Patent GB-421175-A (GB)
Title: Manufacture of solutions of therapeutically valuable compounds
IPC: A61K47/22
Filed: 1933-05-15
Abstract: Salts of amino-acridines with organo-arsonic acids are rendered more soluble in water by adding an easily water-soluble salt of an aminoacridine.  The arsonic acid starting materials may be salts of the kind described in Specification 405,629, in which the arsonic acid residue is combined with an amino group of the acridine compound, or salts of the kind described in Specification 419,603, in which the arsonic acid residue is attached to the nuclear nitrogen atom of the acridine compound.  If desired, the arsonic acid salt may be prepared in the presence of an aqueous solution of the easily water-soluble salt.  The examples describe the preparation of aqueous solutions (1) containing 3 : 6-diamino-10-methylacridinium chloride and the salt prepared by interaction of 3 : 6-diaminoacridine hydrochloride and sodium p-glycollylaminophenylarsonate; (2) containing 3 : 6-diamino-10-methylacridinium chloride and the salt from 2-ethoxy-6 : 9-diaminoacridine lactate (1 mol.) and sodium p-glycollylaminophenylarsonate (1 mol.); (3) containing 2-ethoxy-6 : 9-diaminoacridine lactate and the salt from 3 : 6-diamino-10-methylacridinium choride and 3 - acetylamino - 4 - hydroxyphenyl-1-arsonic acid; (4) containing 3 : 6 - diamino - 10 - methylacridinium chloride or 2 - ethoxy - 6 : 9 - diaminoacridine lactate and the salt from 3 : 6-diamino-10-methylacridinium chloride (1 mol.) and sodium p-glycollylaminophenylarsonate (1 mol); (5) by dissolving sodium p-glycollylaminophenylarsonate in water with an excess of 3 : 6-diamino-10-methylacridinium chloride.  The sample is prepared by dissolving the salt from 3 : 6-diamino-10-methylacridinium chloride and sodium p-glycollylaminophenyl arsonate in water with the addition of 3 : 6-diamino-10-methylacridinium acetate.  The Specification as open to inspection under Sect. 91 refers also to the following arsonic acid components:--3 - acetylamino - 4 - hydroxy - 5 - chlorbenzene - 1 - arsonic acid, 3 - formylamino - 4 - hydroxybenzene - 1 - arsonic acid, 3 - acetylamino - 4 - methoxybenzene - 1 - arsonic acid, 3 - acetylamino - 4 - hydroxyethoxybenzene - 1 - arsonic acid, 4 - benzoylamino - 3 - hydroxybenzene - 1 - arsonic acid, 2 : 4 - dihydroxybenzene - 1 - arsonic acid, 4 - acetylamino - 2 - phenoxyacetic acid - 1 - arsonic acid, 4 - phenylglycinamide - 1 - arsonic acid, acetylaminophenyldimethylpyrazolone - arsonic acid (formula given), benzoxazolone - 5 or 6 - arsonic acid, 3 -methylbenzimidazolone - 6 - arsonic acid, 2-pyridone-5-arsonic acid and 7-nitroketobenzisoxazine-6-arsonic acid (formula given). It also specifies the following additional acridine compounds capable of forming arsonic acid salts:--3 : 6-dimethoxy-10-methylacridinium chloride, 3-hydroxy - 6 - methoxy - 10 - methylacridinium chloride, 3 : 6 - dihydroxyethoxy - 10- hydroxyethylacridinium chloride, 3 : 6 - dimethoxy - 10 - nitrobenzylacridinium chloride, 3 : 6 - diamino - 10 - methyl, ethyl, propyl or benzyl - acridinium chloride and 2 : 7 - dimethyl - 3 : 6 - diamino - 10 - methylacridinium chloride.  The Specification includes two further examples, one corresponding with the above preparation of the sample, and the other describing the preparation of an aqueous solution containing 3 : 6 - diamino - 10 - methylacridinium nitrate and the salt prepared from 3 : 6 - diamino - 10 - methylacridinium chloride and sodium p-glycollylaminophenylarsonate.  This subject-matter does not appear in the Specification as accepted.