CN111333584A - Method for purifying histidine finished product, histidine finished product and pharmaceutical product - Google Patents
Method for purifying histidine finished product, histidine finished product and pharmaceutical product Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Abstract
The invention discloses a method for purifying a finished histidine product, the finished histidine product and a pharmaceutical product, wherein the method for purifying the finished histidine product comprises the following steps: s10, mixing the histidine finished product to be purified with absolute ethyl alcohol, and then carrying out solid-liquid separation to obtain a solid substance and a first filtrate; s20, dissolving the solid substance in water for decompression crystallization to obtain a crystallized solid and a second filtrate; and S30, washing the crystallized solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product. The invention greatly reduces the histamine content in the histidine finished product by purifying the histidine finished product, thereby reducing the side effect of the histidine finished product when being used as the effective component of the medicine.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a method for purifying a histidine finished product, a histidine finished product and a pharmaceutical product.
Background
L-histidine, also known as histidine, chemical name α -amino β -imidazolyl propionic acid, belongs to basic amino acid or heterocyclic amino acid, quasi-essential amino acid, participates in protein synthesis, has various physiological functions, and widely participates in various physiological and biochemical processes of organisms in various forms.
L-histidine is mainly derived from the hydrolysis and microbial fermentation of animal blood meal. The animal source is obtained by hydrolyzing blood powder with hydrochloric acid solution, and filtering to remove leucine. The pH of the filtrate was adjusted to 2.5 and the eluate was concentrated until crystallization occurred. The fermentation method mainly comprises the steps of carrying out mutagenesis on histidine-producing bacteria (corynebacterium glutamicum, brevibacterium flavum and the like) and breeding auxotroph and histidine structural analogue resistant mutant strains so as to relieve feedback inhibition and feedback repression in metabolic regulation, thereby achieving the aim of excessively accumulating histidine.
In the production of L-histidine, histamine is easily produced as a by-product in the finished product due to defects in the production conditions. Histamine binds to specific receptors on target cells, producing a biological effect: such as arterioles, venules, and capillaries, causing blood pressure drop and even shock; increase heart rate and myocardial contractility, inhibit atrioventricular conduction; exciting smooth muscle, causing bronchospasm, and gastrointestinal colic; stimulate the cells of the stomach wall, causing gastric acid secretion. In some pharmaceutical enterprises, the purchased L-histidine contains a small amount of histamine impurities, so that the finished pharmaceutical product taking histidine as a basic raw material is not qualified in blood pressure monitoring, and huge losses are brought to the enterprises. In order to reduce unnecessary loss, amino acid manufacturers or pharmaceutical manufacturers need to remove a trace amount of histamine in L-histidine to reduce the side effects of the finished product of histidine.
Disclosure of Invention
The invention mainly aims to provide a method for purifying a finished histidine product, a finished histidine product and a pharmaceutical product, aiming at reducing the side effect of the finished histidine product when the finished histidine product is used as an active ingredient of the medicament by purifying the finished histidine product.
In order to achieve the above object, the present invention provides a method for purifying a finished histidine product, comprising the following steps:
s10, mixing the histidine finished product to be purified with absolute ethyl alcohol, and then carrying out solid-liquid separation to obtain a solid substance and a first filtrate;
s20, dissolving the solid substance in water for decompression crystallization to obtain a crystallized solid and a second filtrate;
and S30, washing the crystallized solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product.
Optionally, after step S20, the method further includes:
s41, mixing the first filtrate and the second filtrate to obtain a mixed solution;
s42, after adjusting the volume ratio of ethanol in the mixed solution to 90-95%, carrying out normal pressure crystallization, and then separating out precipitates formed in the mixed solution;
and S43, washing the precipitate with absolute ethyl alcohol, and drying to obtain a histidine finished product.
Alternatively, in step S42: the temperature during normal pressure crystallization is 40-50 ℃.
