈疡汤 - Google Patents
一种防治化疗后口腔黏膜炎的三草愈疡汤 Download PDFInfo
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Abstract
本发明属于医药技术领域,具体而言,涉及一种防治化疗后口腔黏膜炎的三草愈疡汤,包括以下原料:生甘草、夏枯草、紫草与薄荷。全方用生甘草为君;夏枯草为臣,与甘草相须为用;紫草清热凉血、散血解毒,善治热毒营血所致疮疡、斑疹;薄荷利咽透疹、疏散头目之风热,疏肝行气,能载药上行,功善清上焦风火,专利咽喉、疗疮疥。四味合用,清热解毒而不伤后天之本,散中寓补而不伤正,共奏清热解毒祛邪,健脾益气扶正之功。采用含漱之法,使药物与发病部位直接接触,药效直达患部,提高局部药物浓度。本发明明显缩短了症状缓解时间,提高患者放疗过程的生存质量,降低因中断放射治疗导致疗程延长的发生,更利于患者配合抗肿瘤治疗。
Description
技术领域
本发明属于医药技术领域,具体而言,涉及一种防治化疗后口腔黏膜炎的三草愈疡汤。
背景技术
口腔黏膜炎(Oral Mucositis,OM)是恶性肿瘤化学治疗中常见的黏膜毒性反应,目前认为其发病主要由于化疗药物对口腔黏膜基底部分裂迅速的上皮细胞非特异性杀伤和骨髓抑制带来的修复障碍等共同作用结果。口腔黏膜炎多发生在化疗后3-8天,一般持续约3-14天不等,广泛累及颊粘膜、舌面、口唇、牙龈及软腭。疼痛是OM难以忍受的症状,甚至影响进食、并发感染、中断化疗进程,酿成严重临床后果。甲氨蝶呤(Methotrexate,MTX)作为经典的抗代谢类肿瘤用药,广泛应用于骨肉瘤(Osteosarcoma,OS),具有严重的黏膜毒性,特别是接受大剂量甲氨蝶呤(HD-MTX)化疗的骨肉瘤患者,OM发病更为普遍。
参照《口腔黏膜病学》口腔黏膜溃疡诊断要点:(1)任何部位口腔溃疡。溃疡表面以黄白色假膜覆盖,周围绕以红晕,表面向内凹陷,疼痛明显。(2)轻则一个或数个,直径1-2mm至4-5mm;重则1-2个,直径1-2cm或更大,溃疡深,疼痛剧烈,愈合时间长,甚至形成瘢痕;疱疹性则溃疡多而小,一般十几个到数十个,直径1-2mm,甚至融合成片。
参照《中药新药临床研究指导原则》中“口疮”的诊断标准:(1)主症:溃疡、自发痛,激惹痛。(2)次症:心烦急躁,口热口干,尿黄便干。(3)口腔检查:口腔黏膜溃疡局部充血水肿,溃疡表面渗出假膜,边缘整齐基线平坦,溃疡呈圆形或者椭圆形,周围有红晕围绕。
参照《中医耳鼻咽喉口腔科学》中“实热证”的标准:起病急,口腔黏膜溃烂,数量多或融合成片,周围肿胀或充血,自觉灼痛,进食痛甚;口渴、口臭,心烦失眠,或伴便秘尿赤;舌红苔黄,脉数。
发明内容
本发明的目的在于为了甲氨蝶呤(Methotrexate,MTX)应用于骨肉瘤(Osteosarcoma,OS),具有严重的黏膜毒性,特别是接受大剂量甲氨蝶呤(HD-MTX)化疗的骨肉瘤患者,OM发病更为普遍的缺陷而提供一种防治大剂量甲氨蝶呤化疗后口腔黏膜炎的三草愈疡汤。
为了实现上述目的,本发明采用以下技术方案:
一种防治化疗后口腔黏膜炎的三草愈疡汤,所述三草愈疡汤的配方包括以下重量份数的原料:生甘草20-40份、夏枯草20-40份、紫草10-20份与薄荷4-8份。
