CN1075254A - Compound with cooperation of anti-malaria - Google Patents
Compound with cooperation of anti-malaria Download PDFInfo
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- CN1075254A CN1075254A CN93101341A CN93101341A CN1075254A CN 1075254 A CN1075254 A CN 1075254A CN 93101341 A CN93101341 A CN 93101341A CN 93101341 A CN93101341 A CN 93101341A CN 1075254 A CN1075254 A CN 1075254A
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- effective dose
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- benflumetol
- malaria
- quinine
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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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
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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
- A61K31/49—Cinchonan derivatives, e.g. quinine
-
- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The present invention relates to contain the synergistic antimalarial compositions that has that the antimalarial of antimalarial agent benflumetol and quinine class such as quinine form.Said composition can be mixed with solid dosage forms such as tablet, and can be used for the treatment of resistant malaria.
Description
The invention relates to cooperative compositions, the method by taking said composition treatment malaria and prepare this and have synergistic antimalarial drug method for compositions.
Resistant malaria is a clinical and sanitarian serious difficult problem.Perhaps owing to the sudden change of heredity, perhaps owing to extragenetic adjustment mechanism, the malarial parasite Plasmodium falciparum has produced many-sided adaptability of escaping general medicine (as chloroquine) effect.The Plasmodium falciparum of anti-chloroquine or anti-other antimalarials is main difficulties of health care plan in the torrid zone and the subtropical zone country.Therefore, for the treatment of success, need the new Pharmaceutical composition that reduces the malarial parasite resistance.
The compositions with malaria effect that contains benflumetol is at the last report of U.S. chemical abstract 97:28538h and 101: 136941u.Other compositions is the combination of known antimalarial.For example, compositions [the Suphat Noey-patimanond of useful clinically amodiaquine and tetracycline, Deng, Trreatment of PlasmodiumFallciparum malaria witha combination of amodiaquine and tetracyclinne in centrral Thailand, Trans.R.Soc, Trop.Med, and Hyg.73(3), 338-340(1983)]. other antimalarial compositions (FANSIMED, mefloquine, pyrimethamine and sulfadoxine) on commercially available, sell [Tropical.Diseases Research, Seventh Programme Report, 2 chapter Malaria, UNDP World Bamk/WHO.Published by WHO, 1985].
Its application of compositions that arteannuin and derivant thereof and other have the chemical compound (as quinine) of malaria effect discloses in German patent application 3715378.The synergism of the compositions of arteannuin and primaquine is known (Wan Yaode, Zang Qizhong; The pharmacy circular, 16 1 phases of volume, 1981).
In european patent application 362810, disclose antimalarial Artemether, arteether, arteannuin, dihydroartemisinine or sodium artesunate and quinine or with the compositions of mefloquine.
Power of the present invention comes from the treatment need have greater activity and low drug-fast improved antimalarial compositions to malarial parasite such as Plasmodium falciparum.
Have now found that the Pharmaceutical composition that contains benflumetol and quinine or derivatives thereof has improved malaria effect, and than only containing single benflumetol or the quinine derivative composition is more effective.
The present invention relates to be applicable to that the malaria effective ingredient has synergistic Pharmaceutical composition, said composition comprises that the following formula: compound of cooperative effective quantity and at least one of cooperative effective quantity are selected from quinine, mefloquine, Halofantrine, chloroquine, primaquine and the malaridine of (II) group or have the salt or the derivant that pharmaceutically are suitable for of malaria effect
General Definition of using in the description of the present invention and term have following meaning:
Term " Pharmaceutical composition " means and contains formula I chemical compound and at least one (II) group combination of compounds mixture.This mixture or be made of the anhydrous formulation of effective ingredient (I) and (II) such as lyophilization product perhaps preferably contains the additive that is suitable for preparing forming agent (as tablet, capsule or suppository).
The effect that term " synergism " means said composition under doses surpasses at least one single effective ingredient (I) or (II).The effect that is preferably in effective ingredient used in this Pharmaceutical composition has all improved.Synergism it would be desirable that low dosage and/or its effect that can use each composition surpass single component.
