WO2024114725A1 - 益气活血解毒方及其应用 - Google Patents

益气活血解毒方及其应用 Download PDF

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WO2024114725A1
WO2024114725A1 PCT/CN2023/135373 CN2023135373W WO2024114725A1 WO 2024114725 A1 WO2024114725 A1 WO 2024114725A1 CN 2023135373 W CN2023135373 W CN 2023135373W WO 2024114725 A1 WO2024114725 A1 WO 2024114725A1
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patients
blood
detoxifying
invigorating
sepsis
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PCT/CN2023/135373
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English (en)
French (fr)
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李俊
唐光华
丁邦晗
刘云涛
陈瑞
徐胜梅
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广东省中医院
广州中医药大学第二附属医院
广州中医药大学第二临床医学院
广东省中医药科学院
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Application filed by 广东省中医院, 广州中医药大学第二附属医院, 广州中医药大学第二临床医学院, 广东省中医药科学院 filed Critical 广东省中医院
Publication of WO2024114725A1 publication Critical patent/WO2024114725A1/zh

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  • the invention belongs to the field of traditional Chinese medicine, and particularly relates to a prescription for invigorating qi, promoting blood circulation and detoxifying and an application thereof.
  • Sepsis refers to life-threatening organ dysfunction caused by host response disorders caused by infection. Septic shock may occur when the condition worsens, which is an important cause of multiple organ failure (MOF) and even death. According to statistics, about 1,400 people die from sepsis every day in the world, and the mortality rate of sepsis is about 20%. Studies on critically ill patients show that the incidence of sepsis is 15.7%, of which 61.1% further develop into multiple organ dysfunction syndrome (MODS), with a mortality rate of 30.6%. The absolute number of deaths due to sepsis is on the rise, and it has become one of the main causes of death in clinical critically ill patients.
  • MODS multiple organ dysfunction syndrome
  • dexmedetomidine for sedation in patients with sepsis undergoing mechanical ventilation is a hot topic in current research, but its clinical efficacy remains controversial.
  • dexmedetomidine may cause adverse reactions such as hypotension, bradycardia, sinus arrest, and transient hypertension when used to treat sepsis.
  • Traditional Chinese medicine emphasizes syndrome differentiation and treatment, and has unique advantages in the treatment of sepsis. Although there is no relevant recommendation in the guidelines for the treatment of sepsis with traditional Chinese medicine, traditional Chinese medicine, as a treatment method, is used to assist Western medicine and Western medicine treatment, and plays an increasingly important role in the treatment of sepsis. Therefore, it is urgent to develop a safe and effective traditional Chinese medicine composition for the treatment of sepsis to assist in the treatment of sepsis.
  • the first purpose of the present invention is to provide a prescription for invigorating qi, promoting blood circulation and detoxifying.
  • the second purpose of the present invention is to provide an application of the prescription for invigorating qi, promoting blood circulation and detoxifying.
  • a prescription for invigorating qi, activating blood circulation and detoxifying is provided, wherein the main active ingredients thereof include, by weight: 10 to 30 parts of raw sun-dried ginseng, 6 to 30 parts of Panax notoginseng, and 3 to 15 parts of rhubarb.
  • the present invention believes that sepsis belongs to febrile diseases, which may be caused by the pathogenic factors of a weak person or be serious due to the pathogenic factors damaging the body's health. It is easy to manifest as a serious injury to the vital energy and the decline of the internal organs.
  • the tonic is comprehensive and is suitable for the characteristics of sepsis that easily damages the five internal organs. Therefore, the present invention uses raw sun-dried ginseng as the main drug.
  • raw sun-dried ginseng is the main drug for replenishing vital energy;
  • Panax notoginseng is used to promote blood circulation and remove blood stasis, while rhubarb is used to clear away heat and detoxify, and the two are both ministerial drugs;
  • rhubarb is used to clear the bowels and purge turbidity, and
  • rhubarb is used as a guiding drug to clear the twelve meridians.