在本技术方案中,OM发病机制尚未完全阐明,既往研究表明T淋巴细胞浸润在OM的发病中扮演重要角色,不同T淋巴细胞在OM周期内呈现动态变化,溃疡开始以T辅助细胞(CD4,Th)为主,溃疡期T毒性细胞(CD8,Ts/c)高表达,恢复期T辅助细胞(CD4,Th)逐渐上升。因此,OM发生与修复和CD4+Th/CD8+Tc状态关系密切;此外,激活的炎细胞,如巨噬细胞分泌IL-12诱导活化的T细胞和NK细胞分泌IFN-γ,激活外周淋巴细胞参与OM炎症反应;IL-12和IL-10之间存在负反馈调节机制,IL-12过分泌刺激IL-10分泌,IL-10升高反向抑制IL-12活性,故OM转归可能与两者协调情况有关。Sonis ST将OM进程分为5步骤:损伤启动、炎症信号激活、信号放大期、溃疡形成期和愈合期。
OM临床表现为口腔溃疡、局部水肿及疼痛等,属于中医学“口疮”、“口糜”范畴。本病最早见于《素问·气交变大论》:“岁金不及,炎火乃行……民病口疮。”历代医家从外邪、内伤、虚实、寒热等多角度分析其病机,认为口疮发病是五脏六腑阴阳失调、外感热邪共同作用的结果,病机大致分为三类,热乘心脾、阴虚火旺和脾肾阳虚。随着现代医学发展,化学疗法在恶性肿瘤疾病治疗中占据重要地位,化疗药物多具有较强毒性,其所致黏膜疾病表现也日渐突出。基于药物的黏膜损害,传统中医药理论逐渐发展形成“药毒理论”。
药毒理论首见《周礼》曰:“医师掌医之政令,聚毒药以供医事。”化疗药物属于“毒药之品”,外邪致病,化火生热,火性炎上,“毒火”循经上攻,直犯口咽,灼伤血络,发为口疮。同时,药毒既是致病原因,亦是病理产物。药毒积聚,机体阴阳、脏腑功能失调,出现气滞、血瘀、痰浊壅塞口腔,以至邪毒难除,口疮经久不愈。化学疗法的非特异性杀伤效应严重影响机体稳态,导致正气耗损、脏腑功能失调。其中对脾胃影响尤为重大,脾胃乃后天之本,气血生化之源。脾胃受纳、运化、输布失调,气血亏虚,血脉失养;心脾之气不足以供养全身,以至皮损难以修复。药毒所致诸如气滞、血瘀、痰浊等次生毒邪相互交织,虚实夹杂,正损难复。
药毒致病是内外因综合作用结果,药毒属于“火热毒邪”,是导致OM的始动因素;随着化疗进展,毒邪聚积,脾胃失输,机体失养终至口腔黏膜损伤经久难愈。发明人经过多年治疗骨肉瘤的临床实践,立足于“药毒化火,邪重伤正”的认知,拟定以“降火解毒,健脾益气”为原则的经验方“三草愈疡汤”,在以往接受HD-MTX化疗出现OM患者的治疗上显示出良好的疗效。
“三草愈疡汤”由生甘草、夏枯草、紫草、薄荷组成。全方重用生甘草为君,其善能清热解毒、缓急止痛,兼补脾益气,既祛“药毒”之热,又能疗疮疡之痛;夏枯草为臣,与甘草相须为用,善清肝胆实火,消肿散结,是治头面火毒之良药,助甘草降火解毒祛邪;紫草清热凉血、散血解毒,善治热毒营血所致疮疡、斑疹;薄荷利咽透疹、疏散头目之风热,疏肝行气,能载药上行,功善清上焦风火,专利咽喉、疗疮疥。四味合用,清热解毒而不伤后天之本,散中寓补而不伤正,共奏清热解毒祛邪,健脾益气扶正之功。采用含漱之法,使药物与发病部位直接接触,药效直达患部,提高局部药物浓度。
作为优选,所述三草愈疡汤的配方包括以下重量份数的原料:生甘草25-35份、夏枯草25-35份、紫草12-18份与薄荷4-8份。
作为优选,所述三草愈疡汤的配方包括以下重量份数的原料:生甘草30份、夏枯草30份、紫草15份与薄荷6份。
作为优选,将原料纳入小神仙煎药机,加入冷水,没过药材2-3cm,充分浸泡30-40min后,在2个大气压120℃标准下,煎煮30-50min,共煎取200mL,分装4袋,每袋50mL。
本发明的有益效果是:“三草愈疡汤”由生甘草、夏枯草、紫草、薄荷组成。全方重用生甘草为君,其善能清热解毒、缓急止痛,兼补脾益气,既祛“药毒”之热,又能疗疮疡之痛;夏枯草为臣,与甘草相须为用,善清肝胆实火,消肿散结,是治头面火毒之良药,助甘草降火解毒祛邪;紫草清热凉血、散血解毒,善治热毒营血所致疮疡、斑疹;薄荷利咽透疹、疏散头目之风热,疏肝行气,能载药上行,功善清上焦风火,专利咽喉、疗疮疥。四味合用,清热解毒而不伤后天之本,散中寓补而不伤正,共奏清热解毒祛邪,健脾益气扶正之功。采用含漱之法,使药物与发病部位直接接触,药效直达患部,提高局部药物浓度。
