CN1191113A - 抗疟疾新药复方萘酚喹 - Google Patents
抗疟疾新药复方萘酚喹 Download PDFInfo
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- CN1191113A CN1191113A CN97114291A CN97114291A CN1191113A CN 1191113 A CN1191113 A CN 1191113A CN 97114291 A CN97114291 A CN 97114291A CN 97114291 A CN97114291 A CN 97114291A CN 1191113 A CN1191113 A CN 1191113A
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- CN
- China
- Prior art keywords
- naphtholquine
- dihydroarteannuin
- trimethoprim
- called
- short
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 10
- 230000000078 anti-malarial effect Effects 0.000 title abstract description 5
- 239000003430 antimalarial agent Substances 0.000 title abstract description 5
- 239000003814 drug Substances 0.000 claims description 16
- 229930187998 Dihydroarteannuin Natural products 0.000 claims description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 8
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 claims description 8
- 229960001082 trimethoprim Drugs 0.000 claims description 8
- QTYPWHKJEDCDNH-UHFFFAOYSA-N 2-[(tert-butylamino)methyl]-4-[(7-chloroquinolin-4-yl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol;phosphoric acid Chemical compound OP(O)(O)=O.OP(O)(O)=O.C1CCCC2=C(O)C(CNC(C)(C)C)=CC(NC=3C4=CC=C(Cl)C=C4N=CC=3)=C21 QTYPWHKJEDCDNH-UHFFFAOYSA-N 0.000 claims description 7
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 claims description 7
- 229960000981 artemether Drugs 0.000 claims description 6
- SXYIRMFQILZOAM-HVNFFKDJSA-N dihydroartemisinin methyl ether Chemical compound C1C[C@H]2[C@H](C)CC[C@H]3[C@@H](C)[C@@H](OC)O[C@H]4[C@]32OO[C@@]1(C)O4 SXYIRMFQILZOAM-HVNFFKDJSA-N 0.000 claims description 6
- 229960004191 artemisinin Drugs 0.000 claims description 5
- 229960004991 artesunate Drugs 0.000 claims description 5
- FIHJKUPKCHIPAT-AHIGJZGOSA-N artesunate Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@@H](OC(=O)CCC(O)=O)[C@@H]4C FIHJKUPKCHIPAT-AHIGJZGOSA-N 0.000 claims description 5
- 229960002970 artemotil Drugs 0.000 claims description 4
- NLYNIRQVMRLPIQ-XQLAAWPRSA-N artemotil Chemical compound C1C[C@H]2[C@H](C)CC[C@H]3[C@@H](C)[C@@H](OCC)O[C@H]4[C@]32OO[C@@]1(C)O4 NLYNIRQVMRLPIQ-XQLAAWPRSA-N 0.000 claims description 4
- 150000004780 naphthols Chemical class 0.000 claims description 4
- 229930191701 arteannuin Natural products 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 229930101531 artemisinin Natural products 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 4
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- YLZYSVYZMDJYOT-UHFFFAOYSA-N 2-methoxypyrimidine Chemical compound COC1=NC=CC=N1 YLZYSVYZMDJYOT-UHFFFAOYSA-N 0.000 abstract 1
- 229910019142 PO4 Inorganic materials 0.000 abstract 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract 1
- 239000010452 phosphate Substances 0.000 abstract 1
- 201000004792 malaria Diseases 0.000 description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229960001962 mefloquine Drugs 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 230000000505 pernicious effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- HQWQVBJUIIJTRE-LKRNKTNVSA-N 4-amino-n-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide;(s)-[2,8-bis(trifluoromethyl)quinolin-4-yl]-[(2r)-piperidin-2-yl]methanol;5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine;hydron;chloride Chemical compound Cl.CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1.COC1=NC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1OC.C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 HQWQVBJUIIJTRE-LKRNKTNVSA-N 0.000 description 1
