IL22583A - Pilocarpine benzoate - Google Patents

Description

This invention consists in a hitherto unknown salt of pilocarpine, the alkaloid obtainable from, for example, the leaves of Pilocarpus Jaborandi or Pilocarpus microphallus. of pilocarpine with conventional acids, the hydrochloride and nitrate, are used for therapeutical purposes, especially for the treatment of glaucoma by external application. In this use they have the drawback that their pH in solution is relatively low and the eye liquid becomes undesirably acidic* The invention provides a new pilocarpine salt which does not have this drawback, namely: pilocarpine benzoate.

This new compound can be prepared by the direct reaction of pilocarpine with benzoic acid, or by the double decompositio of another pilocarpine salt with a benaoate.

The reaction is asa rule carried out in an aqueous or organic-solvent medium.

The new pilocarpine benaoate can be prepared in a pure crystalline form. The purest samples so ar prepared have the melting pint 93 - 95°C and a specific rotation (in a as een oun t at the desired therapeutic ophthalmologlcal properties of pilocarpine benzoate are at least equal to those of the conventional pilocarpine salts, apart from their considerable advantage of not appreciably lowering the pH of the eye liquid.

The invention is illustrated by the following Examples to which it ia not limited* Example 1 grams of pilocarpine base are admixed to the solution of 5.9 grams of benzoic acid in 25 ml of methanol, then the volume of the reaction is reduced to one thir^d by evaporation of the methanol. There forms a white crystalline mass of pilocarpine benzoate which is recrystallized from amyl alcohol. After recrystallization the pure product has the melting point and optical rotation stated above* Example 2 grams of pilocarpine base are taken up in 10 ml of amyl alcohol and admixed with a hot solution of 5.9 grams of benzoic acid i 40 ml of amyl alcohol· The mixture is left to cool and the crystalline mass of pilocarpine benzoate thereby formed is separated from the solvent by filtration. Hecrystabilization from amyl alcohol yields the same pure product as in Example 1.

Example 3 A concentrated aqueous solution of 10 grams of pilocarpine hydrochloride is admixed with the solution of 6.3 grams of sodium benzoate i 10 ml of water. The aqueous reaction solutio is extracted with chloroform whereby pilocarpine benzoate is transferred into the solvent phase while sodium chloride remains in the aqueous phase. The solvent phase is separated and dried over sodium sulfate, then the chloroform is completely evaporated. The dry residue of pilocarpine benzoate is recryatallized from butanol and is then as pure as the product of Examples 1 and 2·

Claims (1)

1. HAVIHCa1 HOW particularly described and ascertained the nature of our said invention and in what manner the same is to be performed, we declare that what we claim is:-1, Pilocarpine benzoate. 2· Pilocarpine benzoate, being a crystalline product of m.p, 93 - 95°C and [dj ^« + 65° (in 25¾«-by-weight aqueous solution), 3. A process for the preparation of pilocarpine benzoate, wherein pilocarpine base is reacted with benzoic acid in an organic solvent medium. 4· A process for the preparation of pilocarpine benzoate, wherein another pilocarpine salt, e.g. the hydrochloride, a reacted with a benzoate, e.g. the sodium salt, in an aqueous medium, the reaction mixture is extracted with an organic solvent, and pilocarpine benzoate is recovered from the solvent extract. 5· Process for the preparation of pilocarpine benzoate substantially as described with reference to the Bxamples. 6. Pilocarpine benzoate, when prepared by the process according to Claim 3, 4 or 5· 7· Therapeutic, especially opthalmological, preparations containing pilocarpine benzoate. Dated this 7th day of December, 1964