CH664284A5 - Chloroquine medicaments without bitter taste - contain complex of chloroquine with copolymer of methacrylic] acid and methyl methacrylate] - Google Patents
Chloroquine medicaments without bitter taste - contain complex of chloroquine with copolymer of methacrylic] acid and methyl methacrylate] Download PDFInfo
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- CH664284A5 CH664284A5 CH2946/85A CH294685A CH664284A5 CH 664284 A5 CH664284 A5 CH 664284A5 CH 2946/85 A CH2946/85 A CH 2946/85A CH 294685 A CH294685 A CH 294685A CH 664284 A5 CH664284 A5 CH 664284A5
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
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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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Abstract
Description
DESCRIPTION DESCRIPTION
La présente invention a pour objet un médicament, plus précisément un médicament à base de chloroquine, dépourvu de saveur amère. The present invention relates to a medicament, more precisely a chloroquine-based medicament, devoid of bitter taste.
Il est notoire que de nombreuses substances médicamenteuses présentent un goût désagréable, que les chercheurs tentent de masquer par tous moyens appropriés. Les substances de la classe des alcaloïdes par exemple se caractérisent par une saveur amére qu'il convient d'atténuer au mieux pour toute administration par voie buccale. Diverses solutions sont actuellement proposées, telles que la dragéification, la fabrication de gélules ou l'enrobage du principe actif par exemple. Lorsque de telles substances médicamenteuses sont administrées par voie buccale, sous forme de solutions ou suspensions tels des sirops, il s'avère pour l'instant difficile de masquer de façon satisfaisante la saveur amére du principe actif sans pour autant ralentir son mode d'action, notamment une fois parvenu dans l'oesophage ou l'estomac. It is well known that many medicinal substances have an unpleasant taste, which researchers try to mask by any appropriate means. Substances of the alkaloid class, for example, are characterized by a bitter taste which should be attenuated as best as possible for any administration by the oral route. Various solutions are currently proposed, such as coating, the manufacture of capsules or coating of the active principle, for example. When such medicinal substances are administered orally, in the form of solutions or suspensions such as syrups, it is for the moment difficult to mask the bitter taste of the active principle satisfactorily without slowing down its mode of action. , especially once it has entered the esophagus or stomach.
La chloroquine est une substance médicamenteuse de formule Chloroquine is a drug substance with the formula
que l'on utilise, de même que certains de ses sels, dans le traitement préventif de la malaria, L'administration la mieux adaptée aux populations victimes de cette maladie consisterait en un sirop, mais la saveur amère caractéristique de la chloroquine le rend difficilement acceptable, en particulier pour les enfants. that one uses, like some of its salts, in the preventive treatment of malaria, The administration best adapted to the populations victims of this disease would consist of a syrup, but the bitter taste characteristic of chloroquine makes it difficult acceptable, especially for children.
Diverses solutions ont été proposées telles que la complexation de sels de chloroquine à l'aide de résines échangeuses d'ions à base de dextranes ou l'enrobage de granulés à l'aide de polymères biocompatibles. Jusqu'à ce jour, aucune forme satisfaisante n'a été trouvée, tant du point de vue stabilité que biodisponibilité du médicament ingéré. La présente invention a précisément pour but de supprimer les inconvénients mentionnés ci-dessus. Elle a pour objet un médicament à base de chloroquine exempt de saveur amère tel que défini à la revendication 1. Various solutions have been proposed, such as the complexation of chloroquine salts using ion exchange resins based on dextrans or the coating of granules using biocompatible polymers. To date, no satisfactory form has been found, both from the point of view of stability and bioavailability of the drug ingested. The object of the present invention is precisely to eliminate the drawbacks mentioned above. It relates to a chloroquine-based medicament free from bitter taste as defined in claim 1.
Il a en effet été trouvé de façon surprenante qu'un complexe préparé à partir d'un sel hydrosoluble de chloroquine et d'un copolymère d'acide méthacrylique et d'ester méthylique d'acide méthacrylique constituerait un ingrédient pharmacologiquement aussi actif que les dérivés actuellement connus de la chloroquine, sans toutefois présenter de saveur amère. On peut de ce fait avantageusement préparer des médicaments à base de chloroquine destinés à l'administration par voie buccale, notamment des sirops. It has in fact been found, surprisingly, that a complex prepared from a water-soluble salt of chloroquine and a copolymer of methacrylic acid and of methyl ester of methacrylic acid would constitute an ingredient which is as pharmacologically active as the derivatives. currently known chloroquine, without however presenting a bitter taste. It is therefore advantageously possible to prepare chloroquine-based medicaments intended for administration by the buccal route, in particular syrups.