Alternatively, in step S10: the volume ratio of the mass of the finished histidine product to be purified to absolute ethyl alcohol is (10-30) g: 1L of the compound.
Alternatively, in step S20: the mass of the solid matter to volume of water is (40-50) g: 1L of the compound.
Alternatively, in step S20: the vacuum degree during the reduced pressure crystallization is 0.02-0.07 MPa, and the temperature is 40-55 ℃.
The invention also provides a finished histidine product which is prepared by the method for purifying the finished histidine product.
Further, the invention also provides a pharmaceutical product, which comprises the finished histidine product.
Optionally, the pharmaceutical preparation comprises a compound amino acid injection.
According to the technical scheme provided by the invention, a finished histidine product to be purified is put into absolute ethyl alcohol to be fully mixed, the characteristic that histidine is not easy to dissolve in the ethyl alcohol and histamine is easy to dissolve in the ethyl alcohol is utilized, histamine in the finished histidine product to be purified is dissolved in the absolute ethyl alcohol, then a solid substance which is insoluble in the absolute ethyl alcohol in the finished histidine product to be purified is separated and collected, the solid substance is subjected to reduced pressure crystallization to prepare a pure substance, finally, the absolute ethyl alcohol is used for cleaning and drying, and the purified finished histidine product is obtained.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other related drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a schematic flow chart of an embodiment of the method for purifying a histidine finished product provided by the present invention.
The implementation, functional features and advantages of the objects of the present invention will be further explained with reference to the accompanying drawings.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
In the production of L-histidine, histamine is easily produced as a by-product in the finished product due to defects in the production conditions. Histamine binds to specific receptors on target cells, producing a biological effect: such as arterioles, venules, and capillaries, causing blood pressure drop and even shock; increase heart rate and myocardial contractility, inhibit atrioventricular conduction; exciting smooth muscle, causing bronchospasm, and gastrointestinal colic; stimulate the cells of the stomach wall, causing gastric acid secretion. In some pharmaceutical enterprises, the purchased L-histidine contains a small amount of histamine impurities, so that the finished pharmaceutical product taking histidine as a basic raw material is not qualified in blood pressure monitoring, and huge losses are brought to the enterprises. In order to reduce unnecessary loss, amino acid manufacturers or pharmaceutical manufacturers need to remove a trace amount of histamine in L-histidine to reduce the side effects of the finished product of histidine.
In view of the above, the present invention provides a method for purifying a finished histidine product, which reduces the side effects of the finished histidine product by purifying the finished histidine product. In an embodiment of the method for purifying a finished histidine product provided by the present invention, referring to fig. 1, the method for purifying a finished histidine product comprises the following steps:
step S10, mixing the histidine finished product to be purified with absolute ethyl alcohol, and then carrying out solid-liquid separation to obtain a solid substance and a first filtrate;
in the research process, the inventor finds that the histamine by-product in the finished histidine product is easily dissolved in ethanol, and the histidine is not easily dissolved in the ethanol, so that the purchased finished histidine product is put into absolute ethanol and fully mixed to ensure that the histamine contained in the finished histidine product to be purified is dissolved in the ethanol, and the dissolving can be assisted by stirring or ultrasonic oscillation and the like if necessary; after the histamine is completely dissolved, for example, mixing and standing for 10-20 min, or mixing and treating for 5-10 min under the action of stirring or ultrasound, and then performing solid-liquid separation to obtain a solid substance and a first filtrate, wherein the solid substance is a histidine component which is not easy to dissolve in ethanol, and the filtrate is an ethanol solution in which the histamine is dissolved. Among them, the solid-liquid separation method may be, for example, filtration or centrifugation. Further, in the present embodiment, the volume ratio of the mass of the final histidine product to be purified to the absolute ethyl alcohol in the step S10 is (10-30) g: 1L of the compound. Under the condition of the feeding ratio, the histamine component in the histidine finished product to be purified can be basically and completely dissolved in the ethanol, and unnecessary waste caused by excessive addition of the ethanol can be avoided.