  • the whole formula has the effect of replenishing qi, promoting blood circulation and detoxifying.
  • the sources of raw materials for this recipe are as follows:
  • Raw sun-dried ginseng The dried root of Panax ginseng C.A.Mey., a plant of the Araliaceae family. Cultivated ginseng is called “garden ginseng”. Garden ginseng is sun-dried or oven-dried and is called “raw sun-dried ginseng”. It enters the spleen, lung, and heart meridians. Sweet, slightly bitter, neutral.
  • Panax notoginseng The dried root of Panax notoginseng (Burk.) F.H.Chen of the Araliaceae family. Sweet, slightly bitter, warm. Enters the liver and stomach meridians.
  • Rhubarb The dried roots and rhizomes of Rheum palmatum L., Rheum offcinale Baill., and Rheum tanguticum Maxim. ex Balf. It tastes bitter and is cold in nature. It enters the spleen, stomach, large intestine, liver, and pericardium meridians.
  • the main active ingredients include, by weight: 30 parts of raw sun-dried ginseng, 30 parts of Panax notoginseng, and 5 parts of rhubarb.
  • medically acceptable adjuvants are also included.
  • the adjuvants used are carriers or excipients commonly used in the art, including but not limited to starch, lactose, glucose, sodium carboxymethyl cellulose, ethyl cellulose and methyl cellulose, malt, gelatin, polyols (such as propylene glycol, glycerol, mannitol), compressed tablets, etc., to help improve the stability or activity of the drug, or produce an acceptable taste or smell in the case of oral administration.
  • the dosage form of the Yiqi Huoxue Jiedu prescription is decoction, granules, powder, tablet, pill or capsule, so as to facilitate clinical administration.
  • a fourth aspect of the present invention there is provided the use of the above-mentioned Qi-invigorating, blood-activating and detoxifying prescription in the preparation of a drug having the effect of reducing the APACHE II score of patients with sepsis secondary to lung infection and/or improving the oxygenation index (PaO2/FiO2) of patients with sepsis.
  • the Yiqi Huoxue Jiedu prescription of the present invention can reduce the APACHE II score of patients with sepsis secondary to lung infection and improve the patient's condition; it also has a clear effect of lowering the patient's white blood cell count and neutrophil count, reducing the patient's inflammatory response.
  • FIG1 is a flowchart of screening and inclusion of subjects in the clinical trial of the present invention.
  • Figure 2 is a graph showing the changing trends of the severity scores and peripheral blood neutrophil counts of the two groups of patients in the clinical trial of the present invention over the treatment time
  • Figure 2(a) is a graph showing the changing trends of the severity scores of the two groups of patients in the clinical trial of the present invention over the treatment time
  • Figure 2(b) is a graph showing the changing trends of the peripheral blood neutrophil counts of the two groups of patients in the clinical trial of the present invention over the treatment time
  • A control group
  • B experimental group.
  • FIG3 is a graph showing the variation trend of oxygenation index of mechanical ventilation subgroups with treatment time in the clinical trial of the present invention, wherein A: control group, B: experimental group.
  • the granules of the Yiqi Huoxue Jiedu prescription of this embodiment are prepared from the following components: 30g of raw sun-dried ginseng, 30g of Panax notoginseng, and 5g of rhubarb.
  • the preparation method thereof comprises the following steps:
  • Second decoction add rhubarb slices, add 6 times water, heat to boiling, keep boiling for 0.5 hours, filter (200 mesh);
  • Decoction three times add 6 times water, heat to boiling, keep boiling for 0.5 hours, filter (200 mesh);
  • Spray drying spray drying the obtained clear paste, and the process parameters are set as follows: inlet air temperature 165-195°C, outlet air temperature 80-105°C, and powder is collected in time to obtain dry paste powder;
  • Granulation The intermediate after extraction is granulated into 12-40 mesh granules by dry method.
