CN117018095B - 一种治疗孤独症的药物组合物及其应用 - Google Patents
一种治疗孤独症的药物组合物及其应用 Download PDFInfo
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Abstract
本发明提供了一种治疗孤独症的药物组合物,其原料配比为:植物甾醇1‑3重量份、二氢槲皮素1‑3重量份、茶叶茶氨酸1‑3重量份、葛根5‑7重量份、槐花5‑7重量份、显齿蛇葡萄叶10‑12重量份、蓝莓花色苷1‑3重量份。本发明的药物组合物配方简单,作用明确,具有很好的降低儿童孤独症评定量表(CARS)和孤独症儿童行为量表(ABC量表)的值,总有效率高,且通过长效毒性动物实验,安全性高。本发明的药物组合物通过相关动物实验,有效改善了孤独症的社会交互能力障碍,重复呆板样行为,狭隘的兴趣活动,学习记忆能力。
Description
技术领域
本发明涉及药物组合物技术领域,尤其涉及一种用于孤独症的药物组合物及其应用。
背景技术
孤独症谱系障碍(autismspectrumdisorder,ASD)又称孤独症,是儿童常见的神经发育障碍性疾病之一,主要表现为不同程度的社交障碍、沟通困难、重复刻板行为及兴趣爱好狭窄等,多数患者伴有明显的精神发育迟滞,且男孩的患病率是女孩的4~5倍。孤独症的病理机制比较复杂,孤独症具体的病因还不明确,公认的病因为:孤独症是由复杂的遗传因素和环境因素造成的。
一方面,遗传因素研究表明,如果双胞胎中有一个孤独症患者,若这对双胞胎是同卵双胞胎,那么二者同时罹患孤独症的概率为60%~90%;若这对双胞胎为异卵双胞胎,那么二者同时罹患孤独症的概率为0%~10%,这一结果充分证明了孤独症的遗传特异性。目前,有关孤独症遗传变异性的研究成果颇丰,已经发现了许多孤独症的易感基因。现在已经发现与孤独症高度相关的基因变异具有多态性,既有[单核苷酸变异]也有碱基对[拷贝数变异]。截止2019年1月为止,已经收录的ASD易感基因有1053个,[拷贝数变异]的基因座有2284个。孤独症的风险基因可能通过影响大脑发育、神经元活动、信号转导和转录调控等方面导致孤独症的发生。
另一方面,环境因素主要通过母体孕早期暴露于不良环境,使得胎儿神经发育受阻,最终导致胎儿罹患孤独症。环境因素包括:①细菌或病毒感染:研究显示,母体妊娠早期因病毒感染而住院,胎儿出生后罹患孤独症的风险增加了将近3倍;母体妊娠中期因细菌感染而住院,胎儿出生后罹患孤独症的风险增加了将近1.5倍。造成这种结果可能的原因是,细菌或病毒会激活母体的免疫反应,导致母体发生较为严重的炎症反应,从而影响胎儿的正常发育。②心理应激:怀孕期间高水平的压力、迁移、免疫力下降等都可能使后代患孤独症的概率增加。研究调查结果显示,在孕期的21周~32周,如果母亲遭遇了较为严重的心理应激,那么子代罹患孤独症的风险将会增加。③药物使用不当:母体孕期尤其是孕早期服用沙利度胺、米索列醇、丙戊酸等药物,会导致胎儿神经发育受阻,胎儿出生后罹患孤独症的风险增加。
因为孤独症的病因尚不明确,目前孤独症的治疗方案只能针对其核心行为展开。常用的治疗方式包括早期行为影响、氟哌啶醇,利培酮和阿立哌唑,西酞普兰、氟西汀、氟伏沙明,美金刚和利鲁唑,阿巴氯芬、巴氯芬等药物抑制部分行为特征、心理干预、高压氧治疗等。这些治疗方法的治疗费用很高收益却很少,其疗效差且不良反应较多如锥体外系反应,嗜睡、疲劳和食欲下降,体重增加,更容易罹患慢性疾病等一系列问题。