Selon l'invention, on utilise un copolymère d'acide méthacrylique et d'ester méthylique de l'acide méthacrylique ayant un poids moléculaire moyen compris entre 130 000 et 150 000 et un rapport des groupements carboxyliques libreslgroupements esters de l'ordre de 1:1. On utilise de préférence un copolymère présentant un poids moléculaire moyen de 135000 environ, tel qu'on le trouve dans le commerce sous la dénomination EUDRAGIT L-100 4. Il s'agit dans le cas précis d'une substance parfaitement biocompatible, notamment utilisée à titre d'agent filmogène gastrosoluble, par exemple dans la préparation de médicaments à effet retard. According to the invention, a copolymer of methacrylic acid and of methyl ester of methacrylic acid is used having an average molecular weight of between 130,000 and 150,000 and a ratio of free carboxylic groups to ester groups of the order of 1: 1. A copolymer is preferably used having an average molecular weight of approximately 135,000, such as it is commercially available under the name EUDRAGIT L-100 4. In the specific case, this is a perfectly biocompatible substance, in particular used. as a gastrosoluble film-forming agent, for example in the preparation of long-acting medicaments.
A titre de sel hydrosoluble de chloroquine, on utilise de préférence le diphosphate de chloroquine, de formule As water-soluble salt of chloroquine, use is preferably made of chloroquine diphosphate, of formula
Selon l'invention, le complexe de chloroquine peut contenir ledit ingrédient en proportions variables. Les effets les plus intéressants ont été observés dans des complexes contenant environ 1 partie en poids de chloroquine pour environ 3,2 à 3,4 parties en poids, de préférence 3,3 parties en poids de copolymére. According to the invention, the chloroquine complex can contain said ingredient in variable proportions. The most interesting effects have been observed in complexes containing about 1 part by weight of chloroquine to about 3.2 to 3.4 parts by weight, preferably 3.3 parts by weight of copolymer.
De tels complexes peuvent être préparés à l'aide d'ingrédients du commerce, en appliquant les techniques usuelles. On obtient un produit pulvérulent convenant à la préparation de suspensions dans un liquide comestible tels des sirops. Les médicaments ainsi préparés présentent une excellente stabilité à la conservation, même pour de longues durées, à des températures de l'ordre de 30, 40, voire 50" C. Such complexes can be prepared using commercially available ingredients, applying the usual techniques. A pulverulent product is obtained which is suitable for the preparation of suspensions in an edible liquid such as syrups. The drugs thus prepared exhibit excellent storage stability, even for long periods, at temperatures of the order of 30, 40, or even 50 ° C.
La biodisponibilité du principe actif (chloroquine) de tels complexes est remarquable. Contrairement à ce que l'art antérieur permettait de supposer, on n'observe pas d'effet retard dû à la présence de copolymère: en milieu gastrique artificiel, le principe actif est libéré à plus de 90% après 10 min, à plus de 97% après 20 min, Des tests in vivo ont en outre permis de conclure qu'une certaine résorption de chloroquine intervenait déjà au niveau de l'oesophage. The bioavailability of the active principle (chloroquine) in such complexes is remarkable. Contrary to what the prior art made it possible to suppose, no retardation effect due to the presence of copolymer was observed: in an artificial gastric medium, the active principle is released at more than 90% after 10 min, at more than 97% after 20 min, In vivo tests have also made it possible to conclude that a certain absorption of chloroquine was already taking place in the esophagus.
Les exemples ci-après illustreront la présente invention de façon plus détaillée. Ils ne sont en aucune façon limitatifs. The following examples will illustrate the present invention in more detail. They are in no way limiting.
