CN111302977A - Purification method of pharmaceutical grade guanidine hydrochloride - Google Patents
Purification method of pharmaceutical grade guanidine hydrochloride Download PDFInfo
- Publication number
- CN111302977A CN111302977A CN202010192916.7A CN202010192916A CN111302977A CN 111302977 A CN111302977 A CN 111302977A CN 202010192916 A CN202010192916 A CN 202010192916A CN 111302977 A CN111302977 A CN 111302977A
- Authority
- CN
- China
- Prior art keywords
- guanidine hydrochloride
- guanidine
- pumping
- crude
- pharmaceutical grade
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229960000789 guanidine hydrochloride Drugs 0.000 title claims abstract description 107
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 title claims abstract description 107
- 238000000034 method Methods 0.000 title claims abstract description 27
- 238000000746 purification Methods 0.000 title claims abstract description 24
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims abstract description 56
- 239000012535 impurity Substances 0.000 claims abstract description 44
- 239000000243 solution Substances 0.000 claims abstract description 35
- 238000002425 crystallisation Methods 0.000 claims abstract description 30
- 230000008025 crystallization Effects 0.000 claims abstract description 30
- 238000005086 pumping Methods 0.000 claims abstract description 29
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims abstract description 28
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229960004198 guanidine Drugs 0.000 claims abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000007864 aqueous solution Substances 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 13
- 230000014759 maintenance of location Effects 0.000 claims abstract description 12
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000013078 crystal Substances 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 230000001939 inductive effect Effects 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 239000007788 liquid Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 4
- 238000005192 partition Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/06—Purification or separation of guanidine
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/10—Process efficiency
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a purification method of pharmaceutical grade guanidine hydrochloride, which comprises the following steps: (a) adding the guanidine hydrochloride crude guanidine into water, stirring and mixing, and then pumping into a coarse filter to remove impurities to obtain a guanidine hydrochloride crude guanidine water solution; the mass ratio of the guanidine hydrochloride crude guanidine to the water is 1.5-3: 1; (b) pumping the crude guanidine hydrochloride aqueous solution into an ultrasonic crystallization system, carrying out continuous and circulating treatment to obtain a guanidine hydrochloride clear solution, and inducing to separate out fine impurities; the control parameters of the ultrasonic crystallization system are as follows: the temperature is 0-120 ℃, the hydraulic retention time is 0.5-2 h and the frequency of an ultrasonic power supply is 10-20 KHz; (c) pumping the guanidine hydrochloride clear solution into a filter to remove fine impurity grains; then pumping into a decolorizer to remove trace cyanamide impurities dissolved in the guanidine hydrochloride clear solution to obtain refined guanidine hydrochloride solution; (d) pumping the refined guanidine hydrochloride solution into a crystallizer for crystallization and purification; separating the crystal, and drying to obtain the pharmaceutical grade guanidine hydrochloride. Greatly improving the production efficiency and reducing the production period.
Description
Technical Field
The invention belongs to the technical field of purification of organic matters, and relates to a purification method of pharmaceutical grade guanidine hydrochloride, in particular to an ultrasonic induction purification method of pharmaceutical grade guanidine hydrochloride.
Background
The pharmaceutical grade guanidine hydrochloride is mainly widely applied in the fields of protein and cell biology; due to the special requirements of the application field, the product has very high requirements on impurities, and besides conventional technical parameters such as conventional content, melting point, pH, insoluble substances, moisture and the like, the most rigorous technical indexes are also reflected in the ultraviolet light absorbance: the ultraviolet absorbance is 260 mu m or less than 0.04 and 280 mu m or less than 0.02.
At present, the purification of guanidine hydrochloride mainly adopts the process of dissolving solid crude guanidine hydrochloride into an aqueous solution, crystallizing and separating solid impurities and separating guanidine hydrochloride by utilizing the solubility difference of the impurities and a product in the aqueous solution. Because the process has more impurities, mainly comprises unreacted raw materials and cyanamide polymers generated by side reaction, the content of each impurity is different, and the solubility difference is large, in order to ensure that each impurity can be removed to the maximum extent, the impurities with low concentration need long crystallization nucleation time, so that the purification period of guanidine hydrochloride is long, and the productivity is severely limited. Therefore, the development of a medical grade guanidine hydrochloride high-treatment-capacity impurity removal process has important significance.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for purifying pharmaceutical grade guanidine hydrochloride.