现有技术中也有一些治疗孤独症相关的中药组合物的专利报道:CN113663048B公开了一种用于孤独症谱系障碍的中药组合物及其制备方法,包含如下重量份的组分:龟甲10~20份、鳌甲10~20份、鸡内金3~7份、乌梅15~25份、山楂15~25份、姜1~5份。CN115040595A公开一种可用于治疗孤独症谱系障碍及其脑部疾病的中药组合物,其由何首乌、广木香、石菖蒲、黄芪、山茱萸、五味子、西红花、枸杞子、女贞子、无花果、熟地、龙葵、龟甲、土虫、地龙、当归、桃仁、虫草、甘草制成。但是以上中药组合物成分复杂,是否有效有待验证。
因此如何提供一种安全且作用效果明确的抗ASD的药物组合物是本领域技术人员亟需解决的问题。
发明内容
针对现有技术的不足,本发明的目的是提供一种药物组合物,该药物组合物由中药和提取物组成,该组方安全有效,且抗ASD效果明显。
本发明的技术方案是:
一种治疗孤独症的药物组合物,原料配比为:植物甾醇1-3重量份、二氢槲皮素1-3重量份、茶叶茶氨酸1-3重量份、葛根5-7重量份、槐花5-7重量份、显齿蛇葡萄叶10-12重量份、蓝莓花色苷1-3重量份;制备方法为:
步骤一、按原料配比将葛根、槐花、显齿蛇葡萄叶加12-15倍量水,煎煮2-3小时,煎煮液用100-200目滤布过滤,滤渣重复煎煮1-2次,合并药液,然后在60~70℃下,-0.06~-0.08Mpa减压浓缩至相对密度为1.20~1.30的稠膏,再在60~70℃,-0.06~-0.08Mpa真空干燥,粉碎,得干膏粉;
步骤二、将干膏粉和植物甾醇、二氢槲皮素、茶叶茶氨酸、蓝莓花色苷混合均匀,得药物组合物。
优选的,由以下重量份的组分组成:植物甾醇1重量份、二氢槲皮素1重量份、茶叶茶氨酸1重量份、葛根5重量份、槐花5重量份、显齿蛇葡萄叶10重量份、蓝莓花色苷1重量份。
优选的,所述药物组合物可以制备成丸剂、膏剂、片剂等各种常规剂型。
本发明还提供了所述药物组合物在制备治疗孤独症的药物中的应用。
下面对本发明做进一步的解释和说明:
二氢槲皮素是来自落叶松、花旗松等松科植物中提取出来的一种活性物质,属于生物黄酮类拟维生素P,其化学结构具有5个-OH基团,具有较强的抗氧化特性、调节酶活性等多种生物活性,临床主要用于抗炎抗氧化、抗心肌纤维化、调节脂代谢、抗病毒、抗肿瘤。
显齿蛇葡萄叶是葡萄科蛇葡萄属的一种多年生藤本植物,俗称“藤茶”,其所含物质主要包括二氢杨梅素、杨梅素、杨梅苷、槲皮素等。黄酮类化合物是显齿蛇葡萄叶中主要的活性物质,具有较强的抗氧化性、抑菌、消炎、抗肿瘤、降血糖、降血脂、保肝等功效。
植物甾醇是一种多用途纯天然的生理活性物质,被誉为“生命的钥匙”。植物甾醇通常以游离甾醇、甾醇酯、甾基糖苷或酰基化甾基糖苷的形式存在于植物油、坚果、植物种子及蔬菜、水果等植物性食物中。体内外及临床试验均表明植物甾醇具有抗炎作用,具体的作用机制主要涉及调节细胞因子和其他炎症相关因子水平,对NF-κB相关信号通路产生的影响,对免疫系统产生的影响等。并能调节肠道微生物区系和黏膜活性;改善氧化应激。植物甾醇已被证实具有显著降低胆固醇的效果,可用来降低患动脉粥样硬化和心血管疾病的风险。
葛根为豆科植物野葛或甘葛藤的干燥根,甘葛藤又习称为粉葛。葛根性甘、辛、平、无毒。葛根的化学成分主要包括黄酮类,香豆素类,三萜皂苷类,生物碱,在现代中医临床上,葛根具有解热、抗炎、收缩平滑肌、扩张冠状动脉血管、降低外周血管阻力、增加脑及冠状动脉血流量、抗心律失常的药理活性,同时还具有增强机体免疫力、降低血压、降血糖、抗氧化和抗肿瘤等活性。
茶叶茶氨酸是一种茶叶特有的水溶性非蛋白氨基酸,有“新天然镇静剂”之称,其具有多靶点、副作用少、协同效果好等优点,并且可以直接穿过血脑屏障在脑部发挥作用,具有良好的镇定作用及其对神经系统疾病的潜在疗效。近10年来对茶叶茶氨酸的研究已经深人对人体的生理、保健和药物功能等领城,许多体外模型和动物试验证实了茶叶茶氨酸具有降血压,镇静,保护神经细胞,增强记忆力以及促进抗肿瘤药物疗效等多种生理功能。
