CN115607589B - 秦艽及其单体化合物在杀螨中的应用 - Google Patents
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Abstract
本发明公开了秦艽及其单体化合物在杀螨中的应用。发明人通过对比多味中药材对螨虫的杀灭效果发现，秦艽可有效减少蠕形螨的存活时间，进一步筛选多种秦艽单体化合物，进行蠕形螨的杀灭实验，通过对比发现，与对照组相比，这些单体化合物均可减少蠕形螨的存活时间，特别是龙胆苦苷可显著缩短蠕形螨存活时间，可用于螨虫杀灭和抑制产品(如药品、化妆品、日用品等)。本发明提供的应用可有效地利用自然资源，提高秦艽的利用价值和商业价值。
Description
技术领域
本发明涉及医药和日护技术领域，具体涉及秦艽及其单体化合物，特别是龙胆苦苷，在杀螨中的应用。
背景技术
螨虫属于节肢动物门蛛形纲广腹亚纲的一类体型微小的动物，身体大小一般都在0.5毫米左右，有些小到0.1毫米，大多数种类小于1毫米。现发现螨虫与人类和动物(如狗、猫等宠物)的健康关系非常密切，诸如革螨、恙螨、疥螨、蠕形螨、粉螨、尘螨和蒲螨等可吸血、侵害皮肤，引起“酒糟鼻”或蠕螨症、过敏症、尿路螨症、肺螨症、肠螨症和疥疮等，严重危害人类和动物的身体健康。
蠕形螨属螨虫(属于蜘蛛纲(Arachnid)和螨目(Acarina))是通常感染皮肤毛囊皮脂腺单位的微观体外寄生虫。在宽范围的所报导物种中，至少毛囊蠕形螨和皮脂蠕形螨已在人类体表上发现，其主要寄居在毛囊和皮脂腺、睑板腺。蠕形螨可吞噬毛囊上皮细胞，引起毛囊扩张和脱毛，表现为临床上的睑缘炎、睑缘角膜结膜炎、睑板腺功能障碍、睫毛脱落、睫毛排列异常 (abnormal eyelash alignment)、结膜炎和睑结膜炎、翼状胬肉、角膜炎、眼睑基底细胞癌等。蠕形螨还可吞噬脂质，引起睑板腺功能障碍、干眼。此外，蠕形螨还可以通过机械性的阻塞造成睑板腺排出管道阻塞，引起脂质排出困难和过量的分泌物潴留，导致霰粒肿的形成。蠕形螨感染眼病的临床表现主要包括：反复发作的眼边红痒；眼干、眼烧灼感、眼部异物感、畏光、分泌物增多；可伴有反复睫毛脱落；重者累及角膜时可有视物模糊、视力下降。除了以上眼病，近年有不少研究指出蠕形螨感染和多种常见的皮肤疾病相关，包括脂溢性皮炎、痤疮、酒糟鼻、毛囊性糠疹、口周皮炎、蠕形螨病、基底细胞癌等(参见，例如，Luo,X.,Li,J.,Chen,C.,Tseng,S.&Liang,L.Ocular Demodicosis as a Potential Causeof Ocular Surface Inflammation.Cornea 36Suppl 1,S9-s14；Karincaoglu,Y.,Tepe,B.,Kalayci,B.,Atambay,M.&Seyhan, M.Is Demodex folliculorum an aetiologicalfactor in seborrhoeic dermatitis？Clinical and experimental dermatology 34,e516-520；Chen,W.&Plewig,G. Human demodicosis:revisit and a proposedclassification.The British journal of dermatology 170,1219-1225)。
螨虫引起的疾病(如眼部疾病、皮肤疾病)目前在临床还没有引起足够重视，经常被误诊为细菌性疾病等，而常规抗菌药治疗常常无明显疗效。
