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WO2003061669A1 - Utilisation d'alkylphosphocholines pour traiter preventivement des maladies causees par des protozoaires - Google Patents

Utilisation d'alkylphosphocholines pour traiter preventivement des maladies causees par des protozoaires Download PDF

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Publication number
WO2003061669A1
WO2003061669A1 PCT/EP2003/000072 EP0300072W WO03061669A1 WO 2003061669 A1 WO2003061669 A1 WO 2003061669A1 EP 0300072 W EP0300072 W EP 0300072W WO 03061669 A1 WO03061669 A1 WO 03061669A1
Authority
WO
WIPO (PCT)
Prior art keywords
use according
active ingredient
hexadecylphosphocholine
leishmaniasis
miltefosine
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.)
Ceased
Application number
PCT/EP2003/000072
Other languages
German (de)
English (en)
Inventor
Jürgen Engel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aeterna Zentaris GmbH
Original Assignee
Zentaris AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Zentaris AG filed Critical Zentaris AG
Priority to MXPA04007193A priority Critical patent/MXPA04007193A/es
Priority to CA002470185A priority patent/CA2470185A1/fr
Priority to JP2003561613A priority patent/JP2005515244A/ja
Priority to IL16249203A priority patent/IL162492A0/xx
Priority to BR0307021-2A priority patent/BR0307021A/pt
Priority to EP03731619A priority patent/EP1467742A1/fr
Priority to AU2003236787A priority patent/AU2003236787B2/en
Publication of WO2003061669A1 publication Critical patent/WO2003061669A1/fr
Priority to IL162492A priority patent/IL162492A/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • 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
    • 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