槐花其味苦、性微寒,归肝、大肠经;入血敛降,体轻微散;具有凉血止血,清肝泻火的功效;主治肠风便血、痔血、血痢、尿血、血淋、崩漏、吐血、衄血、肝火头痛、目赤肿痛、喉痹、失音及痈疽疮疡等,从西医的角度看,槐花含芦丁、槲皮素、鞣质、槐花二醇、维生素A等物质。芦丁能改善毛细血管的功能,保持毛细血管正常的抵抗力,防止因毛细血管脆性过大,渗透性过高引起的出血、高血压、糖尿病,服之可预防出血。槐花有扩张冠状动脉、降血压、降血脂等作用功效,特别可以保持毛细血管正常的抵抗能力,减少血管通透性,可以使出血的毛细血管恢复正常的弹性。
蓝莓花色苷具有改善大脑认知功能等作用,具有清除自由基、提高抗氧化酶活性、抑制脂质过氧化的抗氧化活性,抗突变、抗癌,保护血管、降血压,防治骨质疏松,可用于防止体内氧化应激损伤。蓝莓花色苷存在肝-肠循环,透过血-脑屏障、血-眼屏障,以及代谢产物仍具有活性,这些代谢特征有助于蓝莓花色苷在体内发挥保健作用。在美容养颜、抗衰老、抗氧化、保护视力等方面都拥有特殊的功效。
与现有技术相比,本发明的优势是:
本发明的组合物配方简单,作用明确,具有很好的降低儿童孤独症评定量表(CARS)和孤独症儿童行为量表(ABC量表)的值,总有效率高,通过长效毒性动物实验,安全性高。通过相关动物实验,有效改善了孤独症的社会交互能力障碍,重复呆板样行为,狭隘的兴趣活动,学习记忆能力等。
以下结合附图和具体实施方式对本发明的详细结构作进一步描述。
附图说明
图1为本发明实施例1的制备工艺流程图。
具体实施方式
实施例1
一种药物组合物,由以下重量份的组分组成:植物甾醇1重量份、二氢槲皮素1重量份、茶叶茶氨酸1重量份、葛根5重量份、槐花5重量份、显齿蛇葡萄叶10重量份、蓝莓花色苷1重量份。
原料可以通过市场购买途径直接得到,植物甾醇、二氢槲皮素、茶叶茶氨酸、蓝莓花色苷选择质量百分含量98%以上的。
制备方法具体方案为:
步骤一、将葛根、槐花、显齿蛇葡萄叶加14倍量水,煎煮2小时,煎煮液用200目滤布滤过,重复上述步骤,合并药液,减压浓缩(60~70℃,-0.06~-0.08Mpa)至相对密度为1.20~1.30(60℃)的稠膏,真空干燥(60~70℃,-0.06~-0.08Mpa),得干膏粉;
步骤二、将干膏粉和植物甾醇、二氢槲皮素、茶叶茶氨酸、蓝莓花色苷,混合均匀,得药物组合物。
进一步可制备成丸剂,制备成丸剂为现有技术,具体工艺见图1。
实施例2ASD动物实验
受试品设计
实验材料
2.1受试物(供试品):实施例1的药物组合物(谷医堂(湖南)健康科技有限公司),临床拟用途径:口服,一次5.5g,一日3次;临床拟用疗程:3个月。
2.2实验动物:SPF级SD大鼠30只,雌性20只,雄性10只体重范围:164.5~226.7g;(湖南斯莱克景达实验动物有限公司),实验动物饲养中心清洁级大鼠饲养室饲养一周,给予充分饲料和饮水。日光灯维持每天12h光照,环境安静,室温25℃左右。
实施例1的药物组合物临床拟用剂量为临床拟用剂量为9g/日,根据魏伟编《药理实验方法学》,第四版,动物种属间等效剂量体表面积的折算表,大鼠等效剂量为9×0.018÷0.2=0.81g/kg,本次试验选用最大临床拟用量0.5、1、2倍大鼠等效剂量作为低、中、高剂量组的给药量,分别为0.41、0.81、1.62g/kg。
实施例1药物组合物:称取实施例1的药物组合物,分别按0.41g/kg、0.81g/kg、1.62g/kg配制,每天1次,使用前加纯水搅拌均匀。
给药途径:经口灌服。给药频率与时间:1次/日。
