CN111434342B - 蝉花菌丝体活性物质用于制备预防及/或改善急性肺损伤的组合物的用途 - Google Patents
蝉花菌丝体活性物质用于制备预防及/或改善急性肺损伤的组合物的用途 Download PDFInfo
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- CN111434342B CN111434342B CN201910211121.3A CN201910211121A CN111434342B CN 111434342 B CN111434342 B CN 111434342B CN 201910211121 A CN201910211121 A CN 201910211121A CN 111434342 B CN111434342 B CN 111434342B
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- cordyceps sobolifera
- cordyceps
- mycelium
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- acute lung
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Abstract
本发明提供一种蝉花菌丝体活性物质用于制备预防及/或改善急性肺损伤的组合物的用途,该活性物质的制备方法,包括下列步骤:(a)取一蝉花菌丝体(Cordyceps Cicadae mycelia)于平板培养基上,于15至30℃的温度下培养1至2周;(b)将步骤(a)培养后的蝉花菌丝体接种至一烧瓶内,于15至30℃、pH 2至6的环境培养3至14天;(c)将步骤(b)培养后的蝉花菌丝体接种于一发酵槽内,于15至30℃、pH 2至6的环境下搅拌培养3至21天,形成含有该蝉花菌丝体活性物质的一蝉花菌丝体发酵液。
Description
技术领域
本发明关于一种蝉花菌丝体活性物质、其制备方法及用途。具体来说,关于一种用于预防及/或改善急性肺损伤的蝉花菌丝体活性物质,其制备方法,以及其在食品或医药品中的用途。
背景技术
2017年十大死因中,其中第一大死因中恶性肿瘤中第一位的气管、支气管和肺癌、第三大死因肺炎、第七大死因慢性下呼吸道疾病,共四项十大死因与肺部发炎有着密不可分的相关性。
美国公告的十大死因中,也有三项与肺部发炎相关的疾病,包括肺与支气管癌、慢性呼吸道疾病、流感与肺炎。更进一步统计分析发现,在美国平均每年每100,000 人中就有79与59人发生急性肺损伤(acute lung injury,ALI)与急性呼吸窘迫症(acuterespiratory distress syndrome,ARDS)。其中ALI/ARDS所造成的死亡率约为43%,造成美国每年约有75,000人死亡。由于空气污染日趋严重与平均余命逐年提高的情况下,推测在美国在未来25年内,ALI/ARDS的发生率将成长2倍以上。
ALI与更严重的ARDS为临床常见的急性肺发炎的代表性疾病,皆会引发呼吸衰节而导致死亡,并与许多呼吸道疾病相关。
造成ALI的危险因子分两大类,分别是:直接型因子,指危险因子源自于肺脏,包括细菌或病毒引起感染性肺炎、大量吸入胃酸或异 物、肺部挫伤等;间接型因子,指危险因子非源自于肺脏,包括败血症、长期酒精与药物滥用、输入人工血浆等。其中,细菌感染为ALI主要的危险因子,革兰氏阴性菌为其中一大类,其外套膜的主成分为内毒素,又名脂多醣(lipopolysaccride,LPS)。
由于ALI机制复杂、病死率高,目前临床上尚无确切有效的控制病死率的药物。但常用的治疗方法有机械通气、β2肾上腺素受体刺激剂、抗凝、溶栓、表面活性剂及手术等。因此,研究有效治疗ALI的方法仍是重要的发展方向。
蝉花(Cordyceps cicadae)又名虫花、土蝉花、胡蝉和蝉蛹草等,指在土中蝉幼虫被麦角菌科(Clavicipitaceae)虫草属(Cordyceps)真菌孢子寄生致死的带菌尸体,在蝉体头部长出菌丝形成的子座,外形似花蕾。在本草纲目、证类本草、中华药海中,指出蝉花主治小儿夜啼、心悸、止疟疾,并具散风热、镇惊等功效。经成分分析后发现天然蝉花子实体与冬虫夏草相近。
