Patent GB-626286-A (GB)
Title: Therapeutic compositions comprising 2-amino alkanes
Inventor: SHONLE HORACE ABBOTT
Filed: 1943-03-18
Abstract: 1-R-1-amino ethanes, other than 2-amino heptane, wherein R is a saturated aliphatic hydrocarbon radical having from 4 to 9 carbon atoms are prepared according to any of the following methods from methyl ketones having the general formula CH3-CO-R, where R is as above.  Firstly, the ketone may be reacted with hydroxylamine and the resulting oxime reduced with sodium and alcohol or by catalytic hydrogenation.  Or the ketone may be reacted with formamide or ammonium formate, normally using 1 mol. of ketone and 4 mols. of the other reagent, hydrolysing the resulting product with a mineral acid and treating the amine salt so obtained with a base to liberate the free amine. Alternatively, the ketone is reacted with ammonia and hydrogen in the presence of a hydrogenation catalyst, preferably employing excess of ammonia and hydrogen and, if desired, using the ammonia dissolved in a solvent such as ethanol.  Each method is illustrated in detailed examples wherein the following amines are prepared: 2-amino-4-methylpentane, 2 - amino - 4 : 4 - dimethylpentane, 2 - amino octane, 2 - amino - 4 : 6 - dimethyl heptane, 2 - amino - 5 : 7 - dimethyl-octane.  Acid addition salts of the amines may be prepared by reacting the base with an equivalent of the desired acid, preferably in a solvent such as water, ethanol or ethyl ether.  Examples describe the preparation of 2-amino-3-methyl hexane sulphate, 2-amino-5-methyl hexane tartrate, 2-amino-3 : 4-dimethyl hexane phosphate, 2-amino-5 : 7-dimethyl octane hydrochloride, 2-amino-4-methyl pentane sulphate and a solution of the salt of the enol form of 1 : 3-propanediol and 2-amino octane. The salts formed from valeric, hydrobromic, maleic, malonic, sulphamic and n-hexyl sulphonic acids are also mentioned.  The amines and their salts may be used in vaso constrictor compositions (see Group VI).  The amines obtained as above, comprise racemic mixtures which may be resolved into their d- and l-forms.  The Specification as open to inspection under Sect. 91 includes the preparation of 2-amino heptane and other amines of the above general formula wherein R also represents alkinyl and alkenyl radicals having 4 to 9 carbon atoms, and salts thereof, by the above-mentioned processes. Additional examples are given describing the preparation of 2-amino hexene-5 and its sulphate, 2-amino hexine-5, 2-amino-6-methyl heptene-5 and 2-amino-3-methyl hexene sulphate.  This subject-matter does not appear in the Specification as accepted.ALSO:Therapeutic compositions having vasoconstrictor properties comprising essentially a 1-R-1-amino ethane other than 2-aminoheptane, or an acid addition salt thereof, R being a saturated aliphatic hydrocarbon radical containing 4 to 9 carbon atoms, are prepared by incorporating the amine or salt thereof with a liquid extending medium therefor to form a bland composition compatible with the mucous membrane, said medium being or embodying a pharmaceutical constituent.  The extending medium is a non-toxic solvent, excipient or liquid diluent or carrier such as water, in which case the extending medium contains a pharmaceutical constituent, or an oil.  The pharmaceutical constituent is of the type suitable for vasocarrier, excipient or isotonicity producing agent for example, physiological saline, cottonseed oil, petrolatum, sugar such as glucose, glycerine, gum tragacanth, sodium alginate, methyl cellulose or a local an sthetic base or salt thereof.  The amines may be administered topically in a liquid solvent such as cottonseed oil or petroleum, or in jelly or ointment.  The amine salts are preferably dissolved in physiological saline solution or aqueous sugar solution such as water containing glucose in such proportions as to produce an isotonic solution; they may also be incorporated in water, glycerine and an organic viscous medium or thickening agent such as one of those mentioned above, to form jellies.  The amines or their salts may be combined with local an sthetic bases or their salts; preferably salts of the amines and the bases or their salts are combined in aqueous solution. Suitable bases are cocaine, procaine, p-amino-benzoyl-dimethylamino-methyl butanol, p-amino-benzoyl-D -di-n-butylaminopropanol, p-amino-benzoyl-2 : 2-dimethyl-3-diethyl-amino propanol, monoisobutyl aminoethyl-p-amino benzoate, D  -diethylamino propyl cinnamette, D -(2-methyl-piperidino) propyl benzoate, piperidinopropanediol-diphenylurethane and 2-butyloxyquinoline carboxylic acid-4-diethylethylene diamide.  Specified 1-R-1-aminoethanes and salts thereof are 2-amino-4-methylpentane and its sulphate 2-amino-4 : 4-dimethyl pentane, 2-amino-octane, 2-amino-4 : 6-dimethyl hep-tane, 2-amino-5 : 7-amino-octane and its hydrochloride, 2-amino-3-methyhexane sulphate, 2-amino-5-methyl hexane tartrate, 2 - amino - 3 : 4 - dimethylhexane phosphate, and a solution of the salt of the enol form of 1, 3 propanedial and 2-amino-octane.  Other suitable salts are those of hydrobromic, sulphamic, maleic and butyric acids. The preparation of the amines and their salts is described (see Group IVb).  The Specification as open to inspection under Sect. 91 includes the use of 2-amino heptane and of 1-R-1-amino-ethanes wherein R is an alkenyl or alkinyl group containing 4 to 9 carbon atoms and is not limited to the use, as an extending medium, of water which contains a pharmaceutical constituent.  Additional examples of such amino-ethanes are 2-amino-hexene-5 and its sulphate, 2-amino-hexine-5, 2-amino-6-methyl-heptene-5, and 2-amino-3-methyl hexene-5 sulphate. The amines may be utilized directly by inhalation.  This subject-matter does not appear in the Specification as accepted.