给药期限:14天。
建立孤独症模型鼠
孤独症模型小鼠制备和分组雌雄大鼠数量根据2∶1合笼过夜,发现阴栓的雌性大鼠记为妊娠第1天(E1),受孕雌鼠分笼单独饲养。将受孕雌鼠随机分为对照组和模型组:模型组(n=15)于E12.5时腹腔注射600mg/kg VPA;产下的仔鼠为孤独症仔鼠;对照组(n=5)于E12.5时腹腔注射等量0.9%氯化钠溶液,产下的仔鼠为正常仔鼠,出生当日即为生后第一天。幼鼠出生21d后断乳,选择雄性子鼠进行实验分组。模型组雌鼠新生仔鼠随机分为4组:低剂量组(n=10,0.41g/kg,×14d);中剂量组(n=10,0.81g/kg,×14d);高剂量组(n=10,1.62g/kg,×14d);VPA组(n=10,不给药)。对照组雌鼠新生仔鼠设为空白组(n=10,不给药)。
本试验按照公司规定进行统计分析,数据有效数字修约按照四舍五入进行。用统计学软件分析,体重均采用均数±标准差表示,两组间比较满足正态性和方差齐性时采用t检验,数据不满足正态性或方差齐性时采用Mann-Whitney Test,P<0.05表示有统计学意义,P<0.01表示所检验的差别有非常显著性意义。
实验分组与设计
学习记忆能力检测——Morris水迷宫测试:将空白组、VPA组,低剂量组,中剂量组,高剂量组仔鼠进行水迷宫实验,检测仔鼠的空间学习记忆能力。水迷宫为一个直径为150cm,高50cm的圆形水池,内壁为黑色,深度为40cm,水池中水的温度保持在(25±0.5)℃。水池平均分为四个象限即SW、NW、SE和NE,将逃生平台在泳池一个象限的中心,距离泳池边缘15cm,并浸没在水面下1cm处。
定位航行实验:将仔鼠放入其中一个象限中,从入水开始到爬上平台的时间记为逃避潜伏期。连续训练5天,记录各组仔鼠训练第5天的逃避潜伏期。空间探索实验:在最后一次训练后的24h进行空间探索实验,撤掉水池中的平台,将原来放置平台的象限作为目标象限,将仔鼠随机放入除目标象限的其他3个象限中,记录仔鼠60s内穿越目标象限的次数。
水迷宫实验学习记忆能力检测——Morris水迷宫测试将6周龄空白组、VPA组,低剂量组,中剂量组,高剂量组仔鼠进行水迷宫实验,检测仔鼠的空间学习记忆能力。水迷宫为一个直径为150cm,高50cm的圆形水池,内壁为黑色,深度为40cm,水池中水的温度保持在(25±0.5)℃。水池平均分为四个象限即SW、NW、SE和NE,将逃生平台在泳池一个象限的中心,距离泳池边缘15cm,并浸没在水面下1cm处。实验包括2个阶段:①定位航行试验:实验历时5d,每只仔鼠每天训练4次。训练时将仔鼠从规定的位置面朝池壁靠近水面放入水中,记录其在90s内找到平台的时间(逃避潜伏期)。如果仔鼠在90s内未能找到平台,由测试者将其引导上平台,使其在平台上停留15s后移开,潜伏期记为90s。记录各组仔鼠训练第5天的逃避潜伏期②空间探索实验:在最后一次训练后的24h进行空间探索实验,撤掉水池中的平台,将原来放置平台的象限作为目标象限,将仔鼠随机放入除目标象限的其他3个象限中,由摄像系统和计算机软件记录仔鼠60s内穿越目标象限的次数。
表1 5组仔鼠学习记忆能力的比较
VPA组与空白组对照:“△”P<0.05;“△△”P<0.01;与VPA组对照:“*”P<0.05;“**”P<0.01;
实验结论:在本试验条件下:VPA组与空白组相比,VPA组逃避潜伏期时间明显长于空白组,差异具有统计学意义(P<0.01),VPA组穿越目标象限次数明显小于空白组,差异具有统计学意义(P<0.01),说明造模成功;与VPA相比实施例1制备的药物组合物低、中、高各剂量组逃避潜伏期时间明显减少,差异具有统计学意义(P<0.05或P<0.01);穿越目标象限次数模型组次数VPA组与空白组相比,VPA组明显少于正常组,差异具有统计学意义(P<0.01);与VPA相比实施例1制备的药物组合物低、中、高各剂量组时间明显减少,差异具有统计学意义(P<0.05或P<0.01);实施例1制备的药物组合物低、中、高各剂量能有效改善VPA仔鼠学习记忆能力。