  • rhubarb granules are also prepared, and the preparation method thereof comprises the following steps:
  • rhubarb extract was prepared according to a conventional method in the art, and then the rhubarb extract was granulated into 12-40 mesh granules by dry method.
  • the Yiqi Huoxue Jiedu Fang granules are packed into small aluminum foil bags according to the specifications of 5.1 g per bag and the Dahuang granules are packed into small aluminum foil bags according to the specifications of 0.8 g per bag, thereby facilitating clinical administration.
  • the Yiqi Huoxue Jiedu prescription granules and rhubarb granules prepared in Example 1 were used to conduct the following clinical trials.
  • Inclusion criteria met the Sepsis 3.0 diagnostic criteria set out in the 2016 SSC guidelines; met the diagnostic criteria for lung infection, and the source of sepsis infection was considered to be lung infection; aged 18-85 years; signed informed consent.
  • Exclusion criteria patients who may die within 24 hours; patients with serious conditions requiring cardiopulmonary resuscitation; patients with advanced malignant tumors and cachexia; patients with acute coronary artery disease, such as acute myocardial infarction; patients who are allergic to the medicinal flavor of the Yiqi Huoxue Jiedu prescription, or patients with allergic constitution; pregnant women; patients who have participated in other clinical trials in the past 3 months; patients with other conditions that the clinical researchers believe are not suitable for participating in the study.
  • Dropout and exclusion criteria 1 Those who were later found not to meet the inclusion and exclusion criteria; 2 Those who did not take the Yiqi Huoxue Jiedu prescription for a full course of treatment after enrollment and whose efficacy could not be evaluated.
  • Control group Based on the Western medicine intervention plan in the 2016 Sepsis3.0 guidelines, Yiqi Huoxue Jiedu Fang placebo and Rhubarb placebo granules were added (twice a day, 1 bag of Yiqi Huoxue Jiedu Fang placebo and 2 bags of Rhubarb placebo each time, dissolved in 50 mL of warm water and administered orally/nasogastrically; course of treatment: 7 days).
  • the dose of rhubarb granules and placebo was adjusted according to the patient's stool condition. times/day, reduce dosage.
  • the placebo of Yiqi Huoxue Jiedu Fang is composed of maltodextrin, tartrazine, sunset yellow, caramel pigment, and bittering agent (all of which are food grade). Its appearance, taste, and weight are consistent with those of Yiqi Huoxue Jiedu Fang granules.
  • the rhubarb placebo is composed of maltodextrin, tartrazine, sunset yellow, caramel pigment, and bittering agent (all of which are food grade), and its appearance, taste, and weight are consistent with those of the rhubarb granules.
  • Outcome indicators 28-day mortality rate; 7-day mortality rate; length of hospital stay; duration of mechanical ventilation; SOFA score: time points 1d, 3d, and 7d; APACHE II score: time points 1d, 3d, and 7d; laboratory indicators related to immunity, inflammation, and organ function: WBC, PCT, CRP, LAC, T lymphocyte subsets (CD4+, CD8+, CD4+/CD8+), oxygenation index (PaO2/FiO2), PLT, TBIL, Cr: time points 1d, 3d, and 7d.
  • Safety evaluation indicators Detailed observation and reporting of all kinds of drug allergic reactions (including rash), gastrointestinal reactions (including nausea, vomiting, diarrhea), mental system disorders (insomnia, headache, dizziness) and abnormal changes in laboratory tests.
  • Monitoring of adverse events Timely reporting of serious adverse events; all adverse events were evaluated for their association with the study drug.
  • MI Multiple imputation
  • This study is a multicenter pilot study with three centers and a small number of samples in each center, so the impact of the center effect on the efficacy index is not considered. All tests were two-sided, and P ⁇ 0.05 was considered statistically significant.