All proved the synergism of the present composition by external and the result of the test body inner model.Its result shows, compares with the effect of benflumetol (I), and the effect of composition in single dosage form (I) has improved, and the effect of composition (II) has also improved.
The antimalarial synergism of the present composition allows during the treatment to merge and to use different medicines by taking a kind of dosage form (as every day 1 or 2).
The dosage form of using that contains effective ingredient benflumetol (I) has persistent effect to malaria.This is proved by pharmacology test in the external and body of various standards.Second effective ingredient (II) is present in the same dosage form, behind malaria morbidity plasmodium had directly and effect fast.
Effective ingredient above-mentioned (I) (wherein Bu represents normal-butyl) is known, and its name is called benflumetol (benflumetol), referring to U.S. chemical abstract registration number (C..A.R.N.82186-77-4).The Pharmaceutical composition and their the malaria effect that contain single benflumetol also were known, referring to U.S. chemical abstract 97:28538h and 101: 13694.The preparation method of benflumetol is open in the Chinese patent application 88/07666.X. that announces.
The quinine, mefloquine, Halofantrine, primaquine and the malaridine that are selected from (II) group are the known drugs that is used for malaria treatment.
The quinic salt that pharmaceutically is suitable for is the monobasic acid addition salts that for example forms with the mineral acid or the organic acid of one or two a great deal of, or the bibasic acid addition salts that forms with mineral acid or organic acid.Described acid-addition salts is for example quinic halogen acid salt (example hydrochloric acid salt, hydrobromate, hydriodate, dihydrochloride, two hydrobromates, two hydriodates), disulfate, sulfate, bicarbonate or carbonate, ethyl carbonate salt, formates, acetate, gluconate or tannate.
The quinic derivant that pharmaceutically is suitable for for example has relevant chinidine, cinchonine or cinchonidine derivant on the structure.These derivants preferably are present in the compositions with the form of acid-addition salts (as halogen acid salt or two halogen acid salts, for example hydrochlorate or dihydrochloride).
Quinine and above-mentioned salt and their derivant are known antimalarials.See also ﹠amp by Merch; Co., each clauses and subclauses on the 10th edition (1983) 1164-1166 page or leaf of Merck Index of Inc publication.
Mefloquine (U.S. chemical abstract registration number 53230-10-7) preferably is present in the compositions of the present invention with the form of hydrochlorate (U.S. chemical abstract registration number 51773-92-3).Please see Martindale:TheExtra Pharmacopeia by the outside two of a team of horses, the 29th edition, 1381 clauses and subclauses that Thep-harmaceutical press London is 1989,513 pages.
Halofantrine (U.S. chemical abstract registration number 69756-53-2 and 66051-63-6) preferably is present in the compositions with the form of hydrochlorate (U.S. chemical abstract registration number 36167-63-2).See also Martindale; The Extra Pharmacopeia, 16829 clauses and subclauses that (with above-mentioned quoted passage) is 512 pages.
Chloroquine (7-chloro-4-[4-lignocaine-1-methyl-n-butyl amine base] quinoline) be known 4-quinolin-2-ylamine class antimalarial, and preferably the form with its diphosphate or sulfate is present in the present composition, see also Merck Index, the 11st edition, 334 pages 2163 clauses and subclauses.
Primaquine [8-(4-amino-1-methyl-n-butyl amine base)-the 6-methoxy quinoline] be known 8-quinolin-2-ylamine class antimalarial, its structural formula is as follows:
The antimalarial effect of this chemical compound is edited at W.O.Foye: Principles of Medicinal Chemistry, Lea ﹠amp; Febiger, philadelphia/London, 1989,34 chapter E.B.Roche etc.: report is also arranged among the parasite Chmotherapy.
Malaridine is known antimalarial, and its structural formula is as follows;
This chemical compound synthetic sees Acta pharmacentica sinica 15:630-632(1980).The antimalarial effect of this chemical compound is at Practical Chemotherapy of Malar-ria, Report of a WHO Scientific Graup, Technical Report Series 805, Geneva 1990, see the 8.5th chapter, report is also arranged in the 122-124 page or leaf.
