CN112300166A - Method for separating acyclovir and sodium acetate from mother liquor - Google Patents
Method for separating acyclovir and sodium acetate from mother liquor Download PDFInfo
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- CN112300166A CN112300166A CN202011067623.2A CN202011067623A CN112300166A CN 112300166 A CN112300166 A CN 112300166A CN 202011067623 A CN202011067623 A CN 202011067623A CN 112300166 A CN112300166 A CN 112300166A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
- C07C51/44—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation by distillation
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Abstract
The invention discloses a method for separating acyclovir and sodium acetate from mother liquor, which comprises the following steps: s1, pretreatment: concentrating the mother liquor at a temperature of below 80 ℃ under reduced pressure to 18-26 Be, cooling, adding sodium hydroxide after cooling, and adjusting the pH value to 9-14; s2, separating sodium acetate: cooling, crystallizing, throwing and filtering the mother liquor treated in the step S1 for multiple times, separating sodium acetate trihydrate under an alkaline condition, and controlling the desalting end point crystallization temperature to be 18-24 ℃; s3, separating acyclovir: and (4) adjusting the pH value of the filtrate subjected to the desalting in the step (S2) to 3-7, cooling to 0-10 ℃, crystallizing, performing filter-spinning, and separating acyclovir. The method provided by the invention can separate the acyclovir and the sodium acetate from the mother liquor through the separation method, not only can greatly reduce the subsequent treatment difficulty, but also can recover the acyclovir and the sodium acetate for reuse, and greatly reduces the cost.
Description
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to a method for separating acyclovir and sodium acetate from mother liquor.
Background
Acyclovir is a chemically synthesized broad-spectrum antiviral drug. Currently, there are two main chemical synthesis processes. The first is the process of sodium salt method of acyclovir, and the second is the process of alkali hydrolysis method of acyclovir.
The acyclovir sodium salt method adopts the following synthetic route:
the acyclovir alkaline hydrolysis process adopts the following synthetic route:
the crystal mother liquor obtained in the process of converting the sodium acyclovir salt obtained by the sodium acyclovir salt method process into the acyclovir through acetic acid neutralization in the water solution contains the acyclovir and sodium acetate. The process of the acyclovir base hydrolysis method comprises the following steps: the diacetylacyclovir is hydrolyzed in a sodium hydroxide solution to be converted into acyclovir, the reaction by-product is sodium acetate, meanwhile, the sodium hydroxide in the alkaline hydrolysis reaction ratio is excessive, the alkaline hydrolysis reaction is finished, the excessive sodium hydroxide is neutralized by acetic acid in the process, sodium acetate is further generated, and the crystal mother liquor in the production process also contains acyclovir and sodium acetate. Through the detection of the inventor, mother liquor generated by the two processes contains acyclovir with the mass fraction of 0.05-0.10% and sodium acetate with the mass fraction of 1.0-3.0%, and contains more than 20000mg COD/L.
At present, the mother liquor can be directly treated according to waste water, the treatment process is complex, the treatment cost is high, and the expansion of the production scale of acyclovir is severely restricted.
Disclosure of Invention
The invention provides a method for separating acyclovir and sodium acetate from mother liquor, aiming at least one technical problem in the prior art, the acyclovir and the sodium acetate can be separated from the mother liquor through the separation method, the difficulty of subsequent treatment can be greatly reduced, the acyclovir and the sodium acetate can be recovered and reused, and the cost is greatly reduced.
In order to solve the problems, the technical scheme of the invention is as follows:
a method for separating acyclovir and sodium acetate from mother liquor comprises the following steps:
s1, pretreatment: concentrating the mother liquor at a temperature of below 80 ℃ under reduced pressure to 18-26 Be, cooling, adding sodium hydroxide after cooling, and adjusting the pH value to 9-14;
s2, separating sodium acetate: cooling, crystallizing, throwing and filtering the mother liquor treated in the step S1 for multiple times, separating sodium acetate trihydrate under an alkaline condition, and controlling the desalting end point crystallization temperature to be 18-24 ℃;
s3, separating acyclovir: and (4) adjusting the pH value of the filtrate subjected to the desalting in the step (S2) to 3-7, cooling to 0-10 ℃, crystallizing, performing filter-spinning, and separating acyclovir.
