CN117534581A - Process for preparing L-lysine monohydrate - Google Patents
Process for preparing L-lysine monohydrate Download PDFInfo
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- CN117534581A CN117534581A CN202311543112.7A CN202311543112A CN117534581A CN 117534581 A CN117534581 A CN 117534581A CN 202311543112 A CN202311543112 A CN 202311543112A CN 117534581 A CN117534581 A CN 117534581A
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- lysine
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- mixed solution
- monohydrate
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- HZRUTVAFDWTKGD-JEDNCBNOSA-N (2s)-2,6-diaminohexanoic acid;hydrate Chemical compound O.NCCCC[C@H](N)C(O)=O HZRUTVAFDWTKGD-JEDNCBNOSA-N 0.000 title claims abstract description 55
- 238000004519 manufacturing process Methods 0.000 title claims description 14
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims abstract description 184
- 239000000243 solution Substances 0.000 claims abstract description 116
- 239000004472 Lysine Substances 0.000 claims abstract description 92
- 229960003646 lysine Drugs 0.000 claims abstract description 92
- 235000019766 L-Lysine Nutrition 0.000 claims abstract description 91
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 58
- 239000013078 crystal Substances 0.000 claims abstract description 44
- 239000011259 mixed solution Substances 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 30
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 239000012535 impurity Substances 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 69
- 239000012528 membrane Substances 0.000 claims description 44
- 238000001914 filtration Methods 0.000 claims description 28
- 238000003756 stirring Methods 0.000 claims description 21
- 239000007864 aqueous solution Substances 0.000 claims description 20
- 238000000108 ultra-filtration Methods 0.000 claims description 20
- 238000001035 drying Methods 0.000 claims description 16
- 239000002033 PVDF binder Substances 0.000 claims description 15
- 229920002981 polyvinylidene fluoride Polymers 0.000 claims description 15
- 239000004743 Polypropylene Substances 0.000 claims description 13
- 238000002425 crystallisation Methods 0.000 claims description 13
- 238000001471 micro-filtration Methods 0.000 claims description 11
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims description 10
- 239000003463 adsorbent Substances 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 9
- 230000007935 neutral effect Effects 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 8
- PQHNJDMCWOQAPR-UWVGGRQHSA-N [(2s)-2,6-diaminohexanoyl] (2s)-2,6-diaminohexanoate Chemical compound NCCCC[C@H](N)C(=O)OC(=O)[C@@H](N)CCCCN PQHNJDMCWOQAPR-UWVGGRQHSA-N 0.000 claims description 7
- 238000001179 sorption measurement Methods 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 239000004695 Polyether sulfone Substances 0.000 claims description 4
- 238000005119 centrifugation Methods 0.000 claims description 4
- 238000004042 decolorization Methods 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 238000000967 suction filtration Methods 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000005341 cation exchange Methods 0.000 claims description 3
- 238000010899 nucleation Methods 0.000 claims description 3
- 239000011148 porous material Substances 0.000 claims description 3
- 239000004677 Nylon Substances 0.000 claims description 2
- 229920002301 cellulose acetate Polymers 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 229920001778 nylon Polymers 0.000 claims description 2
- 238000011085 pressure filtration Methods 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 238000004659 sterilization and disinfection Methods 0.000 claims description 2
- 238000004321 preservation Methods 0.000 claims 1
- 238000002834 transmittance Methods 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 24
- 238000001816 cooling Methods 0.000 description 21
- 239000012065 filter cake Substances 0.000 description 20
- 239000008213 purified water Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000007599 discharging Methods 0.000 description 10
- 239000012467 final product Substances 0.000 description 10
- 238000005360 mashing Methods 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 238000001291 vacuum drying Methods 0.000 description 10
- 238000004448 titration Methods 0.000 description 8
- 238000001514 detection method Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 4
- 239000004927 clay Substances 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102100037709 Desmocollin-3 Human genes 0.000 description 1
- 101000968042 Homo sapiens Desmocollin-2 Proteins 0.000 description 1