发明内容
本发明第一方面提供一种秦艽在制备杀螨产品中的应用。
具体地，上述秦艽可以作为唯一的杀螨活性组分，也可以与其他相同或不同的活性的组分组合用于杀螨。
本发明第二方面提供一种秦艽提取物在制备杀螨产品中的应用。
具体地，上述秦艽提取物可通过本领域已知的适当的中药提取方法得到，如煎煮法、浸渍法、浸漉法、回流法、水蒸气蒸馏法、超声波提取法等中的一种或多种的组合。在本发明的一个实施例中，上述秦艽提取物可通过煎煮法得到。
具体地，上述秦艽提取物通过包括以下步骤的方法制备：
(1)将秦艽与提取溶剂混合，浸泡；
(2)将步骤(1)的混合物加热至沸腾，然后煎煮，过滤。
在本发明的一个实施例中，上述提取溶剂为水。
具体地，上述浸泡的时间为1-24小时(具体如，1、2、3、4、5、6、12、18、24小时)。
具体地，上述煎煮时间为10-60分钟(具体如，10、15、20、25、30、35、 40、45、50、55、60分钟)。
具体地，上述方法还可包括：
(3)将步骤(2)所得滤渣与提取溶剂，加热至沸腾，然后煎煮，过滤；将步骤(2)和(3)所得滤液合并。
任选地，上述方法还可包括将所得滤液进行混匀、浓缩、定量、灭菌等处理步骤中一种或多种。
具体地，上述秦艽提取物中包含龙胆苦苷、马钱苷酸、獐芽菜苷、栎樱酸、东莨菪内酯、大叶茜草素、獐牙菜苦苷中的一种或多种。
更具体地，上述秦艽提取物中包含龙胆苦苷。
本发明第三方面提供一种秦艽单体化合物或其盐、酯、异构体、溶剂化物、衍生物在制备杀螨产品中的应用。
具体地，上述秦艽单体化合物的盐、酯、异构体、溶剂化物、衍生物为药学上可接受的相应的盐、酯、异构体、溶剂化物、衍生物。
具体地，上述单体化合物选自龙胆苦苷、马钱苷酸、獐芽菜苷、栎樱酸、东莨菪内酯、大叶茜草素、獐牙菜苦苷中的一种或多种。
具体地，上述单体化合物为龙胆苦苷。
本发明第四方面提供一种龙胆苦苷或其盐、酯、异构体、溶剂化物、衍生物在制备杀螨产品中的应用。
具体地，上述秦艽单体化合物的盐、酯、异构体、溶剂化物、衍生物为药学上可接受的相应的盐、酯、异构体、溶剂化物、衍生物。
具体地，本发明上述杀螨产品可用于治疗/或预防目的，也可用于非治疗/ 或预防目的。
具体地，本发明上述螨虫可以为蠕形螨、尘螨、疥螨等中的一种或多种。在本发明的一个实施例中，本发明上述螨虫为蠕形螨，如毛囊蠕形螨和皮脂蠕形螨。
在本发明的一个实施方式中，本发明上述杀螨产品为药物组合物。
具体地，上述药物组合物还包含药学上可接受的辅料。
具体地，本发明上述药物组合物用于预防和/或治疗螨虫感染引起的疾病。
具体地，上述疾病可以为眼部疾病、皮肤疾病、过敏性疾病等。
具体地，上述眼部疾病可以为睑缘炎、睑缘角膜结膜炎、睑板腺功能障碍、睫毛脱落、睫毛排列异常、结膜炎和睑结膜炎、翼状胬肉、角膜炎、眼睑基底细胞癌、干眼(包括干眼症、干眼病和干眼综合征)、霰粒肿等中的一种或多种；其可具有选自以下的一种或多种症状：眼部红痒、眼干、眼烧灼感、异物感、畏光、眼部分泌物增多、睫毛脱落、视物模糊、视力下降等。
具体地，上述皮肤疾病可以为脂溢性皮炎、痤疮、酒糟鼻、毛囊性糠疹、口周皮炎、蠕形螨病、疥螨病、基底细胞癌等中的一种或多种。
具体地，上述过敏性疾病可以为过敏性哮喘、过敏性鼻炎、过敏性皮炎等中的一种或多种。
具体地，上述药物组合物可以为任何适宜施用的剂型，如外用制剂，特别是眼用制剂、皮肤外用制剂等。
具体地，上述眼用制剂可以为滴眼剂、眼膏剂、眼用凝胶剂、眼用膜剂、洗眼剂、眼内注射剂等。
具体地，上述皮肤外用制剂可以为气雾剂、粉剂、洗剂、酊剂、搽剂、涂膜剂、软膏剂、凝胶剂、糊剂等。
