CN112022795A - 皮肤护理及修复组合物、其制备方法及应用 - Google Patents
皮肤护理及修复组合物、其制备方法及应用 Download PDFInfo
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Abstract
本发明公开的皮肤护理及修复组合物,包括透明质酸钠0.1~0.5份、甘草酸二钾0.1~0.4份、卡波姆0.1~0.5份、山茶油2~8份、灭活的乳酸杆菌1~10份、甘油1~8份、精氨酸0.2~0.5份、适量的水。还提供该组合物的制备方法及应用。各组分搭配,能够很好的为皮肤保湿,促进浅表创面愈合与皮肤修复,对过敏、皮炎、皮肤瘙痒、脱皮、红斑等造成屏障受损的皮肤进行综合的护理与修护,同时原料安全温和,易于吸收,市场应用前景广阔,可用于制备皮肤护理、皮肤修复的制剂或医疗器械等。
Description
技术领域
本发明涉及医药化工及医疗器械技术领域,尤其是涉及皮肤护理及修复组合物、其制备方法及应用。
背景技术
皮肤作为人体表面积最大的器官,皮肤表面上存在很多微生物群,包括细菌、真菌、病毒和衣原体,这些微生物与皮肤表面的组织细胞及各种分泌物、微环境等共同组成一个微生态系统,也就是皮肤微生态。当皮肤微生态处于和谐平衡的状态,将有利于皮肤的健康,反之则会出现痤疮、皮炎等各类皮肤问题。
皮肤屏障功能是皮肤重要的功能之一,其中角质层对于皮肤屏障功能的正常发挥具有十分重要的意义。干燥、粗糙等皮肤问题则是角质层功能失调的外在表现,此时如果单纯地给皮肤补充水分并不能很好的改变皮肤的干燥状态,而更为重要的是通过补充角质层的脂质成分达到恢复和维持正常角质层屏障功能。
另外,因人体免疫系统失调及不正当使用化妆品等,也会使皮肤失去原有的屏障功能,出现过敏、红肿、刺痛等现象。由外因造成皮肤浅表创伤时,如不及时修复,还易造成细菌感染。
现有的具备皮肤修复作用的产品主要为化妆品和医用药膏,大多功能单一,很难同时实现抗敏、减轻瘙痒、促进皮肤创面愈合及皮肤修复功效,同时,大多还存在成分复杂,对人体刺激性大的问题。
发明内容
本发明旨在至少解决现有技术中存在的技术问题之一,提出一种皮肤护理及修复组合物及其制备方法,具有安全温和、抗敏效果好、显著减轻皮肤瘙痒、促进浅表创面的愈合和皮肤修复等作用,能有效改善肌肤过敏问题,促进皮肤修复。可应用于皮肤保湿、皮肤屏障受损的修复及皮肤浅表创伤的愈合等皮肤的护理与修复。
根据本发明第一方面的实施例,所提出的皮肤护理及修复组合物,包括以下按重量份计的组分:
透明质酸钠0.1~0.5份、甘草酸二钾0.1~0.4份、卡波姆0.1~0.5份、山茶油2~8份、灭活的乳酸杆菌1~10份、甘油1~8份、精氨酸0.2~0.5份、适量的水;其中,水的含量示例为80~98份。
更优选包括:
透明质酸钠0.1~0.5份、甘草酸二钾0.1~0.3份、卡波姆0.2~0.5份、山茶油2~6份、灭活的乳酸杆菌4~8份、甘油2~8份、精氨酸0.2~0.4份、适量的水;其中,水的含量示例为90~95份。
在部分实施例中,所述乳酸杆菌选自嗜酸乳杆菌、罗伊氏乳杆菌、副干酪乳杆菌、鼠李糖乳杆菌、发酵乳杆菌、植物乳杆菌中的一种或几种。
在部分实施例中,所述组合物中还添加有适量的防腐剂,示例为0.1~0.6份,所述防腐剂示例为苯甲酸钠、苯甲酸、羟苯甲酯钠、羟苯丙酯钠中的一种或几种。
第二方面,提供上述的皮肤护理及修复组合物的制备方法,包括步骤:
将透明质酸钠、甘草酸二钾、精氨酸、卡波姆、山茶油混合,加水搅拌均匀,再加入甘油、灭活的乳酸杆菌搅拌均匀;以及任选地,在加入甘油前加入防腐剂并搅拌均匀。
