JPS593469B2 - Lysine monohydrate crystals - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to lysine hydrate crystals, and its object is to obtain lysine hydrate crystals that are stable against carbon dioxide gas in the air.

Lysine is a useful substance as an essential amino acid, and in addition to being useful as an additive to feed, it is also an important substance particularly for medicinal purposes such as crystalline amino acid infusions.

However, free lysine has extremely high solubility in water and easily absorbs carbon dioxide gas in the air, making it difficult to crystallize it and currently only using it as a salt such as hydrochloride. . However, when used in crystalline amino acid infusions, which are rapidly developing in recent years, contamination with unnecessary substances is undesirable; for example, chlorine ions cause side effects such as acidosis. Therefore, it is desired to obtain stable lysine crystals at low cost. Regarding the crystallization of free lysine, research by Uitzkelly et al. is known (Journal of Biological Chemistry, Vol. 76, p. 437 (1928)).
According to that, the melting point of free lysine crystals is 224-2
It is described that it is necessary to avoid carbon dioxide gas in the air during crystal 5 breakage and to use specially purified ethanol, and this crystal is lysine anhydrate. As a result of extensive research into a method for producing 10-lysine crystals that are stable against carbon dioxide gas in the air, the present inventor discovered that lysine-hydrate crystals were added to a 55-80% by weight free lysine aqueous solution. It was discovered that lysine hydrate crystals can be produced by adding lysine as a seed crystal, and that this crystal is stable against carbon dioxide gas in the air15, and based on this knowledge, the present invention was completed.

Lysine hydrate crystals do not crystallize without seed crystals, and the crystals were produced by the treatment method using thiamphenicol described in Example 1.

Once the crystals have been obtained, they can be used to crystallize lysine hydrate, and the crystals obtained by crystallization can be repeatedly used as seed crystals for the next crystallization. For example, when a lysine hydrate crystal is brought into contact with a 55 to 80% by weight free lysine water bath solution as a seed crystal, the lysine hydrate crystal is crystallized.

By separating this crystal by a conventional method, the lysine hydrate crystal of the present invention can be produced. This manufacturing method will be explained in detail below.

30 In the present invention, unless the concentration of lysine in the free lysine aqueous solution is 55% by weight or more, lysine-hydrate crystals will not precipitate even if the solution is cooled.

Preferably, the weight is 60 weight or more. In addition, adding a certain amount of seed crystals in a certain shape is useful for reliably precipitating 35 lysine hydrate and obtaining crystals with uniform grains. Addition of seed crystals is sufficient. Moreover, if the concentration exceeds 80%)17-, the whole will tend to solidify when it is cooled, which is not preferable.

A concentration of 60-70% is suitable. It has also been found that lysine monohydrate can be stably crystallized in a temperature range of 60° C. or lower.

At temperatures above that temperature, lysine anhydrate stably crystallizes.
Therefore, the contact temperature with the seed crystal is 60° C. or less, and it goes without saying that the lower the temperature, the better the yield. A conventional concentration or dilution method may be used to prepare an aqueous free lysine solution having the above concentration. It is advantageous for producing lysine monohydrate crystals to crystallize them using a cooling operation.

Lysine monohydrate crystals are identified by observing the endothermic phenomenon at 60° C. by X-ray powder diffraction and infrared absorption spectrum differential thermal analysis, in addition to the melting point.

Next, the crystals of lysine monohydrate thus crystallized are
This may be subjected to solid-liquid separation as it is, but if the viscosity of the mother liquor is high, it is preferable to dilute it with ethanol, n-propyl alcohol, or isopropyl alcohol before solid-liquid separation.

If a solvent other than these specific solvents is used, the precipitated lysine monohydrate crystals may dissolve, new fine suspended particles may precipitate, the solution may become colored, or the solution may form two layers. separation, giving undesirable results. For example, when methanol is used, the crystals dissolve, when n-butyl alcohol is used, the crystals separate into two layers, and when acetone is used, the crystals are colored. Not only is it not necessary to further lower the temperature after adding the solvent, but... Crystals precipitated from systems containing such organic solvents are often small and tend to change in quality and turn into powder, making it difficult to obtain crystals that are not compatible with the purpose of the present invention. Rather, it is preferable not to leave the mixture as it is for too long in order to prevent new solids from precipitating, but to perform solid-liquid separation immediately after the purpose of dilution is achieved. The method for producing lysine monohydrate crystals described above does not require the use of specially purified ethanol and can be easily obtained, and is convenient for industrial implementation.