具体地，本发明上述药物组合物的各种剂型可以按照药学领域的常规生产方法制备。
具体地，本发明上述药物组合物可以含有重量比为0.1-99.5％(具体如， 0.1％、0.5％、1％、2％、3％、4％、5％、6％、7％、8％、9％、10％、20％、30％、40％、50％、60％、70％、80％、90％、95％、99％、99.5％)的活性成分。
具体地，上述药物组合物可用于人类，也可作为兽用药用于宠物动物(如，狗、猫、兔、鼠等)、家畜动物(如，马、牛、羊、猪、狗、兔等)等动物。
在本发明的另一个实施方式中，本发明上述杀螨产品为化妆品。
具体地，上述化妆品还包含化妆品领域可接受的辅料。
具体地，本发明上述化妆品可以为用于面部的化妆品，如洗面奶、香皂、柔肤水、爽肤水、护肤乳、凝露、面霜、防晒霜、精华液、面膜、凝胶、粉底液、磨砂膏。
具体地，本发明上述化妆品可以为用于面部以外其他部位的化妆品，如颈霜、洗发水、沐浴露、香皂、护发素、身体乳、磨砂膏等。
具体地，本发明上述化妆品还可以为用于眼睛和眼周的化妆品，如眼霜、睫毛膏、眼线粉、眼线膏、眼线笔、眼影粉、眼影膏、眉笔、眉粉等。
具体地，本发明上述化妆品的各种形式可以按照化妆品领域的常规生产方法制备。
具体地，本发明上述化妆品可以含有重量比为0.1-99.5％(具体如，0.1％、0.5％、1％、2％、3％、4％、5％、6％、7％、8％、9％、10％、20％、30％、40％、 50％、60％、70％、80％、90％、95％、99％、99.5％)的活性成分。
在本发明的另一个实施方式中，本发明上述杀螨产品为杀螨剂，其可用于杀灭和抑制生活环境中物品(如，枕套、枕芯、床单、被褥、床垫、衣物、地毯、坐垫、沙发、凉席、毛绒玩具、空调等等)上可能寄居的螨虫。
具体地、上述杀螨剂可包含可实现所需性能的任何适宜的辅料。
具体地、上述杀螨剂可以为喷雾剂、洗剂、贴片、小包装等形式。
具体地，本发明上述杀螨剂的各种形式可以按照日护产品领域的常规生产方法制备。
具体地，本发明上述杀螨剂可以含有重量比为0.1-99.5％(具体如，0.1％、0.5％、1％、2％、3％、4％、5％、6％、7％、8％、9％、10％、20％、30％、40％、 50％、60％、70％、80％、90％、95％、99％、99.5％)的活性成分。
本发明还提供一种预防和/或治疗螨虫感染引起的疾病的方法，其包括向需要其的受试者给与秦艽、秦艽提取物、秦艽单体化合物(特别是龙胆苦苷) 或其盐、酯、异构体、溶剂化物、衍生物或本发明上述药物组合物的步骤。
具体地，上述疾病可以为眼部疾病、皮肤疾病、过敏性疾病等。
具体地，上述眼部疾病可以为睑缘炎、睑板腺功能障碍、睫毛脱落、睫毛排列异常、结膜炎和睑结膜炎、翼状胬肉、角膜炎、眼睑基底细胞癌、干眼、霰粒肿等中的一种或多种；其可具有选自以下的一种或多种症状：眼部红痒、眼干、眼烧灼感、异物感、畏光、眼部分泌物增多、睫毛脱落、视物模糊、视力下降等。
具体地，上述皮肤疾病可以为脂溢性皮炎、痤疮、酒糟鼻、毛囊性糠疹、口周皮炎、蠕形螨病、疥螨病、基底细胞癌等中的一种或多种。
具体地，上述过敏性疾病可以为过敏性哮喘、过敏性鼻炎、过敏性皮炎等中的一种或多种。
具体地，上述受试者可以为接受该预防和/或治疗的任何动物，特别是哺乳动物，如人类、猫、狗、兔、鼠、马、牛、羊、猪等。在本发明的一个实施例中，上述受试者为人类；在本发明的另一个实施例中，上述受试者为非人类动物。
具体地，上述秦艽、秦艽提取物、秦艽单体化合物(特别是龙胆苦苷) 或其盐、酯、异构体、溶剂化物、衍生物或本发明上述药物组合物的施用量可根据用药途径、受试者的年龄、体重、所治疗的疾病的类型和严重程度等变化，可以一次或多次施用。