第三方面,提供上述的皮肤护理及修复组合物在制备皮肤护理或皮肤修复的制剂或医疗器械中的应用,包括但不限于皮肤保湿、皮肤屏障受损的修复、皮肤浅表创伤的愈合等。
第四方面,提供一种制剂,其包括上述的皮肤护理及修复组合物。
第五方面,提供一种医疗器械,其包括上述的皮肤护理及修复组合物。
根据本发明的一种或多种实施例至少具有如下有益效果:
山茶油中具有多种活性成分,配合乳酸杆菌对病原菌的对抗作用、透明质酸钠和甘油的保湿作用及甘草酸二钾的抗敏作用,能够很好的为皮肤保湿,促进浅表创面愈合与皮肤修复,对过敏、皮炎、皮肤瘙痒、脱皮、红斑等造成屏障受损的皮肤进行综合的护理与修护。
本发明的组合物原料安全温和,抗敏效果优异,同时能促进浅表创面愈合与皮肤修复,易于吸收,市场应用前景广阔。
附图说明
图1是实施例1~4和对比例1~2的创面愈合情况。
具体实施方式
为使本申请的目的、技术方案和优点更加清楚,下面将结合具体实施例进行详细说明。此处所描述的实施例仅是本申请一部分实施例,不能理解为对本申请保护范围的限制。
本发明实施例提供的皮肤护理及修复组合物,按重量份计,包括以下的组分:
透明质酸钠0.1~0.5份、甘草酸二钾0.1~0.4份、卡波姆0.1~0.5份、山茶油2~8份、灭活的乳酸杆菌1~10份、甘油1~8份、精氨酸0.2~0.5份,以及适量的水,例如水80~98份。
更优选包括:
透明质酸钠0.1~0.5份、甘草酸二钾0.1~0.3份、卡波姆0.2~0.5份、山茶油2~6份、灭活的乳酸杆菌4~8份、甘油2~8份、精氨酸0.2~0.4份,以及适量的水,例如水90~95份。
其中:
山茶油,又名茶油、山茶籽油等,由脂肪酸、山茶苷、磷脂质、皂苷、维生素E、鞣质等成分组成。茶油的不饱和脂肪酸含量丰富,高达85%以上,其脂肪酸组成与橄榄油极为相近。山茶油可以有效的补充皮脂膜中的甘油三酯成分,修复皮肤屏障。《中国药典》(2015年版)将茶油作为药用油收载,茶油因其富含多种营养成分,内服、外用都有很好的效用。
山茶油中含有角鲨烯。角鲨烯是一种抗氧化剂,有助于保持皮肤的柔软,可以有效改善皮肤色泽,可以缓解牛皮癣和皮炎等皮肤疾患,对人类免疫系统有疗效。山茶油可以直接影响皮肤结构,降低皮肤的屏障作用而显示其渗透活性,可促进药物经皮吸收作用,且山茶油成分与人体皮肤成分极其类似,相容性好,无刺激性和过敏性。
乳酸杆菌作为皮肤常驻菌群,可有效维护健康皮肤的正常功能。研究表明,存在于人类皮肤表面的微生物种类及数量却受限于外界的物理和生化因素,酸性的皮肤环境可以阻止细菌的侵驻。乳酸杆菌可以通过发酵产生代谢酸性分子(例如乳酸)、吸收氨基酸、盐类和其他酸性物质,酸化周围环境,为皮肤提供一个潮湿的屏障,维持健康皮肤的菌落水平。
此外,局部应用乳酸杆菌,其含有抗菌素(例如细菌素、细菌素类似物、有机酸、过氧化氢),进而防止病原体粘附,竞争对抗病原菌。同时,乳酸杆菌可以刺激人类皮肤纤维母细胞产生神经酰胺及胶原蛋白等,凝集皮肤病原菌如金黄葡萄球菌、白色念珠菌、马拉色菌等,抑制病原菌结合至细胞。胶原蛋白增生能够促进加速伤口愈合。神经酰胺是人体角质层脂质的主要成分,神经酰胺的减少可引起表皮失水和屏障功能异常,导致皮肤异常如过敏性皮炎,因此局部应用乳酸杆菌可改善皮肤屏障功能并有效抵抗年龄相关皮肤干燥病,促进皮肤修复。
本配方体系中,乳酸杆菌与山茶油产生了明显的协同增效作用,能起到显著的皮肤护理与修复效果。其中,乳酸杆菌可使用嗜酸乳杆菌、罗伊氏乳杆菌、副干酪乳杆菌、鼠李糖乳杆菌、发酵乳杆菌、植物乳杆菌等常见类型或其任意组合。示例为副干酪乳杆菌LP33、副干酪乳杆菌GMNL-133、植物乳杆菌GMNL-6、副干酪乳杆菌LP653、嗜酸乳杆菌DDS-1、发酵乳杆菌GM090、罗伊氏乳杆菌DSM17648等。在示例性实施例中,仅以部分乳酸杆菌为例进行说明。