- 206010048723 Multiple-drug resistance Diseases 0.000 description 1
- 229930192627 Naphthoquinone Natural products 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 208000035999 Recurrence Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940098333 coartem Drugs 0.000 description 1
- QMNFFXRFOJIOKZ-UHFFFAOYSA-N cycloguanil Chemical compound CC1(C)N=C(N)N=C(N)N1C1=CC=C(Cl)C=C1 QMNFFXRFOJIOKZ-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- DYLGFOYVTXJFJP-MYYYXRDXSA-N lumefantrine Chemical compound C12=CC(Cl)=CC=C2C=2C(C(O)CN(CCCC)CCCC)=CC(Cl)=CC=2\C1=C/C1=CC=C(Cl)C=C1 DYLGFOYVTXJFJP-MYYYXRDXSA-N 0.000 description 1
- 229960004985 lumefantrine Drugs 0.000 description 1
- 229940001645 malarone Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002791 naphthoquinones Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- HYWAQJYWMPGRDG-UHFFFAOYSA-N phenol;quinoline Chemical compound OC1=CC=CC=C1.N1=CC=CC2=CC=CC=C21 HYWAQJYWMPGRDG-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000002423 protozoacide Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
本发明提供一种治疗疟疾病的新药复方萘酚喹,它是由磷酸萘酚喹、双氢青蒿素和甲氧苄啶组方而成。该药通过临床实验表明具有工艺简单成熟,稳定性好,药效作用强,杀灭疟原虫速度快,治愈率高,毒副作用少,安全性较大和服药简单方便等特点,对于疟疾病的防治具有重要意义。
Description
本发明涉及一种治疗和预防疟疾新药，特别是复方萘酚喹新药。
目前，多重抗药性恶性疟疾正在全球蔓延，东南亚尤为严重。世界卫生组织寄予很大希望的甲氟喹(Mefloquine)及其复方法西密(Fansimef)，也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。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、双氢青蒿素等具有高速效的优点，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。因此目前尚无更好的恶性疟疾治疗药可供选用。
瑞士NORVATIS制药公司正在重新研制向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 Nellcome公司正在研制的Malarone，由萘醌(Naphthoqinone)和环氯胍组成，其配方中没有速效药物，疗程3天，每天需服药2次。
本发明的目的旨在克服现有技术的不足而提供一种工艺简单成熟、杀灭原虫速度快且毒副反应低、安全稳定，服用简单方便的抗疟疾新药复方萘酚喹。
本发明的目的是这样实现的：
一种复方萘酚喹，其特征是由磷酸萘酚喹(Naphthoquine phosphate)(简称N)、双氢青蒿素(Oihydroartemisinin)(简称O)或其同类药物和甲氧苄啶(Trimethoprim)(简称T)组成，三药的重量配比范围为：
磷酸萘酚喹 5-8份
双氢青蒿素或其同类药物 1-2份
甲氧苄啶 2-3份
即N∶D∶T为5-8∶1-2∶2-3
双氢青蒿素的同类药物是指青蒿琥酯(Artesunate)、蒿乙醚(Arteether)、蒿甲醚(Artemether)和青蒿素(Artemisinin)，及青蒿素衍生物。此类药物经体内最终均转化为双氢青蒿素而发挥其杀灭原虫的作用。
下面通过实施例对本发明进一步详述：
处方
磷酸蔡酚喹(C24H28CLN3O·2H3PO4) 600g
双氢青蒿素(C15H24O5) 100g
甲氧苄啶(C14H18N4O3) 200g
辅料(羟丙基纤维素) 适量
制成 1000片
制剂工艺
先对原辅材料进行检测，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。将磷酸萘酚喹、甲氧苄啶、双氢青蒿素和辅料羟丙基纤维素(HPC)混合，均匀压片，包装，即为成品。
本发明的药品通过临床实验表明该复方药物具有工艺简单、成熟，稳定性好，药效作用强，杀灭疟原出速度高，治愈率高，毒副作用少，安全性较大等特点，尤其是其服药简单方便，仅需1-2次服药，对于疟疾病的防治具有重要意义。
Claims (2)
1、一种复方萘酚喹，其特征是由磷酸萘酚喹(Naphthoquinephosphate)(简称N)、双氢青蒿素(Oihydroartemisinin)(简称O)或其同类药物和甲氧苄啶(Trimethoprim)(简称T)组成，三药的重量配比范围为：
磷酸萘酚喹 5-8份
双氢青蒿素或其同类药物 1-2份
甲氧苄啶 2-3份
即N∶D∶T为5-8∶1-2∶2-3。
2、根据权利要求1所述的复方萘酚喹，其特征是双氢青蒿素的同类药物是指青蒿琥酯(Artesunate)、蒿乙醚(Arteether)、蒿甲醚(Artemether)和青蒿素(Artemisinin)，及青蒿素衍生物。
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97114291A CN1081035C (zh) | 1997-11-18 | 1997-11-18 | 抗疟疾新药复方萘酚喹 |
| ZA9810472A ZA9810472B (en) | 1997-11-18 | 1998-11-16 | An antimalarial composition |