The Pharmaceutical composition of preferentially selecting for use that malaria is had a malaria effective ingredient of synergy is the compositions that is made of quinine, mefloquine and the Halofantrine of the benflumetol with synergism dosage (I) and at least a being selected from (II) group with synergism dosage or their salt that pharmaceutically is suitable for malaria effect or derivant.
Especially the good Pharmaceutical composition that malaria is had a malaria effective ingredient of synergy is the compositions that is made of benflumetol with synergism dosage (I) and the quinic acid-addition salts that pharmaceutically is suitable for synergistic dosage.
Pharmaceutically to be present in the compositions of the present invention be preferably to useful additives.According to general compound method this additive is used for preferably through Enteral formulations or non-through the gastrointestinal tract dosage form.
For oral, suitable additive comprises inert diluent or filler, and the result obtains solid or liquid dosage form, as tablet, powder, capsule, syrup etc.If desired, Pharmaceutical composition of the present invention can contain other composition, as flavoring agent, binding agent, excipient etc.
For example, tablet can contain various solid additives such as starch, dextrin, alginic acid and some compound silicate, and binding agent such as polyvinylpyrrolidone, sucrose, gelatin and arabic gum.In addition, lubricant such as magnesium stearate, sodium lauryl sulphate and Talcum are generally used for preparing tablet.The solid constituent of same-type also can be used as the filler of soft gelatin capsule and hard gelatin capsule, and the material of preferentially selecting for use comprises lactose (C
12H
22O
11H
2O or lactose (C
12H
22O
11) and high-molecular weight Polyethylene Glycol.
For other peroral dosage form, each mixture of ingredients can be taken with gelatine capsule agent form.Said preparation can be a substrate as sunflower oil, Semen Maydis oil, Oleum Arachidis hypogaeae semen, Oleum Cocois or Oleum sesami with suitable refined edible oil.
Preferably among the embodiment, effective ingredient (I) and (II) are mixed with single unit dosage forms such as tablet or capsule in the present invention.
Effective ingredient can also be mixed with two independent dosage forms that are contained in the drug-supplying system (all each compositions), can side by side take, perhaps take continuously.This is fine for same route of administration, for example takes to contain all two single dosage forms of each composition.One is tablet or the capsule that contains composition (I), and takes second dosage form that contains composition (II) continuously.Particularly indivedual dosages can according to circumstances be studied during clinical treatment, for example after malaria occurring for the first time, take the tablet or the capsule that contain heavy dose of effective ingredient (I), perhaps when malaria morbidity begins, give many times of low dosages, and also take tablet or the capsule that contains low dosage effective ingredient (II).In therapeutic process, take the dosage form that contains low dosage composition (I) and high dose composition (II), also can be side by side or take continuously and comprise all different dosage forms of each composition, for example take tablet that contains composition (I) and the suppository that contains composition (II).Dosage range also can change according to above-mentioned dosage regulation.
According to the external and in vivo test result of the test model gained of setting up, the effect of Pharmaceutical composition of the present invention in malaria treatment is conspicuous.The present composition as anti-Bai Shi plasmodium strain (known they even produced tangible resistance to other antimalarials) effectively and the long-lasting antimalarial effect reflect the purposes of the present composition.
The invention still further relates to the treatment to malaria, it takes the above-mentioned Pharmaceutical composition that contains effective ingredient (I) and (II) to the patient after being included in malaria morbidity.Preferably took the present composition at least 4 days, preferably take more than 5 days or 5 days to the patient.
Term " method of treatment " comprises that also the preventative present composition of taking is to prevent that in the hyperendemic area of malaria especially regional healthy person is suffered from this disease between the tropic of Capricorn and the tropic of cancer.
The dosage of the effective ingredient benflumetol that contains in the present composition can change in big scope, and this dosage depends on time of having pass by after patient's situation and the morbidity.According to the test of the sample of reporting in the following example, now definite, the dosage of benflumetol is about 0.2-50.0 milligram/kilogram every day, and better with 0.2-10.0 milligram/kilogram, good especially is about 0.2-5.0 milligram/kilogram.In view of benflumetol has low toxicity and height tolerability, therefore the dosage of described every day can obviously increase until needs.The dosage that it is calculated that composition (II) every day is 0.2-50 milligram/kilogram, and better with 0.3-5.0 milligram/kilogram, good especially is about 0.4-3.0 milligram/kilogram.
