氯己定

化学药剂

氯己定(英语:chlorhexidine[1]是一种消毒剂和抗菌剂,化学分子式为C22H30Cl2N10,用于手术前的皮肤消毒英语skin disinfection以及手术器械英语surgical instrument消毒,[2]也用于清洁伤口、预防牙菌斑、治疗鹅口疮、防止导尿管阻塞。[3]氯己定通常制成类(如葡萄糖酸[4]乙酸盐),[5]以增加其稳定性,并以液体或粉末形式使用。[2][3]

氯己定
临床资料
读音klɔː(r)ˈhɛksɪdiːn
商品名英语Drug nomenclatureBetasept、ChloraPrep、Chlorostat及其他
其他名称CHX, CHG, 1,6-bis(4-chloro-phenylbiguanido)hexane
AHFS/Drugs.comMonograph
核准状况
怀孕分级
  • : A
给药途径外用药物
ATC码
法律规范状态
法律规范
  • S5, S6, S7
  • OTC / Rx-only
识别信息
  • N,N1,6-Hexanediylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]
CAS号55-56-1  checkY
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.000.217 编辑维基数据链接
化学信息
化学式C22H30Cl2N10
摩尔质量505.45 g·mol−1
3D模型(JSmol英语JSmol
熔点134至136 °C(273至277 °F)
水溶性0.8
  • Clc1ccc(NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)Nc2ccc(Cl)cc2)cc1
  • InChI=1S/C22H30Cl2N10/c23-15-5-9-17(10-6-15)31-21(27)33-19(25)29-13-3-1-2-4-14-30-20(26)34-22(28)32-18-11-7-16(24)8-12-18/h5-12H,1-4,13-14H2,(H5,25,27,29,31,33)(H5,26,28,30,32,34) checkY
  • Key:GHXZTYHSJHQHIJ-UHFFFAOYSA-N checkY

使用后的副作用有皮肤不适、牙齿变色和过敏反应[3]氯己定除会导致牙齿变色之外,其使用风险似乎与聚维酮碘相同。[6][7]使用液态氯己定漱口会有苦的金属味馀韵。用水冲洗会增加苦味,因此不建议使用。[8]直接接触眼睛可能导致结膜炎等眼部疾病。[9][10]个体于怀孕期间使用对于胎儿似乎安全。[11]氯己定可与酒精[12][13][14]水或表面活性剂混合。[3]它对多种微生物有作用活性,但不能灭活孢子[2]

氯己定于1950年代开始用于医疗用途,[15]美国可作为非处方药购得。[9]它已被纳入世界卫生组织基本药物标准清单之中。[16][17]此药物于2021年在美国最常使用处方药中排名第247,开立的处方笺数量超过100万张。[18][19]

使用

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氯己定用于消毒(皮肤和手部)、化妆品(乳霜、牙膏、除臭剂和止汗剂)添加剂和药物(滴眼剂中防腐剂、伤口敷料和抗菌漱口水中的活性物质)。 [20]在一份2019年考科蓝合作组织发表的审查报告中的结论是,由重症病患取得品质非常低的证据,"尚不清楚用氯己定洗澡是否会减少医疗照顾相关感染、死亡率或加护病房住院时间,或者是否使用氯己定会导致更多的皮肤反应。"[21]

牙髓病学治疗案例,会普遍使用氯己定于根管冲洗和根管内敷料用途。[22][23]另一种功能类似的药物 - 次氯酸钠也受普遍使用。[24]

抗菌剂

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氯己定对革兰氏阳性菌革兰氏阴性菌兼性厌氧菌需氧菌酵母菌具有活性。[25]它对革兰氏阳性菌特别有效(浓度≥1微克/升(μg/L))。对于革兰氏阴性菌和真菌则需明显更高的浓度(10至超过73微克/毫升(μg/mL))。氯己定对小儿麻痹病毒腺病毒无效。针对疱疹病毒的有效性尚未得到明确确定。[26]

有强有力证据显示氯己定比聚维酮碘对于清洁手术更有效。[27][28]有证据表明它是上肢手术时的有效抗菌剂。[6]

跨越数十年的后设资料显示氯己定针对引起手术部位感染微生物的功效并未改变,[29]消除医界对其有新出现抗药性的担忧。

牙科用途

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商品名为Perichlor的氯己定葡糖酸盐(浓度0.12%)溶液。