Step S20, dissolving the solid matter in water for decompression crystallization to obtain a crystallized solid and a second filtrate;
and (3) the solid substance obtained after the treatment of the absolute ethyl alcohol is the histidine component in the histidine finished product to be purified, and then the solid substance is purified to obtain the high-purity histidine. In this embodiment, the solid material is purified in the following manner: dissolving the solid matter in water to form an aqueous solution, then crystallizing the aqueous solution under reduced pressure until the volume of the aqueous solution is reduced to 1/6-1/10 of the original volume, crystallizing and precipitating histidine component dissolved in the water to form a crystal in the aqueous solution, and then separating the crystal from the aqueous solution by a solid-liquid separation mode such as filtration or centrifugation to respectively obtain a crystalline solid and a second filtrate, wherein the crystalline solid is the required histidine product. Further, in the present embodiment, the ratio of the mass of the solid matter to the volume of water in step S20 is (40-50) g: 1L of the compound. At the feed ratio, the solid substance can be completely dissolved in water, and unnecessary waste caused by excessive addition of water can be reduced.
Further, in this embodiment, the vacuum degree of the vacuum crystallization in step S20 is 0.02 to 0.07MPa, and the temperature is 40 to 55 ℃, under the vacuum degree and temperature conditions, histidine dissolved in water can be promoted to be precipitated as crystalline as much as possible, thereby increasing the yield of histidine as much as possible.
And step S30, washing the crystallized solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product.
And (3) after obtaining the crystalline solid through reduced pressure crystallization, washing the crystalline solid by using absolute ethyl alcohol, and drying the crystalline solid until no solvent is left, so that a purified histidine finished product is obtained. The yield of the histidine finished product obtained by the method is 80-91%, and when the histidine finished product is used as one of raw materials to prepare 15AA (compound amino acid injection), the prepared 15AA can not cause side effects such as blood pressure reduction and the like in application.
According to the technical scheme provided by the invention, a finished histidine product to be purified is put into absolute ethyl alcohol to be fully mixed, the characteristic that histidine is not easy to dissolve in the ethyl alcohol and histamine is easy to dissolve in the ethyl alcohol is utilized, histamine in the finished histidine product to be purified is dissolved in the absolute ethyl alcohol, then a solid substance which is insoluble in the absolute ethyl alcohol in the finished histidine product to be purified is separated and collected, the solid substance is subjected to reduced pressure crystallization to prepare a pure substance, finally, the absolute ethyl alcohol is used for cleaning and drying, and the purified finished histidine product is obtained.
In addition, after the crystalline solid and the second filtrate are obtained through the reduced pressure crystallization process in step S20, since a small amount of histidine component is still dissolved in the second filtrate, in order to increase the final yield of histidine, as a preferred embodiment of the present invention, the method for purifying the finished histidine further comprises:
and a step S40 of extracting the histidine component remaining in the second filtrate.
Specifically, in this embodiment, step S40 specifically includes:
step S41, mixing the first filtrate and the second filtrate to obtain a mixed solution;
s42, after the volume ratio of ethanol in the mixed solution is adjusted to 90-95%, normal pressure crystallization is carried out, and then precipitates formed in the mixed solution are separated;
and step S43, washing the precipitate with absolute ethyl alcohol and drying to obtain a finished product of histidine.
In this example, the manner of further extracting the histidine component remaining in the second filtrate was: crystallizing and separating out histidine component at 90-95% ethanol concentration, separating out crystallized product, cleaning and drying. Because the first filtrate is an ethanol solution, in order to reduce the additional addition of absolute ethanol, the first filtrate and the second filtrate are mixed, the ethanol volume concentration of the mixed solution is adjusted to 90-95%, then the temperature is raised to 40-50 ℃ under normal pressure, histidine components remained in the mixed solution are crystallized and separated out, then crystals are separated out by adopting a filtration or centrifugation mode, finally, the crystals are cleaned by using absolute ethanol and dried until no residual solvent exists, and then the histidine finished product is obtained by further extraction, wherein the yield of the histidine finished product extracted in the step is 5-10%. Therefore, the final yield of the histidine finished product is the sum of the yield of the histidine finished product obtained in the step S30 and the yield of the histidine finished product obtained in the step S40, and can reach 95-97%, so that the yield of the histidine finished product is improved, and unnecessary loss of the histidine finished product in the purification process is avoided.