行为学检测社会交往实验:仔鼠出生后35d,将空白组、VPA组,低剂量组,中剂量组,高剂量组仔鼠进行三箱实验,检测仔鼠的社会交往能力:准备一个大小为60cm×60cm×60cm的透明箱,每个箱子之间的隔板为透明玻璃,中间部分开放,允许自由进入每个箱子。在箱子里的左侧和右侧各放一个规格一致的笼子,用于放置陌生鼠。将测试鼠放进中间的箱子里适应5min;将陌生鼠随机放进左侧或右侧箱子里的笼子里,另外一侧箱子的笼子空着;撤掉玻璃树脂板,使测试鼠可以在三个箱子里自由活动10min;打开图像自动采集系统记录测试鼠与陌生鼠或空的笼子之间接触的时间。
表2 5组仔鼠“社交性”的比较
组别 | 例数 | 陌生鼠 | 空笼 |
空白组 | 10 | 98.28±3.67## | 35.23±4.05 |
VPA组 | 10 | 65.25±3.51△△ | 61.48±5.08△△ |
低剂量组 | 10 | 78.72±3.25*## | 48.64±4.55* |
中剂量组 | 10 | 80.15±3.54*## | 46.83±4.27* |
高剂量组 | 10 | 86.58±3.68**## | 45.22±4.87* |
VPA组与空白组对照:“△”P<0.05;“△△”P<0.01;与VPA组对照:“*”P<0.05;“**”P<0.01;同一组别接触陌生鼠的时间与接触空笼的时间:“#”P<0.05;“##”P<0.01;
实验结论:在本试验条件下:空白组仔鼠接触陌生鼠的时间要长于接触空笼的时间,差异具有统计学意义(P<0.01);VPA组仔鼠接触陌生鼠的时间与接触空笼的时间差异没有统计学意义(P>0.05)。VPA组与空白组相比,VPA组接触陌生鼠的时间要短于空白组,接触空笼的时间要长于空白组,差异具有统计学意义(P<0.05),说明造模成功;实施例1制备的药物组合物低、中、高各剂量组仔鼠接触陌生鼠的时间要长于接触空笼的时间,差异具有统计学意义(P<0.01);与VPA组相比实施例1制备的药物组合物低、中、高各剂量组,接触陌生鼠的时间要长于VPA组,接触空笼的时间要短于空白组,差异具有统计学意义(P<0.05或P<0.01),实施例1制备的药物组合物低、中、高各剂量能有效改善VPA仔鼠社交性。
狭隘的兴趣活动检测旷场测试
旷场测试的装置为一个36cm×36cm×36cm的黑色无顶方盒,其底板为白色,箱底用黑线分成9个等分小格。实验时间为小鼠出生后的第35天。实验前一天将旷场箱放于摄像头下,确保图像能清晰采集,打开图像自动采集系统,将空白组、VPA组,低剂量组,中剂量组,高剂量组仔鼠分别至于中央小方格,观察30s内仔鼠跨格次数、直立次数。检测仔鼠的兴趣活动。
表3 5组仔鼠旷场测试的比较
组别 | 例数 | 站立次数 | 跨格子数 |
空白组 | 10 | 35.14±8.62 | 92.68±3.95 |
VPA组 | 10 | 14.32±7.58△△ | 43.35±4.06△△ |
低剂量组 | 10 | 27.75±5.28** | 61.56±4.29* |
中剂量组 | 10 | 21.15±6.89* | 73.25±5.11** |
高剂量组 | 10 | 26.16±6.32** | 65.22±4.62* |