通过对比多味中药材对螨虫的杀灭效果发现，秦艽可有效减少蠕形螨的存活时间，进一步筛选多种秦艽单体化合物，进行蠕形螨的杀灭实验，通过对比发现，与对照组相比，这些单体化合物均可减少蠕形螨的存活时间，特别是龙胆苦苷可显著缩短蠕形螨存活时间，可用于螨虫杀灭和抑制产品(如药品、化妆品、日用品等)。本发明提供的应用可有效地利用自然资源，提高秦艽的利用价值和商业价值。
附图说明
图1所示为本发明实施例3提供的结膜微生物群的宏基因组测序分析结果。
图2所示为本发明实施例3提供的结膜微生物群的宏基因组测序分析结果。
图3所示为本发明实施例3提供的基因富集分析结果。
图4所示为本发明实施例3提供的球形马拉色菌的检测结果。
图5所示为本发明实施例3提供的球形马拉色菌的检测结果。
具体实施方式
除非另有定义，本发明中所使用的所有科学和技术术语具有与本发明涉及技术领域的技术人员通常理解的相同的含义。
除非另外指出，在本发明中，秦艽是指中药材秦艽，其为龙胆科植物秦艽Gentianamacrophμlla Pall.、麻花秦艽Gentiana straminea Maxim.、粗茎秦艽 Gentiana cras-sicaulis Duthie ex Burk.或秦艽Gentiana dahurica Fisch.的干燥根，炮制：除去杂质，洗净，润透，切厚片，晒干；味辛、苦，性平；归胃、肝、胆经；功效：有祛风湿，清湿热，止痹痛，退虚热的作用。
中药单体是指从单味中药获得(例如通过提取得到)的化合物，特别是具有治疗作用或有益健康等作用的化合物，例如，本发明中所描述的秦艽单体化合物是指从秦艽中获得的单体化合物，例如，但不限于，龙胆苦苷(CAS： 20831-76-9)、马钱苷酸(CAS：22255-40-9)、獐芽菜苷(CAS：14215-86-2)、栎樱酸(CAS：6812-81-3)、东莨菪内酯(CAS：92-61-5)、大叶茜草素(CAS： 55481-88-4)、獐牙菜苦苷(CAS：17388-39-5)。本发明中所述的中药单体化合物可以是市售产品，也可以是临用前自相应中药中获得(例如通过提取得到)，或根据现有技术中已知的方法合成，或通过其他适宜途径得到。
下面将结合本发明实施例，对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1
一、实验方法：
1.实验对象
本研究严格遵循赫尔辛基宣言(The Declaration of Helsinki)、《涉及人的生物医学研究伦理审查办法》的伦理准则，并且获得了中山大学中山眼科中心医学伦理委员会的审查和批准。本研究收集在中山眼科中心确诊为眼蠕形螨感染患者的蠕形螨。符合入选标准的予以知情谈话并签署知情同意书后入组。
2.蠕形螨检测
按照常规的睫毛镜检方法进行蠕形螨检测，每个眼睑拔取3根睫毛，共拔取 12根睫毛，拔下的睫毛立即置于载玻片上，每三根睫毛一片，置于普通光学显微镜下观察。将所有时期的蠕形螨均纳入计数并根据形态学进行分类(具体标准为：头身比为1:1的为皮脂蠕形螨，头身比为1:3～1:4的为毛囊蠕形螨)。只取完全暴露于视野中的成虫作为实验对象(幼虫及虫卵因在生命早期更为脆弱故不作为研究对象)。
3.蠕形螨体外培养
在上述蠕形螨检测的基础上，每张玻片上加入35μl不同溶液，每2个小时观察一次虫体是否存活。通过显微镜下观察虫体是否活动(身体，四肢等)来判断其是否死亡，实验过程中由两位熟练的蠕形螨相关实验者分别观察并判定，若判定结果不相同，则请第三位熟练的实验者进行独立判定。体外培养在气候箱中进行，温度20℃，湿度96％，玻片在观察中湿盒运输已保证高湿状态。