Further, in step S1, 1.3 to 2.8g of sodium hydroxide is added per 1L of the concentrated solution.
Further, in the step S1, the temperature is reduced to 45-60 ℃.
Further, in the step S2, the temperature is reduced for crystallization and the filtration is carried out for 2-4 times.
Further, in step S3, the pH is adjusted with acetic acid.
Further, in step S3, the filtrate from which acyclovir was separated is applied to step S1 for recycling.
Further, after step S3, an operation step of refining the separated acyclovir is further included.
Preferably, the acyclovir refining method comprises the following steps: and (4) dissolving the acyclovir separated in the step (S3) by using water as a solvent, and adding activated carbon for decoloring to finally prepare a pure acyclovir product.
Preferably, the mass ratio of acyclovir, water and activated carbon in the refining process is 1: 18: 0.05.
preferably, the decoloring temperature is controlled to be 90-100 ℃.
The invention has the beneficial effects that: according to the invention, the acyclovir mother liquor is subjected to reduced pressure distillation treatment, inorganic salt and acyclovir are removed from final distilled condensate water, COD is reduced to below 10%, the wastewater treatment is simple, Fenton treatment is not required, and the wastewater treatment cost is reduced; about 400kg of qualified sodium acetate trihydrate product can be produced from every 2000L of concentrated mother liquor, and about 20kg of acyclovir is recovered, so that higher economic value can be created; the final treated mother liquor is recycled, no new pollution is caused, and remarkable social and economic benefits are achieved.
Detailed Description
The principles and features of this invention are described below in conjunction with examples which are set forth to illustrate, but are not to be construed to limit the scope of the invention.
The method for separating acyclovir and sodium acetate from mother liquor comprises the following steps:
s1, pretreatment: concentrating the mother liquor at a temperature of below 80 ℃ under reduced pressure to 18-26 Be, cooling, adding sodium hydroxide after cooling, and adjusting the pH value to 9-14;
s2, separating sodium acetate: cooling, crystallizing, throwing and filtering the mother liquor treated in the step S1 for multiple times, separating sodium acetate trihydrate under an alkaline condition, and controlling the desalting end point crystallization temperature to be 18-24 ℃;
s3, separating acyclovir: and (4) adjusting the pH value of the filtrate subjected to the desalting in the step (S2) to 3-7, cooling to 0-10 ℃, crystallizing, performing filter-spinning, and separating acyclovir.
Before the method, acyclovir synthesis mother liquor is directly discharged after sewage treatment. The prior art found at present improves the yield and purity of acyclovir through process improvement, so as to reduce the content of pollutants in acyclovir synthesis mother liquor and reduce the difficulty of sewage treatment. However, the improvement direction has little effect at present, and acyclovir and sodium acetate still remain in the acyclovir synthesis mother liquor, so that the mother liquor contains COD of over 20000 mg/L.
After the research of the inventor, the content of acyclovir in the mother liquor is higher when the acyclovir is synthesized by the prior art, and the inventor finds that the residual acyclovir can be separated and purified by a convenient means through experiments. The inventor tests show that after the acyclovir mother liquor is subjected to reduced pressure distillation and concentration, about 20kg of acyclovir pure product can be separated from every 2000L of concentrated mother liquor, so that the recovered acyclovir pure product has considerable economic benefit, the difficulty of sewage treatment on the mother liquor in the follow-up process can be greatly reduced, and the method has high value. Therefore, the inventor firstly proposes that the acyclovir mother liquor can be separated, the residual acyclovir and sodium acetate are recycled, the problem of environmental pollution is solved, and the economic benefit can be greatly improved. Therefore, the invention solves the technical problem of how to efficiently, conveniently and quickly process the acyclovir synthesis mother liquor at low cost, which is always needed to be solved in the field but is not solved.