本发明明显缩短化疗后口腔黏膜溃疡持续时间,减少中重度口腔黏膜溃疡的发生,降低后续再发率,明显缓解临床症状,降低因口腔黏膜溃疡而导致化学治疗疗程延长的发生,从而提高临床疗效。
具体实施方式
以下结合具体实施例,对本发明作进一步的解释:
实施例1
一种防治化疗后口腔黏膜炎的三草愈疡汤,所述三草愈疡汤的配方包括以下重量份数的原料:生甘草20份、夏枯草20份、紫草10份与薄荷4份。
将原料纳入小神仙煎药机,加入冷水,没过药材2-3cm,充分浸泡35min后,在2个大气压120℃标准下,煎煮40min,共煎取200mL,分装4袋,每袋50mL。
实施例2
一种防治化疗后口腔黏膜炎的三草愈疡汤,所述三草愈疡汤的配方包括以下重量份数的原料:生甘草40份、夏枯草40份、紫草20份与薄荷8份。
将原料纳入小神仙煎药机,加入冷水,没过药材2-3cm,充分浸泡40min后,在2个大气压120℃标准下,煎煮50min,共煎取200mL,分装4袋,每袋50mL。
实施例3
一种防治化疗后口腔黏膜炎的三草愈疡汤,所述三草愈疡汤的配方包括以下重量份数的原料:生甘草30份、夏枯草30份、紫草15份与薄荷6份。
将原料纳入小神仙煎药机,加入冷水,没过药材2-3cm,充分浸泡30min后,在2个大气压120℃标准下,煎煮30min,共煎取200mL,分装4袋,每袋50mL。
实施例4
一种防治化疗后口腔黏膜炎的三草愈疡汤,所述三草愈疡汤的配方包括以下重量份数的原料:生甘草32份、夏枯草28份、紫草16份与薄荷4份。
将原料纳入小神仙煎药机,加入冷水,没过药材2-3cm,充分浸泡30min后,在2个大气压120℃标准下,煎煮30min,共煎取200mL,分装4袋,每袋50mL。
本发明病例来源于杭州市第三人民医院肿瘤科,2016年1月至2017年12月,收治经病理确定的97例新发骨肉瘤患者,需接受含HD-MTX方案(MTX-MTX-DDP-ADM)治疗,所有患者均签署知情同意书。采用随机数表法分为治疗组49例和对照组48例。治疗过程中,因MTX过敏或严重药物性肝损害更改化疗方案,治疗组剔除21例,对照组剔除19例。最终,治疗组纳入28例,对照组29例,共57例。分别接受2周期化疗,共行4次HD-MTX化疗。观察期内,两组共出现OM病例33例,其中治疗组16例,对照组17例。
化学治疗方案
入组患者均采用MTX-MTX-DDP-ADM方案。其中,MTX用量成人8g/m2,儿童12g/m2,分别在第1、第8天给药;DDP 90-100mg/m2在第15天给药;ADM 60mg/m2在第17天给药,每31天为1周期,术前2周期化疗,化疗过程中充分碱化尿液,监测肝肾功能、MTX血药浓度,骨髓造血功能,胃肠道副作用等,在MTX用药结束后12小时给予甲酰四氢叶酸15mg解救,每6小时1次,共12次。
口腔黏膜炎防治方法
常规口腔护理
各组患者均在HD-MTX化疗第1天开始使用浓度稀释为2.5%碳酸氢钠500ml(回音必集团东亚制药有限公司,国药准字H36020283)漱口,分三餐前和临睡前各1次,每次125ml,持续10min。
治疗组
在常规口腔护理后,加用“三草愈疡汤”50ml,qid含漱,口腔中保存持续10min。未出现OM者中药使用5天,出现OM者使用至OM完全愈合。
对照组