Definitions

  • the present invention relates to alkylphosphocholines, in particular hexadecylphosphocholine (Miltefosine) or octadecyl (1,1-dimethylpiperidino-4-yl) -phosphate (perifosine, D-21266), pharmaceutical compositions for oral administration in the preventive treatment of protozoal diseases , in particular leishmaniasis, and a dosage regimen for the oral administration of said pharmaceutical composition in the preventive treatment of protozoal diseases, in particular leishmaniasis, and a combination comprising said pharmaceutical composition, an antiemetic and / or an antidiarrheal.
  • pharmaceutical compositions for oral administration in the preventive treatment of protozoal diseases in particular leishmaniasis
  • a dosage regimen for the oral administration of said pharmaceutical composition in the preventive treatment of protozoal diseases in particular leishmaniasis
  • a combination comprising said pharmaceutical composition, an antiemetic and / or an antidiarrheal.
  • Leishmaniasis is a term for various tropical diseases, which are caused by flagellates of the genus Leishmania and transmitted by various blood-sucking insects.
  • the manifestations of leishmaniasis may be visceral (Kala-Azar), mucocutaneous (American leishmaniasis) or cutaneous (Aleppo's bump or diffuse cutaneous leishmaniasis).
  • the incubation period is weeks to months. Especially in the case of Kala-Azar and American leishmaniasis a very high mortality rate is observed in untreated cases.
  • Pentavalent antimony compounds eg sodium stibogluconate
  • aromatic diamidines had to be administered by parenteral injection, which not only led to serious side effects due to their high toxicity, but also included a risk of infection.
  • alkylphosphocholines in particular hexadecylphosphocholine (miltefosine)
  • hexadecylphosphocholine vandecylphosphocholine
  • T. Jha et al., Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis N. Engl. J. Med. (1999), 341 (24), 1795-1800 report a study of 120 patients, where 50 to 150 mg of miltefosine per day was used for several weeks.
  • Miltefosine is difficult to handle, although it is available in dry form as crystalline platelets with a defined melting point in excess of 200 ° C since it is very hygroscopic.
  • the uptake of water molecules can lead to an increase in weight of up to 30% by weight, a lowering of the melting point and a caking and clumping of the crystals.
  • the processability of the hydrous miltefosine is insufficient for further processing into solid pharmaceutical compositions such as tablets, capsules or sachets.
  • the fluidity of hydrous miltefosine is insufficient. Satisfactory flowability, however, is one of the indispensable prerequisites for the production of pharmaceutical compositions on an industrial scale.
  • anhydrous miltefosine exhibits a considerable tendency to electrostatic charge, especially when stirred in a dry state.
  • the fluidity of electrostatically charged miltefosine is insufficient for further processing into solid pharmaceutical compositions.
  • electrostatic charges are always associated with significant safety concerns because of the associated risks of both explosions and damage to sensitive electronic parts.
  • WO 99/37289 it is possible, by simple physical mixing of alkylphosphocholines, in particular miltefosinv, to obtain a flow agent and / or lubricant and at least one filler, a solid pharmaceutical mixture having a fluidity which is sufficient for further processing, for example into capsules, Tablets or sachets.
  • the solid pharmaceutical composition can be filled into capsules, preferably hard gelatine capsules, or pressed into tablets or effervescent tablets or, as a drinking mixture or effervescent mixture, filled into sachets.
  • the content of miltefosine per unit dose is in the range of 10 to 800 mg, preferably in the range of 10 to 500 mg and more preferably in the range of 50 to 250 mg. The most preferred content is in the range of 50 to 150 mg.
  • miltefosine is described in detail in the examples of hexadecylphosphocholine in the German patent application DE-A-4132344. Further methods for producing and purifying miltefosine are described, for example, in German patent applications DE-A 2752125, DE-A 3641379, DE-A 3641491, DE-A 4013632 and DE-A 3641377.
  • alkylphosphocholines in particular
  • Hexadecylphosphocholine (Miltefosine) or octadecyl (1,1-dimethylpiperidinio-4-yl) -phosphate (Perifosin, D-21266) are suitable for a preventive treatment of protozoal diseases, in particular leishmaniasis.
  • Alkylphosphocholines in particular hexadecylphosphocholine or octadecyl (1,1-dimethylpiperidinio-4-yl) phosphate for the prevention of protozoal diseases, in particular leishmaniasis, are neither described nor suggested in the prior art reports.
  • a dosage regimen for the preventive treatment of leishmaniasis in humans by oral administration of the pharmaceutical composition is provided.