VPA组与空白组对照:“△”P<0.05;“△△”P<0.01;与VPA组对照:“*”P<0.05;“**”P<0.01
实验结论:在本试验条件下:VPA组与空白组相比,VPA组站立次数、跨格子数明显低于空白组,差异有统计学意义(P<0.01),说明造模成功。与VPA组相比实施例1制备的药物组合物低、中、高各剂量组站立次数、跨格子数高于VPA,差异具有统计学意义(P<0.05或P<0.01)。实施例1制备的药物组合物低、中、高各剂量能有效提高VPA仔鼠站立次数和跨格子数。
实施例3孤独症长效毒性动物实验
本项目研究按照国家GLP规范要求实施,观察SD大鼠经口灌服实施例1制备的药物组合物给予不同剂量药液多次给药毒性试验,评价实施例1制备的药物组合物对SD大鼠多次给药后毒性反应,为临床用药提供参考资料。
试验方法:选用合格SD大鼠120只,雌雄各半,体重173.3~217.7g,475×350×200mm3笼里饲养,每笼5只。按照国际(GB14925-2010)SPF级实验动物环境条件要求进行饲养,动物检疫和适应环境饲养7天。按性别体重随机分为4组,每组30只动物,雌雄各半。试验分为空白对照组、实施例1制备的药物组合物低、中、高剂量组(0.41、0.81、1.62g/kg)灌胃给药,连续给药6个月(26周)。给药中期末(第13周末)、给药末期末(第26周末)和恢复期末(第30周末)按计划分别解剖40只大鼠,雌雄各半。检查项目包括:一般临床观察;体重、摄食量测定;血液学、血液生化、凝血及脏器系数测定。试验结果:试验期间,所有动物均按计划实施安乐死,试验过程无动物死亡。
一般临床观察:观察期间,实施例1制备的药物组合物各剂量组与同期空白对照组比较,动物外观体征、行为活动、各腔道分泌物及动物的一般状况等未出现与药物毒性相关的异常反应。
体重:与同期空白对照组比较,实施例1制备的药物组合物各剂量组对大鼠体重均未见明显影响。
摄食量:与同期空白对照组比较,实施例1制备的药物组合物各剂量组对大鼠摄食量均未见明显影响。
血液学检查:与同期空白对照组比较,实施例1制备的药物组合物各剂量组血液学指标未见有毒理学意义的改变,结果表明实施例1制备的药物组合物对大鼠的血液学指标无明显影响。
血液生化检查:与同期空白对照组比较,实施例1制备的药物组合物各剂量组血液生化指标未见有毒理学意义的改变,结果表明实施例1制备的药物组合物对大鼠的血液生化指标无明显影响。
凝血检查:与同期空白对照组比较,实施例1制备的药物组合物各剂量组凝血指标未见有毒理学意义的改变,结果表明实施例1制备的药物组合物对大鼠的凝血指标无明显影响。
脏器系数:与同期空白对照组比较,实施例1制备的药物组合物各剂量组脏器系数无明显异常,结果表明实施例1制备的药物组合物对大鼠的脏器系数指标无明显影响。结论:在本试验条件下,SD大鼠经口灌服实施例1制备的药物组合物6个月,未见明显与药物有关的毒性反应剂量。
表4 实施例1制备的药物组合物对动物体重的影响
注:与空白对照组比较,*P<0.05。
表5 实施例1制备的药物组合物对动物平均摄食量的影响(g/只/天,)
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注:与空白对照组比较,*P<0.05。
表6 实施例1制备的药物组合物对动物血液学的影响/>
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注:与空白对照组比较,*P<0.05。
表7 实施例1制备的药物组合物对动物血液生化指标的影响
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注:与空白对照组比较,*P<0.05,**P<0.01。