| PCT/CN1998/000274 WO1999025351A1 (fr) | 1997-11-18 | 1998-11-18 | Compositions pharmaceutiques antipaludiques |
| CO98067813A CO4980890A1 (es) | 1997-11-18 | 1998-11-18 | Una composicion antimalarica metodo para tratar la malaria |
| AU12227/99A AU1222799A (en) | 1997-11-18 | 1998-11-18 | Antimalaria pharmaceutical compositions |
| PE1998001114A PE134499A1 (es) | 1997-11-18 | 1998-12-01 | Composicion contra la malaria |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97114291A CN1081035C (zh) | 1997-11-18 | 1997-11-18 | 抗疟疾新药复方萘酚喹 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1191113A true CN1191113A (zh) | 1998-08-26 |
| CN1081035C CN1081035C (zh) | 2002-03-20 |
Family
ID=5172855
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97114291A Expired - Fee Related CN1081035C (zh) | 1997-11-18 | 1997-11-18 | 抗疟疾新药复方萘酚喹 |
Country Status (6)
| Country | Link |
|---|---|
| CN (1) | CN1081035C (zh) |
| AU (1) | AU1222799A (zh) |
| CO (1) | CO4980890A1 (zh) |
| PE (1) | PE134499A1 (zh) |
| WO (1) | WO1999025351A1 (zh) |
| ZA (1) | ZA9810472B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104666300A (zh) * | 2014-07-04 | 2015-06-03 | 昆明制药集团股份有限公司 | 一种磷酸萘酚喹的新用途 |
| CN111265527A (zh) * | 2020-03-05 | 2020-06-12 | 中国人民解放军军事科学院军事医学研究院 | 萘酚喹及其药学上可接受的盐在制备抗冠状病毒药物中的用途 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1135974C (zh) * | 2000-08-23 | 2004-01-28 | 重庆健桥医药开发有限公司 | 抗疟药新药复方双氢青蒿素 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2748333A1 (de) * | 1977-10-28 | 1979-05-03 | Hoechst Ag | Mittel gegen malaria |
| US5219865A (en) * | 1987-05-08 | 1993-06-15 | Hoechst Aktiengesellschaft | Pharmaceutical combination for the prophylaxis and therapy of malaria |
| ES2054975T3 (es) * | 1988-10-07 | 1994-08-16 | Hoechst Ag | Composiciones antimalaricas que emplean quinidina, artemisinina y sus derivados. |
-
1997
- 1997-11-18 CN CN97114291A patent/CN1081035C/zh not_active Expired - Fee Related
-
1998
- 1998-11-16 ZA ZA9810472A patent/ZA9810472B/xx unknown
- 1998-11-18 CO CO98067813A patent/CO4980890A1/es unknown
- 1998-11-18 WO PCT/CN1998/000274 patent/WO1999025351A1/zh active Application Filing
- 1998-11-18 AU AU12227/99A patent/AU1222799A/en not_active Abandoned
- 1998-12-01 PE PE1998001114A patent/PE134499A1/es not_active Application Discontinuation
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104666300A (zh) * | 2014-07-04 | 2015-06-03 | 昆明制药集团股份有限公司 | 一种磷酸萘酚喹的新用途 |
| WO2016000504A1 (zh) * | 2014-07-04 | 2016-01-07 | 昆明制药集团股份有限公司 | 磷酸萘酚喹在制备抗菌药物中的用途 |
| CN104666300B (zh) * | 2014-07-04 | 2017-01-18 | 昆药集团股份有限公司 | 一种磷酸萘酚喹的用途 |
| CN111265527A (zh) * | 2020-03-05 | 2020-06-12 | 中国人民解放军军事科学院军事医学研究院 | 萘酚喹及其药学上可接受的盐在制备抗冠状病毒药物中的用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1081035C (zh) | 2002-03-20 |
| CO4980890A1 (es) | 2000-11-27 |
| PE134499A1 (es) | 2000-01-23 |
| AU1222799A (en) | 1999-06-07 |
| ZA9810472B (en) | 1999-05-21 |
| WO1999025351A1 (fr) | 1999-05-27 |
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Applicant after: Jianqiao Medicine Science & Technology Import & Export Co. Ltd. Applicant before: Jianqiao Sci. & Tech. Dev. Co., Ltd., Guangzhou City |
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