4.药物
4.1中草药7种
本实验所选取的中药饮片(金银花，白鲜皮，黄芩，鱼腥草，秦皮，秦艽，菊花)均购置于广东省中医院中药房。其中，金银花、蒲公英、黄芩、鱼腥草、秦艽、菊花来源于康美药业股份有限公司，白鲜皮、秦皮来源于岭南中药饮片有限公司。
4.2中药水煎剂的制备方法
用电子天平称取干燥中药饮片60g放置于砂锅中，加10倍水量(600ml)泡过夜，武火加热至药液沸腾后改用文火煎15-30分钟(花草类15分钟，根茎类为30分钟)，纱网过滤，滤渣加500ml水同法煎煮，过滤后合并两次滤液于同一烧杯中，混合均匀后，加热蒸发使药液浓缩至100ml后放凉至室温，并置于100ml 容量管中定容。
实验组为分别按照上述方法制备的不同中药煎煮液，阴性对照组为灭菌水。
4.3阳性对照为茶树精油及茶树精油的主要成分4-松油醇
茶树油(Tea Tree Oil，TTO)及4-松油醇(Terpinen-4-ol，T4O)购于Milwaukee(WI,USA)，均稀释于灭菌水，终浓度为10％。
5.统计方法
本实验采用SPSS22.0统计软件进行统计，因共用Shapiro-Wilk检验进行正态性检验，Bartlett检验进行方差齐性检验，对符合正态分布且方差齐的数据进行单因素方差分析(One-way ANOVA)，有统计学意义时应用Bonferroni法进行组间两两比较；数据不符合正态分布时使用Kruskal-Wallis检验进行统计分析，检验水准α＝0.05。
6.实验结果：
1.秦艽能显著缩短体外蠕形螨存活时间
在湿度96％，温度20℃的环境下体外培养蠕形螨，动态观察蠕形螨存活情况并记录存活时间。实验结果如表1所示。与阴性对照组相比，秦艽组的蠕形螨存活时间较对照组显著缩短(21.44±9.76vs.50.81±19.90,P＜0.001)，且与TTO 及T4O组体外蠕形螨存活时间相比更短(21.61±11.95vs.41.39±19.33，21.61± 11.95vs.40.50±13.12，P＜0.01)；其余6种中药与对照组，TTO及T4O组相比，蠕形螨体外存活时间未见明显差异(P＞0.05)。有趣的是，以往被认为能体外杀螨的TTO及其主要有效成分T4O在本体外培养实验中，与阴性对照水溶液相比，蠕形螨存活时间并未见显著差异(P＞0.05)。
表1中草药煎剂体外对毛囊蠕形螨存活时间的影响
用Bonferroni法进行多重比较，与水相比，PA表示P＜0.05，Pa表示P＜0.001，Pa’表示P ＜0.001；与TTO比较：PB表示P＜0.05，Pb表示P＜0.01，Pb’表示P＜0.001；与T4O比较，PC表示P＜0.05，Pc表示：P＜0.01，Pc’表示P＜0.001。
实施例2：体外初筛中药单体对蠕形螨生存时间的影响
方法：
1.中药单体
根据实施例1的实验结果，秦艽能显著缩短蠕形螨体外存活时间，故选取此味中药的单体，单体中英文名称及分子式见下表：
单体购于成都瑞芬思生物科技有限公司，为标准品。
表2中药单体中英文名称及分子式
| 编号 | 中文名称 | 中药 | 英文名称 | 分子式 |
| 1 | 龙胆苦苷 | 秦艽 | Gentiopicroside | C16H20O9 |
| 2 | 马钱苷酸 | 秦艽 | Loganic acid | C16H24O10 |
| 3 | 獐芽菜苷 | 秦艽 | Sweroside | C16H22O9 |