近代药理研究分析,发现蝉花具有免疫调节、抗氧化、抗发炎、神经保护、抗癌的生物活性。然而,目前尚未有蝉花对改善ALI的研究。
发明内容
本发明提供一种蝉花菌丝体活性物质及其制备方法,其可用于制备具预防及/或改善急性肺损伤的组合物。相较于一般西药及治疗方法,本发明提供的液态发酵蝉花菌丝体活性物质的制备方法更为安全、简便,制成的蝉花菌丝体活性物质更天然、安全,并可有效改善ALI。
根据本发明的一实施例,提供用于制备改善ALI的蝉花菌丝体活性物质的制备方法,其包括下列步骤:
(a)取蝉花菌丝体(Cordyceps Cicadae mycelia)于平板培养基上,于15至30℃的温度下培养1至2周;
(b)将步骤(a)培养后的蝉花菌丝体接种至烧瓶内,于15至30℃、pH 2至6 的环境培养3至14天;
(c)将步骤(b)培养后的蝉花菌丝体接种于发酵槽内,于15至30℃、pH 2至 6的环境下搅拌培养3至21天,形成含有蝉花菌丝体活性物质的蝉花菌丝体发酵液。
一实施例中,制备蝉花菌丝体活性物质的方法还包括步骤(d):将蝉花菌丝体发酵液冷冻干燥后磨粉,形成含有该蝉花菌丝体活性物质的一蝉花菌丝体冻干粉。
一实施例中,步骤(c)中的发酵槽进一步通入一气体,此气体包括空气、氧气、二氧化碳、氦气或其组合,发酵槽的槽压为0.5至1.0kg/cm2且通气速率为0.01至1.5 VVM。
本发明的另一实施态样是提供一种蝉花菌丝体活性物质,其为以上述制备方法制造而成。
本发明的又一实施态样是提供一种用于预防及/或改善急性肺损伤的组合物,其为包含上述的蝉花菌丝体活性物质,以及药学上可接受的载剂、赋形剂、稀释剂或辅剂。
本发明的再一实施态样是提供一种上述蝉花菌丝体活性物质的用途,其为用于制备预防及/或改善急性肺损伤的组合物。
一实施例中,所述改善急性肺损伤是指肺部发炎的病理症状减缓。
一实施例中,所述肺部发炎病理减缓是指肺泡的结构由破坏或融合趋向完整。
一实施例中,所述改善急性肺损伤是指蛋白质渗出反应降低。
一实施例中,所述改善急性肺损伤是指发炎细胞浸润程度降低。
一实施例中,所述发炎细胞是指白血球、吞噬细胞及/或嗜中性白血球。
附图说明
图1表示蝉花菌丝体冻干粉经由腹腔注射,再利用内毒素经由鼻腔吸入诱发急性肺发炎模式中,可有效改善ALI的病理变化。
图2表示蝉花菌丝体冻干粉经由腹腔注射,再利用内毒素经由鼻腔吸入诱发急性肺发炎模式中,可有效改善ALI的肺泡微血管障壁破坏。
图3表示蝉花菌丝体冻干粉经由腹腔注射,再利用内毒素经由鼻腔吸入诱发急性肺发炎模式中,可有效改善ALI的白血球浸润(A)、吞噬细胞(B)、嗜中性白血球 (PMN)(C)。
图4表示蝉花菌丝体冻干粉经由口服施加,再利用内毒素经由鼻腔吸入诱发急性肺发炎模式中可有效改善ALI的病理变化。
图5表示蝉花菌丝体冻干粉经由口服施加,再利用内毒素经由鼻腔吸入诱发急性肺发炎模式中,可有效改善ALI的肺泡微血管障壁破坏。
图6表示蝉花菌丝体冻干粉经由口服施加,再利用内毒素经由鼻腔吸入诱发急性肺发炎模式中,可有效改善ALI的白血球浸润(A)、吞噬细胞(B)、嗜中性白血球 (PMN)(C)。
具体实施方式
为使本发明的上述及其它方面更为清楚易懂,下文特举实施例,并配合所附图式详细说明。
实施例一:蝉花菌丝体培养
本发明的实施例所用的蝉花(Cordyceps cicadae)菌丝体是由采集而得的中国台湾野生蝉花子实体经分离而得其菌丝体,并继代保存于平板培养基上。经中国台湾食品工业发展研究所做鉴定其基因序列后,证实为蝉花(Cordyceps cicadae),此菌株已公开寄存于中国台湾食品工业发展研究所的生物资源研究中心(BCRC),其寄存编号为MU30106。但本发明所述的蝉花菌丝体活性物质的来源不限于由此菌种所得。
(1)平板培养:将蝉花菌丝体接种于平板上,于15至30℃下培养1至2周(本实施例中,于25℃下培养7天)。平板培养基的成分可包含马铃薯糊精培养基(Potato DextroseAgar,PDA)、碳源及氮源,并无特别限制。