Exemple 1: Préparation d'un complexe à base de chloroquine et de copolymère 333 g de copolymère d'acide méthacrylique et d'ester méthylique d'acide méthacrylique de poids moléculaire moyen env. 135000 et présentant un rapport COOH/COOH3 d'env. 1:1 (EUDRAGIT L100, marque déposée, commercialisée par ROEHM et HAAS, Pharma GmbH, Darmstadt, République fédérale d'Allemagne) ont été mis en suspension dans 4750 ml d'eau déminéralisée, dans un réacteur de 10 1 muni d'un dispositif d'agitation efficace. Une fois la suspension homogène, on y a ajouté 320 ml d'une solution aqueuse de NaOH 1N et poursuivi l'agitation jusqu'à obtention d'un mélange quasi limpide. Example 1: Preparation of a complex based on chloroquine and copolymer 333 g of methacrylic acid-methacrylic acid methyl ester copolymer with an average molecular weight of approx. 135,000 and with a COOH / COOH3 ratio of approx. 1: 1 (EUDRAGIT L100, registered trademark, marketed by ROEHM and HAAS, Pharma GmbH, Darmstadt, Federal Republic of Germany) were suspended in 4750 ml of demineralized water, in a 10 L reactor fitted with an efficient stirring device. Once the suspension was homogeneous, 320 ml of a 1N aqueous solution of NaOH were added thereto and stirring continued until a virtually clear mixture was obtained.
Une solution de 165,12 g de diphosphate de chloroquine dans 768 ml d'eau déminéralisée a ensuite été ajoutée goutte à goutte au mélange préparé ci-dessus, à température ambiante et sous vigoureuse agitation. Après avoir poursuivi l'agitation durant 2 h, on a filtré le mélange réactionnel et recueilli le précipité. Après un premier séchage suivi de broyage, ledit précipité a été lavé sur filtre avec de l'eau déminéralisée jusqu'à ce que les eaux de lavage ne contiennent pas plus de 3 gamma de chloroquine/ml. A solution of 165.12 g of chloroquine diphosphate in 768 ml of demineralized water was then added dropwise to the mixture prepared above, at room temperature and with vigorous stirring. After continuing to stir for 2 h, the reaction mixture was filtered and the precipitate collected. After a first drying followed by grinding, said precipitate was washed on a filter with demineralized water until the washing water did not contain more than 3 gamma of chloroquine / ml.
Le précipité ainsi purifié a ensuite été séché et pulvérisé selon les techniques usuelles pour donner le produit désiré sous une forme prête à l'emploi. The precipitate thus purified was then dried and pulverized according to the usual techniques to give the desired product in a form ready for use.
Un échantillon du produit ainsi préparé est mis en suspension dans de l'eau potable (type ÉVIAN): de l'avis des experts, il était exempt de la saveur amère caractéristique de la chloroquine. A sample of the product thus prepared is suspended in drinking water (EVIAN type): in the opinion of the experts, it was free from the bitter taste characteristic of chloroquine.
La figure 3 en annexe représente le spectre d'absorption infrarouge du complexe ainsi obtenu. La figure 1 correspond au spectre IR du diphosphate de chloroquine et la figure 2 au spectre IR d'EU DRAGIT L-100. FIG. 3 in the appendix represents the infrared absorption spectrum of the complex thus obtained. Figure 1 corresponds to the spectrum IR of Chloroquine Diphosphate and Figure 2 at IR Spectrum of EU DRAGIT L-100.
Exemple 2: Préparation d'un sirop médicamenteux à base de chloroquine Ingrédients Quantités Complexe à base de chloroquine et de copolymère selon l'exemple 1 4,300 g Cellulose microcristalline' 1,364 g Gomme xanthène2 0,140 g Tampon phosphate 0,500 g Sucre pulvérulent 63,950 g Arôme caramel 0,106 g Eau distillée q.s. ad 100 ml Le sirop ainsi préparé s'est révélé exempt de saveur amère; il est particulièrement adapté à l'administration à des enfants. Il contient l'équivalent de 10 mg de chloroquine base par ml de sirop. Example 2: Preparation of a medicated chloroquine syrup Ingredients Quantities Chloroquine complex and of copolymer according to Example 1 4.300 g Microcrystalline cellulose '1.364 g Xanthene gum2 0.140 g Phosphate buffer 0.500 g Powdered sugar 63.950 g Caramel flavor 0.106 g Distilled water q.s. ad 100 ml The syrup thus prepared was found to be free from bitter taste; it is particularly suitable for administration to children. It contains the equivalent of 10 mg of chloroquine base per ml of syrup.