患者若出现OM,在常规口腔护理后,加用康复新液(四川好医生攀西药业有限责任公司,国药准字Z51021834)10ml,qid含漱,口腔中保存持续10min,直至OM完全愈合;无OM者不使用。
临床观察指标和方法
安全性指标
(1)一般生命体征:体温、血压、心率。(2)三大常规、肝肾功能(治疗前后必检项目)。(3)心电图检查(治疗前后必检项目)。
一般指标
(1)OM发生率:观察期内,出现OM的总人数与纳入试验的总人数的百分比,即OM发生率=OM总人数/试验总人数×100%。(2)OM发生部位:分颊黏膜、口唇内侧、舌、牙龈、软腭及口咽。(3)OM持续时间:从出现之日至OM完全愈合,以天数计算。(4)口腔黏膜毒性分级:参照WHO抗癌药物急性和亚急性毒副反应的表现和分级标准:0度:正常;I度:黏膜红斑、疼痛;II度:黏膜红斑、溃疡,可进食;III度:黏膜溃疡,只能进流质饮食;IV度:黏膜溃疡,不能进食。(5)OM再发率:治疗组或对照组接受干预性防治过程中初次出现过OM,经治疗后痊愈,在后续HD-MTX化疗中再次出现即为再发,再发率=再发例数/发生OM总例数×100%。
中医症候观察和疗效评价方法
口腔黏膜炎中医症状量化分级标准
参考《中药新药临床研究指导原则》[3],依据各OM患者临床症状不同,分轻、中、重度,分别计为1、2、3分。计数统计,分别于OM高峰期计算初始临床症状积分,并于出现OM第6天再次评估计算药物干预后的临床症状积分。中医症状分级量化标准见表1。
表1 OM中医症状量化分级标准
中医疗效评价方法
参考《中药新药临床研究指导原则》[7],按照尼莫地平法计算各个OM患者治疗前后积分减少的百分比,确定临床疗效。计算公式(尼莫地平法)为:(治疗前积分-治疗后积分)÷治疗前积分×100%。见表2。
表2OM临床疗效评价标准
临床疗效 | 判定标准 |
痊愈 | 单项症状、体征用药3天以内明显减轻,用药5天内症状、体征消失,积分减少≥95% |
显效 | 单项症状、体征用药5天以内明显减轻,积分减少≥70% |
有效 | 单项症状、体征用药5天以内减轻,积分减少≥30% |
无效 | 单项症状、体征用药5天以内无明显改善,甚至加重,积分减少<30% |
免发功能与血细胞因子测定及方法
血标本留取及储存方法
患者入组后,分别于每周期第1次HD-MTX用药前1天和第2次HD-MTX化疗后第3天,使用负压BD Vacutainer EDTA采血管通过静脉穿刺以无菌方式采集血液各3-5ml,室温(20-25℃)保存,24小时内送流式细胞检测;同时在每次HD-MTX化疗前1天及化疗后第3天,使用负压BD Vacutainer SSTTM II Advance采血管通过静脉穿刺以无菌方式采集血液3-5ml,室温静置60min后,4℃,3000rpm,离心20-30min,留取上清分装入冻存管,立即保存于-80℃超低温冰箱备用。
流式细胞术检测外周血淋巴细胞亚群CD4+、CD8+计数
(1)对于每个患者标记,使用样本识别标记1支BD Trucount管。(2)将20μl的BDMultitestCD3 FITC/CD8 PE/CD45 PerCP/CD4 APC试剂移取到标记管的底部。(3)混匀器混匀全血,使用反向移液技术将BD Vacutainer EDTA采血管中50μl充分混匀的抗凝全血移取至标记管底部。(4)盖上管盖并轻轻震荡进行混匀,于室温(20-25℃)环境下避光孵育15min。(5)向BD Trucount管中添加450μl的1×BD Multitest溶血素,并避免受直射光照射,在室温(20-25℃)下保存,细胞染色24小时内进行检测。(6)盖上管盖并轻轻震荡进行混匀,室温(20-25℃)环境下避光孵育15min后,放置于FACSCaliburTM流式细胞仪上进行样本分析,使用BD Multitest软件计算样本中CD4+、CD8+细胞绝对值。