| 4 | 栎樱酸 | 秦艽 | Roburic acid | C30H48O2 |
| 5 | 东莨菪内酯 | 秦艽 | Scopoletin | C10H8O4 |
| 6 | 大叶茜草素 | 秦艽 | Rubimaillin | C17H16O4 |
| 7 | 獐牙菜苦苷 | 秦艽 | Swertiamarine | C16H22O10 |
2.中药单体溶液的制备
将表2中所示中草药单体参考品粉末先于二甲基亚砜(DMSO)溶解，再用灭菌双蒸水稀释，使DMSO的终浓度为10％，经对照试验，此浓度不能缩短蠕形螨存活时间。阴性对照为与灭菌水混合的DMSO，终浓度为10％。
3.蠕形螨体外培养
同实施例1，每张玻片上加入35μl不同溶液，每2个小时在光学显微镜下观察一次虫体是否存活。通过显微镜下观察虫体是否活动(身体，四肢等)来判断其是否死亡，实验过程中由两位熟练的蠕形螨相关实验者分别观察并判定，若判定结果不相同，则请第三位熟练的实验者进行独立判定。体外培养在气候箱中进行，温度20℃，湿度96％，玻片在观察中湿盒运输已保证高湿状态。
4.统计方法
本实验采用SPSS22.0统计软件进行统计，因共用Shapiro-Wilk检验进行正态性检验，Bartlett检验进行方差齐性检验，对符合正态分布且方差齐的数据进行单因素方差分析(One-way ANOVA)，有统计学意义时应用Bonferroni法进行组间两两比较；数据不符合正态分布时使用Kruskal-Wallis检验进行统计分析，检验水准α＝0.05。
5.实验结果：
中草药单体对毛囊蠕形螨存活时间的影响
在湿度96％，温度20℃的环境下体外培养蠕形螨，动态观察蠕形螨存活情况并记录存活时间。结果如表3所示。与阴性对照10％DMSO相比，表2所示秦艽单体化合物均可缩短蠕形螨体外存活时间，特别是，龙胆苦苷组的蠕形螨存活时间较对照组显著缩短(37.31±36.06vs.80.79±25.34,P＜0.001)。
表3中药单体外对毛囊蠕形螨存活时间的影响
用Duncan法进行多重比较，与对照组相比，P*：P＜0.05，P**：P＜0.01，P***＜0.001。
实施例3：毛囊蠕形螨影响眼部的微生物群实验
蠕形螨极大地改变了睑脂中的脂质组，从而进一步改变眼表环境，最终导致眼球蠕形螨病的发作。为了进一步研究蠕形螨病的发病机理，本发明对 30只健康眼和35只患有蠕形螨病眼的结膜微生物群进行了宏基因组测序分析。结果表明，健康者和患者的结膜宏基因组在病毒组成上和细菌组成上没有差异，而蠕形螨病患者结膜上的真菌种类与健康个体的真菌种类明显不同。如图1和图2所示，在健康的结膜上发现的多种真菌被转换为以球形马拉色菌为主的去多样化真菌群落。如图3所示，通过脂肪酸降解和生物合成，富集了球形马拉色菌和毛囊蠕形螨的显著同源性的基因。重要的是，如图4所示，健康的睑脂在体外阻止了球形马拉色菌的生长。相反，如图5所示，蠕形螨感染者睑脂和硬脂酸(C18：0)和油酸(C18：1)在体外促进了球形马拉色菌的生长。这些数据强烈表明蠕形螨的侵染会导致眼表微生物群失调。
球形马拉色菌是亲脂性真菌，已知在多种皮肤病学疾病中发挥致病作用，包括脂溢性皮炎，头皮屑，酒渣鼻和毛囊炎，以及眼部表现包括睑缘炎。本发明发现蠕形螨会创造一个脂质环境，从而促进球形马拉色菌的过度生长，其可能为皮肤/眼蠕形螨病和脂溢性皮炎等疾病发病机理的一部分。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换等，均应包含在本发明的保护范围之内。
本发明中描述的前述实施例和方法可以基于本领域技术人员的能力、经验和偏好而有所不同。