The inventor designs the process of the invention by the physicochemical characteristics that the solubility of sodium acetate and acyclovir in an aqueous solution is different along with the change of pH value. The change of the pH value and the solubility of the sodium acetate is small; the solubility of acyclovir changes remarkably with the change of pH value, the solubility is improved with the increase of pH value, the solubility is reduced with the decrease of pH value, and the solubility is remarkably reduced when the pH value is less than or equal to 7. The obvious difference of the physicochemical characteristics of the sodium acetate and the acyclovir in the water solution creates conditions for separating the sodium acetate and the acyclovir in the water solution with high purity.
According to the invention, the mother liquor is pretreated by reduced pressure distillation and concentration, and then the temperature is reduced under an alkaline condition for crystallization and separation of sodium acetate.
Through the test and determination of the inventor, about 400kg of sodium acetate trihydrate can be separated from every 2000L of concentrated mother liquor, and the benefit is considerable.
For the separation of acyclovir, the method adopts the acid condition to reduce the temperature for crystallization, the separation efficiency is also higher, 30-40 kg of acyclovir can be separated from every 2000L of concentrated mother liquor, and the benefit is also considerable.
The invention aims to separate acyclovir and sodium acetate and reduce the difficulty of subsequent sewage treatment. The inventor surprisingly finds that the sodium acetate trihydrate obtained by temperature reduction, crystallization and filtration has extremely high purity, can completely compound the sodium acetate trihydrate standard specified by GB/T693-1996 national standard, and can be directly collected and reused. Unexpected effects are generated, subsequent treatment processes such as purification and the like are directly avoided, the resource utilization cost is greatly reduced, and the resource utilization efficiency is greatly improved. The inventor conjectures that the crystallization speed and the crystallinity of the sodium acetate can be controlled by adopting a fractional crystallization mode under the alkaline condition, so that the crystallization of the acyclovir is effectively prevented, the phenomena of mixed crystallization and crystal coating are avoided, and the purity of the obtained sodium acetate trihydrate is effectively ensured. The inventor also speculates that the purity of the separated sodium acetate trihydrate is ensured by adopting multiple temperature-reducing crystallization and filtration, controlling the pH value to be 9-14, accurately controlling the final crystallization temperature to be 18-24 ℃, and preventing other impurity components in the acyclovir and the mother liquor from crystallizing and separating out under the conditions.
In a more preferred embodiment of the present invention, in the step S1, 1.3 to 2.8g of sodium hydroxide is added per 1L of the concentrated solution.
By adopting the addition amount, the using amount of the sodium hydroxide can be accurately controlled, and the using amount of the sodium hydroxide can be saved as far as possible on the premise of ensuring that the pH value is adjusted to be optimal, so that the cost is reduced.
In a more preferred embodiment of the present invention, in the step S1, the temperature is decreased to 45 to 60 ℃.
The mother liquor is subjected to concentration pretreatment and then is subjected to cooling treatment, and on the one hand, safety accidents caused by that the solution is subjected to bumping when sodium hydroxide is subsequently added due to overhigh temperature are avoided; on the other hand, the temperature is controlled in advance for the subsequent temperature reduction crystallization. The inventor finds that the purity of the sodium acetate trihydrate is higher when the temperature is controlled to be 45-60 ℃ in advance and the sodium acetate is separated subsequently after repeated tests. The inventor speculates that other impurities in the mother liquor can not be separated out in the process of adjusting the pH value at the temperature, and the temperature reduction range can be controlled in a small range when sodium acetate is separated by subsequent temperature reduction crystallization, so that the impurities are further prevented from being separated out due to large temperature change.
In a preferred embodiment of the present invention, in the step S2, the temperature reduction crystallization and the filtration are performed for 2 to 4 times.
And the temperature reduction crystallization is carried out for multiple times, so that the temperature reduction amplitude at each time can be further controlled, and the purity of the obtained sodium acetate trihydrate is further improved. The inventor is tested and researched, the method is reasonable for 2-4 times, the purity can be guaranteed, and the removal rate of sodium acetate can be guaranteed. This embodiment may work in synergy with the control of the cooling temperature in step S1.
In a more preferred embodiment of the present invention, in step S3, acetic acid is used to adjust the pH.