It should be noted that, in the embodiment provided by the present invention, after the first filtrate is obtained through step S10 and the second filtrate is obtained through step S20, the sequence of step S30 and step S40 is not limited, and may be before step S30 and after step S40, or before step S40 and after step S30, or synchronously perform step S30 and step S40, which may all be used as embodiments of the method for purifying a finished histidine product provided by the present invention. In addition, the filtrate discarded after the atmospheric pressure crystallization in the step S42 and the cleaning solution after the product cleaning in the steps S30 and S43 contain a large amount of ethanol, and the ethanol in the filtrate can be extracted by rectification and the like and recovered for reuse.
The invention also provides a finished histidine product which is prepared by the method for purifying the finished histidine product. The purified histidine finished product obtained by the embodiment provided by the invention basically does not contain histamine components, so that the side effect of the histidine finished product when being used as a medicinal effective component is greatly reduced.
The invention further provides a pharmaceutical product which comprises the finished histidine product as described above. The purified histidine finished product obtained by the method does not contain histamine basically, so that the method can be applied to various drug finished products which take histidine as a basic raw material in the field of medicine, such as targeted drugs or carriers thereof, amino acid injection and the like. As a preferred embodiment of the pharmaceutical product, the pharmaceutical product comprises 15AA (compound amino acid injection), and the 15AA prepared by the purified histidine finished product does not have side effects such as blood pressure reduction and the like in the application process, so that the use safety is higher.
The technical solutions of the present invention are further described in detail below with reference to specific examples and drawings, it should be understood that the following examples are merely illustrative of the present invention and are not intended to limit the present invention.
Example 1
(1) Adding a purchased histidine finished product into absolute ethyl alcohol according to the feed liquid mass ratio of 20g of solid material added into each liter of absolute ethyl alcohol, fully mixing, and filtering to obtain a solid material and a first filtrate;
(2) dissolving solid materials into water according to the feed liquid mass ratio of 45g of solid materials added into each liter of water, then carrying out reduced pressure crystallization under the conditions of a vacuum degree of 0.05-0.07 MPa and a temperature of 50-55 ℃ until the volume of the solution is reduced to 1/8 of the original volume, and filtering again to obtain a crystallized solid and a second filtrate;
(3) and washing the obtained crystalline solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product.
Example 2
(1) Adding a purchased histidine finished product into absolute ethyl alcohol according to the feed liquid mass ratio of 10g of solid material added into each liter of absolute ethyl alcohol, fully mixing, and filtering to obtain a solid material and a first filtrate;
(2) dissolving solid materials into water according to the feed liquid mass ratio of 40g of solid materials added into each liter of water, then carrying out reduced pressure crystallization under the conditions of a vacuum degree of 0.03-0.05 MPa and a temperature of 50-55 ℃ until the volume of the solution is reduced to 1/6 of the original volume, and filtering again to obtain a crystallized solid and a second filtrate;
(3) and washing the obtained crystalline solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product.
Example 3
(1) Adding a purchased histidine finished product into absolute ethyl alcohol according to the feed liquid mass ratio of 30g of solid material added into each liter of absolute ethyl alcohol, fully mixing, and filtering to obtain a solid material and a first filtrate;
(2) dissolving solid materials into water according to the feed liquid mass ratio of 50g of solid materials added into each liter of water, then carrying out reduced pressure crystallization under the conditions of a vacuum degree of 0.03-0.05 MPa and a temperature of 40-45 ℃ until the volume of the solution is reduced to 1/10 of the original volume, and filtering again to obtain a crystallized solid and a second filtrate;
(3) and washing the obtained crystalline solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product.
