Untitled record

Representative: Cabinet G. Beau de Loménie, André Armengaud, G. Houssard, JF Boissel and M. de Haas.

□ o) Conventional priority:

© @©

Sale of booklets at IMPRIMERIE NATIONALE. 27. rue de la Convention - PARIS (15 ·)

The present invention relates to a substance with analgesic action obtained from the root fraction of Petasites offîcînalis Moench.

Therapeutically active substances obtained from plants or certain parts of plants have been an important part of folk medicine for centuries;

Among the genus of Petasites plants, the species Petasites offîcînalis Moench was described with precision for the first time in 1678 by Mat hioli, although it was reported as early as 1489 by Hîeronymus Tragus. We had discovered that a juice extracted from the root has an effective action against difficult breathing and whooping cough.

However, it was only in 1951 that an antispasmodic principle found in Petasites offîcînalis Moench was first described by pharmacologists (Bucher, Archiv. Fü'r exper. Pathologie und Pharmakologie 21 3 Vol. 1, N ° 2 , 1951).

It is known that the extract obtained by exhaustion with ethanol or methanol and treated for several hours with oxygen and ultraviolet rays constitutes a preparation with antispasmodic activity.

We also know that an extract obtained in the same way, alkalinized and added with acetone, precipitates the anti-spasmodic substance.

The active substance according to the present invention is obtained by a process in opposition to the extraction methods known hitherto, according to which a disintegration process analogous to a hydrolysis is used, while maintaining a determined concentration of hydrogen ions up to the obtaining the final product.

The process for preparing the active substance according to the present invention essentially consists in extracting the ground root of the plant of the species Petasites offîcînalis Moench with water at approximately 65 ° C., and the active substance is isolated by chloroform precipitation.

The following example of preparation of the active substance according to the present invention is indicated, without limitation.

EXAMPLE.

1 kg of ground Petasites offîcînalis Moench, ground with 2 liters of water, is heated to 63 ° C. with the prior addition of an organic acid to bring the pH to 4.5. The maceration is carried out, that is to say the extraction for a few hours. The raw juice thus obtained is concentrated under vacuum. The residual substance thus obtained confides analogously to the solubilization product of the cells: albumins, bitter substances and tannins, as well as resins, essential oils and, moreover, secondary products, still incompletely characterized.

The active substance is isolated by precipitation with chloroform, which is recovered by evaporation. "The residue is a syrupy mass, dark brown, containing 50 to 80% of pure petasine of global formula C _notH „, O.

2u z * o

The petasine corresponds well by its analysis to said formula and has a specific rotary power:

/«7 ^21,5 = + 49 * (CHCL)

D ^J

Molecular weight measurements of well-defined decomposition products confirmed the accuracy of the above raw formula.

The active substance according to the present invention is similar in structure to angelic acid, but not identical. It has not yet been synthesized.

By applying the Régnier's cornea test, modified by Eichholtz from Slizys, we brought within the framework of the present invention the proof of the analgesic properties (pain-suppressing action with conservation of consciousness) of the crude extract according to the invention, obtained by the process described above.

In the single figure of the attached drawing, your results have been shown on rabbits. On the abscissa of the graph, the durations of analgesia have been reported in minutes. On the ordinate, the number of stimulations is indicated. Arrow 1, on the abscissa, indicates a local control infection of Percai'ne (butyl-Caine) at 1/400% in the conjunctival sac, Arrow 2, on the abscissa, indicates an intravenous injection of the crude extract according to the invention.

The injected doses were varied in weight of extract per kg of body weight of the treated animal, as follows.

For 1 mg of extract / kg, the solid line marked with a cross indicates no analgesia.

For 5 mg of extract / kg, the dotted line shows analgesia for 5 minutes.

For 10 mg of extract / kg, the solid line marked with dots shows analgesia for 10 minutes.

The crude extract according to the invention thus proves to be an effective analgesic; in particular its activity is proportional to the doses injected.

The toxicity tests showed that the extract was practically devoid of toxic effect.

The medicament according to the invention also exhibits soporific activity.

The active substance according to the present invention can be administered in particular externally, orally or parenterally.

As an indication, some suitable forms of drug administration are given below: alcohol solutions, tinctures, gelatin capsules, dragees, or suitable solutions in ampoules for intramuscular injections.