使用以氯己定为主成分的漱口水与正常的牙齿护理相结合可帮助减少牙菌斑积聚,并改善轻度牙龈病[30]没有足够的证据来确定其对中度至重度牙龈病的效果。[30]将其用作漱口水成分会产生许多不良反应,包括损害口腔内膜、牙齿变色、牙结石堆积和味觉受损。[30]当使用氯己定漱口液为期四个星期或更长时间,就会发生外源性牙齿变色。[30]

含有氯己定的漱口水,其对牙齿的染色程度比经典溶液(其中有许多含有螯合物)为少。[31][32][33]

氯己定是一种阳离子,可与牙膏中的阴离子成分(例如十二烷基硫酸钠单氟磷酸钠)相互作用,形成溶解度低且抗菌活性降低的盐。因此,为增强氯己定的抗牙菌斑作用," 刷牙和用CHX[氯己定]漱口水之间的时间间隔以超过30分钟为佳,为求谨慎,可间隔两小时" 。[34]

外用药

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葡萄糖酸氯己定被用作手术皮肤洗刷清洁剂、皮肤伤口清洁剂、术前皮肤准备和杀菌洗手液。[25]氯己定眼药水曾被用于缓解棘阿米巴角膜炎英语Acanthamoeba keratitis所引起的症状。[35]

氯己定是一种非常有效的抗菌剂,其在新生儿脐带护理方面的使用在世界各地不断增长。在一份2015年考科蓝合作组织发表的审查报告,有高品质的证据显示在社区环境中,使用氯己定进行皮肤或脐带护理可将新生儿脐炎英语Omphalitis of newborn的发生率降低50%,将新生儿死亡率降低12%。[36]

副作用

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使用后的副作用有皮肤不适、牙齿变色和过敏反应,[3]氯己定除会导致牙齿变色之外,其使用风险似乎与聚维酮碘相同。[6][7]

氯己定具有耳毒性英语Ototoxicity,如果进入破裂的耳道,可能会导致听力丧失。[37]

氯己定不符合欧洲手部消毒剂规范。在欧洲标准EN 1499的测试条件下,含4%的葡萄糖酸氯己定溶液与肥皂的功效并无显著差异。美国里士满退伍军人管理医疗中心英语Richmond Veterans Medical Cente于2007年至2009年间进行一项整群随机试验,结论是每天对加护病房患者使用浸有氯己定葡糖酸盐的毛巾洗澡,可降低其发生医疗照顾相关感染的风险。[38]

医界对于多年长期接触此药物是否有致癌可能尚无清楚概念。美国食品药物管理局(FDA)建议将葡萄糖酸氯己定漱口水的使用期限限定为最多六个月。[39]

个体摄入氯己定后,因在消化道中吸收不良,会引起胃部不适或恶心[40][41]有一例报告,当个体将足够高浓度的氯己定吸入肺部,有导致急性呼吸窘迫症候群的高风险,有致命可能。[41][42]

作用机转

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氯己定盐在生理pH值下会解离并释放带正电荷的阳离子。杀菌作用是阳离子与带负电的细菌细胞壁结合的结果。低浓度的氯己定可产生抑菌作用,而浓度升高后,会导致细菌膜破裂,而致死亡。[25]

化学

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氯己定是一种阳离子双胍类[43]

效用钝化

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当氯己定与阴离子化合物形成不溶性盐时,其活性会钝化,此类阴离子化合物包括牙膏和漱口水中常用作清洁剂的阴离子表面活性剂、聚丙烯酸等阴离子增稠剂和阴离子乳化剂等。因此应在使用其他牙科产品后至少30分钟才使用氯己定漱口水。[44]

合成

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氯己定结构是由两个普罗胍尼英语Proguanil分子为基础,以己二胺作为连结基构成。

社会与文化

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品牌

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氯己定外用药的商品名称有Betasept、Biopatch、Calgon Vesta、ChloraPrep One-Step、Dyna-Hex、Hibiclens、Hibistat Towelette、Scrub Care Exidine和Spectrum-4等。[45]

葡萄糖酸氯己定漱口水的商品名称有Dentohexin、Paroex、Peridex、PerioChip、Corsodyl和 Periogard等。[46]

兽医学

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氯己定在动物治疗中可用于伤口局部消毒,[47]皮肤感染治疗。[48]乳牛养殖业会使用以氯己定为主成分的消毒剂产品。[49]

猫术后的呼吸系统问题与使用氯己定产品有关联。[50]

参考文献

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