In order to achieve the purpose, the invention adopts the technical scheme that: a method for purifying pharmaceutical grade guanidine hydrochloride comprises the following steps:
(a) adding the guanidine hydrochloride crude guanidine into water, stirring and mixing, and then pumping into a coarse filter to remove impurities to obtain a guanidine hydrochloride crude guanidine water solution; the mass ratio of the guanidine hydrochloride crude guanidine to the water is 1.5-3: 1;
(b) pumping the crude guanidine hydrochloride aqueous solution into an ultrasonic crystallization system, carrying out continuous and circulating treatment to obtain a guanidine hydrochloride clear solution, and inducing to separate out fine impurities; the control parameters of the ultrasonic crystallization system are as follows: the temperature is 0-120 ℃, the hydraulic retention time is 0.5-2 h and the frequency of the ultrasonic power supply is 10-20 KHz;
(c) pumping the guanidine hydrochloride clear solution into a filter to remove fine impurity grains; then pumping into a decolorizer to remove trace cyanamide impurities dissolved in the guanidine hydrochloride clear solution to obtain refined guanidine hydrochloride solution;
(d) pumping the refined guanidine hydrochloride solution into a crystallizer for crystallization and purification; separating the crystal, and drying to obtain the pharmaceutical grade guanidine hydrochloride.
Optimally, in the step (a), the crude guanidine hydrochloride and water are stirred and mixed at the temperature of 20-120 ℃, and the stirring time is 0.5-1 h.
Optimally, in the step (b), the ultrasonic crystallization system is provided with an internal circulation system for circulating the crude guanidine hydrochloride aqueous solution.
Preferably, in step (c), the filter is a precision filter.
Further, in step (c), the control parameters of the decolorizer are: the temperature is 50-90 ℃, the pressure is normal pressure to 0.2MPa, and the hydraulic retention time is 0.5-1 h.
Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages: according to the purification method of the pharmaceutical grade guanidine hydrochloride, the mixing ratio of the crude guanidine hydrochloride and water is controlled, and the technological parameters of the ultrasonic crystallization system are accurately controlled, so that the productivity of the pharmaceutical grade guanidine hydrochloride can be improved by 7-10 times, the production period is reduced to about 3 days from 20-30 days, the production efficiency is greatly improved, and the production period is shortened.
Drawings
FIG. 1 is a process flow diagram of the purification method of pharmaceutical grade guanidine hydrochloride of the present invention;
FIG. 2 is a diagram of the apparatus for purifying pharmaceutical grade guanidine hydrochloride of the present invention.
Detailed Description
The purification method of the pharmaceutical grade guanidine hydrochloride of the invention is shown in figure 1 and comprises the following steps: (a) adding the guanidine hydrochloride crude guanidine into water, stirring and mixing, and then pumping into a coarse filter to remove impurities to obtain a guanidine hydrochloride crude guanidine water solution; the mass ratio of the guanidine hydrochloride crude guanidine to the water is 1.5-3: 1; (b) pumping the crude guanidine hydrochloride aqueous solution into an ultrasonic crystallization system, carrying out continuous and circulating treatment to obtain a guanidine hydrochloride clear solution, and inducing to separate out fine impurities; the control parameters of the ultrasonic crystallization system are as follows: the temperature is 0-120 ℃, the hydraulic retention time is 0.5-2 h and the frequency of the ultrasonic power supply is 10-20 KHz; (c) pumping the guanidine hydrochloride clear solution into a filter to remove fine impurity grains; then pumping into a decolorizer to remove trace cyanamide impurities dissolved in the guanidine hydrochloride clear solution to obtain refined guanidine hydrochloride solution; (d) pumping the refined guanidine hydrochloride solution into a crystallizer for crystallization and purification; separating the crystal, and drying to obtain the pharmaceutical grade guanidine hydrochloride. By controlling the mixing ratio of the crude guanidine hydrochloride and water and accurately controlling the technological parameters of the ultrasonic crystallization system, the production capacity of the pharmaceutical grade guanidine hydrochloride can be improved by 7-10 times, the production period is reduced from 20-30 days to about 3 days, the production efficiency is greatly improved, and the production period is shortened.