In a more preferred embodiment of the present invention, in step S3, the filtrate from which acyclovir is separated is applied to step S1 for recycling.
Acetic acid is adopted to adjust the pH value, so that the acetic acid and sodium hydroxide can form reaction to generate sodium acetate, and new impurities are prevented from being introduced. And the filtrate after the acyclovir is separated is applied to the step S1 for circular treatment, so that the effective utilization rate of resources can be improved. The technical characteristics are cooperated, so that the sewage finally discharged by the invention is only the concentrated distilled water of the mother liquor, and the generation of new sewage is avoided.
In a preferred embodiment of the present invention, after step S3, an operation step of refining the separated acyclovir is further included.
Preferably, the acyclovir refining method comprises the following steps: and (4) dissolving the acyclovir separated in the step (S3) by using water as a solvent, and adding activated carbon for decoloring to finally prepare a pure acyclovir product.
Preferably, the mass ratio of acyclovir, water and activated carbon in the refining process is 1: 18: 0.05.
preferably, the decoloring temperature is controlled to be 90-100 ℃.
The inventor tests that the purity of the acyclovir separated by the method is about 96 percent, the impurity content of the acyclovir is high after the acyclovir is directly recycled, the acyclovir serving as a raw material medicine is not high in quality, and the economic value is limited. After decoloration and refining, the purity of the acyclovir can exceed the drug-grade purity, the impurity content can be controlled within the drug quality control limit, the acyclovir belongs to a high-purity high-quality raw material drug, and the economic value can be greatly improved.
The key point of the invention is that sodium hydroxide and acetic acid are used as pH regulators, a process route of circular treatment is adopted, the acyclovir synthesis mother liquor is distilled and concentrated, then the sodium acetate is separated by alkaline cooling crystallization, and the acyclovir is separated by acidic cooling crystallization, so that the finally discharged sewage contains less than 2000 COD2000mg/L, and simultaneously, high-quality sodium acetate trihydrate and acyclovir with considerable magnitude can be recovered. The optimal effect of the invention is the result of the synergistic effect of the above technical characteristics.
The following are specific examples of the present invention.
Example 1
Firstly, inputting acyclovir refined mother liquor into a triple-effect evaporator, controlling the temperature below 80 ℃ to reduce pressure and concentrate, and accumulating continuous feeding to about 40m3The volume of the acyclovir refined mother liquor is concentrated to about 2000L to reach 19 Be; then inputting into an enamel kettle, controlling the temperature below 80 ℃, concentrating under reduced pressure to 23Be, cooling to 45 ℃, adding 3kg of sodium hydroxide, and adjusting the pH value to 12.
Secondly, cooling the pretreated mother liquor to 40 ℃, and performing filter spinning to obtain 264kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 32 ℃ for the second time, and performing filter throwing to obtain 87kg of sodium acetate trihydrate; and (4) inputting the filtrate into an enamel kettle, cooling to 22 ℃ for the third time, and performing filter spinning to obtain 52kg of sodium acetate trihydrate.
And then, inputting the filtrate subjected to the three-time desalting into an enamel kettle, adding 6L of glacial acetic acid to adjust the pH value to 4, cooling to 8 ℃, and performing filter-spinning to obtain 43kg of acyclovir recovered matter, wherein the purity of the acyclovir reaches 96.3% by using a high performance liquid chromatograph.
And finally, refining the acyclovir recovered substance by using purified water and activated carbon to obtain a pure acyclovir product.
The total amount of the sodium acetate trihydrate obtained in the embodiment is 403kg, and the detection result shows that the sodium acetate trihydrate meets the GB/T693-1996 quality standard. 27.2kg of acyclovir pure product is finally prepared in the embodiment, and the purity of the acyclovir is detected by a high performance liquid chromatograph to meet the requirement of high-quality medicine grade purity.