(2)烧瓶培养:刮取(1)平板上的菌丝体接种于烧瓶中,并以15至30℃、pH 2至6及转速110至130rpm的条件震荡培养3至14天(本实施例中,于25℃、pH 5、转速120rpm的下震荡培养7天)。此震荡培养是以下表1所示的培养基进行培养。
表1、培养基配方
上述培养基配方中,综合性碳氮源可选自谷类(如:麦粉)或豆类(如:黄豆粉、绿豆粉、大豆粉、肉桂粉等);醣类可为葡萄糖、果糖、麦芽糖、蔗糖等;无机盐类可为硫酸镁、磷酸氢二钾、磷酸二氢钾、硫酸铁等。特别说明的是,表1培养基配方仅为其中一种范例,使用时成分可依需求调整,或搭配市售培养基使用,并无特别限制。
(3)发酵槽培养:将(2)中烧瓶培养的菌丝体接种于发酵槽内,以15至30℃、槽压0.5至1.0kg/cm2、pH 2至6及搅拌速度50至150rpm条件下,以0.1至1.5VVM 的通气速率培养3至21天,形成一蝉花菌丝体发酵液(本实施例中,是在25℃、槽压0.5kg/cm2、pH 5,搅拌速度80rpm及1.0VVM(空气)的条件下培养14天),即得蝉花菌丝体发酵液。发酵槽培养使用的培养基可与步骤(2)烧瓶培养使用的培养基相同、亦可另外配置适当培养基(本实施例以相同于步骤(2)的培养基培养)。此蝉花菌丝体发酵液内即含本发明的蝉花菌丝体活性物质。蝉花菌丝体发酵液可进一步通过冷冻干燥步骤制备为蝉花菌丝体发酵液冻干粉。于本实施例中,100L的蝉花菌丝体发酵液可制得约3kg冻干粉。
蝉花菌丝体活性物质的态样可被包含于蝉花菌丝体发酵液(菌丝体与澄清液)、发酵液冻干粉、以及冻干粉回溶于溶剂的型态或其他剂型。在一较佳实例中,该回溶冻干粉的溶剂为水、乙醇或其组合。在一较佳实例中,作为该回溶冻干粉的溶剂的水与乙醇的比例为1:1。以下实施例二中,是以蝉花菌丝体发酵液冻干粉作为蝉花菌丝体活性物质态样进行后续相关实验分析。
实施例二:蝉花菌丝体冻干粉改善ALI的分析
细菌感染为ALI主要的危险因子,革兰氏阴性菌为其中一大类,其外套膜的主成分为内毒素,又名脂多醣(lipopolysaccride,LPS)。在许多致病源中LPS是广泛被接受造成肺部急性发炎最佳的诱发物,也是最接近临床上急性发炎的模式。因此,若能抑制LPS造成的肺部发炎、免疫调解作用及机制,即能达到改善ALI的效果。目前已有实验利用内毒素诱发的ALI疾病动物模式。可参照Yunhe Fu et al.(2017), Protective effect of TM6 onLPS-induced acute lung injury in mice,SCIENTIFIC REPORTS,7:572.。根据此篇论文中利用LPS建立老鼠的急性肺部发炎模式,在鼻腔内引入(intranasally,i.n.)LPS 50μg/20μL造成急性肺损伤,后续进行肺部病理、肺泡冲洗液总细胞数、蛋白质浓度及各种细胞激素的变化分析,用以评估合成肽例如:细胞可渗透衍生自TIR结构域的诱导胜肽(cell-permeable TIR domain-derived decoy peptide)对ALI的改善结果。本实验中亦以LPS建立老鼠的急性肺部发炎模式,进行肺部病理、肺泡冲洗液总细胞数、蛋白质浓度及各种细胞激素的变化分析,评估蝉花菌丝体活性物质对ALI的改善结果。
运用BALB/c小鼠进行动物实验,按施加途径分为腹腔注射及口服两大组,每大组再以施加物质不同,分为不施加任何物质的控制组(Control组)、仅施加LPS作为负对照组(LPS组)、施加LPS也施加蝉花菌丝体活性物质冻干粉组(CC mycelia组)、施加LPS也施加地塞米松(Dexamethasone)作为正对照组(DEX组),共计8组如下表2。每组6只小鼠,共48只小鼠。
表2、实验分组