Exemple 3: Détermination de la vitesse de dissolution en milieu gastrique du complexe à base de chloroquine et de copolymère Les mesures ont été effectuées dans un milieu gastrique artificiel dépourvu de pepsine, par dosages successifs de la chloroquine base progressivement mise en solution (vitesse d'agitation de l'appareillage: 120 tours/min). Example 3: Determination of the dissolution rate in gastric medium of the complex based on chloroquine and copolymer The measurements were carried out in an artificial gastric medium devoid of pepsin, by successive dosages of the chloroquine base gradually placed in solution (speed of agitation of the apparatus: 120 revolutions / min).
a) Echantillon de sirop selon l'exemple 2 contenant 10 mg de chloroquine base par ml Temps (min) Quantité dissoute (%) 5 61,66 + 4,3 10 91,66 + 3,0 20 97,13 + 4,2 30 96,93 + 3,8 60 95,90 4,0 1 AVICEL RC-591 2 KETROL F b) Echantillon de sirop selon l'exemple 2 contenant 15 mg de chloroquine base par ml Temps (min) Quantité dissoute (%) 5 54,00 10 79,50 20 97,50 30 99,50 Exemple 4: Tests de stabilité thermique du complexe à base de chloroquine et de copolymère Des échantillons de sirops selon l'exemple 2 contenant l'équivalent de 10, respectivement 15 mg de chloroquine base par ml ont été conservés durant une période maximum de 8 mois, à différentes températures. Des prélèvements successifs ont été effectués et finalement dosés comme indiqué dans les tableaux ci-dessous. a) Syrup sample according to Example 2 containing 10 mg of chloroquine base per ml Time (min) Amount dissolved (%) 5 61.66 + 4.3 10 91.66 + 3.0 20 97.13 + 4.2 30 96.93 + 3.8 60 95.90 4.0 1 AVICEL RC-591 2 KETROL F b) Syrup sample according to Example 2 containing 15 mg of chloroquine base per ml Time (min) Amount dissolved (%) 5 54.00 10 79.50 20 97.50 30 99.50 Example 4: Thermal stability tests of the chloroquine and copolymer-based complex Samples of syrups according to Example 2 containing the equivalent of 10, respectively 15 mg of chloroquine base per ml were stored for a maximum period of 8 months, at different temperatures. Successive samples were taken and finally assayed as indicated in the tables below.
Tableau 1: 10 mg de chloroquine base/ml Table 1: 10 mg chloroquine base / ml
Temps Dosage (mg/ml) (20"C) (37"C) (50 C) 0 jour 9,80,2 - 7 jours 10,0+0,2 10,4+0,2 10,6*0,4 17 jours 9,90,2 10,40,2 10,3*0,4 27 jours 9,70,2 11,0+0,5 12,0*0,5 1,5 mois 10,0+0,2 10,5 9,70,4 2,5 mois 10,5*0,5 11,0+0,5 101+0,2 4,4mois 10,2+0,2 10,6+0,2 8 mois 10,10,2 9,90,2 Tableau 2: 15 mg de chloroquine base/ml Time Dosage (mg / ml) (20 "C) (37" C) (50 C) 0 day 9.80.2 - 7 days 10.0 + 0.2 10.4 + 0.2 10.6 * 0 , 4 17 days 9.90.2 10.40.2 10.3 * 0.4 27 days 9.70.2 11.0 + 0.5 12.0 * 0.5 1.5 months 10.0+ 0.2 10.5 9.70.4 2.5 months 10.5 * 0.5 11.0 + 0.5 101 + 0.2 4.4 months 10.2 + 0.2 10.6 + 0, 2 8 months 10,10,2 9,90,2 Table 2: 15 mg chloroquine base / ml
Temps Dosage (mg/ml) (20" C) (37" C) (50" C) 0 jour 15,2+0,4 7 jours 14,804 15,5*0,4 15,1*0,4 17 jours 14,8+0,4 15,1*0,4 14,8+0,4 27 jours 15,2+0,4 14,6*0,4 15,10,4 44 jours 15,2+0,4 15,0+0,4 15,30,4 2,5 mois 14,6+0,4 15,00,4 14,7*0,4 4,4mois 15,30,4 15,4+0,4 8 mois 15,00,4 14,8 0,4 Time Dosage (mg / ml) (20 "C) (37" C) (50 "C) 0 days 15.2 + 0.4 7 days 14.804 15.5 * 0.4 15.1 * 0.4 17 days 14.8 + 0.4 15.1 * 0.4 14.8 + 0.4 27 days 15.2 + 0.4 14.6 * 0.4 15.10.4 44 days 15.2 + 0, 4 15.0 + 0.4 15.30.4 2.5 months 14.6 + 0.4 15.00.4 14.7 * 0.4 4.4 months 15.30.4 15.4 + 0, 4 8 months 15.00.4 14.8 0.4
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2946/85A CH664284A5 (en) | 1985-07-08 | 1985-07-08 | Chloroquine medicaments without bitter taste - contain complex of chloroquine with copolymer of methacrylic] acid and methyl methacrylate] |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2946/85A CH664284A5 (en) | 1985-07-08 | 1985-07-08 | Chloroquine medicaments without bitter taste - contain complex of chloroquine with copolymer of methacrylic] acid and methyl methacrylate] |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH664284A5 true CH664284A5 (en) | 1988-02-29 |
