Patent GB-809912-A (GB)
Title: Active substance from plants of the rauwolfia species and process for manufacturing same
Filed: 1955-09-07
Abstract: A new alkaloid, deserpidine, is extracted from Rauwolfia species, especially the roots, by making an extract thereof and treating it with an organic solvent only partially miscible with water (e.g. a halogenated aliphatic hydrocarbon), if desired in the presence of a polar solvent (e.g. a lower alcohol) with or without water.  The initial extract may be made with a lower alcohol or an aqueous acid (especially a lower fatty acid such as acetic) and may be first treated with a lipoid solvent.  The invention includes deserpidine itself and its salts. Deserpidine is obtained from the above solutions by adding an acid or salt to form a salt of the base and fractionally crystallizing it from the accompanying reserpine.  It may also be purified by chromatography (e.g. on alumina), electrodialysis, paper-ionophoresis or methanol-extraction and these processes may be combined suitably to form a multi-stage process. Examples are given of the extraction of deserpidine from R. canescens and R. indecora by the above techniques and formation of the sulphate, hydrochloride, nitrate, oxalate and phosphate salts.  Other suitable starting materials are R. vomitoria, R. hirsuta (= R. heterophylla), R. tetraphylla and R. cubana.  Other salts that may be prepared are the perchlorate, acetate, propionate, lactate, succinate, malate, tartrate, citrate, ascorbate, methanesulphonate, ethanesulphonate, isethionate, benzoate, salicylate, p-aminosalicylate, p-toluenesulphonate, picrate, picrolonate, phosphotungstate, phosphomolybdate and mercuric iodate.  Deserpidine can be partially hydrolysed to methyl deserpidate and re-esterified, e.g. with furoic or 3:4-dimethoxybenzoic acid, as described in Specification 809,913.ALSO:The alkaloid deserpidine (see Group IV (b)) is obtained substantially free from other alkaloids and materials associated with Rauwolfia sp., and made up with a solid or liquid pharmaceutical carrier, preferably in unit dosage form containing 0.05-100 mg. (preferably 0.1-20 mg.) of deserpidine.  The form may comprise tablets, powder, capsules, pills, or solutions, emulsions or suspensions in ampoules.  The deserpidine can be present as a salt with an inorganic or organic acid.  Examples show hypotensive compositions of deserpidine with various of the following:-lactose, gelatine, starch, talcum, magnesium stearate, tragacanth, citric acid, ethanol, propylene glycol, benzyl alcohol, polyethylene glycol, 1-hydrazino-phthalazine and diethylaminoethyl a -cyclohexyl-a -phenyl-glycollate methobromide.  In general, inert materials that may be present are vegetable oils, gums, ascorbic acid, petroleum jelly, cholesterol, preservatives, stabilizers, wetting or emulsifying substances, buffers and salts for controlling the osmotic pressure.  Other active substances that can be added are ganglionic blockers, e.g. N : N : N1 : N1 : 3 - pentamethyl - N : N1 - diethyl - 3 - azapentylene - 1 : 5 - diammonium bromide, pentamethylene bis - methylpyrrolidinium tartrate, 2 - (21 - dimethylaminoethyl) - 4 : 5 : 6 : 7 - tetrachloro - isoindoline dimethochloride; adrenergic blockers, e.g. 2-(N1-p-tolyl - N1 - m - hydroxyphenylaminomethyl) - imidazoline or ergot alkaloid derivatives; 1 : 4-dihydrazino-phthalazine; other Rauwolfia alkaloids (e.g. reserpine), or analogues thereof, especially methyl O-(3 : 4 : 5-trimethoxycinnamoyl)-reserpate or -deserpidate or methyl O-acetylreserpate; sedatives, e.g. barbiturates, B - ethyl - b  - phenylglutarimide or N - (31 - dimethylaminopropyl) - 3 - chlorophenthiazine; stimulants such as methyl a  - (2 - piperidyl) - phenylacetate or a -methylphenylethylamine; cholinergic blocking agents such as atropine or diethylaminoethyl xanthene - 9 - carboxylate methobromide: or antihistaminics such as 2-[benzyl - (21 - dimethylaminoethyl) - amino] - pyridine, besides those mentioned above in the examples.  Specification 809,913 is referred to.