FR2492368A1 - Urea:magnesium acetyl salicylate complex - is water soluble, neutral analgesic and antipyretic - Google Patents
Urea:magnesium acetyl salicylate complex - is water soluble, neutral analgesic and antipyretic Download PDFInfo
- Publication number
- FR2492368A1 FR2492368A1 FR8022528A FR8022528A FR2492368A1 FR 2492368 A1 FR2492368 A1 FR 2492368A1 FR 8022528 A FR8022528 A FR 8022528A FR 8022528 A FR8022528 A FR 8022528A FR 2492368 A1 FR2492368 A1 FR 2492368A1
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- FR
- France
- Prior art keywords
- urea
- analgesic
- antipyretic
- magnesium
- neutral
- 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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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/14—Acetic acid esters of monohydroxylic compounds
- C07C69/145—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols
- C07C69/157—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols containing six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Le secteur de la technique sur lequel porte la présente invention est celui des médicaments à usage humain et vétérinaire, et plus précisément celui des antalgiques. The technical sector to which the present invention relates is that of drugs for human and veterinary use, and more precisely that of analgesics.
L'aspirine est connue et utilisée depuis de très nombreuses années pour ses propriétés analgésiques, antalgiques et antipyrétiques. Cependant ce médicament présente, à côté d'une efficacité confirmée et dont la dé- monstration n'est plus à faire, quelques inconvénients dont le principal est sa très faible solubilité dans l'eau et son caractère acide. Aspirin has been known and used for many years for its analgesic, analgesic and antipyretic properties. However, apart from confirmed efficacy, the drug of which has no longer been proven, this drug has some drawbacks, the main one being its very low solubility in water and its acidic character.
On a donc recherché des moyens de remédier à ces inconvénients d'abord par la formation de sels avec des cathions monovalents ou divalents. Le caractère acide de l'aspirine était ainsi supprimé et la solubilité du produit obtenu grandement améliorée. Cependant on obtenait ainsi des composés de caractère nettement instables,-le radical acétyl de la molécule d'aspirine étant hydrolysé. Les produits de dégradation étaient l'acide acétique et l'acide salicylique tous deux plus ou moins salifiés par le cathion utilisé. Ways have therefore been sought of overcoming these drawbacks first by the formation of salts with monovalent or divalent cathions. The acidic nature of aspirin was thus eliminated and the solubility of the product obtained greatly improved. However, compounds of clearly unstable character were thus obtained, the acetyl radical of the aspirin molecule being hydrolyzed. The degradation products were acetic acid and salicylic acid both more or less salified by the cathion used.
On a alors découvert que l'acétylsalicylate de calcium était capable de donner une molécule complexe en se combinant avec une molécule d'urée. It was then discovered that calcium acetylsalicylate was able to give a complex molecule by combining with a molecule of urea.
Le nouveau corps était très soluble dans l'eau et présentait un pH voisin de 5,6 en solution. Cependant, il était encore très fragile à l'hydrolyse et très difficile à obtenir pur, exempt d'ions salicylate. The new body was very soluble in water and had a pH close to 5.6 in solution. However, it was still very fragile on hydrolysis and very difficult to obtain pure, free of salicylate ions.
La présente invention concerne un dérivé proche de l'acétylsalicylate de calcium - urée, obtenu par un procédé original. The present invention relates to a derivative close to calcium acetylsalicylate - urea, obtained by an original process.
Il s'agit de l'acétylsalicylate de magnésium - urée, de formule
de formule brute C19 Hie Ca N2 O9 de poids moléculaire 442,65.This is magnesium acetylsalicylate - urea, of formula
of crude formula C19 Hie Ca N2 O9 with molecular weight 442.65.
Le procédé de fabrication fait appel à la réaction classique d'un acide sur un carbonate. Mais l'originalité consiste à introduire dans le milieu réactionnel, en préalable à cette réaction, la quantité nécessaire d'urée pour obtenir la formation du complexe au fur et à mesure de la formation du sel de magnésium. The manufacturing process uses the classic reaction of an acid on a carbonate. However, the originality consists in introducing into the reaction medium, prior to this reaction, the necessary quantity of urea to obtain the formation of the complex as and when the magnesium salt is formed.
Le milieu réactionnel peut être constitué par de l'éthanol, de l'acétone ou de l'eau, mais, pour des raisons économiques, on préfère utiliser ce dernier solvant. The reaction medium can consist of ethanol, acetone or water, but, for economic reasons, it is preferred to use the latter solvent.
La température à laquelle on opère est la température ordinaire. The temperature at which we operate is the ordinary temperature.
Une fois la solution finale obtenue, clarifiée par filtration, il est nécessaire d'opérer une évaporation sous vide du solvant pour obtenir, après concentration, la cristallisation de la substance en une poudre microcristalline blanche. Once the final solution obtained, clarified by filtration, it is necessary to carry out an evaporation under vacuum of the solvent to obtain, after concentration, the crystallization of the substance into a white microcrystalline powder.
Les caractéristiques physiques de cette substance sont les suivantes poudre microcristalline blanche à odeur rappelant celle de l'aspirine, de saveur légérement amère, très soluble dans l'eau, faiblement soluble dans l'alcool et l'acétone, pratiquement insoluble dans les autres solvants organiques tels que le chloroforme et les solvants chlorés, les hydrocarbures benzéniques et cyclaniques. The physical characteristics of this substance are as follows: white microcrystalline powder with an odor reminiscent of that of aspirin, slightly bitter flavor, very soluble in water, slightly soluble in alcohol and acetone, practically insoluble in other solvents organic such as chloroform and chlorinated solvents, benzene and cyclanic hydrocarbons.