In the step (a), the guanidine hydrochloride crude guanidine and water are preferably stirred and mixed at the temperature of 20-120 ℃, and the stirring time is 0.5-1 h. In the step (b), the ultrasonic crystallization system is provided with an internal circulation system for circulating the crude guanidine hydrochloride aqueous solution, so that the precipitation effect of fine impurity grains is improved. In the step (c), the filter is a precision filter, so that the filtering effect of fine impurity grains is improved. In the step (c), the control parameters of the decolorizer are as follows: the temperature is 50-90 ℃, the pressure is normal pressure to 0.2MPa, and the hydraulic retention time is 0.5-1 h, so as to improve the decoloring effect.
The following detailed description of preferred embodiments of the invention will be made.
Example 1
This example provides a method for purifying pharmaceutical grade guanidine hydrochloride, comprising the steps of:
(a) adding 500g of water into a mixer under normal pressure, adding 1200g of crude guanidine hydrochloride, stirring for 30min at 60 ℃, pumping into a coarse filter after uniformly stirring, and removing mechanical impurities and solid particle impurities which are not completely dissolved to obtain crude guanidine hydrochloride aqueous solution;
(b) pumping the guanidine hydrochloride crude guanidine water solution obtained by removing mechanical impurities and incompletely dissolved solid particle impurities through a strainer into an ultrasonic crystallization system for continuous and circulating treatment to obtain a guanidine hydrochloride clear solution so as to induce and separate out fine impurities (the ultrasonic crystallization system adopts a continuous treatment type, and an in-band circulating system is used for circulating treatment of the guanidine hydrochloride crude guanidine water solution), so as to obtain the guanidine hydrochloride clear solution; the operation control parameters of the ultrasonic crystallization system are as follows: the temperature is 60 ℃, the pressure is normal pressure, the hydraulic retention time is 60min and the frequency of the ultrasonic power supply is 20 KHz; the ultrasonic crystallization system adopts self-developed equipment, and comprises a standing component 1, an ultrasonic induced crystallization component 2 and a filter press 3 as shown in figure 2. The ultrasonic induced crystallization component 2 comprises a liquid inlet pipeline 22 for feeding a crude guanidine hydrochloride aqueous solution, a plurality of ultrasonic crystallizers 21 (three in the embodiment, the specific number can be selected according to actual needs) which are communicated with one end of the liquid inlet pipeline 22 and are connected in series through pipelines, and a liquid outlet pipeline 23 of which one end is communicated with the ultrasonic crystallizer 21 (the most downstream one is defined according to the flowing direction of the crude guanidine hydrochloride aqueous solution); the standing assembly 1 comprises a standing tank body 10, a clear liquid outlet pipe 11 with one end communicated with the upper end of the standing tank body 10, an impurity enriched liquid outlet pipe 12 with one end communicated with the lower end of the standing tank body 10, a liquid guide pipe 13 arranged in the standing tank body 10 and with one end communicated with the other end of the liquid outlet pipe 23, and a conical partition plate assembly 14 arranged in the standing tank body 10 and matched with the liquid guide pipe 13 (the conical partition plate assembly 14 is arranged below the other end of the liquid guide pipe 13 and communicated with the liquid guide pipe 13, comprises a central pipe and conical partition plates arranged on the side wall of the central pipe and communicated with the central pipe, and the conical partition plates are sequentially stacked from bottom to top and extend downwards so as to guide the liquid outlet of the ultrasonic induced crystallization assembly into the standing tank body 10 after being buffered, so that impurities can be gradually enriched towards the bottom of the standing tank body 10; the filter press 3 is respectively connected with the other end of the impurity enrichment liquid outlet pipe 12 and the middle part of the liquid inlet pipeline 22 through pipelines and is used for carrying out filter pressing on the impurity enrichment liquid, then reintroducing filter pressing liquid into the liquid inlet pipeline 22 for circulation treatment, and the filter cake generated by filter pressing can be disposed outside;
(c) pumping the guanidine hydrochloride clear solution subjected to the induced impurity removal treatment of the ultrasonic crystallization system into a precision filter to remove fine impurity grains which are not completely removed by the ultrasonic crystallization system; and then pumping the guanidine hydrochloride solution passing through the precision filter into a decolorizer to remove trace cyanamide impurities dissolved in the solution to obtain refined guanidine hydrochloride solution, wherein the process conditions of the decolorizer are as follows: temperature 60 deg.C, pressure 0.15MPa (G) and hydraulic retention time 30 min;
(d) pumping the refined guanidine hydrochloride solution into a finished product crystallizer for crystallization and purification; separating the crystal, and drying to obtain pharmaceutical grade guanidine hydrochloride; yield 85% (based on crude guanidine) and purity 99.7%.
