CN109364078A - 纳洛酮在制备镇痛药物中的应用 - Google Patents

纳洛酮在制备镇痛药物中的应用 Download PDF

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Publication number
CN109364078A
CN109364078A CN201811521708.6A CN201811521708A CN109364078A CN 109364078 A CN109364078 A CN 109364078A CN 201811521708 A CN201811521708 A CN 201811521708A CN 109364078 A CN109364078 A CN 109364078A
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naloxone
analgesic
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鲍杨
俞卫锋
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Shanghai Jiading District Central Hospital
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Shanghai Jiading District Central Hospital
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

纳洛酮在制备镇痛药物中的应用，其特征是镇痛药物中纳洛酮的含量为0.05‑0.1ug·kg‑1·h‑1。本发明可以显著增强治疗肝胆手术术后疼痛的疗效，且不增加副反应的发生；可以显著降低治疗肝胆手术术后疼痛时恶心的发生率，且不降低其镇痛效果。

Description

纳洛酮在制备镇痛药物中的应用
技术领域
本发明涉及纳洛酮的用途，尤其涉及在制备镇痛药物中的用途。
背景技术
纳洛酮(17-烯丙基-4,5a-环氧基-3,14-二羟基吗啡喃-6-酮盐酸盐二水合物)为一种无色澄明液体，为纯粹的阿片受体拮抗药，本身无内在活性。但能竞争性拮抗各类阿片受体。对μ受体有很强的亲和力。纳洛酮生效迅速，拮抗作用强。纳洛酮同时逆转阿片激动剂所有作用，包括镇痛。另外其还具有与拮抗阿片受体不相关的回苏作用，可迅速逆转阿片镇痛药引起的呼吸抑制，可引起高度兴奋，使心血管功能亢进。还有抗休克作用，不产生吗啡样的依赖性、戒断症状和呼吸抑制。
但在具体使用中发现，超低剂量纳洛酮无镇痛作用，高剂量(>1ug/kg)时显著减弱阿片类药，甚至有引发爆发痛可能，所以临床上常规使用的剂量只是用于拮抗阿片类使用过量所致的各种副作用而不用于术后镇痛。
发明内容
本发明的目的是公开一种超低剂量纳洛酮在制备镇痛药物中的应用，以增强镇痛药的镇痛作用和降低其副作用。
为实现上述目的，本发明在制备镇痛药物中的纳洛酮的含量为0.05-0.1ug·kg-1·h-1。
作为一个实施例，其中镇痛药物中每100毫升生理盐水中含地佐辛25mg，氟比洛芬酯250mg。
本发明采用超低剂量纳洛酮(＜1μg/kg)与阿片类药物联用，可以减轻阿片类药物的副作用，不减弱、甚至增强其镇痛作用。
具体实施方式
为了更好地理解本发明的实质，下面以地佐辛+氟比洛芬酯+纳洛酮为例，对其药理试验及结果作进一步的说明。
选择择期行肝胆手术的患者60例，排除患有严重心、肝、肺、肾及神经系统疾病、过敏体质、长期服用镇痛镇静药、对阿片类药物成瘾的患者，术后镇痛按方法的不同将患者随机分为A、B、C三组，每组20例。
A组为地佐辛25mg+氟比洛芬酯250mg；
B组为地佐辛25mg+氟比洛芬酯250mg+纳洛酮0.05ug·kg-1·h-1；
C组为地佐辛25mg+氟比洛芬酯250mg+纳洛酮0.1ug·kg-1·h-1组。
比较三组患者手术后2h、4h、8h、24h、44h等时间点静息状态及深呼吸状态下NRS评分，表情评分、镇静评分及不良反应发生情况。
结果：
一、B组(复合0.05ug·kg-1·h-1浓度纳洛酮)的患者静息状态下采用数字分级法(NRS)评分，在术后2h、24h、44h等时点显著低于A组(无纳洛酮组)，患者深呼吸时NRS评分在术后24h、44h等时点显著低于A组，患者表情评分在术后2h、8h、24h等时点显著低于A组，A组和B组的镇静评分及恶心、呕吐、寒战、头晕等不良反应发生率无显著差异。
二、C组(复合0.1ug·kg-1·h-1浓度纳洛酮)的患者术后恶心的发生率显著低于A组，余无显著差异。
三、B组与C组相比，仅术后24h患者表情评分显著较低，余无显著差异。
结论：
超低剂量纳洛酮可以增强地佐辛复合氟比洛芬酯的镇痛作用或降低其副作用，与纳洛酮的浓度相关。复合0.05-0.1ug·kg-1·h-1浓度的纳洛酮可以显著增强地佐辛复合氟比洛芬酯治疗肝胆手术术后疼痛的疗效，且不增加副反应的发生；可以显著降低地佐辛复合氟比洛芬酯治疗肝胆手术术后疼痛时恶心的发生率，且不降低其镇痛效果。

Claims (2)

1.纳洛酮在制备镇痛药物中的应用，其特征是镇痛药物中纳洛酮的含量为0.05-0.1ug·kg-1·h-1。
2.根据权利要求1所述的应用，其中，所述的镇痛药物中每100毫升生理盐水中含地佐辛25mg，氟比洛芬酯250mg。
CN201811521708.6A 2018-12-13 2018-12-13 纳洛酮在制备镇痛药物中的应用 Pending CN109364078A (zh)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101534827A (zh) * 2006-11-07 2009-09-16 尼克塔治疗亚拉巴马公司 阿片样物质激动剂和阿片样物质拮抗剂的剂型和联合给药

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101534827A (zh) * 2006-11-07 2009-09-16 尼克塔治疗亚拉巴马公司 阿片样物质激动剂和阿片样物质拮抗剂的剂型和联合给药

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
鲍杨: "超低剂量纳洛酮对地佐辛术后镇痛效能的影响", 《中国博士学位论文全文数据库 医药卫生科技辑》 *

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Application publication date: 20190222