- 101000880960 Homo sapiens Desmocollin-3 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- RRNJROHIFSLGRA-JEDNCBNOSA-N acetic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.NCCCC[C@H](N)C(O)=O RRNJROHIFSLGRA-JEDNCBNOSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000012490 blank solution Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 229960005357 lysine acetate Drugs 0.000 description 1
- 229960005337 lysine hydrochloride Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000003918 potentiometric titration Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
- C07C227/42—Crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of L-lysine monohydrate, which comprises the following steps: adding a poor solvent of L-lysine into the L-lysine water solution to obtain a mixed solution, and controlling the water content of the mixed solution to be 7-13% and the L-lysine content to be 7-25%; the water content refers to the ratio of the mass of water to the mass of the mixed solution; adding an L-lysine monohydrate seed crystal into the mixed solution for crystal growth, and then crystallizing to obtain an L-lysine monohydrate; the yield of the L-lysine monohydrate prepared by the preparation method is high and can reach more than 75 percent; the method has no more accurate parameter control, and is convenient for industrial production; the L-lysine monohydrate prepared by the method has high purity, high light transmittance and low impurity.
Description
Technical Field
The invention particularly relates to a preparation method of L-lysine monohydrate.
Background
L-lysine is the most important one of the eight amino acids necessary for the composition of proteins, is a first lacking and limiting amino acid which cannot be synthesized by itself in humans and animals and must be supplied in vitro, and plays an irreplaceable role in the growth and metabolism of humans and animals. Although the production of lysine at home and abroad is vigorous, the production of lysine salt such as lysine hydrochloride and lysine acetate is mainly used, and little L-lysine anhydride exists, and L-lysine monohydrate is almost absent. L-lysine is inferior in quality because it is unstable in its hydrochloride property as compared with L-lysine. However, in some applications, L-lysine hydrochloride cannot be used instead of L-lysine, and a method for preparing high-purity L-lysine monohydrate is highly desired.
The preparation process of the L-lysine related product is generally as follows, fermentation broth of L-lysine is obtained by adopting a microbial fermentation process, and L-lysine hydrochloride is obtained by the processes of neutralization, crystallization, recrystallization and the like. The L-lysine hydrochloride is treated by cation exchange column, ammonia water eluting, ammonia expelling and other processes to obtain solution of L-lysine, and the solution is concentrated to dryness or crystallized with poor solvent to obtain anhydrous L-lysine.
There is no patent related to the preparation of L-lysine monohydrate. There are literature disclosures that crystallization is performed in three ways in the crystallization study of L-lysine, wherein an anhydrous L-lysine is obtained by spray drying, an anhydrous L-lysine is obtained by poor solvent crystallization, and an monohydrate L-lysine is obtained by pure water crystallization. However, the pure water crystallization method adopted by the method is unstable in process, only one batch of L-lysine monohydrate is successfully obtained in five batches of pilot scale-up, and the yield is low, namely, only 18.4%.
Disclosure of Invention
The invention solves the technical problem of low yield of L-lysine monohydrate in the prior art, and provides a preparation method of L-lysine monohydrate. The L-lysine monohydrate prepared by the method has the advantages of high yield, simple preparation method, convenience for industrial production, high product purity and high light transmittance.
The invention solves the technical problems by the following technical proposal:
the invention provides a preparation method of L-lysine monohydrate, which specifically comprises the following steps:
(1) Adding a poor solvent of L-lysine into an L-lysine aqueous solution to obtain a mixed solution, and controlling the water content of the mixed solution to be 7-13%, wherein the water content of the L-lysine is 7-25%, the water content refers to the mass fraction of water in the mixed solution, and the L-lysine content refers to the mass fraction of L-lysine in the mixed solution;
(2) And adding an L-lysine monohydrate seed crystal into the mixed solution for crystal growth, and then crystallizing to obtain the L-lysine monohydrate.