Example 2
This example provides a purification process for pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in step (a), 500g of water is added to a mixer and 750g of crude guanidine hydrochloride is added; yield 87% (based on crude guanidine) and purity 99.6%.
Example 3
This example provides a purification process for pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in step (a), 500g of water is added into a mixer, and 1500g of crude guanidine hydrochloride is added; yield 83.5% (based on crude guanidine) and purity 99.8%.
Example 4
This example provides a purification process for pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in step (a), stirring at 120 ℃ for 45 min; yield 86% (based on crude guanidine) and purity 99.6%.
Example 5
This example provides a purification process for pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in the step (a), stirring for 1h at 20 ℃; yield 84.5% (based on crude guanidine) and purity 99.8%.
Example 6
This example provides a purification process for pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in the step (b), the temperature is 0 ℃, the pressure is normal pressure, the hydraulic retention time is 2h and the frequency of the ultrasonic power supply is 10 KHz; yield 83.5% (based on crude guanidine) and purity 99.7%.
Example 7
This example provides a purification process for pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in the step (b), the temperature is 120 ℃, the pressure is normal pressure, the hydraulic retention time is 0.5h and the frequency of the ultrasonic power supply is 15 KHz; yield 84.0% (based on crude guanidine) and purity 99.5%.
Comparative example 1
This example provides a method for purifying pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in step (a), 500g of water is added to a mixer and 2000g of crude guanidine hydrochloride is added; yield 74% (based on crude guanidine) and purity 99.7%.
Comparative example 2
This example provides a method for purifying pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in the step (b), the frequency of the ultrasonic power supply is 50 KHz; yield 80% (based on crude guanidine) and purity 98.5%.
Comparative example 3
This example provides a method for purifying pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in the step (b), the frequency of the ultrasonic power supply is 5 KHz; yield 75% (based on crude guanidine) and purity 98.7%.
Comparative example 4
This example provides a method for purifying pharmaceutical grade guanidine hydrochloride, which is essentially the same as that of example 1, except that: in the step (b), the temperature in the ultrasonic crystallization system is controlled to be 130 ℃; yield 70% (based on crude guanidine) and purity 98.5%.
Comparative example 5
The embodiment provides a method for purifying the conventional pharmaceutical grade guanidine hydrochloride, which comprises the following specific steps:
(a) adding 500g of water into a mixer under normal pressure, adding 1200g of crude guanidine hydrochloride, stirring for 30min at 60 ℃, pumping into a coarse filter after uniformly stirring, and removing mechanical impurities and solid particle impurities which are not completely dissolved to obtain crude guanidine hydrochloride aqueous solution;
(b) pumping the crude guanidine hydrochloride aqueous solution obtained by removing mechanical impurities and incompletely dissolved solid particle impurities by a coarse filter into an impurity removal sedimentation tank, and standing for 20 days at ambient temperature;
(c) pumping the supernatant of the impurity removal sedimentation tank into a decolorizer to obtain a refined guanidine hydrochloride solution, wherein the decolorizer has the following process conditions: temperature 60 deg.C, pressure 0.15MPa (G) and hydraulic retention time 30 min;
(d) pumping the refined guanidine hydrochloride solution into a finished product crystallizer for crystallization and purification; separating the crystal, and drying to obtain the pharmaceutical grade guanidine hydrochloride.
The final pharmaceutical grade guanidine hydrochloride yield was 83% (based on crude guanidine) and the purity was 99.6% (the total time of treatment of the entire purification process amounted to about 23 days).