针对施加途径为腹腔注射的组别,内毒素组(LPS)利用鼻腔吸入施加20μl,LPS浓度为每只小鼠50μg,24小时后牺牲小鼠取其检体进行后述分析。CC mycelia 组首先将蝉花菌丝体冻干粉回溶于水与乙醇以比例1:1配制的溶剂中,经超声震荡以均质化,并确认无沉淀后,作为要施加的样品。利用腹腔注射(i.p.)向小鼠施加 50μl的蝉花样品,30分钟后经鼻腔施加内毒素(LPS),施加与牺牲的方法同上。DEX 组将DEX溶于生理食盐水(saline)中,利用腹腔注射(i.p.)向小鼠施加50μl,30 分钟后经鼻腔施加内毒素(LPS),施加与牺牲的方法同上。
针对施加途径为口服的组别,内毒素组(LPS)利用鼻腔吸入施加20μl,LPS浓度为每只小鼠50μg,24小时后牺牲小鼠取其检体进行后述分析。CC mycelia组首先将蝉花菌丝体冻干粉回溶于水与乙醇以比例1:1配制的溶剂中,经超声震荡以均质化,并确认无沉淀后,作为要施加的样品。利用口服管喂施加小鼠200μl的蝉花样品三天,每天一次,三天后经鼻腔施加内毒素(LPS),施加与牺牲的方法同上。DEX 组将DEX溶于生理食盐水(saline)中,利用口服管喂施加小鼠200μl三天,每天一次,三天后经鼻腔施加内毒素(LPS),施加与牺牲的方法同上。
肺组织病理形态观察:取未进行肺泡灌洗的小鼠右肺,立即以福尔马林液固定,并制成石蜡切片,再以苏木精-伊红染色(hematoxylin and eosin stain、H&E stain)的常规方法染色,于光学显微镜下观察其病理组织学变化。
气管肺泡灌洗术(Bronchoalveolar lavage,BAL):小鼠的左肺用1ml PBS经气管插管灌洗三次,将支气管肺泡腔中的内含物冲出以取得冲洗液(BAL fluid,BALF)。冲洗液离心后,沉淀出来的细胞的部分进行血球分类与计数;上清液的部分,则利用布拉德福蛋白质定量法(Bradford protein assay)进行蛋白质浓度分析。
白血球计数与种类分析:利用流式细胞仪分析:为灵敏度高且人为误差小的分析方法,将血液与BALF检体利用白血球的表面具有专一性抗原的特性,进行白血球分型,包括有(1)分析BALF中细胞总数;(2)白血球(CD45)总数;(3)吞噬细胞 (CD45+/CD11b+)总数;(4)嗜中性球(CD45+/Ly6G+)总数;(5)巨噬细胞 [(CD45+/CD11b+)-(CD45+/Ly6G+)]总数。
统计方法:实验数据皆以Mean±standard deviation(SD)表示,统计以one-wayANOVA进行分析,并以LSD事后检定比较各组差异,分析结果若p小于0.05,视为具有统计上的显著意义。
腹腔注射的结果如图1显示蝉花菌丝体冻干粉可有效改善肺部发炎病理变化。Control组未见明显改变,肺泡结构多数保持完整。LPS组肺组织病变明显,肺泡结构破坏、融合,而CC mycelia组及DEX组小鼠肺部病情情况明显减轻。
于腹腔注射后分析内毒素诱发肺部发炎所导致的蛋白质渗出反应,发现蝉花菌丝体活性物质冻干粉可有效降低蛋白质渗出反应如图2及下表3。#P<0.05与对照组比较,*P<0.05与LPS组比较。
表3、腹腔注射的蛋白质渗出结果
组别 | 蛋白质渗出(mg/mL) |
Control组 | 2.87±1.02 |
LPS组 | 9.93±1.52# |
CC mycelia组 | 5.39±1.27* |
DEX组 | 3.83±1.72* |
(n=6)
#表示与Control组统计上具显著差异(p<0.05)
*表示与LPS组统计上具显著差异(p<0.05)
于腹腔注射后分析内毒素诱发肺部发炎所导致的(A)白血球(CD45)、(B)吞噬细胞(CD45+/CD11b+)、及(C)嗜中性球(CD45+/Ly6G+)浸润反应,发现蝉花菌丝体活性物质冻干粉可有效改善白血球、吞噬细胞及嗜中性白血球(PMN)浸润如图3(A至C)及下表4至6。#P<0.05与control组比较;*P<0.05与LPS组比较。
表4、腹腔注射的白血球浸润结果
组别 | 白血球浸润(10<sup>5</sup>) |
Control组 | 0.14±0.06 |
LPS | 3.29±1.95# |
CC mycelia组 | 0.46±0.34* |
DEX组 | 0.56±0.29* |
(n=6)
#表示与Control组统计上具显著差异(p<0.05)