Example 2
Firstly, inputting acyclovir refined mother liquor into a triple-effect evaporator, controlling the temperature below 80 ℃ to reduce pressure and concentrate, and accumulating continuous feeding to about 40m3The volume of the acyclovir refined mother liquor is concentrated to about 2000L to reach 18 Be; then inputting into an enamel kettle, controlling the temperature below 80 ℃, concentrating under reduced pressure to 24Be, cooling to 45 ℃, adding 4kg of sodium hydroxide, and adjusting the pH value to 13.
Secondly, cooling the pretreated mother liquor to 40 ℃, and performing filter spinning to obtain 244kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 32 ℃ for the second time, and performing filter throwing to obtain 86kg of sodium acetate trihydrate; and (4) inputting the filtrate into an enamel kettle, cooling to 18 ℃ for the third time, and performing filter spinning to obtain 52kg of sodium acetate trihydrate.
And then, inputting the filtrate subjected to the three-time desalting into an enamel kettle, adding 5.5L of glacial acetic acid to adjust the pH value to 5, cooling to 4 ℃, and performing filter-spinning to obtain 41kg of acyclovir recovered matter, wherein the purity of the acyclovir reaches 95.8% by using a high performance liquid chromatograph.
And finally, refining the acyclovir recovered substance by using purified water and activated carbon to obtain a pure acyclovir product.
The total mass of the sodium acetate trihydrate obtained in the embodiment is 382kg, and the detection result shows that the sodium acetate trihydrate meets the GB/T693-1996 quality standard. In this example, 26.7kg of acyclovir pure product is finally prepared, and the purity of acyclovir detected by a high performance liquid chromatograph meets the requirement of high quality pharmaceutical grade purity.
Example 3
Firstly, inputting acyclovir refined mother liquor into a triple-effect evaporator, controlling the temperature below 80 ℃ to reduce pressure and concentrate, and accumulating continuous feeding to about 40m3The volume of the acyclovir refined mother liquor is concentrated to about 2000L to reach 16 Be; then inputting into an enamel kettle, controlling the temperature below 80 ℃, concentrating under reduced pressure to 23Be, cooling to 45 ℃, adding 2kg of sodium hydroxide, and adjusting the pH value to 11.
Secondly, cooling the pretreated mother liquor to 42 ℃, and performing filter spinning to obtain 238kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 30 ℃ for the second time, and performing filter throwing to obtain 91kg of sodium acetate trihydrate; and (4) inputting the filtrate into an enamel kettle, cooling to 22 ℃ for the third time, and performing filter spinning to obtain 47kg of sodium acetate trihydrate.
And then, inputting the filtrate subjected to the three-time desalting into an enamel kettle, adding 6L of glacial acetic acid to adjust the pH value to 5.5, cooling to 2 ℃, and performing filter-spinning to obtain 47kg of acyclovir recovered matter, wherein the purity of acyclovir reaches 96.7% by using a high performance liquid chromatograph.
And finally, refining the acyclovir recovered substance by using purified water and activated carbon to obtain a pure acyclovir product.
The total amount of the sodium acetate trihydrate obtained in the embodiment is 376kg, and the detection proves that the sodium acetate trihydrate meets the GB/T693-1996 quality standard. In this example, 28.6kg of acyclovir pure product is finally prepared, and the purity of acyclovir detected by a high performance liquid chromatograph meets the requirement of high quality pharmaceutical grade purity.
Example 4
Firstly, inputting acyclovir refined mother liquor into a triple-effect evaporator, controlling the temperature below 80 ℃ to reduce pressure and concentrate, and accumulating continuous feeding to about 40m3The volume of the acyclovir refined mother liquor is concentrated to about 2000L to reach 18Be, the temperature is reduced to 60 ℃, 1.3kg of sodium hydroxide is added, and the pH value is adjusted to 9.
Secondly, cooling the pretreated mother liquor to 52 ℃, and performing filter spinning to obtain 146kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 44 ℃ for the second time, and performing filter throwing to obtain 122kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 34 ℃ for the third time, and performing filter spinning to obtain 77kg of sodium acetate trihydrate; and (4) inputting the filtrate into an enamel kettle, cooling to 24 ℃ for the fourth time, and performing filter spinning to obtain 46kg of sodium acetate trihydrate.