透明质酸钠(Sodium Hyaluronate,HA)是由N-乙酰氨基葡萄糖及D-葡萄糖醛酸双糖单位重复连接而成的高分子酸性粘多糖,广泛存在于动物和人体结缔组织细胞外基质中。HA最重要的生理功能是其保水作用,HA分子在水溶液中高度伸展和随机卷曲的构型使其占有很大区域,而且分子链之间互相缠绕形成连续的网状结构,其作用于皮肤表面,形成一层透气的薄膜即屏障,能有效抑制肌肤细胞的水分蒸发,并可阻隔外来细菌、灰尘、紫外线的侵入,以及防止细菌生成,保护皮肤免受侵害。其应用于本配方体系中,可进一步改善皮肤过敏、皮炎、皮肤瘙痒、脱皮、红斑等皮肤屏障受损问题。
甘草酸二钾为甘草酸的衍生物,有着很好的抗炎、抗过敏、保湿、抗氧化等功效,在许多药品、日化用品、护肤品中都会有所添加,甚至还会被添加在食品中。甘草酸二钾具有良好的抗过敏作用,对抑制组胺生产和皮肤发红发痒有很好的效果,尤其是对某些过敏性休克有明显的保护作用,类似于肾上腺皮脂激素,长期使用亦无副作用。
各组分复配,利用山茶油中的多种活性成分,配合乳酸杆菌对病原菌的对抗作用、透明质酸钠和甘油的保湿作用及甘草酸二钾的抗敏作用,实现较好的皮肤保湿,对由皮肤敏感带来的刺激、红肿以及瘙痒症状具有良好的缓解作用,并能促进浅表创面愈合与皮肤修复,从而对过敏、皮炎、皮肤瘙痒、脱皮、红斑等造成屏障受损的皮肤进行综合的护理与修护。同时,各组分原料安全温和,易于吸收,市场应用前景广阔。
在实际应用中,可加入适量的防腐剂,其用量示例为0.1~0.6份,对防腐剂的类型没有特别限定,示例为苯甲酸钠、苯甲酸、羟苯甲酯钠、羟苯丙酯钠中的一种或几种。
本发明实施例的皮肤护理及修复组合物的制备方法,包括步骤:
将透明质酸钠、甘草酸二钾、精氨酸、卡波姆、山茶油混合,加水搅拌均匀,再加入甘油、灭活的乳酸杆菌搅拌均匀;以及任选地,在加入甘油前加入防腐剂并搅拌均匀。
本发明产品实施例的皮肤护理及修复组合物及方法实施例制备的皮肤护理及修复组合物可用于制备皮肤护理、皮肤修复的制剂或医疗器械,该制剂示例为皮肤修复液等,医疗器械示例为皮肤修护敷料(如皮肤修复膜)等。
以下通过示例性实施例对本发明作进一步地详细描述。其中,所用益生菌均为灭活菌。
实施例1
按重量份计,配方如下:
透明质酸钠0.2份、甘草酸二钾0.2份、卡波姆0.5份、山茶油2份、副干酪乳杆菌LP653为5份、甘油5份、精氨酸0.3份、苯甲酸钠0.3份、苯甲酸0.3份、纯化水90份。
实施例2
按重量份计,配方如下:
透明质酸钠0.4份、甘草酸二钾0.1份、卡波姆0.2份、山茶油3份、罗伊氏乳杆菌DSM17648为4份、嗜酸乳杆菌DDS-1为2份、甘油5份、精氨酸0.3份、羟苯甲酯钠0.3份、羟苯丙酯钠0.3份、纯化水90份。
实施例3
按重量份计,配方如下:
透明质酸钠0.2份、甘草酸二钾0.2份、卡波姆0.5份、山茶油3份、副干酪乳杆菌LP33为3份、副干酪乳杆菌LP653为4份、甘油2份、精氨酸0.2份、苯甲酸钠0.3份、纯化水92份。
实施例4
按重量份计,配方如下:
透明质酸钠0.5份、甘草酸二钾0.2份、卡波姆0.5份、山茶油2份、副干酪乳杆菌LP653为3份、植物乳杆菌GMNL-6为3份、甘油5份、精氨酸0.3份、苯甲酸钠0.2份、苯甲酸0.2份、纯化水90份。
实施例5
按重量份计,配方如下:
透明质酸钠0.1份、甘草酸二钾0.4份、卡波姆0.1份、山茶油8份、副干酪乳杆菌LP653为1份、甘油8份、精氨酸0.5份、苯甲酸钠0.3份、纯化水95份。
实施例1~5的组合物的制备方法,包括以下步骤:
按配方量称取各组分;将透明质酸钠、甘草酸二钾、精氨酸、卡波姆、山茶油、防腐剂加至烧杯中,加入纯化水,搅拌至充分溶胀,再加入甘油、乳酸杆菌搅拌均匀,出料即得。
对比例1
与实施例1相比,区别在于,不含山茶油。
对比例2
与实施例1相比,区别在于,不含副干酪乳杆菌LP653。
对比例3
与实施例1相比,区别在于,不含透明质酸钠,甘油为5.2份。
测试例1:抗右旋糖酐致小鼠全身瘙痒实验
取小鼠90只,按每组10只随机分为9组。各组分别为实施例1、实施例2、实施例3、实施例4、实施例5、对比例1、对比例2、对比例3和模型对照组。各组小鼠腹部同一部位脱毛2cm×2cm,24小时后分别将实施例1、实施例2、实施例3、实施例4、实施例5、对比例1、对比例2、对比例3的组合物均匀涂抹于脱毛区,每日2次,每次间隔12h,连续3天,模型对照组涂抹0.9%氯化钠注射液。末次给药1h后,于每只小鼠尾静脉注射0.02%右旋糖酐40注射液0.1ml,以小鼠出现前爪搔抓头部、后抓搔抓躯干、嘴咬全身部位作为瘙痒指征,观察并记录每只小鼠30min内小鼠瘙痒次数及瘙痒持续总时间。结果统计见表1。
表1
结果显示各实施例与模型组比较均有统计学差异(P<0.05或P<0.01)。实施例1~5较各对比例体现出更好的抗过敏作用,体现了组分间抗过敏的协同增效作用。
测试例2:浅表创面皮肤愈合实验
选取体重为20±2g的清洁级雄性小鼠70只,随机分为7组,每组10只,分别作为阴性对照组、实施例1~4组、对比例1~2组。腹腔注射10%水合氯醛麻醉小鼠,在其尾部脱毛,制造1cm×2cm的全皮层创伤模型,并分笼单独饲养。除阴性对照组外,每组每天分别涂抹实施例1~4、对比例1~2的组合物,于1天、2天、4天、8天、10天、15天对创面观察,拍照。结果见图1。
可以看出,从第10天开始,实施例1~4的伤口愈合情况明显好于对比例1~2,而对比例1和对比例2的伤口愈合又要好于阴性对照组。
测试例3:皮肤刺激性实验
按GB/T 16886.10-2017中的规定,取体重为2.0kg~2.4kg的新西兰兔,实验前24h在兔脊柱两侧除去3cm×3cm被毛,作为试验和对照部位,取实施例1~5的样品分别涂于试验部位,然后用二层纱布(2.5cm×2.5cm)和一层玻璃纸覆盖,再用无刺激性胶布和绷带加以固定。另一侧皮肤作为对照。每天涂1次,连续涂抹14d。从第二天开始,每次涂抹前剪毛,用水清除残留受试物。一小时后观察结果,按注释评分,对照区和受试区同样处理。
结果如表2所示:
表2
受试家兔在14天对实施例1~5的组合物样品均未表现任何不良反应,没有出现红斑和水肿等症状,每天每只动物平均积分为0,未见其他其他毒性反应特征,说明本发明的组合物对皮肤安全无刺激,具有高度安全性。
测试例4:迟发型超敏反应实验
按照GB/T16886.10-2017中迟发型超敏反应中反应封闭贴敷试验方法规定,取体重为390~410g豚鼠,于实验前24h剃除动物左上背被毛。每个样品取10只豚鼠作为实验组,另取5只豚鼠作为对照组。
诱导:取样品20g,以2g/10mL比例,用0.9%氯化钠注射液与37℃浸提24h,取上清液20份,0.5mL/份,分别涂抹于实验组10只动物左上背无毛区,面积为2.5cm×2.5cm,另取浸湿0.9%氯化钠注射液的无菌纱布4cm2的小块共5份,分别贴敷于阴性对照组5只豚鼠的左上背无毛区作阴性对照,用绷带包扎固定6h后去除。1周中连续3天重复此步骤,同法操作3周。
激发:最后一次诱导涂抹后14天,将浸提样品以0.5mL/只分别贴在试验组和对照组豚鼠的右上背无毛区,用绷带包扎固定6h,进行激发。观察:激发后24h剃去右上背毛,用温水清晰并擦干。脱毛至少2h,按Magnusson和Kligman分级标准对试验部位评分,并在除去激发敷贴后48h进行再次评分。