  • the control group had a higher level of total bilirubin in peripheral blood (16.2 VS 7.9), and a lower level of IL-6 in peripheral blood (22.01 VS 32.35), as shown in Table 1 for details.
  • the Yiqi Huoxue Jiedu recipe can reduce the APACHE II score of patients with sepsis secondary to lung infection and improve the patient's condition; it also has a clear effect of lowering the patient's white blood cell count and neutrophil count, reducing the patient's inflammatory response.

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Abstract

一种益气活血解毒的中药组合物及其应用，其原料为：生晒参10-30份，三七6-30份，大黄3-15份。所述中药组合物可改善肺部感染继发脓毒症患者的病情，通过通腑、抗炎作用改善患者氧合，从而缩短患者机械通气时间。

Description

益气活血解毒方及其应用 技术领域
本发明属于中药领域，具体涉及一种益气活血解毒方及其应用。
背景技术
脓毒症(Sepsis)是指由感染引起的宿主反应失调导致的危及生命的器官功能障碍，病情加重可出现脓毒性休克，是引发多器官衰竭(Multiple Organ Failure,MOF)甚至死亡的重要原因。据统计，全世界每天约有1400人死于脓毒症，脓毒症的病死率约20％。对危重病患者的研究显示脓毒症发病率为15.7％，其中61.1％进一步发展为多器官功能障碍综合征(MODS)，病死率为30.6％。因脓毒症死亡的绝对数字呈上升趋势，其已成为临床急危重病患者死亡的主要原因之一。
2016年脓毒症和脓毒症休克治疗国际指南推荐将机械通气用于治疗脓毒症。有研究表明，脓毒症休克患者吸痰后采用高呼气末正压肺复张能有效改善肺泡萎陷及肺容积减小，并可改善血流动力学指标及呼吸力学指标。
右美托咪定用于脓毒症患者机械通气的镇静治疗是目前研究的热点，但其临床疗效尚存在争议。一项包含201例患者的研究未发现右美托咪定对死亡率和非机械通气时间有显著的影响(参见Kawazoe Y，Miyamoto K，et al.Effect of dexmedetomidine on mortality and ventilator-free days in patients requiring mechanical ventilation with sepsis a randomized clinical trial[J].JAMA,2017，317(13):1321-1328.)。此外，右美托咪定用于治疗脓毒症可能引发低血压、心动过缓及窦性停搏、暂时性高血压等不良反应。
中医讲究辨证论治，在脓毒症的治疗上具有独特的优势。虽然中医药治疗脓毒症指南无相关推荐，但中医药作为一种治疗手段，用以辅助西医西药治疗，在脓毒症的治疗中发挥着越来越重要的作用。因此，急需开发一种安全有效的治疗脓毒症的中药组合物，用以辅助脓毒症的治疗。
发明内容
本发明的第一个目的，在于提供一种益气活血解毒方，本发明的第二个目的，在于提供该益气活血解毒方的应用。
根据本发明的第一个方面，提供了一种益气活血解毒方，其主要活性成分以质量份计包括：生晒参10～30份，三七6～30份，大黄3～15份。
本发明认为，脓毒症属于温热病证，或因虚人感邪而发，或因邪毒伤正而重，均易表现为元气大伤，脏气衰亏。生晒参味甘微寒，主补五脏，性味中性， 补益全面，适用于脓毒症易损五脏元气的特点。因此，本发明以生晒参为君药。
