CH394236A - Process for the preparation of lysine hydrochloride - Google Patents

Description

  

  



  Process for preparing lysine aspartate
 The present invention relates to a process for preparing a new compound: lysine aspartate of the crude formula: C10H21O6N3. H4O and of structural formula:
EMI1.1

 This compound has been found to have interesting therapeutic properties; it exerts a tonic and energetic action.



   Its molecular weight is 297, its total nitrogen content is 14.14 / o and its composition corresponds to:
 -Aspartic acid 44.8%
 Lysine 49, 1 ouzo
   -Water 6, 10 / o
 It has the following physical properties: -White crystalline powder.



     ¯ Very soluble in distilled water (1 part in
 3 parts at 200 C-1 part in 1 part at
   1000 C).



     ¯ Very slightly soluble in ethanol: 1 part is not
 not dissolved in 240 parts of methanol at 950 to
 the temperature of 20 C.



   It decomposes without melting from 3350 to 3400 C.



   The pH of the 10 / e aqueous solution is 6.8-7.2.



   The process for preparing lysine aspartate according to the invention is characterized in that it cob sists in reacting aspartic acid with lysine.



   The reaction is advantageously carried out in aqueous solution at around room temperature, the reactants being in substantially equimolecular proportions.



   When the reaction is complete, a water-miscible organic solvent in which lysine aspartate is sparingly soluble is advantageously added to the reaction medium, in order to facilitate its precipitation. Ethanol is a particularly suitable solvent for this use.



   An example of implementation of the process for preparing lysine aspantate will be given below.



   In a 2000 ml crystallizer, weigh:
50% lysine base solution 292.0 g
Heat in a baimnarie to a temperature of 450 C.



   Add: -Aspartic acid 133, 1 g
 The addition should be made in small quantities, stirring each time until complete dissolution.



   Continue stirring for about sixty minutes. Leave to cool to a temperature of 200 C.



   At this point, add a seed of lysine aspartate and shake vigorously.



   Let stand for twelve hours at 200 C.



   Add: -Ethanol to 950 600 ml in small quantities, stirring at each addition for a long time so as to incorporate this solvent into the crystalline mass. Continue to agitate frequently for two hours.



   When this operation is completed, close the crystallizer and leave to stand for forty-eight hours, stirring several times so as to ensure the homogeneity of the mass and to avoid setting in lumps.



   The very homogeneous mass, or made homogeneous if necessary by grinding, is filtered, drained and washed with 300 ml of 95 ° ethanol.



   After spinning, it is dried under vacuum at a temperature of 40O C.



   Yield obtained: 270-275 g (93.5 / o).



   The product thus obtained must meet the chemical standards indicated (solubility, melting point, pH, identity characteristics).



   On the other hand, it must also comply with the quantitative determinations indicated below.



   The identity characteristics of lysine aspartate can be determined in a 10 "/ o solution, on which the following reactions are carried out: (a) To 2 ml of this solution, add 10 drops of
 ninhydrin solution at 1%. Wear to bath
 married.



   A purple coloration occurs.



  (b) Take 2 ml of this solution. Add 2 ml of
 saturated aqueous picric acid solution. At
 after fifteen minutes it starts to happen
 some crystals. These invade the masses
 completely after twenty-five minutes at
 thirty minutes.



  (c) Take 2 ml of this solution, add 2 ml
 dilute hydrochloric acid (R) and 2 ml of solution
 tion of phosphotungstic acid.



   There is an abundant white precipitate, very
 dense.



  (d) To 2 ml of this solution, add 2 ml of reagent
 prepared according to the formula: -paradimethylaminobenzaldehyde 5 g -sulfuric acid 10 g -water q. s. 100 g
 An abundant white precipitate occurs.



   Bring to a bain-marie; after two minutes
 this precipitate dissolves, while a
 blue coloration which, on cooling becomes
 Blue green.



   A slight precipitate forms.



  (e) To 2 ml of this solution add 2 ml of acid
 dilute hydrochloric acid (R) and 2 ml of reagent
   of Erhlich, previously defined. There is a
 green yellow coloring.



   The following quantitative determinations make it possible to verify the purity of the lysine aspartate: (a) Titration of total nitrogen by the method described in
 Codex, page 1068.



   The title must not be less than 13.5 or greater
 laughing at 14, 5 / o.



  (b) Titration of amino nitrogen by the poten method
   tiometric described by Monsieur Vigneron in
 its communication to the Academy of Pharmacy, the
 February 3, 1960 (Ann. Pharm. Franc. 1960-under
 hurry).



   Lysine aspartate, rigorously dehydrated by a stay in an oven for two hours at 350 C, reacts with perchloric acid, in anhydrous acetic medium, like a compound containing three basic nitrogen atoms. . 1 ml of N / 10 perchloric acid corresponds to 0.0099 g of lysine saspalrtate.



   The pharmacological study of lysine aspartate shows the following results: A-toxicity
 By the venous route, in mice, the lethal dose is 8.7 g / kg.



   The minimum lethal dose, peritoneally, in mice is less than 10 g / kg.



   Orally, in mice, the minimum lethal dose is less than 20 g / kg.



     B-Physiological effects
 At doses of 10, 20, 40 mg / kg, in rats, no significant changes in blood pressure or respiration were noted, but increased diuresis and tonic activity were detected. resulting in an increase in swimming time, under the conditions described by Labrit.



   The therapeutic indications of lysine aspartate should be linked to its role as a hub of intermediate metabolism, and particularly of transamination.



   This product acts on protein synthesis by helping to make the nitrogen balance positive, and as a growth factor.



     Lysine aspartate is therefore usable in therapy for its tonic and energy properties.



   Under these conditions, it is advantageously administered in the form of tablets, the formula of which is, for example, the following: -Lysine aspartate 0, 400 g -Starch 0, 085 g -French 0, 043 g ¯ Talc .. .. 0, 064 g ¯ Magnesia stearate 0, 008 g
 for a tablet finished at 0.60 g
 Lysine aspartate can be administered in this form at doses varying between 0.40 g and 3.20 g per day.



   The product can also be administered in the form of an injection solution containing an aqueous solution at 10 "/ o, as well as in the form of suppositories with the excipients specific to this formulation.


 

Claims (1)

CLAIM Preparation process, from the laps; lysine artate spreading to your faraude: EMI3.1 characterized in that it consists in reacting to the partial acid under the analysis. SUB-CLAIMS 1. Method according to claim, characterized in that the reaction is carried out in aqueous solution at around room temperature, the reactants being in substantially equimolecular proportions. 2. Method according to sub-claim 1, charac terized in that the reaction completed, is added to reaction medium a water-miscible organic solvent in which r. Lysine aspactate is poorly soluble in order to facilitate its precipitation. 3. A method according to sub-claim 2, charac- ter. ized in that said solvent is ethanol.