In the present invention, in the step (1), the mass fraction of L-lysine in the L-lysine aqueous solution may be conventional in the art, and is preferably 10 to 50%, for example 30%.
In the present invention, in the step (1), the L-lysine aqueous solution may be prepared by a method conventional in the art, for example, by using an L-lysine anhydride or L-lysine hydrochloride as a raw material.
Wherein, when the L-lysine anhydride is used as a raw material, the preparation method of the L-lysine aqueous solution preferably comprises the following steps: and mixing pure water with the L-lysine anhydride, and stirring for dissolution to obtain the L-lysine aqueous solution.
Wherein, when L-lysine hydrochloride is used as a raw material, the preparation method of the L-lysine aqueous solution preferably comprises the following steps: and carrying out cation exchange treatment on the L-lysine hydrochloric acid to obtain the L-lysine aqueous solution.
In the present invention, in the step (1), the poor solvent for L-lysine may be a solvent which is generally used in the art and is miscible with water and has poor solubility for L-lysine, preferably one or more of methanol, ethanol, n-propanol, isopropanol and acetone, for example ethanol.
In the present invention, in the step (1), the amount of the poor solvent for L-lysine to be added is not particularly limited, and the content of L-lysine in the mixed solution may be controlled to 7 to 25%.
In the present invention, in the step (1), the content of L-lysine in the mixed solution is 10 to 25%, for example, 20% and 25%.
In the present invention, in the step (1), the method for controlling the water content of the mixed solution to be 7 to 13% preferably comprises: concentrating the L-lysine aqueous solution, and then adding a poor solvent and pure water to make the water content of the mixed solution be 7-13%.
In the present invention, in the step (1), the method for controlling the water content of the mixed solution to be 7 to 13% preferably comprises: concentrating the L-lysine aqueous solution, and then adding a poor solvent to make the water content of the concentrated solution be 7-13%.
Wherein the concentration of the concentrated L-lysine aqueous solution can be determined according to the actual production line conditions, for example, the concentration after concentration is 70%; when the concentration cannot be controlled accurately, the water content of the mixed solution can be controlled to be 7-13% by further adding pure water.
Wherein the concentration method may be conventional in the art, such as concentration under reduced pressure.
In the present invention, in the step (1), the water content of the mixed solution is controlled to be preferably 7%.
In the present invention, the step (1) may further comprise a step of sterilizing the aqueous L-lysine solution before adding the poor solvent for L-lysine.
Wherein, the sterilization and impurity removal treatment method preferably adopts ultrafiltration treatment.
Wherein, the ultrafiltration treatment of the L-lysine aqueous solution can be a treatment method which is conventional in the art and can remove microorganisms, endotoxin and macromolecular impurities in the L-lysine aqueous solution, and is preferably carried out by adopting an ultrafiltration membrane, and the membrane entrapment molecular weight of the ultrafiltration membrane is preferably 1K to 10K, for example 5K.
The ultrafiltration membrane material can be ultrafiltration membrane materials which are commonly used in the field for underwater use, and is preferably PVDF, PES, PP or modified cellulose acetate.
In the invention, in the step (2), before the mixed solution is subjected to crystal growth, the step of carrying out microfiltration treatment on the mixed solution can be further included so as to further sterilize.
Wherein, the mixed solution is preferably subjected to microfiltration treatment by adopting a filter membrane or a filter element.
Wherein, the material of the filter membrane or the filter element can be one of PES, PVDF, PP and nylon which are conventional in the art.
Wherein the pore diameter of the microfiltration treatment of the mixed solution may be a conventional microfiltration pore diameter in the art, and is preferably 0.2 to 1.0 μm.
In the invention, in the step (2), before the mixed solution is subjected to crystal growth, the method can further comprise the step of removing impurities and decoloring the mixed solution.