Dose ratio between composition (I) and the composition (II) also can change in the larger context.Compare with the weight of composition (II), if take equal weight or surpass the benflumetol of composition (II) weight, synergism can be good especially so.Therefore, the consumption of benflumetol can change with 1-10 part fluorenol by every part of composition (II).Every part of composition is preferably with (II) with 3-7 part benflumetol, is good especially with 5-6 part benflumetol.Dosage that provides and dose ratio refer to the dosage and the ratio of taking every day.
The invention still further relates to and be applicable to that the malaria effective ingredient has the preparation method of synergistic Pharmaceutical composition, this method comprises that the formula I chemical compound that makes effective dose mixes with the composition (II) of effective dose, and under the situation that adds the addition product that pharmaceutically is suitable for arbitrarily, the compositions of described effective ingredient is mixed with suitable dosage form.
New Pharmaceutical composition is to contain for example 10%-80%, preferably the mixing active ingredients thing of 20%-60%.Pharmaceutical composition of the present invention is applicable to the enteral administration, and for example can be mixed with oral dosage unit form (as dragee, tablet, capsule) or suppository.These preparations can for example be prepared with conventional mixing, system granule, confection, dissolving or cryodesiccated method with known method itself.For example oral pharmaceutical formulation can be pressed method and make: active ingredient is mixed with solid carrier, with the selectable granule of making of the mixture that obtains, if desired or necessary, after adding proper additive, mixture or granule are processed into tablet or dragee so.
At said method preferably among the embodiment, with effective ingredient (I) and (II) individually or levigate together, making granular size is about 10 microns-Yue 400 microns, is preferably 20 microns-200 microns.The crystallization of at least 90% effective ingredient is in this scope.
The granule of above-mentioned size can obtain by general breaking method, for example pulverizes with aerojet pulverizer or ball mill or vibrating pulverizer.Micronization is preferably pressed known method, with ultrasonic disintegrator such as J.pharm.Sci.53(99), 1040-1045(1965) described Branson Sonifier type ultrasonic disintegrator carries out, and perhaps uses high speed agitator (as Brogli ﹠amp; Co., the Homorex type that provides of Basel stirs and trembles device) stir suspension and carry out.In above-mentioned method preferably; micronization can be undertaken by purgation: the mixing active ingredients thing is dissolved in or is suspended in the organic solvent (as methanol, ethanol or propylene glycol); with about 500-10; the 000rpm(revolutions per minute) stirs; and its form with crystallite is deposited in water or the saline solution (as 2% sodium chloride solution) in 0 ℃-5 ℃; contain low concentration (as 0.1-1%) protecting colloid (gelatin) or cellulose ether (as methylcellulose or hydroxypropyl emthylcellulose) in the solution in addition, filter the stirring suspension that obtains then.Filter cake is dry down in low temperature (as 0 ℃-5 ℃) and vacuum (as below 50 millibars, being preferably 0.5 millibar).Then carry out drying in about 50 ℃-90 ℃.
The crystallization that will obtain as stated above is mixed with granule then, preferably by conventional method with wet method system granule.
Preferably prepare the present composition: the granular recipe that obtains below the compacting by following method, for example sieve, if desired, pulverize medicine, be pressed into granule together with excipient (perhaps different excipient) and other solvent (as ethanol or water) and lubricant or flowable (as magnesium stearate) or tween then, pulverize this granule and sieve once more.
With the pressure of about 10KN above-mentioned granule is made label with general tablet machine (for example EKO Korsch centering type tablet machine).Use water-ethanol solution (Polyethylene Glycol and sucrose dissolved or be dispersed in wherein) and carry out coating.
With the suitable coating that can resist gastric juice, the dense sugar juice that especially contains arabic gum, Talcum, polyvinylpyrrolidone or Polyethylene Glycol prepares dragee.Various dose for the ease of identification, taste masking or indication effective ingredient can be added to coloring agent, flavoring agent or pigment in syrup, tablet or the dragee.