*表示与LPS组统计上具显著差异(p<0.05)
表5、腹腔注射的吞噬细胞浸润结果
组别 | 吞噬细胞浸润(10<sup>5</sup>) |
Control组 | 0.07±0.03 |
LPS组 | 1.62±0.67# |
CC mycelia组 | 0.25±0.14* |
DEX组 | 0.27±0.26* |
(n=6)
#表示与Control组统计上具显著差异(p<0.05)
*表示与LPS组统计上具显著差异(p<0.05)
表6、腹腔注射的嗜中性球浸润结果
组别 | 嗜中性球浸润(10<sup>5</sup>) |
Control组 | 0.04±0.02 |
LPS组 | 1.12±0.80# |
CC mycelia组 | 0.15±0.10* |
DEX组 | 0.16±0.16* |
(n=6)
#表示与Control组统计上具显著差异(p<0.05)
*表示与LPS组统计上具显著差异(p<0.05)
经由口服的结果如图4显示蝉花菌丝体活性物质冻干粉可有效改善肺部发炎病理变化。Control组未见明显改变,肺泡结构多数保持完整。LPS组肺组织病变明显,肺泡结构破坏、融合,而CC mycelia组及DEX组小鼠肺部病情情况明显减轻。
于口服施加后分析内毒素诱发肺部发炎所导致的蛋白质渗出反应,发现蝉花菌丝体活性物质冻干粉可有效降低蛋白质渗出反应如图5及下表7。#P<0.05与对照组比较,*P<0.05与LPS组比较。
表7、口服施加的蛋白质渗出结果
组别 | 蛋白质渗出(mg/mL) |
Control组 | 2.60±0.24 |
LPS组 | 6.65±1.18# |
CC mycelia组 | 2.48±0.35* |
DEX组 | 3.11±0.64* |
(n=6)
#表示与Control组统计上具显著差异(p<0.05)
*表示与LPS组统计上具显著差异(p<0.05)
于口服施加后分析内毒素诱发肺部发炎所导致的(A)白血球(CD45)、(B)吞噬细胞(CD45+/CD11b+)、及(C)嗜中性球(CD45+/Ly6G+)浸润反应,发现蝉花菌丝体活性物质冻干粉可有效改善白血球、吞噬细胞及嗜中性白血球(PMN)浸润如图6(A至C)及下表8至10。#P<0.05与control组比较;*P<0.05与LPS组比较。
表8、口服施加的白血球浸润结果
组别 | 白血球浸润(10<sup>5</sup>) |
Control组 | 0.38±0.22 |
LPS组 | 3.17±0.82# |
CC mycelia组 | 0.70±0.46* |
DEX组 | 0.88±0.25* |
(n=6)
#表示与Control组统计上具显著差异(p<0.05)
*表示与LPS组统计上具显著差异(p<0.05)
表9、口服施加的吞噬细胞浸润结果
(n=6)
#表示与Control组统计上具显著差异(p<0.05)
*表示与LPS组统计上具显著差异(p<0.05)
表10、口服施加的嗜中性球浸润结果
组别 | 嗜中性球浸润(10<sup>5</sup>) |
Control组 | 0.02±0.01 |
LPS组 | 0.29±0.09# |
CC mycelia组 | 0.04±0.02* |
DEX组 | 0.04±0.02* |
(n=6)
#表示与对照组(control)统计上具显著差异(p<0.05)
*表示与负对照组(LPS)统计上具显著差异(p<0.05)
本发明的蝉花菌丝体活性物质经上述实验,已证实具有改善ALI的作用。
实施例三:组合物的制备
本发明提供一组合物,其包含蝉花菌丝体活性物质,以制备为医药组合物,亦可作为保健营养食品。
该组合物进一步包含添加剂。在一较佳的实施态样中,该添加剂可为赋型剂、防腐剂、稀释剂、填充剂、吸收促进剂、甜味剂、润滑剂、黏稠剂、或其组合。该赋型剂可选自柠檬酸钠、碳酸钙、磷酸钙、蔗糖或其组合。该防腐剂可延长医药组合物的储藏期限,例如苯甲醇、对羟基苯甲酸(parabens)、二氧化硅或其组合。该稀释剂可选自水、乙醇、丙二醇、甘油或其组合。该填充剂可选自乳糖、高分子量聚乙二醇或其组合。该吸收促进剂可选自二甲基亚砜(DMSO)、月桂氮卓酮、丙二醇、甘油、聚乙二醇或其组合。该甜味剂可选自安塞甜(Acesulfame K)、阿斯巴甜(aspartame)、糖精(saccharin)、三氯蔗糖/蔗糖素(sucralose)、纽甜(neotame)或其组合。该润滑剂可选自硬脂酸镁或阿拉伯胶。该黏稠剂可为玉米淀粉。除上述所列举的添加剂以外,在不影响组合物的医药效果前提下,可依需求选用适合的其他添加剂。