Wherein, the impurity removal and decoloration treatment method can be conventional in the field, and preferably comprises the following steps: and adding an adsorbent into the mixed solution for adsorption treatment and filtering.
Wherein the adsorbent mass is preferably 5 to 20%, for example 10% of the L-lysine mass.
Wherein the adsorbent may be one or more of a conventional adsorbent capable of adsorbing small molecule impurities in the art, preferably neutral alumina, activated carbon or silica gel.
Wherein the adsorption treatment temperature and time may be conventional in the art. The temperature of the adsorption treatment is preferably 40 to 60 ℃. The holding time of the adsorption treatment is preferably 1 to 2 hours.
Wherein the filtration method may be conventional in the art, such as suction filtration, pressure filtration or centrifugation.
When the impurity removal and decolorization treatment step is performed and the microfiltration treatment step is performed, the impurity removal and decolorization treatment step and the microfiltration treatment step can be adjusted in the front-rear sequence as required, and generally, the impurity removal and decolorization treatment step is preceded by the microfiltration treatment step.
In the present invention, in the step (2), the crystal growth temperature is preferably 5 to 15 ℃, for example 10 ℃; the seeding time is preferably 1 to 3 hours, for example 2 hours.
In the present invention, in the step (2), the crystallization method may be a cooling crystallization method which is conventional in the art.
Wherein the temperature after the temperature reduction is preferably-5-0 ℃.
Wherein, the temperature reduction is preferably gradual temperature reduction, and the gradual temperature reduction rate is preferably 1-3 ℃/h.
In the present invention, in the step (2), the amount of the L-lysine monohydrate seed crystal added may be conventional in the art, preferably 0.1 to 1%, for example 0.2% or 0.5%, and% refers to the ratio of the mass of the L-lysine monohydrate seed crystal to the mass of the L-lysine.
In the present invention, in the step (2), the step of filtering and drying may be further included after the crystallization.
Wherein the filtration method may be conventional in the art, such as suction filtration or centrifugation.
Wherein the drying temperature is preferably 40 to 60 ℃.
The drying means may be conventional in the art, such as drying under reduced pressure.
On the basis of conforming to the common knowledge in the field, the above preferred conditions can be arbitrarily combined to obtain the preferred examples of the invention.
The reagents and materials used in the invention are commercially available.
The invention has the positive progress effects that:
(1) The yield of the L-lysine monohydrate prepared by the preparation method is high and can reach more than 75 percent; the method has no more accurate parameter control, and is convenient for industrial production;
(2) The L-lysine monohydrate prepared by the method has high purity, high light transmittance and low impurity.
Drawings
FIG. 1 is a DSC chart of the product of the present invention;
FIG. 2 is a DSC chart of an L-lysine monohydrate standard;
FIG. 3 is an infrared spectrum of the product of the present invention;
FIG. 4 is an infrared spectrum of L-lysine monohydrate standard.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
L-lysine was purchased from Hebei Guangrui biologicals Co., ltd.
Example 1
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane material is PVDF, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 11%, and the mass fraction of L-lysine is 25%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of neutral alumina into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.2% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) And transferring the filter cake into a double-cone vacuum drying oven to be dried for 6 hours at 45 ℃ under reduced pressure, and obtaining 20.7kg of a final product which is white crystalline powder.
Example 2
The main difference from example 1 is that: the water content of solution 2 was 7%.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 7%, and the mass fraction of L-lysine is 25%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of neutral alumina into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) The filter cake is transferred into a bipyramid vacuum drying oven for drying under reduced pressure at 60 ℃ for 6 hours, and 22.5kg of final product is obtained, and the product is white crystalline powder.
Example 3
The main difference from example 1 is that: the water content of solution 2 was 13%.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 13%, and the mass fraction of L-lysine is 25%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of neutral alumina into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) The filter cake is transferred into a biconical vacuum drying oven for drying under reduced pressure at 50 ℃ for 6 hours to obtain 19.1kg of final product which is white crystalline powder.