Example 4
(1) Adding a purchased histidine finished product into absolute ethyl alcohol according to the feed liquid mass ratio of adding 15g of solid material into each liter of absolute ethyl alcohol, fully mixing, and filtering to obtain a solid material and a first filtrate;
(2) dissolving the solid materials into water according to the feed liquid mass ratio of adding 42g of the solid materials into each liter of water, then carrying out reduced pressure crystallization under the conditions of a vacuum degree of 0.03-0.05 MPa and a temperature of 40-45 ℃ until the volume of the solution is reduced to 1/7 of the original volume, and filtering again to obtain a crystallized solid and a second filtrate;
(3) and washing the obtained crystalline solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product A.
(4) And mixing the obtained first filtrate and second filtrate, adjusting the volume concentration of ethanol in the mixed solution to 90-95%, crystallizing at the normal temperature of 44-46 ℃, separating out precipitates formed in the mixed solution, washing the precipitates by using absolute ethyl alcohol, and drying to obtain a histidine finished product B.
Example 5
(1) Adding 25g of solid material into each liter of absolute ethyl alcohol according to the feed liquid mass ratio, putting the purchased histidine finished product into the absolute ethyl alcohol, fully mixing, and filtering to obtain a solid material and a first filtrate;
(2) dissolving solid materials into water according to the feed liquid mass ratio of 48g of solid materials added into each liter of water, then carrying out reduced pressure crystallization under the conditions of the vacuum degree of 0.03-0.05 MPa and the temperature of 40-45 ℃ until the volume of the solution is reduced to 1/9 of the original volume, and filtering again to obtain a crystallized solid and a second filtrate;
(3) and washing the obtained crystalline solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product A.
(4) And mixing the obtained first filtrate and second filtrate, adjusting the volume concentration of ethanol in the mixed solution to 90-95%, crystallizing at normal temperature at 40-42 ℃, separating out precipitates formed in the mixed solution, washing the precipitates by using absolute ethyl alcohol, and drying to obtain a histidine finished product B.
Example 6
(1) Adding a purchased histidine finished product into absolute ethyl alcohol according to the feed liquid mass ratio of 20g of solid material added into each liter of absolute ethyl alcohol, fully mixing, and filtering to obtain a solid material and a first filtrate;
(2) dissolving solid materials into water according to the feed liquid mass ratio of 45g of solid materials added into each liter of water, then carrying out reduced pressure crystallization under the conditions of a vacuum degree of 0.03-0.05 MPa and a temperature of 40-45 ℃ until the volume of the solution is reduced to 1/8 of the original volume, and filtering again to obtain a crystallized solid and a second filtrate;
(3) and washing the obtained crystalline solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product A.
(4) And mixing the obtained first filtrate and second filtrate, adjusting the volume concentration of ethanol in the mixed solution to 90-95%, crystallizing at the normal temperature of 48-50 ℃, separating out a precipitate formed in the mixed solution, washing the precipitate with absolute ethanol, and drying to obtain a histidine finished product B.
The final histidine products obtained in examples 1 to 6 were weighed, and the yield of histidine was calculated, and the results are shown in table 1 below.