表8 实施例1制备的药物组合物对动物凝血的影响
注:与空白对照组比较,*P<0.05。
表9 实施例1制备的药物组合物对动物脏器系数情况统计表(mg/g)/>
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注:与空白对照组比较,*P<0.05。
实施例4 ASD人体实验
临床使用效果实验:
选取符合孤独症诊断标准或者既往于专业机构诊断为“孤独症谱系障碍”的患者30例,其中男童23名,女童7名;平均年龄为(4.58±1.73)岁。诊断标准:参照《精神疾病诊断与统计手册-第5版》(DSM-V)中关于ASD的诊断标准。排除脑性麻痹、结节性硬化症、脆性X染色体综合征、苯丙酮尿症等疾病。
疗效评价:(1)比较患儿治疗前、治疗3个月后的儿童孤独症评定量表(CARS)评分和孤独症儿童行为量表(ABC量表)评分。CARS包括人际关系、模仿行为、情感反应等15个条目,每个条目评分1~4分,满分60分,得分越高表示患儿的病情越严重。ABC包含感觉、交往、语言、躯体运动、生活自理等5个方面,共计57个条目,每个条目评分1~4分,总分158分,分数越高表示患儿症状越严重。(4)比较两组患儿的治疗效果。治疗3个月后,患儿CARS评分较治疗前下降10~15分,ABC评分下降≥10分;患儿CARS评分较治疗前下降5~9分,ABC评分下降3~9分;患儿未达到上述标准者为无效。治疗总有效率=(显效例数+有效例数)/总例数×100%。
服用方法:口服。一次3g,一日3次,三个月为一个疗程。
表10 总有效率观察
表11 两组患儿治疗前后的CARS量表、ABC量表评分比较
实施例5
一种药物组合物,由以下重量份的组分组成:植物甾醇2重量份、二氢槲皮素2重量份、茶叶茶氨酸2重量份、葛根7重量份、槐花7重量份、显齿蛇葡萄叶12重量份、蓝莓花色苷1重量份。
原料可以通过市场购买途径直接得到,植物甾醇、二氢槲皮素、茶叶茶氨酸、蓝莓花色苷选择质量百分含量98%。
制备方法同实施例1,该组方安全有效,抗ASD效果明显。
以上所述为本发明的具体实施方式,但本发明的保护范围不局限于此,任何熟悉技术领域的技术人员在本发明揭露的技术范围内,根据本发明的技术方案及其构思加以等同替换或改变,都应涵盖在本发明权利要求的保护范围之内。
Claims (4)
1.一种治疗孤独症的药物组合物,其特征是,其原料配比为:植物甾醇1-3重量份、二氢槲皮素1-3重量份、茶叶茶氨酸1-3重量份、葛根5-7重量份、槐花5-7重量份、显齿蛇葡萄叶10-12重量份、蓝莓花色苷1-3重量份;其制备方法为:
步骤一、按原料配比将葛根、槐花、显齿蛇葡萄叶加12-15倍量水,煎煮2-3小时,煎煮液用100-200目滤布过滤,滤渣重复煎煮1-2次,合并药液,然后在60~70℃下,-0.06~-0.08Mpa减压浓缩至相对密度为1.20~1.30的稠膏,再在60~70℃,-0.06~-0.08Mpa真空干燥,粉碎,得干膏粉;
步骤二、将干膏粉和植物甾醇、二氢槲皮素、茶叶茶氨酸、蓝莓花色苷混合均匀,得药物组合物。
2.根据权利要求1所述一种治疗孤独症的药物组合物,其特征是,其原料配比为:植物甾醇1重量份、二氢槲皮素1重量份、茶叶茶氨酸1重量份、葛根5重量份、槐花5重量份、显齿蛇葡萄叶10重量份、蓝莓花色苷1重量份。
3.根据权利要求1所述一种治疗孤独症的药物组合物,其特征是,所述药物组合物制备成丸剂、膏剂或片剂。
4.根据权利要求1-3之一所述药物组合物在制备治疗孤独症的药物中的应用。
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