方中，生晒参大补元气为君药；三七活血化瘀，大黄清热解毒，二者共为臣药；大黄通腑泻浊为佐药，大黄通行十二经为使药。全方共奏益气活血解毒的功效。
本方的原料来源如下：
生晒参：五加科植物人参Panax ginseng C.A.Mey.的干燥根，栽培者为“园参”，园参经晒干或烘干，称“生晒参”。归脾、肺、心经。甘、微苦，平。
三七：五加科植物三七Panax notoginseng(Burk.)F.H.Chen的干燥根。甘、微苦，温。归肝、胃经。
大黄：掌叶大黄(Rheum palmatum L.)、药用大黄(Rheum offcinale Baill.)、唐古特大黄(Rheum tanguticum Maxim.ex Balf.)的干燥根和根茎。味苦、性寒。归脾、胃、大肠、肝、心包经。
在一些实施方式中，其主要活性成分以质量份计包括：生晒参30份，三七30份，大黄5份。
在一些实施方式中，还包括医学上可接受的辅料。具体地，所用辅料为本领域常用的载体或赋形剂，包括但不限于淀粉、乳糖、葡萄糖、羧甲基纤维素钠、乙基纤维素和甲基纤维素、麦芽、明胶、多元醇(如丙二醇、甘油、甘露糖醇)、压片剂等，以帮助提高药物的稳定性或提高活性，或在口服情况下产生可接受的口感或气味。
在一些实施方式中，益气活血解毒方的剂型为汤剂、颗粒剂、散剂、片剂、丸剂或胶囊剂。由此，以方便临床给药。
根据本发明的第二个方面，提供了上述的益气活血解毒方在制备治疗脓毒症的药物中的应用。
根据本发明的第三个方面，提供了上述的益气活血解毒方在制备治疗肺部感染继发脓毒症的药物中的应用。
根据本发明的第四个方面，提供了上述的益气活血解毒方在制备具有降低肺部感染继发脓毒症患者的APACHE II评分和/或改善脓毒症患者氧合指数(PaO2/FiO2)的药物中的应用。
本发明的有益效果包括：
临床试验表明，本发明的益气活血解毒方可降低肺部感染继发脓毒症患者的APACHE II评分，改善患者病情；同时具有明确的下调患者白细胞计数及中性粒细胞计数的作用，降低患者炎症反应。通过亚组分析发现，益气活血解毒方对机械通气的患者表现出明确的改善患者氧合的作用，表明其在一定程度上可以通过方药的通腑作用及抗炎作用而改善患者氧合，从而可以起到缩短患者机械通气时间的作用。
附图说明
图1是本发明临床试验中的筛选与纳入受试者流程图。
图2是本发明临床试验中的两组患者的重症评分和外周血中性粒细胞计数随治疗时间的变化趋势，其中，图2(a)是本发明临床试验中的两组患者的重症评分随治疗时间的变化趋势，图2(b)是本发明临床试验中的两组患者的外周血中性粒细胞计数随治疗时间的变化趋势，图中，A：对照组，B试验组。
图3是本发明临床试验中的机械通气亚组氧合指数随治疗时间的变化趋势，图中，A：对照组，B试验组。
具体实施方式
下面结合具体实施例对本发明作进一步详细的说明。如无特别说明，本发明所用原料均为市场购买得到。
实施例1
本实施例的益气活血解毒方颗粒剂，由以下组分制备得到：生晒参30g，三七30g，大黄5g。
示例性地，其制备方法包括以下步骤：
(1)提取：
一煎：投入三七和人参饮片，加10倍水，加热至沸，保持微沸1小时，抽滤(200目)；
二煎：再投入大黄饮片，加6倍水，加热至沸，保持微沸0.5小时，抽滤(200目)；
三煎：加6倍水，加热至沸，保持微沸0.5小时，抽滤(200目)；
(2)浓缩：滤液减压浓缩为一定比重的清膏；
(3)喷雾干燥：对所得清膏进行喷雾干燥，工艺参数设置为：进风温度165-195℃，出风温度80-105℃，适时收粉，得到干膏粉；
(4)过筛混合：过筛所得干膏粉，混合30分钟均匀，得到提取后中间体；
(5)制粒：将提取后中间体采用干法制粒制成12-40目颗粒。
益气活血解毒方中大黄的量可以视情况进行加减，为了便于对本实施例的益气活血解毒方颗粒剂中大黄的量进行加减，还制备了大黄颗粒剂，其制备方法包括以下步骤：