Family
ID=4245190
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH2946/85A CH664284A5 (en) | 1985-07-08 | 1985-07-08 | Chloroquine medicaments without bitter taste - contain complex of chloroquine with copolymer of methacrylic] acid and methyl methacrylate] |
Country Status (1)
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| CH (1) | CH664284A5 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4971791A (en) * | 1985-08-26 | 1990-11-20 | The Procter & Gamble Company | Taste masking compositions |
| EP0417588A2 (en) * | 1989-09-14 | 1991-03-20 | Röhm Gmbh | Process for the preparation of a complexed drug |
| EP0721785A2 (en) * | 1994-12-17 | 1996-07-17 | Röhm Gmbh | Delittered ranitidin preparation |
| FR2812199A1 (en) * | 2000-07-31 | 2002-02-01 | Maximun Frederic Yanze | Effervescent antimalarial compositions containing chloroquine, optionally other active agents, effervescent couple and taste modifiers, is dissolved in water to give a pleasant tasting solution for oral administration |
| EP1720563A2 (en) * | 2004-02-10 | 2006-11-15 | Integrated Botanical Technologies | Methods and compositions for the treatment of inflammation |
| WO2008067991A2 (en) * | 2006-12-08 | 2008-06-12 | Antares Pharma Ipl Ag | Skin-friendly drug complexes for transdermal administration |
| CN111201013A (en) * | 2017-10-13 | 2020-05-26 | 研究三角协会 | Hydroxychloroquine sulfate formulations and methods of making and using same |
| WO2021259673A1 (en) * | 2020-06-24 | 2021-12-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Hydroxychloroquine liquid compositions |
-
1985
- 1985-07-08 CH CH2946/85A patent/CH664284A5/en not_active IP Right Cessation
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4971791A (en) * | 1985-08-26 | 1990-11-20 | The Procter & Gamble Company | Taste masking compositions |
| EP0417588A2 (en) * | 1989-09-14 | 1991-03-20 | Röhm Gmbh | Process for the preparation of a complexed drug |
| EP0417588A3 (en) * | 1989-09-14 | 1991-07-10 | Roehm Gmbh | Process for the preparation of a complexed drug |
| EP0721785A2 (en) * | 1994-12-17 | 1996-07-17 | Röhm Gmbh | Delittered ranitidin preparation |
| EP0721785A3 (en) * | 1994-12-17 | 1997-08-06 | Roehm Gmbh | Delittered ranitidin preparation |
| US5708021A (en) * | 1994-12-17 | 1998-01-13 | Roehm Gmbh Chemische Fabrik | Debittered ranitidine preparation |
| FR2812199A1 (en) * | 2000-07-31 | 2002-02-01 | Maximun Frederic Yanze | Effervescent antimalarial compositions containing chloroquine, optionally other active agents, effervescent couple and taste modifiers, is dissolved in water to give a pleasant tasting solution for oral administration |
| EP1720563A2 (en) * | 2004-02-10 | 2006-11-15 | Integrated Botanical Technologies | Methods and compositions for the treatment of inflammation |
| EP1720563A4 (en) * | 2004-02-10 | 2010-04-14 | Integrated Botan Technologies | Methods and compositions for the treatment of inflammation |
| WO2008067991A2 (en) * | 2006-12-08 | 2008-06-12 | Antares Pharma Ipl Ag | Skin-friendly drug complexes for transdermal administration |
| WO2008067991A3 (en) * | 2006-12-08 | 2008-10-09 | Antares Pharma Ipl Ag | Skin-friendly drug complexes for transdermal administration |
| CN111201013A (en) * | 2017-10-13 | 2020-05-26 | 研究三角协会 | Hydroxychloroquine sulfate formulations and methods of making and using same |
| EP3694488A4 (en) * | 2017-10-13 | 2021-07-07 | Research Triangle Institute | Hydroxychloroquine sulfate formulations and methods for preparation and use thereof |
| WO2021259673A1 (en) * | 2020-06-24 | 2021-12-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Hydroxychloroquine liquid compositions |
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