酶联免疫分析法(ELISA)检测外周血细胞因子IL-10、IL-12、TNF-α表达(1)检测前,将解冻的血清移液至EP管,在4℃,1500rpm条件下再次离心15-20min,收取上清液编号备用。(2)标准本加样:设置标准品孔和样本孔,标准品孔各加入不同浓度的标准品50μl。(3)加样:在96T酶标板上分别设空白孔(空白对照孔不加样品及酶标试剂,其余各步骤操作相同)、待检样品孔、在酶标包被板上待测样品孔中先加样品稀释液40μl,然后再加待测样品10μl于酶标板孔底部,轻轻晃动均匀(样品最终稀释浓度为5倍)。(4)加酶:每孔加入酶标试剂100μl,空白孔除外。(5)温育:用封板膜封板后置于37℃生化培养箱中温育60min。(6)配液:将20倍浓缩洗涤液用蒸馏水20倍稀释备用。(7)洗涤:小心揭掉封板膜,弃去液体,甩干,每孔加满洗涤液,静置30s后弃去,如此重复5次,拍干。(8)显色:每孔先入加显色剂A50μl,再加入显色剂B50μl,轻轻震荡均匀,37℃避光显色15min。(9)终止:每孔加终止液50μl,终止应(此时蓝色立转为黄色)。(10)测定:加终止液15min内,以空白孔调零,450nm波长依序测量各孔的吸光度(OD度)。(11)计算:用标准品浓度与OD值计算出标准曲线的直线回归方程式,将样品的OD值代入方程式,计算出样品浓度,再乘以稀释倍数,即为样品的实际浓度。
统计学分析方法
所有数据均采用SPSS 19.0软件进行统计学分析。数值变量资料采用均数±标准差表示;数值变量资料,数据服从正态分布的采用t检验,资料不符合正态分布的采用秩和检验(Z);多样本均数间的比较采用单因素方差分析,若方差齐,采用LSD法,方差不齐,采用Games-Howell法;单因素2个水平的有序分类变量资料采用卡方检验(χ2),2个以上水平的有序分类资料采用秩和检验。
结果
一般资料及安全性分析
性别构成
57例患者中,男性26例,女性31例。治疗组28例,其中男性14例,女性14例;对照29例,其中男性12例,女性17例;两组患者在性别分布上基本相当,基线平齐;采用卡方检验,结果提示,治疗组和对照组在性别构成上无统计学差异(P>0.05)。见表3
表3性别构成(n=57)
年龄构成
治疗组患者年龄最大53岁,最小9岁,平均年龄21.36±10.77岁;对照组患者中,年龄最大54岁,最小4岁,平均年22.62±13.42岁;两组患者在年龄分布上大致相当,基线平齐;数据不符合正态性,采用两样本秩和检验,结果提示:两组患者在年龄构成上无统计学差异(P>0.05)。见表4。
表4年龄构成(n=57,岁)
口腔黏膜炎的发生部位
两组患者OM发生在颊粘膜23例,牙龈4例,口唇内3例,软腭及咽2例,舌面1例。其中,颊粘膜占69.7%,其次为牙龈和口唇内,分别占12.1%和9.1%。采用卡方检验,结果提示:两组患者在OM发生部位的差异无统计学意义(P>0.05)。
A正常口腔黏膜B口唇内C牙龈及颊粘膜D软腭及咽部E舌面F颊粘膜三草愈疡汤防治口腔黏膜炎的安全性
治疗组28例患者在整个OM防治过程中均未出现中药过敏、口腔感染或者其他明显不舒适,所有患者均反映“三草愈疡汤”口感微甜,应用安全方便,依从性100%。
两组患者临床情况比较
口腔黏膜炎的发生率
