JPS6320220B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a new and economical process for producing L-lysine carbamate.

L-lysine carbamate is particularly used as a component of effervescent mixtures used to produce effervescent pharmaceutical compositions such as effervescent beverages, effervescent cassiers or tablets. In particular, it is often applied to effervescent drug compositions that contain no or only small amounts of alkaline ions. With this type of pharmaceutical composition, there is no risk of alkaline ions accumulating in the human body;
It can also be used in patients on a sodium-free diet.

L-lysine carbamate also has very good gastric tolerance due to the inclusion of a buffering medium and is absorbed almost immediately into the blood.

With the present invention, the inventors have discovered a new process for the production of L-lysine carbamate, which allows the use of feed-grade L-lysine monohydrochloride as starting material and is therefore relatively inexpensive.

This L-lysine monohydrochloride is first decolorized using carbon black as an aqueous solution, and the carbon black is then removed by, for example, a filtration method.

In the second step, the L-lysine monohydrochloride is treated with a base such as KOH or NaOH to remove the resulting salts, potassium chloride or sodium chloride, etc. by known methods (e.g. spin drying), and then a solvent,
Preferably methanol is added.

In the third step of the present invention, the filtrate obtained in the second step is treated to react with carbon dioxide (or dry ice) and the resulting precipitate, which is the desired product, is recovered.

The L-lysine carbamate thus obtained is in the form of a white crystalline powder, and this product is highly soluble in water but insoluble in methanol, as described above. The precipitate can be washed with methanol.

Without limiting the invention, the inventors have determined that the L-lysine carbamate produced from the combination of 1 mole of L-lysine and ₁ mole of CO2 is further stabilized by 1 mole of L-lysine. I think it is possible.

This can be confirmed by the results of the analysis. The following examples illustrate the invention but do not limit the scope of the invention.

Example 1 300 g of "feed grade" L-lysine monohydrochloride (ie animal feed grade) (titer >98%) are dissolved in 300 cm ³ of water at a temperature between 50°C and 60°C.

This mixture is stirred with 6 g of decolorized carbon black for 15 minutes at 60°C.

This is then filtered through paper.

110 g of KOH are added slowly at about 40° C. while stirring, the mixture is cooled to room temperature and then stirred for 1 hour. 1500 cm ³ of methanol are gradually added and the mixture is stirred for 2.5 hours and the potassium chloride formed is spun dry.

60 to 80 g of carbon dioxide are slowly added to the filtrate over about 1 hour, the mixture is left overnight, filtered, washed in 95% methanol and dried at about 40°C. 200 g of desired product are obtained.

MP249-250℃ Analysis: C ₁₃ H ₂₈ N ₄ O ₆ Calculated amount: C%46.41 H%8.39 N%16.65 O%28.54 Measured amount: C%46.62 H%8.37 N%28.33 Example 2 300g of “feed grade” ” L-lysine monohydrochloride (titration concentration >98%) was added to 450 cm ³ of water at 30°C.
Dissolve with.

The solution was incubated at 30°C with 6g of decolorized carbon black.
Stir for 15 minutes.

Then filter through paper.

79 g of sodium hydroxide are added slowly at about 20° C. and the mixture is cooled to room temperature and then stirred for 1 hour. Then 2000 cm ³ of methanol are gradually added and the mixture is stirred for 3 hours and the sodium chloride formed is spun dry.

60 to 80 g of carbon dioxide was slowly added to the filtrate over about 1 hour, the mixture was allowed to stand overnight and then filtered, washed in 95% methanol and incubated at 40°C.
Dry with. 189 g of desired product are obtained.

MP246-250℃ Analysis: C ₁₃ H ₂₈ N ₄ O ₆ Calculated amount: C%46.41 H%8.39
N%16.65 O%28.54 Measured amount: C%46.23 H%8.43
N% 16.67 O% 28.29 Example 3 Until no more white precipitate is formed
The same method as Example 1 is used except that instead of bubbling CO ₂ dry ice is gradually introduced. The mixture was then allowed to cool to room temperature and 3
Stir for half an hour. The product is filtered and washed in 800 cm ³ of methanol to give 192 g of desired product.

MP247-250℃ Reference Example 1 Effervescent tablet containing acetylsalicylic acid and no alkaline ions Form an effervescent mixture in the following proportions: Acetylsalicylic acid 0.500g L-lysine carbamate 16g Citric acid 0.4g of the above The values relate to tablets dosed in the conventional manner with 0.5 g of acetylsalicylic acid.

Reference Example 2 A effervescent composition for an effervescent beverage is formed according to the following proportions: Sugar 17g L-lysine carbamate 1.4g Citric acid 2.7g The composition is flavored with fruit extract in powdered form. be able to. When using orange flavor, vitamin C may be added as necessary.

Reference Example 3 Manufacture of effervescent tablets for administering 0.5 g of phosphorus For example, the following formula can be used: L-lysine carbamate 1.4 g Glycocol phosphate 1.397 g Anhydrous magnesium-base phosphate 0.881 g Example 4 and The tablets of No. 6 are manufactured by methods known to those skilled in the art of the present invention, and the ingredients are separated, dried, sieved, mixed and formed into tablets.

Therapeutic effects, dosages and methods are also known.

Claims (1)

[Scope of Claims] 1 A step of decolorizing an aqueous solution of "feed grade" L-lysine monohydrochloride with a titration concentration of 98% or more with carbon black while stirring, a step of filtering it through paper, and a step of filtrate-resistant. Adding a base, then adding methanol to produce an aqueous methanol solution containing L-lysine base, and filtering; and treating the filtrate consisting of the aqueous methanol solution containing L-lysine base by reacting it with carbon dioxide. and filtration, washing the precipitate with methanol, and recovering the L-lysine carbamate. 2. Process according to claim 1, characterized in that the strong base added is potassium hydroxide or sodium hydroxide. 3. In the step of treating the filtrate with carbon dioxide,
2. A method as claimed in claim 1, characterized in that it consists of bubbling carbon dioxide into the filtrate or gradually introducing dry ice into the filtrate.