And then, inputting the filtrate subjected to four-time desalting into an enamel kettle, adding 6.5L of glacial acetic acid to adjust the pH value to 3, cooling to 2 ℃, and performing filtration to obtain 42kg of acyclovir recovered matter, wherein the purity of the acyclovir reaches 96.2% by using a high performance liquid chromatograph.
And finally, refining the acyclovir recovered substance by using purified water and activated carbon to obtain a pure acyclovir product.
The total amount of the sodium acetate trihydrate 391kg obtained in the embodiment meets the GB/T693-1996 quality standard through detection. In this example, 23.7kg of acyclovir pure product is finally prepared, and the purity of acyclovir detected by a high performance liquid chromatograph meets the requirement of high quality pharmaceutical grade purity.
Example 5
Firstly, inputting acyclovir refined mother liquor into a triple-effect evaporator, controlling the temperature below 80 ℃ to reduce pressure and concentrate, and accumulating continuous feeding to about 40m3The volume of the acyclovir refined mother liquor is concentrated to about 2000L to reach 26Be, the temperature is reduced to 50 ℃, 2.8kg of sodium hydroxide is added, and the pH value is adjusted to 14.
Secondly, cooling the pretreated mother liquor to 44 ℃, and performing filter spinning to obtain 133kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 38 ℃ for the second time, and performing filter throwing to obtain 137kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 30 ℃ for the third time, and performing filter spinning to obtain 92kg of sodium acetate trihydrate; and (4) inputting the filtrate into an enamel kettle, cooling to 22 ℃ for the fourth time, and performing filter spinning to obtain 43kg of sodium acetate trihydrate.
And then, inputting the filtrate subjected to four-time desalting into an enamel kettle, adding 4.8L of glacial acetic acid to adjust the pH value to 7, cooling to 0 ℃, and performing filtration to obtain 46kg of acyclovir recovered matter, wherein the purity of the acyclovir reaches 96.8% by using a high performance liquid chromatograph.
And finally, refining the acyclovir recovered substance by using purified water and activated carbon to obtain a pure acyclovir product.
The total amount of the sodium acetate trihydrate obtained in the embodiment is 405kg, and the detection result shows that the sodium acetate trihydrate meets the GB/T693-1996 quality standard. 25.9kg of acyclovir pure product is finally prepared in the embodiment, and the purity of the acyclovir is detected by a high performance liquid chromatograph to meet the requirement of high-quality medicine grade purity.
Example 6
Firstly, inputting acyclovir refined mother liquor into a triple-effect evaporator, controlling the temperature below 80 ℃ to reduce pressure and concentrate, and accumulating continuous feeding to about 40m3The volume of the acyclovir refined mother liquor is concentrated to about 2000L to reach 20Be, the temperature is reduced to 55 ℃, 1.8kg of sodium hydroxide is added, and the pH value is adjusted to 12.
Secondly, cooling the pretreated mother liquor to 50 ℃, and performing filter spinning to obtain 141kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 40 ℃ for the second time, and performing filter throwing to obtain 114kg of sodium acetate trihydrate; inputting the filtrate into an enamel kettle, cooling to 30 ℃ for the third time, and performing filter throwing to obtain 67kg of sodium acetate trihydrate; and (4) inputting the filtrate into an enamel kettle, cooling to 20 ℃ for the fourth time, and performing filter spinning to obtain 38kg of sodium acetate trihydrate.
And then, inputting the filtrate subjected to four-time desalting into an enamel kettle, adding 5.4L of glacial acetic acid to adjust the pH value to 5, cooling to 6 ℃, and performing filtration to obtain 44kg of acyclovir recovered matter, wherein the purity of the acyclovir reaches 96.3% by using a high performance liquid chromatograph.
And finally, refining the acyclovir recovered substance by using purified water and activated carbon to obtain a pure acyclovir product.
The total weight of the sodium acetate trihydrate obtained in the embodiment is 370kg, and the detection result shows that the sodium acetate trihydrate meets the GB/T693-1996 quality standard. In this example, 24.9kg of acyclovir pure product is finally prepared, and the purity of acyclovir detected by a high performance liquid chromatograph meets the requirement of high quality pharmaceutical grade purity.