另取大黄10g，按照本领域常规方法制得大黄提取物后，将大黄提取物采用干法制粒制成12-40目颗粒。
制得颗粒剂后，分别将益气活血解毒方颗粒按照每袋装净重5.1g、大黄颗粒按照每袋装净重0.8g的规格包装成铝箔小袋，由此，方便临床给药。
下面，为探究本发明的益气活血解毒方对肺部感染继发脓毒症患者免疫功能及临床预后的影响，采用实施例1制备的益气活血解毒方颗粒剂和大黄颗粒剂进行以下临床试验。
一、病例来源
2020年11月-2021年10月于广东省某医院急诊科、ICU住院的肺部感染继发脓毒症患者。
纳入标准：符合2016年SSC指南中制定的Sepsis 3.0诊断标准；符合肺部感染诊断标准，且脓毒症感染源考虑为肺部感染；年龄18-85周岁；签署知情同意者。
排除标准：24小时内可能死亡者；病情严重需要心肺复苏者；晚期恶性肿瘤存在恶液质者；有急性冠状动脉疾病者，如急性心肌梗死等；对益气活血解毒方中的药味过敏，或过敏体质者；妊娠妇女；近3个月参加过其他临床实验者；临床研究者认为有不适合参加研究的其他情况。
脱落及剔除标准：①后期发现不符合纳入、排除标准者；②入组后未服用足疗程益气活血解毒方，无法评价其疗效者。
二、随机双盲方案
患者以1:1的比例随机接受益气活血解毒方或安慰剂(安慰剂与益气活血解毒方的包装、颜色、颗粒性质一致)治疗。所有顺序号、随机号由临床方法学研究团队负责管理。盲法编码在随机化操作后制作，受试者顺序号及对应的随机数字和分组结果(即受试者分配到A或B组)为一级盲底；再将A、B两组用药编盲，此即为二级盲底(即A、B组中哪一组使用中医药或安慰剂)，并依顺序随机编制每位受试者的药物编号，所有操作过程记录并妥善保存。
在研究期间，研究者通过随机信封按顺序号获取随机号。参与研究的患者、研究人员、统计分析人员等所有人员对采用何种治疗方案并不知情，待研究结束后先进行一级揭盲，明确分组，进行统计分析，待临床研究方法学团队出具统计分析报告后进行二级揭盲，明确治疗组与对照组。
三、干预
试验组：在2016 Sepsis3.0指南西医干预方案基础上，同时加用实施例1制备的益气活血解毒方颗粒剂和大黄颗粒剂(每日2次，每次益气活血解毒方颗粒剂1袋和大黄颗粒剂2袋，50mL温开水溶化后口服/鼻饲；疗程：7天)。
对照组：在2016 Sepsis3.0指南西医干预方案基础上，同时加用益气活血解毒方安慰剂和大黄安慰剂颗粒剂(每日2次，每次益气活血解毒方安慰剂1袋和大黄安慰剂2袋，50mL温开水溶化后口服/鼻饲；疗程：7天)。
大黄颗粒剂及安慰剂的剂量根据患者大便情况加减，如大便次稀烂且超过3 次/天，减量。
益气活血解毒方安慰剂由麦芽糊精、柠檬黄色素、日落黄色素、焦糖色素、苦味剂(均为食品级)组成，其外观、味道和重量等均与益气活血解毒方颗粒剂一致。
大黄安慰剂由麦芽糊精、柠檬黄色素、日落黄色素、焦糖色素、苦味剂(均为食品级)组成，其外观、味道和重量等均与大黄颗粒剂一致。
益气活血解毒方颗粒剂及安慰剂均由江阴制药有限公司生产。
四、评价指标
结局指标：28天病死率；7天病死率；住院天数；机械通气时间；SOFA评分：时点1d、3d、7d；APACHE Ⅱ评分：时点1d、3d、7d；免疫-炎症及器官功能相关实验室指标：WBC、PCT、CRP、LAC、T淋巴细胞亚群(CD4+、CD8+、CD4+/CD8+)、氧合指数(PaO2/FiO2)、PLT、TBIL、Cr：时点1d、3d、7d。
安全性评价指标：详细观察和报告各类药物过敏反应(包括皮疹)、胃肠道反应(包括恶心、呕吐、腹泻)、精神系统障碍(失眠、头痛、头晕)以及实验室检查异常变化。监测不良事件发生情况：严重不良事件及时报告；所有不良事件均做出与研究药物关联性的评价。
五、统计分析