入组患者共计57例,出现OM者33例;其中,治疗组16例,对照组17例,两组总体发病率57.89%,治疗组57.14%,对照组58.62%,各组OM发生率基本相当;采用卡方检验,结果提示:两组OM发生率的差异无统计学意义(P>0.05)。见表5。
表5OM发生率(n=57)
口腔黏膜炎的持续时间
治疗组患者OM持续时间最长12天,最短2天,平均持续4.63±3.07天;对照组患者OM持续时间最长15天,最短3天,平均持续7.00±4.06天。两组数据符合非正态分布,采用秩和检验,结果提示:与对照组干预性防治相比,治疗组OM持续时间显著缩短,差异有统计学意义(P<0.05)。见表6。
表6OM持续时间(n=33,天)
口腔黏膜炎患者黏膜毒性分级
两组患者分别表现出不同程度的口腔黏膜毒性,以I-II度最为常见(40.35%),其次为III度(10.53%);治疗组中重度口腔黏膜毒性(III-IV度)明显少于对照组;但两组口腔黏膜毒性分级差异无统计学意义(P>0.05)。见表7。
表7OM黏膜毒性分级(n=57)
基于中医临床症状积分的临床疗效
两组OM在出现第6天均有好转,总体有效率47.37%,治疗组有效率93.75%,对照组有效率70.59%,治疗组明显优于对照组,两组差异有统计学意义(P<0.05)。OM出现第6天,对比两组患者症状及体征好转>70%者(显效以上),治疗组13例(81.25%),对照组8例(47.06%),治疗组明显多于对照组,两组差异有统计学意义(P<0.05)。见表8。
表8OM临床疗效(n=33)
观察期内口腔黏膜炎的再发率
两组OM患者经干预性防治后均有再发,总体再发率36.36%,治疗组12.50%,对照组58.82%。与对照组相比,治疗组OM再发率显著降低,两组差异有显著统计学意义(P<0.01)。见表9。
表9OM再发情况(n=33,例)
两组患者外周血CD4+、CD8+细胞计数
治疗组未出现OM患者与OM患者间,CD4+、CD8+细胞计数无明显差异;对照组未出现OM患者与OM患者间也无明显差异;比较治疗组和对照组未出现OM患者的CD4+、CD8+细胞计数,发现各个时期均无显著差异;比较治疗组和对照组OM患者CD4+、CD8+细胞计数,提示治疗组OM患者血CD4+细胞明显高于同一时期对照组,但差异无统计学意义(P>0.05)。见表10。
表10血CD4+、CD8+计数(n=57,106/L)
注:OM:各组出现OM的患有,正常:各组未出现OM的患有。MTX1前为第1周期第1次MTX化疗前1天;MTX2后为第1周期第2次MTX化疗后第3天;MTX3前为第2周期第1次MTX化疗前1天;MTX4后为第2周期第2次化疗后第3天。
两组患者外周血细胞因子测定
两组患者血清TNF-α表达结果
比较第1次HD-MTX化疗前各组患者外周血TNF-α的表达,差异无统计学意义,提示各组之间情况基本一致,基线平齐。治疗组内OM患者血TNF-α表达高于同组正常患者,但无统计学意义;对照组内TNF-α表达差异较大,呈动态变化趋势,其中OM患者血TNF-α明显呈现高表达。从第1次HD-MTX化疗后,对照组内,OM患者血TNF-α表达明显高于同组正常患者,差异有统计学意义(P<0.05);第3次HD-MTX化疗前开始,治疗组OM患者血TNF-α表达低于对照组,差异有统计学意义(P<0.05)。见表11。
表11血清TNF-α表达(n=57,pg/ml)
注:OM:各组出现OM的患者,正常:各组未出现OM的患者。MTX1前、MTX2前、MTX3前、MTX4前分别表示MTX化疗前1天;MTX1后、MTX2后、MTX3后、MTX4后分别表示MTX化疗后第3天(表12、13相同)。同期组内比较,*P<0.05;同期组间比较,★P<0.05。
