CH636844A5 - PROCESS FOR OBTAINING SALTS of aspartic acid. - Google Patents

Description

636844

PATENT CLAIMS 1. Process for obtaining salts of aspartic acid of the formula

HOOC-CH-CH2-COO-

i

NH2

Men + • XH2O

in which either n = 1 and Me is an alkali metal or n = 2 and Me is an alkaline earth metal or a divalent heavy metal and X is a whole or fractional number from zero to 4, depending on the cation contained, characterized in that one Solution of these salts spray dried at a temperature of 500 to 20 ° C. 2. The method according to claim 1, characterized in that one carries out the spray drying at temperatures between 300 and 80 ° C.

The invention relates to a method for obtaining salts of aspartic acid of the formula

HOOC-CH-CH2-COO-

I.

NH2

Me "+ • XH2O

in which either n = 1 and Me is an alkali metal or n = 2 and Me is an alkaline earth metal or a divalent heavy metal and X is a whole or fractional number from zero to 4, depending on the cation contained. The alkali, alkaline earth and heavy metal salts of aspartic acid are of considerable importance as active pharmaceutical ingredients and as components of infusion solutions. They are very easily soluble in water and organic solvents or in mixtures of water and organic solvents in which salt formation is carried out. As a result, their isolation in crystalline form is technically very complex and, above all, very lossy. The process according to the invention is now characterized in that the solutions of the salts are spray-dried at temperatures between 500 and 20 ° C.

The desired salts are obtained in spray drying in virtually quantitative yield and in high purity. They can be used for any application without any additional cleaning measures. By varying the spray drying conditions, the salts can easily be produced in different grain sizes with a relatively narrow grain spectrum and with defined physical properties.

The salts obtained by the process according to the invention are obtained in the same composition as the corresponding salts which have been isolated by the customary crystallization process. Above all, it is surprising that the spray water does not remove the water of crystallization over a wide temperature range, so that the salts containing water of crystallization are obtained as defined hydrates. The process according to the invention is particularly suitable for the preparation of salts of aspartic acid with alkali metals, in particular lithium, sodium or potassium; with alkaline earth metals, especially magnesium or calcium, and with divalent heavy metals, especially zinc, iron, manganese, cobalt or copper.

The spray drying can be subjected to solutions which have been specially prepared for this purpose, as well as the mother liquors which are obtained after a partial crystallization of salts of aspartic acid.

The salt solutions are expediently prepared by reacting stoichiometric amounts of aspartic acid with the corresponding oxides or hydroxides of the metals in water and / or organic solvents. Suitable organic solvents are preferably alcohols having 1 to 8 carbon atoms, in particular methanol, ethanol or isopropyl alcohol.

The minimum amount of solvent required for salt formation depends on the solubility of the respective salt in the solvent chosen at boiling temperature. In principle, any diluted salt solutions can be used for spray drying. For economic reasons, it is of course advisable to start with solutions that are as concentrated as possible.

15 Aspartic acid can be used both in the form of its optical isomers and in the form of the racemate. The spray drying of the salt solutions can be carried out in all conventional atomizing dryers. The inlet temperature of the drying air should expediently not exceed 500 ° C. and the outlet temperature and product temperature should not fall below 20 ° C. Drying is preferably carried out at temperatures between 300 and 80 ° C.

25th

Example 1 Sodium L-aspartate • H2O 133.1 g (1 mol) L-aspartic acid are suspended in 200 ml water and mixed in portions with 40 g (1 mol) NaOH. After the addition of 10 g of activated carbon, the mixture is heated to reflux temperature for 15 minutes and then filtered hot. The colorless solution is injected into a spray tower at a temperature of 280 ° C. The solid product is removed from the spray tower at a temperature of 35-120 ° C. The colorless powder is obtained in 98% yield (169.5 g). The specific rotation [«] □ is + 19.8 ° (10% solution in 2.5N hydrochloric acid).

40 Example 2

Magnesium bis-L-aspartate • 2H2O The salt solution is prepared from 266.2 g (2 mol) L-aspartic acid and 40.3 g (1 mol) magnesium oxide in 300 ml water. Spray drying is carried out at

45 doors between 300 ° C (inlet) and 110 ° C (product outlet). The product is obtained as a colorless crystalline powder in 99.5% yield (322.5 g). The specific rotation [a] o is + 19.6 ° (2% solution in 5N hydrochloric acid).

50

Example 3 Potassium L-aspartate • 0.5H2Û A salt solution is prepared from 133.1 g (1 mol) L-aspartic acid and 56.1 g (1 mol) KOH in 200 ml water.

55 This is spray dried at temperatures between 180 ° C and 95 ° C. 175 g (99.7% of theory) of colorless, powdery product are obtained. The specific rotation [a] o is + 18.6 ° (2% solution in 5N hydrochloric acid).

60

Example 4 Zinc bis-L-aspartate • H2O A salt solution is prepared from 133.1 g (1 mol) L-aspartic acid and 40.7 g (0.5 mol) ZnO in 300 ml water.

65 Spray drying takes place at temperatures between 230 ° C and 110 ° C. 343.5 g (99% of theory) of the colorless, powdery product are obtained. The specific rotation [a] o is + 18.2 ° (2% solution in 5N hydrochloric acid).

j 636844

Example 5 Example 7

Lithium L-aspartate • HzO potassium-D, L-aspartate-0.5 H2O

133.1 g (1 mole) of L-aspartic acid and 24.0 g (1 mole) of 133.1 g (1 mole) of D, L-aspartic acid and 56.1 g (1 mole) of KOH

Lithium hydroxide are reacted in 600 ml of water. They are implemented in 200 ml of water. Spray drying the

Spray drying of the solution takes place at temperatures between solution at temperatures between 180 ° C and 115 ° C.

see 190 ° C and 120 ° C. 154 g (98% of theory) of 178 g (99% of theory) of the colorless product of colorless, powdery product are obtained. Get the specific Dre. The nitrogen content is 7.73%, corresponding to hung [a] o is + 210 (2% solution in 5N hydrochloric acid). 99.5% of theory Th.

Example 6 10 Example 8 Calcium bis-L-aspartate Magnesium-bis-D, L-aspartate • 4 H2O 133.1 g (1 mol) L-aspartic acid and 37 g (0.5 mol) calci- 266.2 g (2 mol) D, L-aspartic acid and 40.3 g (1 mol) umhydroxide are reacted in 300 ml water. The spray magnesium oxide are reacted in 500 ml of water. Drying takes place at temperatures between 250 ° C and spray drying takes place at temperatures between 200 ° C and 130 ° C. There are 301 g (99% of theory) of colorless, powdery is and 95 ° C. 352 g (98% of theory) of the colorless pro product are obtained. The specific rotation [a] p is + duct obtained. The nitrogen content is 7.72%, corresponding to 20.6 ° (2% solution in 5N hydrochloric acid). 99.5% of the Th.