Other composition for oral liquid is the capsule that is made of gelatin of dry method filling, also has by the soft capsule that seal of gelatin with plasticizer (as glycerol and Sorbitol) formation.The capsule of dry method filling can contain filler (as lactose), binding agent (as starch) and/or flowable (as Talcum or magnesium stearate) and selectable stabilizing agent.In the soft capsule, preferably effective ingredient is dissolved in the suitable liquid (as fatty oil, paraffin oil or liquid macrogol), wherein can adds stabilizing agent.
Be suitable for also having suppository through the dosage form of enteral administration, this suppository system is made of effective ingredient and suppository base mixture.Suitable suppository base has for example natural or synthetic triglyceride, paraffin, Polyethylene Glycol or higher alkanols.Can also use the gelatin rectal capsule agent, it contains the mixture of effective ingredient and substrate, and suitable substrate has for example liquid triglycerides, Polyethylene Glycol or alkane.
Following example is described in detail above content, but in no case should be seen as limitation of the scope of the invention.
Example: preparation tablet
120 milligrams of benflumetol
20 milligrams of quinine dihydrochlorides
100 milligrams of corn starchs
40 milligrams in dextrin
0.6 milligram of tween 80
15% masa capacity
3 milligrams of magnesium stearate
100 mesh sieves are crossed in the quinine dihydrochloride crystallization.Strong brilliant 60 mesh sieves of crossing of benflumetol mix with quinine pressed powder, starch and dextrin then.Make mixture cross 40 mesh sieves 3 times.With tween 80 be added to the blended gelatinized corn starch of above-mentioned prescription in.With wet method mixture is made granule.Cross 40 mesh sieves, under reduced pressure in 50 ℃ of-60 ℃ of dryings.Add magnesium stearate and tabletting.
Claims (8)
1, the malaria effective ingredient has a synergistic suitable Pharmaceutical composition, at least one their pharmaceutically suitable salt or derivant that is selected from (II) group chemical compound of forming by quinine, mefloquine, Halofantrine, chloroquine, primaquine and malaridine or has the malaria effect that said composition comprises following formula: compound with synergism effective dose and has a synergism effective dose
2, according to the described Pharmaceutical composition of claim 1, said composition comprises that at least one that have synergistic effective dose benflumetol (I) and have a synergistic effective dose is selected from quinine, mefloquine and the Halofantrine of (II) group or has their salt or the derivant that pharmaceutically are suitable for of malaria effect.
3, according to the described Pharmaceutical composition of claim 1, said composition comprise have synergistic effective dose benflumetol (I) and have synergistic effective dose the salt of the quinine (II) that pharmaceutically is suitable for.
4, the described Pharmaceutical composition of preparation claim 1 folding method, this method comprise with have synergistic effective dose benflumetol with have a synergistic effective dose at least one be selected from quinine, mefloquine, Halofantrine, chloroquine, primaquine and the malaridine of (II) group or their salt or the derivant that pharmaceutically are suitable for mixed, and this mixture is mixed with suitable dosage form selectively adding under the situation of useful additives pharmaceutically.
5, in accordance with the method for claim 4, this method comprises that benflumetol (I) the quinic salt upward suitable with having synergistic effective dose of medicine that makes effective dose mixes.
6, according to the described method for preparing Pharmaceutical composition of claim 4, this method is included under the situation that adds solid additive each mixing active ingredients thing is pressed into tablet.
7, at least one their salt or derivant of pharmaceutically being suitable for that is selected from quinine, mefloquine, Halofantrine, chloroquine, primaquine and the malaridine of (II) group or is used to prepare the present composition that the application of the present composition, said composition comprise the benflumetol (I) with synergism effective dose and have a synergism effective dose.