The invention takes the prior treatment process for directly treating the mother liquor in sewage treatment as a comparative example, and compares the treatment process with the treatment processes of examples 1 to 6.
Adopts the prior mode of directly treating the mother liquor by sewage treatment, 40m3The processing cost of the acyclovir refined mother liquor is 4301.6 yuan. The mother liquor is treated by the treatment process of the embodiment 1-6 of the invention, and the treatment process is 40m3The processing cost of the acyclovir refined mother liquor distillate is 7050.8 yuan on average; the average 387.8kg of sodium acetate trihydrate can be recovered by recycling, and the covalent value is 930.72 yuan calculated according to the current market price; the average 26.1kg of high-quality acyclovir pure products can be recovered by recycling, and the covalent value is 9135 yuan calculated according to the current market price. Through calculation, the method for treating the acyclovir synthesis mother liquor by the treatment process provided by the invention has the advantage that 40m3The cost of (2) is 7500.8 yuan, which saves 6866.52 yuan compared with the prior art.
Taking pharmaceutical enterprises with annual yield of 500 tons of acyclovir as examples, the acyclovir synthetic mother liquor is produced by 10000m in total every year3The invention can save 3433260 yuan cost, with remarkable economic benefit.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (10)
1. A method for separating acyclovir and sodium acetate from mother liquor is characterized by comprising the following steps:
s1, pretreatment: concentrating the mother liquor at a temperature of below 80 ℃ under reduced pressure to 18-26 Be, cooling, adding sodium hydroxide after cooling, and adjusting the pH value to 9-14;
s2, separating sodium acetate: cooling, crystallizing, throwing and filtering the mother liquor treated in the step S1 for multiple times, separating sodium acetate trihydrate under an alkaline condition, and controlling the desalting end point crystallization temperature to be 18-24 ℃;
s3, separating acyclovir: and (4) adjusting the pH value of the filtrate subjected to the desalting in the step (S2) to 3-7, cooling to 0-10 ℃, crystallizing, performing filter-spinning, and separating acyclovir.
2. The method for separating acyclovir and sodium acetate from mother liquor according to claim 1, wherein in step S1, 1.3-2.8 g of sodium hydroxide is added per 1L of the concentrated solution.
3. The method for separating acyclovir and sodium acetate from mother liquor as claimed in claim 1, wherein in step S1, the temperature is reduced to 45-60 ℃.
4. The method for separating acyclovir and sodium acetate from mother liquor as claimed in claim 1, wherein in step S2, the temperature-reducing crystallization is performed by filtration in 2-4 times.
5. The method for separating acyclovir and sodium acetate from mother liquor as claimed in claim 1, wherein the pH value is adjusted by acetic acid in step S3.
6. The method for separating acyclovir and sodium acetate from mother liquor as claimed in claim 1, wherein in step S3, the filtrate after the separation of acyclovir is applied to step S1 for recycling.
7. The method for separating acyclovir and sodium acetate from mother liquor as claimed in claim 1, wherein after the step S3, the method further comprises a step of refining the separated acyclovir.
8. The method for separating acyclovir and sodium acetate from mother liquor as claimed in claim 6, wherein the purification of acyclovir comprises the following steps: and (4) dissolving the acyclovir separated in the step (S3) by using water as a solvent, and adding activated carbon for decoloring to finally prepare a pure acyclovir product.
9. The method for separating acyclovir and sodium acetate from mother liquor as claimed in claim 7, wherein the mass ratio of acyclovir, water and activated carbon in the refining process is 1: 18: 0.05.
10. the method for separating acyclovir and sodium acetate from mother liquor as claimed in claim 7, wherein the decolorizing temperature is controlled at 90-100 ℃.
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| CN202011067623.2A CN112300166A (en) | 2020-10-06 | 2020-10-06 | Method for separating acyclovir and sodium acetate from mother liquor |
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| CN202011067623.2A CN112300166A (en) | 2020-10-06 | 2020-10-06 | Method for separating acyclovir and sodium acetate from mother liquor |
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