Example 4
The main difference from example 1 is that: the water content of solution 2 was 5%.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 5%, and the mass fraction of L-lysine is 20%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of neutral alumina into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) The filter cake is transferred into a biconical vacuum drying oven to be dried under reduced pressure at 60 ℃ for 6 hours, and 12.1kg of a final product is obtained, wherein the product is white crystalline powder.
Example 5
The main difference from example 1 is that: the water content of solution 2 was 15%.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 15%, and the mass fraction of L-lysine is 20%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of neutral alumina into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) The filter cake is transferred into a bipyramid vacuum drying oven for drying under reduced pressure at 60 ℃ for 6 hours, and 4.8kg of final product is obtained, and the product is white crystalline powder.
Example 6
The main difference from example 1 is that: activated clay is used as an adsorbent.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 7%, and the mass fraction of L-lysine is 25%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of activated clay into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) The filter cake is transferred into a double cone vacuum drying oven for drying under reduced pressure at 60 ℃ for 6 hours, and 22.0kg of final product is obtained, and the product is pale yellow crystalline powder.
Example 7
The main difference from example 1 is that: diatomite is used as an adsorbent.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 8%, and the mass fraction of L-lysine is 20%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of activated clay into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) And transferring the filter cake into a biconical vacuum drying oven, and drying at 60 ℃ under reduced pressure for 6 hours to obtain 21.8kg of final product which is yellow-white crystalline powder.
Example 8
The main difference from example 1 is that: no adsorbent was added.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 9%, and the mass fraction of L-lysine is 25%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Cooling the solution 3 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(5) And transferring the filter cake into a biconical vacuum drying oven, and drying at 60 ℃ under reduced pressure for 6h to obtain 21.6kg of final product which is yellow-white crystalline powder.
Example 9
The main difference from example 1 is that: the mass fraction of L-lysine in solution 2 was 7%.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2) Concentrating the solution 1 under reduced pressure, adding ethanol or ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 11%, and the mass fraction of L-lysine is 7%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of neutral alumina into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) The filter cake is transferred into a bipyramid vacuum drying oven for drying under reduced pressure at 60 ℃ for 6 hours, and 9.1kg of a final product is obtained, and the product is white crystalline powder.
Example 10
The main difference from example 1 is that: the mass fraction of L-lysine in solution 2 was 33%.
The specific steps of the embodiment include:
(1) 100L of purified water and 30kg of L-lysine were charged into the reaction vessel, and dissolved by stirring. Ultrafiltering the solution (ultrafiltration membrane is PP, molecular weight cut-off is5 KD) to obtain ultrafiltrate 1;
(2, concentrating the solution 1 under reduced pressure, adding ethanol or an ethanol solution to obtain a solution 2, wherein the mass fraction of water in the solution 2 is 11%, and the mass fraction of L-lysine is 33%;
(3) Filtering the solution 2 by a 0.45 mu m filter membrane, wherein the filter membrane is made of PVDF, so as to obtain a clear solution 3;
(4) Adding 3kg of neutral alumina into the solution 3, keeping the temperature at 50 ℃ and stirring for 1h, and filtering to obtain a solution 4;
(5) Cooling the solution 4 to 10 ℃, adding a small amount of L-lysine monohydrate as seed crystals (the adding amount of the seed crystals is 0.5% of the mass of the L-lysine), and preserving heat and growing crystals for 2 hours; gradually cooling to-2deg.C, discharging, centrifuging, and mashing filter cake;
(6) The filter cake is transferred into a bipyramid vacuum drying oven for drying under reduced pressure at 60 ℃ for 6 hours, and 23.1kg of a final product is obtained, and the product is white crystalline powder.
Product identification:
the products prepared in the above examples were analyzed by DSC detection and infrared detection, the DSC detection equipment model METTLER tolio model DSC3, the infrared spectrometer equipment model Nicolet iS5 infrared spectrophotometer (Thermo Fisher, usa).