两组患者血清IL-12表达结果
第1次HD-MTX化疗后,治疗组内OM患者血IL-12表达明显高于同组正常患者,差异有统计学意义(P<0.05);从第1次HD-MTX化疗前开始,对照组内OM患者血IL-12表达高于同组正常患者,差异有统计学意义(P<0.05)。比较两组正常患者血IL-12表达,差异无统计学意义(P>0.05);从第2次HD-MTX化疗后,治疗组OM患者血IL-12表达低于对照组,差异有统计学意义(P<0.05)。见表12。
表12血清IL-12表达(n=57,pg/ml)
注:同期组内比较,*P<0.05;同期组间比较,★P<0.05。
两组患者血清IL-10表达结果
治疗组在第2次HD-MTX化疗前至第3次化疗后,OM患者血IL-10表达明显高于同组正常患者,差异有统计学意义(P<0.05);对照组从第1次HD-MTX化疗前开始,OM患者血IL-10表达高于同组正常患者,差异有统计学意义(P<0.05)。比较两组正常患者血IL-10表达水平,差异无统计学意义(P>0.05)。第3次HD-MTX化疗前后,治疗组OM患者血IL-10表达低于对照组,差异有统计学意义(P<0.05)。见表13。
表13血清IL-10表达(n=57,pg/ml)
注:同期组内比较,*P<0.05;同期组间比较,★P<0.05。
本发明对57例骨肉瘤患者接受HD-MTX化疗2个周期内出现OM的发生情况及中医临床症状积分、T淋巴细胞亚群、血细胞因子进行观察和测定,发现“三草愈疡汤”在缩短OM病程,提升临床疗效,降低再发率,改善预后等多个方面疗效斐然。“三草愈疡汤”主要通过缩短OM持续时间,改善中医临床症状,降低OM再发率等作用提高临床疗效。两组OM患者在血清IL-12、IL-10、TNF-α等表达上明显高于正常患者,提示OM发生与上述血细胞因子有一定的正相关性。“三草愈疡汤”可能主要通过抑制IL-12、IL-10、TNF-α表达,从而调控机体免疫功能,改善症状。与对照组相比,治疗组OM患者上述细胞因子异常值出现时间明显较晚,且持续时间较短,下降速率更快,提示“三草愈疡汤”在调控抑制IL-12、IL-10、TNF-α表达方面效果优于对照组。对入组患者外周血淋巴细胞进行检测对比,发现两组间及组内无统计学差异,但HD-MTX化疗后期,治疗组OM患者血CD4+细胞明显高于对照组,“三草愈疡汤”调控CD4+细胞增殖,介导炎症参与组织修复。本发明运用中药含漱方法治疗OM,因其发病位置表浅,含漱药物可以直接与患部接触,保证最佳药物浓度,最大限度保证药物疗效。本发明中,治疗组患者均反映良好,疼痛时间减少,愈合时间缩短,进食情况好转,没有因严重OM而中止化疗的病例;且患者普遍反应“三草愈疡汤”口感微甜,依从率100%。提示“三草愈疡汤”可以明显缓解OM症状,并保证化疗周期顺利完成。“三草愈疡汤”安全性高、使用方法简单有效、患者依从性高,值得推广应用。
Claims (3)
1.一种防治化疗后口腔黏膜炎的三草愈疡汤,其特征在于,所述三草愈疡汤由以下重量份数的原料组成:生甘草20-40份、夏枯草20-40份、紫草10-20份与薄荷4-8份。
2.一种防治化疗后口腔黏膜炎的三草愈疡汤,其特征在于,所述三草愈疡汤由以下重量份数的原料组成:生甘草25-35份、夏枯草25-35份、紫草12-18份与薄荷4-8份。
3.一种防治化疗后口腔黏膜炎的三草愈疡汤,其特征在于,所述三草愈疡汤由以下重量份数的原料组成:生甘草30份、夏枯草30份、紫草15份与薄荷6份。
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