在本发明中仅按一定顺序列出方法的步骤并不构成对方法步骤顺序的任何限制。
Claims (14)
1.一种秦艽水提取物作为主要有效成分在制备杀蠕形螨产品中的应用。
2.如权利要求1所述的应用，其特征在于，所述秦艽水提取物中包含龙胆苦苷、马钱苷酸、獐芽菜苷、栎樱酸、东莨菪内酯、大叶茜草素、獐牙菜苦苷中的一种或多种。
3.如权利要求1所述的应用，其特征在于，所述秦艽水提取物中包含龙胆苦苷。
4.如权利要求1-3任一项所述的应用，其特征在于，所述蠕形螨为毛囊蠕形螨和皮脂腺蠕形螨中的一种或多种。
5.如权利要求1-3任一项所述的应用，其特征在于，所述杀蠕形螨产品为药物组合物、化妆品或杀螨剂。
6.如权利要求5所述的应用，其特征在于，所述药物组合物为用于预防和／或治疗蠕形螨感染引起的疾病的药物组合物。
7.如权利要求6所述的应用，其特征在于，所述药物组合物为外用制剂。
8.如权利要求6所述的应用，其特征在于，所述药物组合物为眼用制剂。
9.如权利要求8所述的应用，其特征在于，所述眼用制剂选自：滴眼剂、眼膏剂、眼用凝胶剂、眼用膜剂、洗眼剂、眼内注射剂。
10.如权利要求6所述的应用，其特征在于，所述药物组合物为皮肤外用制剂。
11.如权利要求10所述的应用，其特征在于，所述皮肤外用制剂选自：气雾剂、粉剂、洗剂、酊剂、搽剂、涂膜剂、软膏剂、凝胶剂、糊剂。
12.如权利要求6所述的应用，其特征在于，所述药物组合物为人用药物组合物或兽用药物组合物。
13.如权利要求5所述的应用，其特征在于，所述化妆品的形式选自：洗面奶、香皂、柔肤水、爽肤水、护肤乳、凝露、面霜、防晒霜、精华液、面膜、凝胶、粉底液、磨砂膏、颈霜、洗发水、沐浴露、护发素、眼霜、睫毛膏、眼线粉、眼线膏、眼线笔、眼影粉、眼影膏、眉笔、眉粉。
14.如权利要求5所述的应用，其特征在于，所述杀螨剂的形式选自：喷雾剂、洗剂、贴片。
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| EP21791582.6A EP4129316A4 (en) | 2020-04-24 | 2021-04-23 | USE OF RADIX GENTIANAE MACROPHYLLAE AND MONOMER COMPOUND THEREOF FOR KILLING MITES |
| US17/920,725 US20230165922A1 (en) | 2020-04-24 | 2021-04-23 | Application of radix gentianae macrophyllae and monomer compound thereof in killing mites |
| PCT/CN2021/089107 WO2021213484A1 (zh) | 2020-04-24 | 2021-04-23 | 秦艽及其单体化合物在杀螨中的应用 |
| JP2022564791A JP7627433B2 (ja) | 2020-04-24 | 2021-04-23 | ジンギョウ及びそのモノマー化合物のダニ殺滅への使用 |
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| EP4129316A4 (en) | 2023-11-01 |
| US20230165922A1 (en) | 2023-06-01 |
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