评分结果见表3。
表3
结果表明:动物在去除敷贴24h和48h,观察试验结果表明,实验组和对照组中豚鼠的反应等级均为0,表明各实施例组合物均未发现迟发型超敏反应。
测试例5:细胞毒性试验
按照GB/T16886.5-2017中体外细胞毒性试验MTT法规定实施。
(1)供试液的制备:
样品浸提液制备:取实施例1~5样品,按2g/10mL的比例加入含10%血清的1640培养基,37℃浸提24h,备用;
空白对照液:同批含10%血清的1640培养基;
阴性对照液:按2g/10mL的比例加入含10%血清的1640培养基;
阳性对照液:5%DMSO的培养液。
(2)试验方法:按照GB/T16886.5-2017规定的MTT试验方法进行,将1×104/mL细胞悬液接种于96孔板,每孔100μL。置5%CO2培养箱中37℃培养24h后,弃去原培养液。加入样品浸提液、空白对照液、阴性对照液和阳性对照液,每孔100μL置5%CO2培养箱中37℃培养72h,然后每孔加入20μL浓度5g/L的MTT溶液,培养4h后弃去孔内溶液,加入150μL的DMSO,振荡10min后,在酶标仪570nm和630nm双波长下测定吸光度(OD值)。按下式计算细胞相对增殖率(RGR):
存活率(%)=A/A0×100%
注:A:供试品组(阴性组、阳性组)吸光度;A0:空白对照组吸光度。
按表4进行分级判定。结果如表5所示。
表4细胞毒性实验反应分级
级别 | 0 | 1 | 2 | 3 | 4 |
存活率(%) | ≥100 | 80~99 | 50~79 | 30~49 | 0~29 |
表5
组别 | OD值(x±s) | 存活率(%) | 反应分级 |
空白对照组 | 0.7539±0.013 | / | / |
阴性对照组 | 0.7243±0.023 | 96 | 1级 |
阳性对照组 | 0.1099±0.011 | 15 | 4级 |
实施例1 | 0.7067±0.021 | 94 | 1级 |
实施例2 | 0.6988±0.035 | 93 | 1级 |
实施例3 | 0.6807±0.037 | 90 | 1级 |
实施例4 | 0.6983±0.028 | 93 | 1级 |
实施例5 | 0.6995±0.035 | 93 | 1级 |
结果表明:实施例1~5的细胞存活率均不低于90%,细胞毒性结果为1级,表明基本无细胞毒性作用。
Claims (10)
1.皮肤护理及修复组合物,其特征在于,包括以下按重量份计的组分:
透明质酸钠0.1~0.5份、甘草酸二钾0.1~0.4份、卡波姆0.1~0.5份、山茶油2~8份、灭活的乳酸杆菌1~10份、甘油1~8份、精氨酸0.2~0.5份、适量的水。
2.根据权利要求1所述的皮肤护理及修复组合物,其特征在于,包括:
透明质酸钠0.1~0.5份、甘草酸二钾0.1~0.3份、卡波姆0.2~0.5份、山茶油2~6份、灭活的乳酸杆菌4~8份、甘油2~8份、精氨酸0.2~0.4份、适量的水。
3.根据权利要求1所述的皮肤护理及修复组合物,其特征在于,所述乳酸杆菌选自嗜酸乳杆菌、罗伊氏乳杆菌、副干酪乳杆菌、鼠李糖乳杆菌、发酵乳杆菌、植物乳杆菌中的一种或几种。
4.根据权利要求1所述的皮肤护理及修复组合物,其特征在于,所述组合物中还添加有适量的防腐剂。
5.根据权利要求4所述的皮肤护理及修复组合物,其特征在于,所述防腐剂为苯甲酸钠、苯甲酸、羟苯甲酯钠、羟苯丙酯钠中的一种或几种。
6.根据权利要求1所述的皮肤护理及修复组合物,其特征在于,水的含量为80~98份。
7.权利要求1-6任一所述的皮肤护理及修复组合物的制备方法,其特征在于,包括步骤:
将透明质酸钠、甘草酸二钾、精氨酸、卡波姆、山茶油混合,加水搅拌均匀,再加入甘油、灭活的乳酸杆菌搅拌均匀;以及任选地,在加入甘油前加入防腐剂并搅拌均匀。
8.权利要求1-6任一所述的皮肤护理及修复组合物在制备皮肤护理或皮肤修复的制剂或医疗器械中的应用。
9.一种制剂,其特征在于,包括权利要求1-6任一所述的皮肤护理及修复组合物。
10.一种医疗器械,其特征在于,包括权利要求1-6任一所述的皮肤护理及修复组合物。
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CN113456735A (zh) * | 2021-06-02 | 2021-10-01 | 广州市锦盛生物科技有限公司 | 一种灭活益生菌草本凝胶及其制备方法和应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108670943A (zh) * | 2018-09-06 | 2018-10-19 | 浙江施维康科技有限公司 | 一种保湿、美白、淡斑植物提取物组合物 |
CN111265468A (zh) * | 2020-03-13 | 2020-06-12 | 佛山市奥姿美生物科技有限公司 | 皮肤双屏障修复组合物及其应用 |
CN111407719A (zh) * | 2020-04-02 | 2020-07-14 | 广州一一生物技术有限公司 | 一种皮肤屏障修护复合物、面霜及其制备方法 |
-
2020
- 2020-08-21 CN CN202010850421.9A patent/CN112022795A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108670943A (zh) * | 2018-09-06 | 2018-10-19 | 浙江施维康科技有限公司 | 一种保湿、美白、淡斑植物提取物组合物 |
CN111265468A (zh) * | 2020-03-13 | 2020-06-12 | 佛山市奥姿美生物科技有限公司 | 皮肤双屏障修复组合物及其应用 |
CN111407719A (zh) * | 2020-04-02 | 2020-07-14 | 广州一一生物技术有限公司 | 一种皮肤屏障修护复合物、面霜及其制备方法 |
Non-Patent Citations (1)
Title |
---|
湖南天根乐微君科技有限公司: "《http://ftba.nmpa.gov.cn:8181/ftban/itownet/hzp_ba/fw/pz.jsp?processid=202001151333223qyna&nid=202001151333223qyna》", 21 January 2021, 国产非特殊用途化妆品备案服务平台 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112754988A (zh) * | 2021-03-22 | 2021-05-07 | 中南大学湘雅二医院 | 一种降低皮肤致敏性的益生菌护肤品及其制备方法 |
CN113456735A (zh) * | 2021-06-02 | 2021-10-01 | 广州市锦盛生物科技有限公司 | 一种灭活益生菌草本凝胶及其制备方法和应用 |
CN113456735B (zh) * | 2021-06-02 | 2022-11-25 | 广州市锦盛生物科技有限公司 | 一种灭活益生菌草本凝胶及其制备方法和应用 |
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