CN1305810A - 抗疟药新药复方双氢青蒿素 - Google Patents

抗疟药新药复方双氢青蒿素 Download PDF

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CN1305810A
CN1305810A CN00113134A CN00113134A CN1305810A CN 1305810 A CN1305810 A CN 1305810A CN 00113134 A CN00113134 A CN 00113134A CN 00113134 A CN00113134 A CN 00113134A CN 1305810 A CN1305810 A CN 1305810A
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dihydroartemisinin
dihydroarteannuin
medicine
malaria
piperaquine
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CN1135974C (zh
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李国桥
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Jianqiao Medicine Development Co Ltd Chongqing City
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Priority to PCT/CN2001/000884 priority patent/WO2002026226A1/zh
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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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • 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
    • A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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  • Tropical Medicine & Parasitology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract

本发明提供一种治疗多重抗药性恶性疟疾的新药复方双氢青蒿素片，由双氢青蒿素、哌喹、甲氧苄啶组方制成。该药通过动物试验和临床试用表明具有速效、高效、低毒、短疗程的特点,其疗效和低毒副作用明显优于目前国内外的同类药。本复方中两个主要成分,即双氢青蒿素和哌喹配伍也有较好效果,为本发明专利的重要组成部分。

Description

抗疟药新药复方双氢青蒿素
本发明涉及用于治疗和预防恶性疟疾和其他类型疟疾的新药复方双氢青蒿素。
多重抗药性恶性疟疾正在全球蔓延，东南亚尤为严重。世界卫生组织把“遏制疟疾”列入了21世纪的重要计划之一。原对甲氟喹(Mefloquine)及其复方法西密(Fansimef)寄予很大希望，但由于其抗药性的迅速出现，首先在泰国，继而在越南已经处于疗效很差，而毒性不小的境地(李国桥等在越南Xuan Loc医院用Fansimef治疗恶性疟，治愈率55％，未发表资料1995)。我国七十年代以来研制发明的青蒿素及其衍生物青蒿琥酯、蒿甲醚、蒿乙醚、双氢青蒿素等具有高效、速效的优点，但必须服药7天才能达到高治愈率，否则复燃率高，不利于疟疾传染源的控制。
瑞士NORVATIS制药公司从中国购买的一项技术复方蒿甲醚(由蒿甲醚和本芴醇组成)，有可能优于现有抗疟药，但其疗程仍需3天，且成本较高。英国Glaxo Wellcome公司正在研制的Malarone，由奈醌(Naphthoquinone)和环氯胍组成，其配方中没有速效药物，疗程3天，每天服药2次。若将每天药量改为一次服用，则恶心、呕吐副作用严重。
本发明的目的在于提供一种速效、高效、低毒、短疗程的治疗多重抗药性恶性虐疾的新药复方双氢青蒿素。
本发明的上述目的是通过这样的技术方案实现的，即一种抗疟药新药复方双氢青蒿素，其特征是：它是以下述重量(份)配比的原料制成的药剂：
双氢青蒿素(Dihydroartemisinin)或其同类药物    1份
哌喹(piperaquine)                             3～7份
甲氧苄啶(Trimethoprim)                        0～5份
本发明药物中双氢青蒿素的同类药物为青蒿素及其衍生物，如青蒿素、青蒿琥酯、蒿甲醚、蒿乙醚。此类药物经体内最终转化为双氢青蒿素而发挥其杀灭原虫的作用。
本发明的上述解决方案是基于祖国医学对虐疾的发病机理的认识及治疗原则，参考现代药理研究成就而得出的，即本发明配方的原理是：双氢青蒿素具有速效、低毒，可迅速大量杀灭抗药性恶性疟原虫，但若不连续服药7天，则复发率高；哌喹具有长效特点，可使疗程缩短为2天；可补双氢青蒿素之不足；甲氧苄啶是一种增效剂，有助于提高治愈率降低复燃率。双氢青蒿素又可延缓哌喹和甲氧苄啶抗药性的出现。
本发明药物的最佳重量(份)配比是：
双氢青蒿素    1份
哌喹          5份
甲氧苄啶      2.5份
本发明药物也可以是双氢青蒿素与哌喹的配伍制剂，其最佳重量(份)配比是：
双氢青蒿素    1份
哌喹          6份
本发明药物经过药效学、毒理学、一般药理试验和临床研究以及制备工艺、质量检测及稳定性考察等研究，并在我国海南省和越南、泰国、柬埔寨抗药性疟疾流行地区，对恶性疟的疗效进行试验。研究结果证明其对恶性疟的疗效优于现有的任何抗疟药，可用于治疗恶性疟，问日疟和其他类型疟疾，是迄今为此世界上对恶性疟具有治愈率高，杀虫速度快且毒副反应低，安全性大，工艺简单，成熟，稳定性好的新药。其中主要成分之一哌喹不用其磷酸盐，减少用药量，减轻副作用，降低了成本，其最大特点是服用简单方便，仅需一天2次服药即可治愈。实际应用价值很大。
本发明所述的制剂是将上述药物与多种药学上可接受的赋形剂或载体结合，采用混合、溶解、粒化、成片、糖包衣或膜包衣等已知方法制备成固态或液态形式的制剂，如片剂、胶囊、栓剂、颗粒剂及注射剂等。
将上述各组分制成本发明药物的生产方法是：
先对原辅料进行检测，将合格之原料分别粉碎，过100目筛，然后按处方量准确称取原料及辅料。将各组分混合均匀压片，包装即为成品。
例如：生产本发明药物1000片按下述配方取量：
双氢青蒿素或其同类药                     75g
哌喹                  375g
甲氧苄啶              187.5g
辅料(羟丙其纤维素)    适量。
本发明药物的服用剂量：成人用量为2天，疗程总量4片，即0小时，8小时，24时时和32小时，每次服1片。通过500多例临床实验证明本药具有速效、高效、低毒、短疗程的特点，其疗效明显优于目前国内外的同类药。