FIGS. 1 and 2 are DSC spectra of the product prepared in example 1 and an L-lysine monohydrate standard (derived from Sigma-Aldrich, cat. No. L9037), respectively, and FIGS. 3 and 4 are IR spectra of the product prepared in example 1 and an L-lysine monohydrate standard, respectively, and it can be seen that the product prepared in example 1 is L-lysine monohydrate.
Performance test:
and (3) measuring the moisture content: the water content measurement method of the four general rules 0832 of the edition 2020 of Chinese pharmacopoeia is referred to, and the first method Fei Xiushi is used for measurement. The solvent adopts absolute methanol, and is titrated by an automatic potentiometric titrator.
Light transmittance (1:20) measurement: referring to the Chinese pharmacopoeia 2020 edition four general rules 0401 ultraviolet-visible spectrophotometry: 1g of the sample solution was prepared by adding 20ml of purified water, and the transmittance of the sample solution at a wavelength of 450nm was measured.
And (3) content measurement: about 70mg of the product is taken, precisely weighed, placed in a titration cup, 5ml of anhydrous formic acid is added to dissolve the product, and 50ml of glacial acetic acid is added. Titration was carried out by a potentiometric titration method (rule 0701 of four portions of Chinese pharmacopoeia 2020 edition) using 0.1mol/l perchloric acid titration solution, and a blank solution was prepared by the same method to carry out titration, and the result was corrected by a blank test, wherein each 1ml perchloric acid titration solution (0.1 mol/l) is equivalent to 7.3095mg of C 6 H 14 N 2 O 2 。
Wherein, V sample is the volume of titration liquid consumed by the sample;
v blank is the volume of titration solution consumed by blank;
c1 is the actual concentration of the titration solution;
m is the sample weighing amount of the sample;
the moisture content is the moisture content of the product measured by a moisture measurement method.
Bacterial endotoxin detection: and (3) performing gel method test according to four general rules 1143 of Chinese pharmacopoeia 2020 edition.
Microbial limit detection: microbiological limit inspection of non-sterile products according to the fourth general rule 1105 of the chinese pharmacopoeia 2020 edition: the microorganism counting method is used for detection, and the counting method adopts a thin film filtering method.
Table 1 shows the results of the performance test of the products of the above examples.
TABLE 1
The moisture content of the product of example 4 was 8.4%, indicating that the product was a mixture of anhydrate and monohydrate, failing to obtain a single L-lysine monohydrate; the moisture content of the product of example 10 was 6.4%, indicating that the product was a mixture of anhydrate and monohydrate, failing to obtain a single L-lysine monohydrate; other embodiments of the invention may result in a single L-lysine monohydrate.
Claims (10)
1. A process for the preparation of L-lysine monohydrate, characterized in that it comprises the steps of:
(1) Adding a poor solvent of L-lysine into an L-lysine aqueous solution to obtain a mixed solution, and controlling the water content of the mixed solution to be 7-13%, wherein the water content of the L-lysine is 7-25%, the water content refers to the mass fraction of water in the mixed solution, and the L-lysine content refers to the mass fraction of L-lysine in the mixed solution;
(2) And adding an L-lysine monohydrate seed crystal into the mixed solution for crystal growth, and then crystallizing to obtain the L-lysine monohydrate.
2. The method for producing L-lysine monohydrate according to claim 1, wherein in the step (1), the mass fraction of L-lysine in the L-lysine aqueous solution is 10 to 50%;
and/or, in the step (1), using an L-lysine anhydride or L-lysine hydrochloride as a raw material to prepare the L-lysine aqueous solution;
when an L-lysine anhydride is used as a raw material, the preparation method of the L-lysine aqueous solution preferably comprises the following steps: mixing pure water with the L-lysine anhydride, and stirring for dissolution to obtain the L-lysine aqueous solution;
when L-lysine hydrochloride is used as a raw material, the preparation method of the L-lysine aqueous solution preferably comprises the following steps: and carrying out cation exchange treatment on the L-lysine hydrochloric acid to obtain the L-lysine aqueous solution.