  • the following dosage regimen is useful for the preventive treatment of leishmaniasis in humans by oral administration:
  • Total daily dose 10-250 mg of miltefosine active, preferably 20-150 mg, especially 30-100 mg; daily single or multiple dose: a total daily dose of 10-50 mg of active ingredient is preferably administered as a single daily dose; a dose of 50-250 mg active ingredient, preferably 50-150 mg active ingredient, is administered orally daily as a multiple daily dose, preferably as two doses per day (total daily dose 100 mg active ingredient) or as three doses per day (total daily dose 150 mg active ingredient).
  • a daily dose divided into 4-5 doses is generally considered to be the upper limit. For preventive purposes, however, it is also possible to administer the remedy differently than divided into 1-5 doses per day.
  • Prophylaxis is also possible with an initial dose followed by maintenance doses using as initial dose e.g. 100 mg or more of active ingredient, followed by maintenance doses of e.g. B. 30 mg of active ingredient.
  • Prophylactic duration of use 2 weeks to 6 months, preferably over the duration of the risk of infection.
  • a dosage regimen for the preventive treatment of leishmaniasis in non-human mammals by oral administration of the pharmaceutical composition of the invention is provided.
  • the dosing regimen enables the preventive treatment of all types of leishmaniasis, in particular leishmaniasis major and leishmaniase infantum.
  • the total daily dose in the case of prophylactic treatment in the case of oral administration is in the range of 0.5-15 mg of miltefosine or perifosin active ingredient per kg body weight of the animal (mg active substance / kg).
  • prophylaxis is initiated with a total initial dose (loading dose) in the range of 3-15, preferably 5-10 mg / kg and then with a total daily dose (maintenance doses) in the range of 1-10, preferably 3-5 mg of drug / kg continued.
  • the preventive application period is in the range from 2 weeks to 6 months, preferably over the duration of the risk of infection.
  • the pharmaceutical composition according to the invention is administered in combination with an antiemetic and / or an antidiarrhoeal agent.
  • Administration may be simultaneous or sequential.
  • Antiemetic and antidiarrhoeal can be administered independently.
  • the antiemetic and / or antidiarrhoeal agent may be contained either in the described pharmaceutical composition or in a pharmaceutical formulation independent thereof.
  • Suitable antiemetics include, for example, 5-HT3 receptor antagonists, substituted benzamides, corticosteroids, antihistamines, phenothiazine-type neuroleptics, butyrophenone-type neuroleptics, benzodiazepines, and cannabinoids.
  • Preferred antiemetics include metoclopramide, domperidone and alizapride.
  • Suitable antidiarrhoeal agents include, but are not limited to, the opioids, e.g. Loperamide.
  • the solid oral pharmaceutical compositions are preferably useful for the preventative treatment of leishmaniasis.
  • Other diseases caused by protozoa include malaria, trypanosomiasis, toxoplasmosis, babesiosis, amoebic dysentery and lambliasis.
  • Example 1 hard gelatin capsule (content: 10 mg of miltefosine)
  • hexadecylphosphocholine 100 g of hexadecylphosphocholine, 808.50 g of lactose, 448.50 g of microcrystalline cellulose, 26 g of talc and 13 g of finely divided silica are passed through a sieve with a mesh size of 0.8 mm and then homogenized for 30 minutes in a suitable mixer. Then add 4 g of magnesium stearate (0.8 mm sieve) and mix the components for another 5 minutes. The resulting mixture is filled in known manner in 140 mg portions into hard gelatin capsules weighing 50 mg, using a suitable encapsulating machine. Each of the capsules thus obtained (total weight: 190 mg) contains 10 mg of hexadecylphosphocholine. The ratio of hexadecylphosphocholine: flow agent / surfactant: fillers in the filling mixture is 1: 0.4: 12.4 (parts by weight).
  • Example 2 hard gelatin capsule (content: 100 mg of miltefosine)
  • the resulting filling mixture is filled in known manner into 200 mg portions in hard gelatin capsules weighing 76 mg, using a suitable encapsulating machine.
  • Each of the capsules thus obtained contains 100 mg of hexadecylphosphocholine.
  • the ratio of hexadecylphosphocholine: flow agent: fillers in the filling mixture is 1: 0.07: 0.9 (parts by weight).
  • Example 3 Hard gelatin capsule (content: 250 mg of Miltefosine)
  • Example 2 250 g of hexadecylphosphocholine, 80 g of lactose, 50 g of microcrystalline cellulose, 5 g of talc, 5 g of finely divided silicon dioxide and 15 g of magnesium stearate were mixed according to Example 1.
  • the thus obtained Filling mixture is filled in known manner in 405 mg portions in hard gelatin capsules with a weight of 97 mg, using a suitable Einkapselmaschine.
  • Each of the capsules thus obtained has a total weight of 502 mg and contains 250 mg of hexadecylphosphocholine.