L'acétylsalicylate de magnésium - urée, obtenu par ce procédé, présente l'avantage d'une bonne stabilité à l'état sec, et la solution aqueuse obtenue par dissolution, de pH voisin de 6, peut rester plusieurs heures à la température ordinaire avant de présenter une hydrolyse notable. Cependant, comme l'aspirine elle-même, il y aura lieu de préserver ce composé de l'humidité pour lui conserver ses propriétés initiales. Magnesium acetylsalicylate - urea, obtained by this process, has the advantage of good stability in the dry state, and the aqueous solution obtained by dissolution, with a pH close to 6, can remain for several hours at ordinary temperature. before presenting significant hydrolysis. However, like aspirin itself, it will be necessary to preserve this compound from humidity to preserve its initial properties.
Le pH de la solution aqueuse proche de la neutralité, autorise l'utilisation de ce composé en injections parenthérales. The pH of the aqueous solution close to neutral, authorizes the use of this compound in parenteral injections.
Les études pharmacologiques du produit résultant de l'invention sont encore actueellement en cours, mais elles ont déjà permis de dégager diverses propriétés permettant d'envisager l'utilisation de l'acétylsalicylate de magnésium - urée comme médicament à action antalgique, antipyrétique, analgésique et anti-inflammatoire. Les premières indications obtenues laissent supposer, en particulier, une action myo-relaxante de la musculature lisse explicable par l'action conjuguee du maintien du tonus de la fibre lisse par l'aspirine, et de l'action spasmolytique légère exercée par les sels de magnésium. Pharmacological studies of the product resulting from the invention are still currently in progress, but they have already made it possible to identify various properties making it possible to envisage the use of magnesium acetylsalicylate - urea as a drug with analgesic, antipyretic, analgesic and anti-inflammatory. The first indications obtained suggest, in particular, a myo-relaxing action of the smooth muscles explainable by the combined action of the maintenance of the tone of the smooth fiber by aspirin, and the light spasmolytic action exerted by the salts of magnesium.
Les essais de toxicité sont eux aussi en cours de réalisation, mais les premiers résultats laissent supposer une toxicité légèrement inférieure à celle de l'aspirine. Ainsi la DL50 per os, sur diverses espèces animales, se situe entre 2000 mg/kg et 3500 mg/kg, alors que la DL50 en IP est supérieure à 500 mg/kg chez la souris. The toxicity tests are also in progress, but the first results suggest a slightly lower toxicity than that of aspirin. Thus the LD50 per os, on various animal species, is between 2000 mg / kg and 3500 mg / kg, while the LD50 in PI is greater than 500 mg / kg in mice.
En résumé, les premiers résultats des études toxico-pharmacologiques, en cours actuellement sur le produit de l'invention, permettent d'envisager des utilisations médicales de cette substance au moins aussi étendues que celles de l'aspirine. In summary, the first results of the toxicopharmacological studies, currently underway on the product of the invention, make it possible to envisage medical uses of this substance at least as extensive as those of aspirin.
Claims (3)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8022528A FR2492368A1 (en) | 1980-10-20 | 1980-10-20 | Urea:magnesium acetyl salicylate complex - is water soluble, neutral analgesic and antipyretic |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8022528A FR2492368A1 (en) | 1980-10-20 | 1980-10-20 | Urea:magnesium acetyl salicylate complex - is water soluble, neutral analgesic and antipyretic |
Publications (1)
Publication Number | Publication Date |
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FR2492368A1 true FR2492368A1 (en) | 1982-04-23 |
Family
ID=9247166
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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FR8022528A Withdrawn FR2492368A1 (en) | 1980-10-20 | 1980-10-20 | Urea:magnesium acetyl salicylate complex - is water soluble, neutral analgesic and antipyretic |
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FR (1) | FR2492368A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2580634A1 (en) * | 1985-04-19 | 1986-10-24 | Rhone Poulenc Sante | NEW ACETYLSALICYLIC ACID DERIVATIVE, ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME |
EP0233459A1 (en) * | 1986-01-22 | 1987-08-26 | Artika International (Hong-Kong) Limited | Medicament containing a magnesium-urea complex of acetylsalicylic acid and process for the preparation of this complex |
FR2638742A1 (en) * | 1988-11-04 | 1990-05-11 | Voisin Philippe | Complex formed from divalent cation salts of acetylsalicylic acid and from urea - process for their manufacture and their therapeutic applications based on the pharmacological activities |
-
1980
- 1980-10-20 FR FR8022528A patent/FR2492368A1/en not_active Withdrawn
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2580634A1 (en) * | 1985-04-19 | 1986-10-24 | Rhone Poulenc Sante | NEW ACETYLSALICYLIC ACID DERIVATIVE, ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME |
EP0200628A1 (en) * | 1985-04-19 | 1986-11-05 | Rhone-Poulenc Sante | Derivative of acetylsalicylic acid, its preparation and pharmaceutical compositions containing it |
US4764637A (en) * | 1985-04-19 | 1988-08-16 | Rhone-Poulenc Sante | Hydrated magnesium acetylsalicylate/urea complex preparation |
US4849417A (en) * | 1985-04-19 | 1989-07-18 | Rhone-Poulenc Sante | Acetylsalicylic acid derivative and pharmaceutical composition thereof |
EP0233459A1 (en) * | 1986-01-22 | 1987-08-26 | Artika International (Hong-Kong) Limited | Medicament containing a magnesium-urea complex of acetylsalicylic acid and process for the preparation of this complex |
FR2638742A1 (en) * | 1988-11-04 | 1990-05-11 | Voisin Philippe | Complex formed from divalent cation salts of acetylsalicylic acid and from urea - process for their manufacture and their therapeutic applications based on the pharmacological activities |
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