基线组间均衡性评价：对于服从正态分布的定量资料，采用均数±标准差表示，两组的比较采用t检验；对于不服从正态分布的定量资料，采用中位数(四分位数)表示，两组的比较采用Man-Whitney U检验；对于定性资料，采用频数和率表示，组间的比较采用卡方检验或者fisher确切概率法。对结局指标采用意向性分析(ITT)，受试者所在组别即为随机化分配应至的组别。采用多重填补(MI)对检查结果缺失值进行填补；结局指标28天死亡率比较采用卡方检验；对单个时点结局指标，服从正态分布的定量资料采用t检验，否则采用Man-Whitney U检验或卡方检验；对多次测量的免疫炎症指标，单个时点组间比较采用协方差分析，多个时点的组间比较采用混合效应模型分析。
本研究为多中心预试验，试验中心3个而每个中心样本例数较少，因此不考虑中心效应对疗效指标的影响。所有检验均采用双侧检验，以P<0.05为差异有统计学意义。
六、试验结果
1、病例脱落情况与基线对比
本研究共纳入受试者60例。其中因完善检查后明确诊断为非肺部感染继发脓毒症剔除4例：1例为尿路梗阻导致脓毒症、1例为肠穿孔腹腔感染脓毒症、1例为严重咽喉部及纵隔感染脓毒症、1例为急性大面积脑梗死。药物干预过程中8例受试者因未完成药物干预方案脱落：7例为家属签字放弃治疗出院，1例 为家属签字放弃治疗后受试者死亡。干预后随访过程中8例受试者因家属保守治疗而死亡或出院，记为脱落。详见图1。
最终40例受试者完成研究，其中男性33例(82.5％)，女性7例(17.5％)；平均年龄66.83(±10.56)岁，年龄最小32岁，最大86岁，年龄≥65岁的老年患者为25例(62.5％)。受试者7天内死亡0例，28内天死亡3例，28天病死率7.5％。
经检验，试验组与对照组的年龄、性别、基础疾病、SOFA评分、APACHEII评分、机械通气比例等均无统计学差异，对照组的外周血总胆红素水平更高(16.2 VS 7.9)，外周血IL-6水平更低(22.01 VS 32.35)，详见表1。
表1两组受试者基线人口学情况及临床特征比较

2、临床预后
统计分析发现：与对照组相比，试验组患者的28天病死率有下降趋势(9.5％VS 5.26％)，尚无统计学意义。在治疗第7天时，试验组的APACHE II评分更低(P＜0.05)(图2(a))、SOFA评分有更低的趋势(P＞0.05)。试验组患者的总住院时间(如患者因基础疾病需长期住院患者，则住院时间记为0)有缩短趋势(18.69天VS 19.79天)，但尚无统计学意义(P＞0.05)。详见表2。
表2两组受试者的临床预后比较
3、免疫-炎症
通过对两组的免疫-炎症指标进行重复测量的方差分析及混合效应模型分析 发现：在治疗后的第3天及第7天，试验组患者的外周血中性粒细胞计数均更低，且差异有统计学意义(P＜0.05)(图2(b))。与对照组相比，试验组的外周血白细胞计数有更低的趋势，淋巴细胞计数有升高的趋势。详见表3。
表3两组受试者免疫-炎症与肝肾功能相关指标比较
4、亚组分析
针对进行机械通气的患者进行亚组分析发现：与对照组相比，试验组患者较对照组患者治疗第3天的氧合指数改善更为明显(P＜0.05)。详见表4和图3。
表4机械通气亚组氧合指数比较
5、安全性
在整个研究过程中，无不良事件及严重不良事件发生。对两组患者的肝肾功能指标进行重复测量的方差分析发现：两组患者的血肌酐水平、总胆红素水平、血乳酸水平无统计学差异，提示益气活血解毒方的安全性良好。详见表5。
表5两组受试者肝肾功能及血乳酸情况比较

6、总结
从整体上看，益气活血解毒方可降低肺部感染继发脓毒症患者的APACHE II评分，改善患者病情；同时具有明确的下调患者白细胞计数及中性粒细胞计数的作用，降低患者炎症反应。通过亚组分析发现，益气活血解毒方对机械通气的患者表现出明确的改善患者氧合的作用，表明其在一定程度上可以通过方药的通腑作用及抗炎作用而改善患者氧合，从而可以起到缩短患者机械通气时间的作用。
以上所述的仅是本发明的一些实施方式。对于本领域的普通技术人员来说，在不脱离本发明创造构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。

Claims (7)

  1. 益气活血解毒方，其特征在于，其主要活性成分以质量份计包括：生晒参10～30份，三七6～30份，大黄3～15份。