  • the ratio of hexadecylphosphocholine: flow agent: fillers in the filling mixture is 1: 0.1: 0.52 (parts by weight).
  • Example 4 Tablets (content: 250 mg hexadecylphosphocholine)
  • hexadecylphosphocholine 50 g of hexadecylphosphocholine, 24.25 g of microcrystalline cellulose and 22.00 g of anhydrous dicalcium phosphate are sieved and blended. 3.75 g of magnesium stearate are sieved and added to the mixture. The mixture is then mixed again. The resulting mixture is then compressed into tablets weighing 500 mg each. The tablets each contain 250 mg of hexadecylphosphocholine. The ratio of hexadecylphosphocholine: flow agent / surfactant: fillers in the tablet is 1: 0.07: 0.925 (parts by weight).
  • Example 5 Tablets (content: 30 mg hexadecylphosphocholine)
  • the resulting mixture is then compressed into tablets weighing 130.5 mg each.
  • the tablets each contain 30 mg of hexadecylphosphocholine.
  • Fillers in the tablet is 1: 0.087: 0.31 (parts by weight).
  • Example 6 Effervescent Tablets and Effervescent Mixture (content of hexadecylphosphocholine: 250 mg) 1700 g of granular sodium bicarbonate are heated in an oven at 100 ° C for 60 min. After cooling to room temperature, the converted bicarbonate is mixed with 160 g of granular monobasic calcium phosphate, 1030 g of granular anhydrous citric acid, 100 g of talc and 50 g of magnesium stearate. The 'mixture thus obtained is mixed with 300 g of hexadecylphosphocholine und blended for 10 minutes.
  • the effervescent mixture thus obtained is compressed into tablets each weighing 278 mg.
  • the effervescent tablets each contain 250 mg of hexadecylphosphocholine.
  • the ratio of hexadecylphosphocholine: flow agent / surfactant: fillers in the tablet is 1: 0.50: 0.53 (parts by weight).
  • Example 7 Effervescent Tablets and Effervescent Mix (Content: 50 mg hexadecylphosphocholine)
  • 1600 g of granular sodium bicarbonate are heated in an oven at 100 ° C for 60 minutes. After cooling to room temperature, the converted bicarbonate is mixed with 150 g of granular monobasic calcium phosphate, 900 g of granular anhydrous citric acid, 80 g of talc and 30 g of magnesium stearate. The mixture thus obtained is admixed with 200 g of hexadecylphosphocholine and mixed for 10 minutes.
  • the resulting mixture is compressed into tablets weighing 740 mg each.
  • the effervescent tablets each contain 50 mg of hexadecylphosphocholine.
  • the ratio of hexadecylphosphocholine: flow agent / surfactant: fillers in the tablet is 1: 0.55: 0.75 (parts by weight).
  • Example 8 Drinking mixture (sachets) (content: 50 mg hexadecylphosphocholine)
  • hexadecylphosphocholine 5 g of hexadecylphosphocholine, 308 g of lactose, 280 g of microcrystalline cellulose, 5 g of saccharin and 2 g of colloidal silica are mixed.
  • the mixture is filled into sachets.
  • the sachets each weigh 6 g and contain 50 mg of hexadecylphosphocholine.
  • the ratio of hexadecylphosphocholine: flow agent surfactant: fillers in the mixture is 1: 0.4: 117.5 (parts by weight).
  • Example 9 Drinking mixture (sachets) (content: 200 mg hexadecylphosphocholine)
  • the examples may also contain perifosine instead of the active ingredient miltefosine.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hospice & Palliative Care (AREA)
  • Otolaryngology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques, contenant des alkylphosphocholines, en particulier de l'hexadécylphosphocholine ou du octadécyl-(1,1-diméthyl-pipéridinio-4-yl)-phosphate. Ces compositions sont administrées de manière préventive en cas de maladies causées par des protozoaires, en particulier en cas de leishmaniose. L'invention se rapporte en outre à un schéma posologique de ces compositions servant à traiter préventivement lesdites maladies.
PCT/EP2003/000072 2002-01-25 2003-01-07 Utilisation d'alkylphosphocholines pour traiter preventivement des maladies causees par des protozoaires Ceased WO2003061669A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
MXPA04007193A MXPA04007193A (es) 2002-01-25 2003-01-07 Uso de alquilfosfocolinas para el tratamiento preventivo de enfermedades protozoicas.
CA002470185A CA2470185A1 (fr) 2002-01-25 2003-01-07 Utilisation d'alkylphosphocholines dans la prevention de maladies causees par des protozoaires
JP2003561613A JP2005515244A (ja) 2002-01-25 2003-01-07 原虫症の予防的処置のためのアルキルホスホコリンの使用
IL16249203A IL162492A0 (en) 2002-01-25 2003-01-07 Use of alkylphosphocholines for the preventative treatment of protozoandiseases
BR0307021-2A BR0307021A (pt) 2002-01-25 2003-01-07 Uso de alquilfosfocolinas no tratamento preventivo de doenças de protozoários
EP03731619A EP1467742A1 (fr) 2002-01-25 2003-01-07 Utilisation d'alkylphosphocholines pour traiter preventivement des maladies causees par des protozoaires
AU2003236787A AU2003236787B2 (en) 2002-01-25 2003-01-07 Use of alkylphosphocholines for the preventative treatment of protozoan diseases
IL162492A IL162492A (en) 2002-01-25 2004-06-14 Use of alkylphosphocholines for producing a medicament for the preventative treatment of protozoan diseases