3. The method for producing L-lysine monohydrate according to claim 1, wherein in the step (1), the poor solvent of L-lysine is one or more of methanol, ethanol, n-propanol, isopropanol and acetone;
and/or, in the step (1), the addition amount of the poor solvent of the L-lysine can be controlled to be 7-25% of the L-lysine in the mixed solution;
and/or, in the step (1), the content of the L-lysine in the mixed solution is 10-25%.
4. The method for producing L-lysine monohydrate according to claim 1, wherein in step (1), the method for controlling the water content of the mixed solution to 7 to 13% comprises: concentrating the L-lysine water solution, and then adding a poor solvent and pure water to ensure that the water content of the mixed solution is 7-13%; or concentrating the L-lysine water solution, and then adding a poor solvent to ensure that the water content of the concentrated solution is 7-13%;
the concentration method is preferably reduced pressure concentration;
and/or, in the step (1), controlling the water content of the mixed solution to be 7%.
5. The method for producing L-lysine monohydrate according to claim 1, wherein in the step (1), the step of sterilizing and purifying the L-lysine aqueous solution is further included before adding the poor solvent for L-lysine;
the sterilization and impurity removal treatment method preferably adopts an ultrafiltration membrane for ultrafiltration treatment; the membrane package interception molecular weight of the ultrafiltration membrane is preferably 1K-10K; the ultrafiltration membrane is preferably PVDF, PES, PP or modified cellulose acetate.
6. The method for producing L-lysine monohydrate according to claim 1, further comprising the step of subjecting the mixed solution to microfiltration treatment before seeding the mixed solution in step (2);
preferably, the mixed solution is subjected to microfiltration treatment by adopting a filter membrane or a filter element; the filter membrane or the filter element is preferably made of one of PES, PVDF, PP and nylon; the pore size of the filter membrane or the filter element is preferably 0.2-1.0 μm.
7. The method for producing L-lysine monohydrate according to claim 1, further comprising the step of subjecting the mixed solution to a impurity removal and decolorization treatment before the step of seeding the mixed solution;
preferably, the impurity removal and decoloration treatment method comprises the following steps: adding an adsorbent into the mixed solution for adsorption treatment and filtering;
the adsorbent mass is preferably 5 to 20% of the L-lysine mass, more preferably 10%;
the adsorbent is preferably one or more of neutral alumina, activated carbon or silica gel;
the temperature of the adsorption treatment is preferably 40-60 ℃; the heat preservation time of the adsorption treatment is preferably 1-2 h;
the filtration method is preferably suction filtration, pressure filtration or centrifugation;
when both the impurity removal and decoloration treatment step and the microfiltration treatment step of claim 5 are performed, the microfiltration treatment step precedes the impurity removal and decoloration treatment step.
8. The method for producing L-lysine monohydrate according to claim 1, wherein in the step (2), the crystallization temperature is5 to 15 ℃; the crystal growing time is 1-3 h;
and/or, in the step (2), the adding amount of the L-lysine monohydrate seed crystal is 0.1-1%, wherein the% refers to the ratio of the mass of the L-lysine monohydrate seed crystal to the mass of the L-lysine.
9. The method for producing L-lysine monohydrate according to claim 1, wherein in step (2), the crystallization method is a temperature-decreasing crystallization method;
the temperature after the temperature reduction is preferably-5-0 ℃;
the temperature reduction is preferably gradual, and the gradual temperature reduction rate is preferably 1-3 ℃/h.
10. The method for producing L-lysine monohydrate according to claim 1, wherein in step (2), the step of filtering and drying may be further included after the crystallization;
the filtration method is preferably suction filtration or centrifugation;
the drying temperature is preferably 40-60 ℃;
the drying means is preferably drying under reduced pressure.
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