Patent GB-625085-A (GB)
Title: Therapeutic compositions derived from 2-aminoheptane and its salts
Inventor: SHONLE HORACE ABBOTT
Filed: 1943-03-12
Abstract: 2-Amino heptane is prepared from 2-heptanone by any of the following methods.  The ketone may be reacted with hydroxylamine and the resulting oxime reduced by catalytic hydrogenation or with sodium and a primary alcohol.  Or, the ketone may be reacted with formamide or ammonium formate and the resulting product hydrolysed with mineral acid to yield the amine salt which may be treated with a base to liberate the free amine.  Alternatively, the ketone may be reacted with ammonia and hydrogen in the presence of hydrogenation catalyst, preferably using excess ammonia and hydrogen and, if desired, a solvent for the ammonia such as ethanol.  The detailed procedure is given and the first and last methods are illustrated by examples. The salts of the amine are prepared by reacting the amine with an equivalent of the desired acid, generally in the presence of a solvent such as water, ethanol or ethyl ether and examples are given illustrating the preparation of 2-amino heptane sulphate, n-hexyl sulphonate, malate, benzoate, glycollate, nicotinate, hydrochloride, maleate, glyconate, phosphate, succinate and oleate; the acetate, hydrobromide, propionate and malonate are also mentioned.  The products are obtained as racemic mixtures of the d- and l-form of the amine or its acid salts and these may be resolved.  The amine and its salts may be used as vaso constrictors in therapeutic compositions (see Group VI).ALSO:Vasoconstrictor compositions comprising essentially 2-amino heptane or an acid-addition salt thereof, having relatively low toxicity and lack of substantial secondary vasodilatory effect, are prepared by incorporating the 2-amino heptane or its acid addition salt with a liquid extending medium as hereinafter defined to form a bland composition compatible with the mucous membrane.  The extending medium is a pharmaceutical vehicle chosen for its utility as solvent and diluent for the amine, its acid salts and the pharmaceutical constituents employed in the composition.  The extending medium may itself be the pharmaceutical constituent, for example, petroleum, or it may be water, in which case the extending medium contains a pharmaceutical constituent.  The extending medium and pharmaceutical constituents are of the type normally employed in vasoconstrictor compositions.  2-amino heptane may be administered topically as a solution in, for example, cottonseed oil or liquid petroleum, or may be prepared in a jelly or ointment.  The acid addition salts may be administered in, for example, physiological saline, solutions containing up to 4 per cent of the amine sulphate being well tolerated by the human mucosa, sugar solutions such as glucose and isotonic aqueous solutions, isotonic solutions containing 1/2 per cent to 4 per cent amine sulphate being mentioned; alternatively, jellies may be used, prepared by incorporating the amine salt in water, glycerine and a viscous medium or thickening agent such as gum tragacanth, sodium alginate or methyl cellulose.  In addition, the amine and its salts may be incorporated with local anaesthetic bases in solutions, jellies and ointments. Preferably, an acid addition salt of the amino heptane is combined with an acid salt of the anaesthetic base in aqueous solution. Anaesthetic bases specified are cocaine, procaine, D -(2-methyl-piperidino) propyl benzoate, p-amino-benzoyldimethylamino - methylbutanol, p - amino-benzoyl - \yL - di - n - butylaminopropanol, p - amino - benzoyl-2:2-dimethyl-3-diethyl aminopropanol, monoisobutylaminoethylp - aminobenzoate, piperidino-propanedioldi-phenylurethane, 2-butyloxy \yK quinoline carboxylic acid-4-diethyl-ethylene diamide and D  diethylaminopropyl cinnamate.  Examples describe (1) an inhalent comprising 2-aminoheptane, menthol, camphor, oil of thyme and liquid petrolatum; (2) a jelly comprising 2-aminoheptane, glycerine, tragacanth, methyl salicylate, sodium phosphate and water; (3) an ointment comprising 2-aminoheptane, menthol, camphor, oil of wintergreen, anhydrous wool fat and liquid and white petrolatum; (4) a solution for use as a nasal spray comprising 2-aminoheptane sulphate, physiological saline and a little chlorobutanol.  Oil-soluble acid salts of the amine may replace 2-aminoheptane in Example 1.  Acid addition salts may be used instead of the free amine in Examples 2 and 3.  Numerous other aminoheptane salts of inorganic and organic acids are mentioned.  The preparation of the amine and its salts is described, (see Group IV(b)).  The Specification as open to inspection under Sect 91 relates to the preparation of vasoconstrictor compositions by dissolving the 2-aminoheptane or acid salt thereof in any solvent including water.  This subject-matter does not appear in the Specification as accepted.