TABLE 1 yield of histidine product from each example
| Yield of the product | ||
| Example 1 | Histidine finished product | 80％ |
| Example 2 | Histidine finished product | 85％ |
| Example 3 | Histidine finished product | 87％ |
| Example 4 | Histidine product A | 90％ |
| Histidine product B | 5％ | |
| Total amount of histidine | 95％ | |
| Example 5 | Histidine product A | 91％ |
| Histidine product B | 6％ | |
| Total amount of histidine | 97％ | |
| Example 6 | Histidine product A | 89％ |
| Histidine product B | 7％ | |
| Total amount of histidine | 96％ |
Using the histidine finished products prepared in the above examples 1 to 6 as raw materials and using the purchased unpurified histidine finished product as a comparative example, 15AA (compound amino acid injection) was prepared, wherein the formula of the 15AA was as follows: 8.0g/L of L-proline, 5.0g/L of L-serine, 7.7g/L of L-alanine, 6.0g/L of L-arginine, 2.4g/L of L-histidine, 0.66g/L of L-tryptophan, 8.4g/L of L-valine, 4.5g/L of L-threonine, 11.0g/L of L-leucine, 1.0g/L of L-methionine, 9.0g/L of L-isoleucine, 8.6g/L of L-lysine, 1.0g/L of L-phenylalanine, 0.2g/L of cysteine and 9.0g/L of glycine. The blood pressure was monitored using the carotid artery of the cat, and the monitoring results are shown in table 2 below.
TABLE 2 Cat carotid blood pressure monitoring results
As can be seen from the results in tables 1 and 2, when the histidine finished product purified by the method of the embodiment of the present invention is used as a raw material of a compound amino acid injection, no side effects such as blood pressure drop will occur, which indicates that the method provided by the embodiment of the present invention effectively reduces the histamine by-product in the histidine finished product, thereby reducing the side effects of the histidine finished product as an active pharmaceutical ingredient. In addition, the histidine finished product yield is higher by purifying histidine through the method provided by the embodiment of the invention, wherein the yield can reach 80-91% when only one purification extraction is carried out in the embodiments 1-3, and the yield can reach 95-97% when two extractions are carried out in the embodiments 4-6, so that the recovery rate of the histidine finished product is further improved.
The above is only a preferred embodiment of the present invention, and it is not intended to limit the scope of the invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention shall be included in the scope of the present invention.
Claims (9)
1. A method for purifying a finished histidine product, comprising the steps of:
s10, mixing the histidine finished product to be purified with absolute ethyl alcohol, and then carrying out solid-liquid separation to obtain a solid substance and a first filtrate;
s20, dissolving the solid substance in water for decompression crystallization to obtain a crystallized solid and a second filtrate;
and S30, washing the crystallized solid by using absolute ethyl alcohol, and drying to obtain a purified histidine finished product.
2. The method for purifying a finished histidine according to claim 1, further comprising, after step S20:
s41, mixing the first filtrate and the second filtrate to obtain a mixed solution;
s42, after the volume ratio of ethanol in the mixed solution is adjusted to 90-95%, carrying out normal pressure crystallization, and then separating and collecting precipitates formed in the mixed solution;
and S43, washing the precipitate with absolute ethyl alcohol, and drying to obtain a histidine finished product.
3. The method for purifying a finished histidine according to claim 2, wherein in step S42: the temperature during normal pressure crystallization is 40-50 ℃.
4. The method for purifying a finished histidine according to claim 1, wherein in step S10: the volume ratio of the mass of the finished histidine product to be purified to absolute ethyl alcohol is (10-30) g: 1L of the compound.
5. The method for purifying a finished histidine according to claim 1, wherein in step S20: the mass of the solid matter to volume of water is (40-50) g: 1L of the compound.
6. The method for purifying a finished histidine according to claim 1, wherein in step S20: the vacuum degree during the reduced pressure crystallization is 0.02-0.07 MPa, and the temperature is 40-55 ℃.
7. A finished histidine product obtained by the method for purifying a finished histidine product according to any one of claims 1 to 6.
8. A pharmaceutical product comprising the histidine tag of claim 7.
9. The pharmaceutical product of claim 8, wherein the pharmaceutical product comprises a compound amino acid injection.
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| CN114133354A (en) * | 2021-12-10 | 2022-03-04 | 河北一品生物医药有限公司 | Industrial preparation method of L-histidine |
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| CN114133354B (en) * | 2021-12-10 | 2023-08-29 | 河北一品生物医药有限公司 | Industrial preparation method of L-histidine |
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