Patent GB-808093-A (GB)
Title: Therapeutically valuable calcium salts
IPC: A61K33/06
Filed: 1956-12-19
Abstract: The invention comprises calcium salts of N : N - di - (carboxyalkyl) - N - di - or polyhydroxy-alkylamines obtainable by treating the free acids or salts thereof, e.g. metal or ammonium salts or acid-addition salts, with compounds yielding calcium ions, preferably, in the case of the free acid, calcium oxide, hydroxide or carbonate, or, in the case of the salt, a calcium salt such as the chloride or acetate, or by thus treating esters, amides or nitriles of these acids or acid-addition salts thereof, under saponifying conditions, preferably with calcium oxide or hydroxide, or by di- or poly-hydroxyalkylating the calcium salts of di-(carboxyalkyl), amines, e.g. by condensation with a hydroxy-alkyl epoxide, a hydroxyalkyl halogenide or a reactive ester of an aliphatic hydroxy alcohol, and these methods of preparation.  In examples: (1) 2 : 3 - dihydroxypropylamino - N : N - diacetic acid, calcium carbonate and a small amount of methyl p-hydroxybenzoate are dissolved in distilled water to give a solution of pH 5; (2) the same acid is stirred with chalk and water, the solution filtered and alcohol added to the filtrate to give a precipitate analysing as 3C7H11O6NCa.C7H13O6N. 2H2O; (3) the same acid is stirred with calcium oxide and water at elevated temperature and the product, the calcium salt of 2 : 3-dihydroxypropylamino-N : N-diacetic acid, C7H11O6NCa12H2O, is precipitated by passing in CO2 until the solution is neutral; (4) iminodiacetic acid is stood with milk of lime and glycide, CO2 is added at 90 DEG  C., the product is filtered, the filtrate is concentrated and a product analysing as 3C7H11O6N Ca C7H13O6N is precipitated by the addition of alcohol; (5) a -monochlorohydrin replaces the glycide of (4), the product being the calcium salt of 2 : 3-dihydroxypropylamino-N : N-diacetic acid, C7H11O6NCa\ 1/2 H2O; (6) glucose is catalytically hydrogenated in ammonia solution, the resulting glucamine solution is stood with hydrocyanic acid and formaldehyde, the mixture is ether-extracted and the aqueous phase is heated with calcium oxide to give, on working up, the calcium salt of glucamine N : N-, diacetic acid C10H17ONCa.2H2O; (7) a mixture of iminodiacetonitrile and glucose in methanol is catalytically hydrogenated and a hot solution of oxalic acid in methanol is added to give a precipitate of N : N - bis - cyanomethyl glucamine-oxalate C10H17O5N3. C2H2O4. 2H2O which, on heating with milk of lime and working up, gives the product of (6). Reference is also made to 2-methyl-1 : 3-dihydroxypropyl - 2 - amino - N : N - diacetic acid, 2 - hydroxymethyl - 1 : 3 - dihydroxypropyl - 2-amino - N : N - diacetic acid and 1 : 3 - dihydroxypropyl - 2 - amino - N : N - bis - (a  - butyric acid) as compounds which form calcium salts according to the invention and to the use of epoxides and reactive esters of glycerol, tetritols, pentitols, hexitols, heptitols and their partial deshydroxy derivatives and higher analogues and to the use of iminodipropionic acids and higher hemologues in the processes of the invention.ALSO:Therapeutic compositions comprise a calcium salt of an N : N-di-(carboxyalkyl) N-di- or polyhydroxy - alkylamine and a liquid carrier.  Aqueous solutions are preferred and reference is made to the addition of further substances.  In an example 2 : 3 - dihydropropylamino - N : N-diacetic acid, calcium carbonate and a small amount of methyl p-hydroxybenzoate are dissolved in water.