  2. 根据权利要求1所述的益气活血解毒方，其特征在于，其主要活性成分以质量份计包括：生晒参30份，三七30份，大黄5份。
  3. 根据权利要求1或2所述的益气活血解毒方，其特征在于，还包括医学上可接受的辅料。
  4. 根据权利要求1或2所述的益气活血解毒方，其特征在于，所述益气活血解毒方的剂型为汤剂、颗粒剂、散剂、片剂、丸剂或胶囊剂。
  5. 权利要求1～4任一项所述的益气活血解毒方在制备治疗脓毒症的药物中的应用。
  6. 权利要求1～4任一项所述的益气活血解毒方在制备治疗肺部感染继发脓毒症的药物中的应用。
  7. 权利要求1～4任一项所述的益气活血解毒方在制备具有降低肺部感染继发脓毒症患者的APACHE II评分和/或改善脓毒症患者氧合指数的药物中的应用。
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* Cited by examiner, † Cited by third party
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CN115708843A (zh) * 2022-12-02 2023-02-24 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） 益气活血解毒方及其应用

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
LIN, LIN ET AL.: "Clinical study of combined stasis-dissolving and blood-activating therapy and western medicine in treating sepsis", SHANGHAI JOURNAL OF TRADITIONAL CHINESE MEDICINE, vol. 45, no. 6, 10 June 2011 (2011-06-10) *
LYU, DEKE ET AL.: "Effect of Dushen Decoction on blood pressure and fluid resuscitation in patients with septic shock", ZHEJIANG JOURNAL OF INTEGRATED TRADITIONAL CHINESE AND WESTERN MEDICINE, vol. 29, no. 4, 20 April 2019 (2019-04-20) *
MING, ZIQIANG ET AL.: "Observation on the efficacy of rhubarb and notoginseng powder in treating sepsis and gastrointestinal bleeding", CHINESE JOURNAL OF INTEGRATED TRADITIONAL AND WESTERN MEDICINE IN INTENSIVE AND CRITICAL CARE, vol. 13, no. 06, 28 November 2006 (2006-11-28) *
WAN, XINHONG ET AL.: "Effects of Shenqihuang Wenban Capsule fur Prevention and Treatment of Atherosclerotic Plaque in Rabbits", CHINESE JOURNAL OF INTEGRATIVE MEDICINE ON CARDIO-/CEREBROVASCULAR DISEASE, vol. 07, no. 09, 10 September 2009 (2009-09-10) *

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