该组合物于医药领域中可开发为不同商品。在一较佳实施态样中,该组合物为一药品、饲料、饮料、营养补充品、乳制品、食品或保健食品。
该组合物可根据受施加者的需要,而采用不同形态。在一较佳实施态样中,该组合物的形态为粉剂、锭剂、造粒、栓剂、微胶囊、安瓶(ampoule/ampule)、液剂喷剂或塞剂。
本发明的组合物可使用于动物或是人类。在不影响效果的前提下,该组合物可制为任何药物型态,并根据药物型态以适用的途径向该动物或人类施加。
本发明的蝉花菌丝体活性物质若应用于食品用途,则以下组合物1的态样作为例示性实例。
组合物1:取蝉花菌丝体活性物质冻干粉(20wt%)与作为润滑剂的硬脂酸镁(8wt%)、作为防腐剂的二氧化硅(7wt%)充分混合,并溶于纯水(65wt%)中,存放于4℃备用。前述wt%是指各成分占组合物总重的比例。
本发明的蝉花菌丝体活性物质若以液体剂型应用于医药用途,则以下组合物2 的态样作为例示性实例。
组合物2:取蝉花菌丝体活性物质冻干粉(20wt%)与作为甜味剂的蔗糖素(8wt%)、作为润滑剂的阿拉伯胶(7wt%)、作为赋型剂的蔗糖(10wt%)充分混合,并溶于纯水(55wt%)中,存放于4℃备用。前述wt%是指各成分占组合物总重的比例。
虽然本发明已用实施例提供如上,然其并非用以限制本发明。本领域的通常知识者,于参酌以上说明后,当能对上述实施例的内容进行适当修改,而仍然能达到本发明所主张的功效。因此,本发明的保护范围应以所附的权利要求为准。
Claims (6)
1.一种蝉花菌丝体活性物质用于制备预防及/或改善急性肺损伤的组合物的用途,所述蝉花菌丝体活性物质的制备方法包括下列步骤:
(a)取一蝉花菌丝体于平板培养基上,于15至30℃的温度下培养1至2周;
(b)将步骤(a)培养后的蝉花菌丝体接种至一烧瓶内,于15至30℃、pH 2至6的环境培养3至14天;
(c)将步骤(b)培养后的蝉花菌丝体接种于一发酵槽内,向发酵槽通入一气体,该气体包括空气,该发酵槽的槽压为0.5至1.0 kg/cm2 且通气速率为0.01至1.5 VVM,于15至30℃、pH 2至6的环境下搅拌培养3至21天,形成一蝉花菌丝体发酵液;及
(d)将步骤(c)的该蝉花菌丝体发酵液冷冻干燥后磨粉,形成含有该蝉花菌丝体活性物质的一蝉花菌丝体冻干粉;
其中,所述蝉花菌丝体公开寄存于中国台湾食品工业发展研究所的生物资源研究中心,其寄存编号为MU30106。
2.如权利要求1所述的用途,其中所述改善急性肺损伤是指肺部发炎的病理症状减缓。
3.如权利要求2所述的用途,其中所述肺部发炎病理减缓是指肺泡的结构由破坏或融合趋向完整。
4.如权利要求1所述的用途,其中所述改善急性肺损伤是指蛋白质渗出反应降低。
5.如权利要求1所述的用途,其中所述改善急性肺损伤是指发炎细胞浸润程度降低。
6.如权利要求5所述的用途,其中所述发炎细胞指白血球、吞噬细胞及/或嗜中性白血球。
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TWI701335B (zh) | 2020-08-11 |
JP2020105159A (ja) | 2020-07-09 |
KR102223608B1 (ko) | 2021-03-08 |
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CN111434342A (zh) | 2020-07-21 |
CA3040916A1 (en) | 2020-06-25 |
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