Next, the rate at which lysine monohydrate crystals obtained by the present invention and lysine anhydrate crystals obtained by a known method absorb carbon dioxide gas in the air is shown in FIG. In FIG. 1, A shows the carbon dioxide absorption curve of lysine monohydrate crystals, and B shows the carbon dioxide absorption curve of lysine anhydrate crystals. The analysis method was to determine the decrease in the carbon content ratio due to the absorption of carbon dioxide gas by elemental analysis. According to this figure, lysine anhydrate crystals have a high carbon gas absorption value from the beginning and a fast absorption rate, whereas lysine monohydrate crystals obtained by the present invention have a low carbon dioxide absorption value. It can be seen that the absorption rate is slow and that it is stable against carbon dioxide gas. Furthermore, when comparing the hygroscopic properties of lysine monohydrate crystals and lysine anhydrate crystals, it is found that lysine anhydrate crystals absorb moisture when the humidity exceeds 45%, whereas lysine monohydrate crystals obtained by the present invention absorb moisture. does not absorb moisture if the humidity is below 63%.

FIG. 2 shows the relationship between humidity and absorbed water content of lysine monohydrate crystals and lysine anhydrate crystals. In this figure, A is the lysine monohydrate crystal, and B is the lysine anhydrate crystal.
℃, shows the relationship between humidity and absorbed moisture in an equilibrium state. It can be seen that the lysine monohydrate crystals of the present invention are stable against carbon dioxide gas in the air and have low hygroscopicity. The present invention will be explained in detail by way of examples.

Example 1 500 η of thiamphenicol was added to 10 ml of an aqueous solution of free L-lysine of 557/Dj and stirred at room temperature for 30 minutes, resulting in a homogeneous solution.

When this solution was left at 5° C. overnight, crystals were formed. When this crystal was separated and subjected to powder X-ray analysis, it was found to be an L-lysine hydrate crystal containing a small amount of thiamphenicol. When this crystal was added to 0.51% of a 65% by weight aqueous solution of free L-lysine and left overnight, 71tf) L-lysine hydrate crystals (melting point 60°C) were obtained. It was confirmed that the crystals were L-lysine hydrate crystals based on elemental analysis and water content measured by Karl Fischer method. FIG. 3 shows the infrared absorption spectrum of the L-lysine hydrate crystal measured by the nujiol method. 80 y of L-lysine hydrochloride (647 as free lysine) was dissolved in 2.2 ml of water and added to H-type strongly acidic ion exchange resin Duolite C-2.
After passing the solution through a 0500d column, the column was washed with 11 parts of water and eluted with 1.5 parts of 1N aqueous ammonia.

Next, the eluate was concentrated under reduced pressure to 600 me, decolorized with activated carbon, and further concentrated under reduced pressure to a total weight of 95 t.The lysine content was confirmed to be 61% by weight, and L-
When 0.1 f of lysine hydrate crystals were added as a seed crystal and the mixture was left at room temperature overnight, crystals precipitated, so the mixture was further cooled to 5° C. overnight with gentle stirring. Then 5℃
60 ml of cooled ethanol was added thereto and quickly filtered, and the crystals were further washed with 20 ml of 60% ethanol. The yield of the obtained crystals was 307. In the above example, when the same experiment as in the above example was conducted without adding seed crystals, no crystals were obtained.

That is, no crystals were obtained even if the concentration or cooling temperature was changed. Incidentally, when concentrated at a temperature of 60°C or higher, L-lysine anhydrate, which is a known crystal, crystallized. on the other hand,
According to the method described in the above-mentioned known literature, 240 ml of ethanol was added at room temperature to 40 f of a 50% by weight free L-lysine aqueous solution obtained in the same manner as in the above example, and when the mixture was left at 0° C. overnight, crystals were precipitated.

The obtained crystals were 5f7, and powder X-ray analysis revealed that they were L-lysine anhydrate crystals. Example 2 L-lysine hydrate crystals were produced in the same manner as in Example 1, except that n-propyl alcohol was used instead of ethanol added before filtration after crystallizing L-lysine hydrate. Obtained.

The yield of the obtained crystals was 257. Example 3 L-lysine hydrate crystal 31V was obtained in the same manner as in Example 1 except that isopropyl alcohol was used instead of ethanol.

Example 4 0.1 t of L-lysine hydrate crystals were added as seed crystals to 1k9 of a 65% by weight free L-lysine aqueous solution obtained in the same manner as in Example 1, and the mixture was left at 20°C overnight. Lysine-hydrate crystallized.

From this, solid-liquid separation was performed using a basket centrifuge at 0°C. 1472 L-lysine hydrate crystals were obtained.

[Brief explanation of drawings]

FIG. 1 shows carbon dioxide absorption curves of lysine monohydrate crystals and lysine anhydrate crystals.

Claims (1)

[Claims] 1 Lysine monohydrate crystal.