8, the described Pharmaceutical composition of claim 1 that is used for the treatment of malaria.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP92810089.0 | 1992-02-07 | ||
EP92810089 | 1992-02-07 | ||
EP9281030.2 | 1992-02-21 | ||
EP92810130 | 1992-02-21 | ||
SG1996001151A SG45193A1 (en) | 1992-02-07 | 1993-01-25 | Antimalarial synergistic compositions containing benflumetol |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1075254A true CN1075254A (en) | 1993-08-18 |
CN1087168C CN1087168C (en) | 2002-07-10 |
Family
ID=27234886
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN93101341A Expired - Lifetime CN1087168C (en) | 1992-02-07 | 1993-02-06 | Compound with cooperation of anti-malaria |
Country Status (9)
Country | Link |
---|---|
JP (1) | JP3560970B2 (en) |
CN (1) | CN1087168C (en) |
AU (1) | AU668376B2 (en) |
CA (1) | CA2105773A1 (en) |
FI (1) | FI934360A0 (en) |
HU (1) | HU220605B1 (en) |
NZ (1) | NZ246606A (en) |
SG (1) | SG45193A1 (en) |
WO (1) | WO1993015727A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1109546C (en) * | 1998-06-17 | 2003-05-28 | 中国疾病预防控制中心寄生虫病预防控制研究所 | Compound antimalarial medicine containing artemisine medicines and malaridine |
CN1859945B (en) * | 2003-10-01 | 2010-07-28 | 奥林巴斯株式会社 | Capsule medication administration system |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9622427D0 (en) * | 1996-10-28 | 1997-01-08 | Pharma Mar Sa | Antimalarial drugs |
DE00993875T1 (en) * | 2000-05-31 | 2004-04-15 | Nicholas Piramal India Ltd. | KIT FOR THE TREATMENT OF MALARIA CONTAINING CHLOROQUINE AND 3- (1 - (((4 - ((6-METHOXY-8-QUINOLINYL) AMINO) PENTYL) AMINO) -ETHYLIDENE) -DIHYDRO-2 (3H) FURANONE |
WO2018198021A1 (en) * | 2017-04-24 | 2018-11-01 | Novartis Ag | Therapeutic regimen of 2-amino-l-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8h)-yl)ethanone and combinations thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IN166154B (en) * | 1987-05-08 | 1990-03-24 | Hoechst India | |
DE68906345T2 (en) * | 1988-10-07 | 1993-10-28 | Hoechst Ag | Antimalarial compositions utilizing quinidine, artemisinin and their derivatives. |
CN1058717A (en) * | 1990-08-08 | 1992-02-19 | 中国人民解放军军事医学科学院微生物流行病研究所 | New antimalarial agent-Coartem and preparation method thereof |
-
1993
- 1993-01-25 HU HU9303152A patent/HU220605B1/en unknown
- 1993-01-25 CA CA002105773A patent/CA2105773A1/en not_active Abandoned
- 1993-01-25 NZ NZ246606A patent/NZ246606A/en not_active IP Right Cessation
- 1993-01-25 JP JP51371093A patent/JP3560970B2/en not_active Expired - Lifetime
- 1993-01-25 WO PCT/EP1993/000163 patent/WO1993015727A1/en active IP Right Grant
- 1993-01-25 SG SG1996001151A patent/SG45193A1/en unknown
- 1993-01-25 AU AU33522/93A patent/AU668376B2/en not_active Expired
- 1993-02-06 CN CN93101341A patent/CN1087168C/en not_active Expired - Lifetime
- 1993-10-04 FI FI934360A patent/FI934360A0/en unknown
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1109546C (en) * | 1998-06-17 | 2003-05-28 | 中国疾病预防控制中心寄生虫病预防控制研究所 | Compound antimalarial medicine containing artemisine medicines and malaridine |
CN1859945B (en) * | 2003-10-01 | 2010-07-28 | 奥林巴斯株式会社 | Capsule medication administration system |
Also Published As
Publication number | Publication date |
---|---|
CN1087168C (en) | 2002-07-10 |
FI934360A (en) | 1993-10-04 |
HUT66452A (en) | 1994-11-28 |
AU3352293A (en) | 1993-09-03 |
HU220605B1 (en) | 2002-03-28 |
AU668376B2 (en) | 1996-05-02 |
JP3560970B2 (en) | 2004-09-02 |
FI934360A0 (en) | 1993-10-04 |
SG45193A1 (en) | 1998-01-16 |
JPH06506706A (en) | 1994-07-28 |
NZ246606A (en) | 1995-09-26 |
CA2105773A1 (en) | 1993-08-08 |
WO1993015727A1 (en) | 1993-08-19 |
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