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10203195.9 2002-01-25
DE10203195A DE10203195A1 (de) 2002-01-25 2002-01-25 Verwendung von Alkylphosphocholinen in der Präventivbehandlung von Protozoenerkrankungen

Publications (1)

Publication Number Publication Date
WO2003061669A1 true WO2003061669A1 (fr) 2003-07-31

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PCT/EP2003/000072 Ceased WO2003061669A1 (fr) 2002-01-25 2003-01-07 Utilisation d'alkylphosphocholines pour traiter preventivement des maladies causees par des protozoaires

Country Status (16)

Country Link
EP (1) EP1467742A1 (fr)
JP (1) JP2005515244A (fr)
CN (1) CN1622811A (fr)
AR (1) AR038224A1 (fr)
AU (1) AU2003236787B2 (fr)
BR (1) BR0307021A (fr)
CA (1) CA2470185A1 (fr)
CO (1) CO5601024A2 (fr)
DE (1) DE10203195A1 (fr)
IL (2) IL162492A0 (fr)
MX (1) MXPA04007193A (fr)
NZ (1) NZ548040A (fr)
PE (1) PE20030732A1 (fr)
TW (1) TWI339582B (fr)
WO (1) WO2003061669A1 (fr)
ZA (1) ZA200404690B (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007071658A3 (fr) * 2005-12-19 2007-10-04 Aeterna Zentaris Gmbh Nouveaux derives d'alkylphospholipide ayant une cytotoxicite reduite et utilisations de ceux-ci
TWI391137B (zh) * 2005-12-19 2013-04-01 Aeterna Zentaris Gmbh 細胞毒性減低之新穎烷基磷脂衍生物及其用途

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT501545B1 (de) * 2005-02-23 2007-10-15 Obwaller Andreas Dr Reinigungsmittel für kontaktlinsen
CN104473941A (zh) * 2014-12-20 2015-04-01 长沙佰顺生物科技有限公司 一种含有米替福新的药物制剂及其制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999037289A1 (fr) * 1998-01-22 1999-07-29 Asta Medica Ag Compositions pharmaceutiques solides contenant miltefosine et servant a traiter la leishmaniose par administration orale

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4132345A1 (de) * 1991-09-27 1993-04-01 Max Planck Gesellschaft Ether-lysolecithine und alkylphosphocholine in liposomen
DE4132344A1 (de) * 1991-09-27 1993-04-01 Max Planck Gesellschaft Verfahren zur herstellung eines arzneimittels zur oralen oder topischen verabreichung bei der behandlung von leishmaniasis
ATE202701T1 (de) * 1992-03-06 2001-07-15 Lica Pharmaceuticals As Behandlung und prophylaxe von durch parasiten oder bakterien verursachten erkrankungen
DE10020812C2 (de) * 2000-04-20 2003-06-26 Robert Koch Inst Verwendung von Naphthindazol-4,9-chinonen als Antiparasitika
AU2002232400A1 (en) * 2000-11-06 2002-05-15 U.S. Army Medical Research And Materiel Command Reversed amidines and methods of using for treating, preventing, or inhibiting leishmaniasis

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999037289A1 (fr) * 1998-01-22 1999-07-29 Asta Medica Ag Compositions pharmaceutiques solides contenant miltefosine et servant a traiter la leishmaniose par administration orale

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PROF. DR. EIBL: "Tödliche Tropenkrankheit jetzt heilbar", MAX-PLANCK-INSTITUT FÜR BIOPHYSIKALISCHE CHEMIE, 28 January 2000 (2000-01-28), XP002239911, Retrieved from the Internet <URL:http://www.mpibpc.gwdg.de/abteilungen/293/PR/00_01/leish.html> [retrieved on 20030430] *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007071658A3 (fr) * 2005-12-19 2007-10-04 Aeterna Zentaris Gmbh Nouveaux derives d'alkylphospholipide ayant une cytotoxicite reduite et utilisations de ceux-ci
RU2469727C2 (ru) * 2005-12-19 2012-12-20 Этерна Центарис ГмбХ Способ лечения или профилактики заболеваний и/или патофизиологических состояний, вызванных микроорганизмами, посредством производных алкилфосфолипидов
TWI391137B (zh) * 2005-12-19 2013-04-01 Aeterna Zentaris Gmbh 細胞毒性減低之新穎烷基磷脂衍生物及其用途

Also Published As

Publication number Publication date
IL162492A0 (en) 2005-11-20
DE10203195A1 (de) 2003-08-07
NZ548040A (en) 2007-06-29
MXPA04007193A (es) 2004-10-29
CA2470185A1 (fr) 2003-07-31
ZA200404690B (en) 2004-09-27
TW200302103A (en) 2003-08-01
TWI339582B (en) 2011-04-01
BR0307021A (pt) 2004-11-03
CN1622811A (zh) 2005-06-01
IL162492A (en) 2009-12-24
AU2003236787B2 (en) 2007-03-22
PE20030732A1 (es) 2003-09-27
JP2005515244A (ja) 2005-05-26
EP1467742A1 (fr) 2004-10-20
CO5601024A2 (es) 2006-01-31
AR038224A1 (es) 2005-01-05

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