Claims (3)

1．一种抗疟药新药复方双氢青蒿素，其特征是：它是以下述重量(份)配比的原料制成的药剂：
双氢青蒿素(Dihydroartemisinin)或其同类药物    1份
哌喹(piperaquine)或其磷酸盐                   3～7份
甲氧苄啶(Trimethoprim)                        0～5份。
2．根据权利要求1所述的复方双氢青蒿素片，其特征是：双氢青蒿素的同类药是指青蒿素、青蒿琥酯、蒿甲醚、蒿乙醚或青蒿素的其他衍生物。
3．根据权利要求1所述的复方双氢青蒿素片，其特征是：所述的制剂是片剂、胶囊栓剂、颗粒剂及注射剂。
CNB001131346A 2000-08-23 2000-08-23 抗疟药新药复方双氢青蒿素 Ceased CN1135974C (zh)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CNB001131346A CN1135974C (zh) 2000-08-23 2000-08-23 抗疟药新药复方双氢青蒿素
AU2001289506A AU2001289506A1 (en) 2000-08-23 2001-05-31 Pharmaceutical composition of dihydroartemisinin for treating malaria
PCT/CN2001/000884 WO2002026226A1 (fr) 2000-08-23 2001-05-31 Composition pharmaceutique contenant de la dihydroartemisinine indiquee pour le traitement de la malaria

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CNB001131346A CN1135974C (zh) 2000-08-23 2000-08-23 抗疟药新药复方双氢青蒿素

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005030197A1 (fr) 2003-09-26 2005-04-07 Guoqiao Li Compose a base d'artemisinine
CN1833644B (zh) * 2005-03-18 2010-07-21 中国人民解放军第三军医大学 青蒿素及其衍生物二氢青蒿素、蒿甲醚、蒿乙醚、青蒿琥酯在制药中的应用
CN107929240A (zh) * 2017-12-13 2018-04-20 桂林南药股份有限公司 磷酸哌喹口服液及其制备方法

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7842719B2 (en) 2002-10-31 2010-11-30 Kemin Foods, L.C. Use of endoperoxides for the treatment of infections caused by flaviviridae, including hepatitis C, bovine viral diarrhea and classical swine fever virus
BRPI0711585A2 (pt) * 2006-05-17 2011-11-16 Ranbaxy Lab Ltd terapia antimalárica

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5219865A (en) * 1987-05-08 1993-06-15 Hoechst Aktiengesellschaft Pharmaceutical combination for the prophylaxis and therapy of malaria
CN1081035C (zh) * 1997-11-18 2002-03-20 广州市健桥医药科技发展有限公司 抗疟疾新药复方萘酚喹
CN1092048C (zh) * 1998-06-02 2002-10-09 广州市健桥医药科技发展有限公司 复方哌喹片

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005030197A1 (fr) 2003-09-26 2005-04-07 Guoqiao Li Compose a base d'artemisinine
US7851512B2 (en) 2003-09-26 2010-12-14 Li Guogiao Composition containing artemisinin for treatment of malaria
AP2485A (en) * 2003-09-26 2012-10-03 Guoqiao Li Compound artemisinin
CN1833644B (zh) * 2005-03-18 2010-07-21 中国人民解放军第三军医大学 青蒿素及其衍生物二氢青蒿素、蒿甲醚、蒿乙醚、青蒿琥酯在制药中的应用
CN107929240A (zh) * 2017-12-13 2018-04-20 桂林南药股份有限公司 磷酸哌喹口服液及其制备方法

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