The above-mentioned embodiments are merely illustrative of the technical concept and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the content of the present invention and implement the invention, and not to limit the scope of the present invention, and all equivalent changes or modifications made according to the spirit of the present invention should be covered by the scope of the present invention.
Claims (5)
1. A method for purifying pharmaceutical grade guanidine hydrochloride is characterized by comprising the following steps:
(a) adding the guanidine hydrochloride crude guanidine into water, stirring and mixing, and then pumping into a coarse filter to remove impurities to obtain a guanidine hydrochloride crude guanidine water solution; the mass ratio of the guanidine hydrochloride crude guanidine to the water is 1.5-3: 1;
(b) pumping the crude guanidine hydrochloride aqueous solution into an ultrasonic crystallization system, carrying out continuous and circulating treatment to obtain a guanidine hydrochloride clear solution, and inducing to separate out fine impurities; the control parameters of the ultrasonic crystallization system are as follows: the temperature is 0-120 ℃, the hydraulic retention time is 0.5-2 h and the frequency of an ultrasonic power supply is 10-20 KHz;
(c) pumping the guanidine hydrochloride clear solution into a filter to remove fine impurity grains; then pumping into a decolorizer to remove trace cyanamide impurities dissolved in the guanidine hydrochloride clear solution to obtain refined guanidine hydrochloride solution;
(d) pumping the refined guanidine hydrochloride solution into a crystallizer for crystallization and purification; separating the crystal, and drying to obtain the pharmaceutical grade guanidine hydrochloride.
2. The method of claim 1, wherein the step of purifying the pharmaceutical grade guanidine hydrochloride comprises: in the step (a), the guanidine hydrochloride crude guanidine and water are stirred and mixed at the temperature of 20-120 ℃, and the stirring time is 0.5-1 h.
3. The method of claim 1, wherein the step of purifying the pharmaceutical grade guanidine hydrochloride comprises: in the step (b), the ultrasonic crystallization system is provided with an internal circulation system for circulating the crude guanidine hydrochloride aqueous solution.
4. The method of claim 1, wherein the step of purifying the pharmaceutical grade guanidine hydrochloride comprises: in step (c), the filter is a precision filter.
5. The method of purifying pharmaceutical grade guanidine hydrochloride according to claim 1 or 4, wherein: in the step (c), the control parameters of the decolorizer are as follows: the temperature is 50-90 ℃, the pressure is normal pressure-0.2 MPa, and the hydraulic retention time is 0.5-1 h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010192916.7A CN111302977B (en) | 2020-03-18 | 2020-03-18 | Purification method of pharmaceutical grade guanidine hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010192916.7A CN111302977B (en) | 2020-03-18 | 2020-03-18 | Purification method of pharmaceutical grade guanidine hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111302977A true CN111302977A (en) | 2020-06-19 |
| CN111302977B CN111302977B (en) | 2022-05-17 |
Family
ID=71153510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010192916.7A Active CN111302977B (en) | 2020-03-18 | 2020-03-18 | Purification method of pharmaceutical grade guanidine hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111302977B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113754567A (en) * | 2021-10-13 | 2021-12-07 | 宁夏蓝白黑循环科技有限公司 | Novel preparation process of refined guanidine carbonate |
| CN115286538A (en) * | 2022-07-12 | 2022-11-04 | 烟台三鼎化工有限公司 | Antibacterial guanidine hydrochloride efficient crystallization drying process |
| CN116283830A (en) * | 2023-01-08 | 2023-06-23 | 湖南吴赣药业有限公司 | Preparation method of high-purity 3-morpholinopropane sulfonic acid |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4542240A (en) * | 1980-02-28 | 1985-09-17 | Degussa Aktiengesellschaft | Process for the production of guanidine hydrochloride |
| CN1385419A (en) * | 2002-06-14 | 2002-12-18 | 方建文 | Process for preparing guanidine hydrochloride |
| CN103951591A (en) * | 2014-05-19 | 2014-07-30 | 宁夏贝利特化工有限公司 | Production technique of guanidine hydrochloride |
| CN104860849A (en) * | 2015-06-04 | 2015-08-26 | 西安近代化学研究所 | Continuous crystallization process for preparing nitroguanidine through nitric acid method |
| CN107721884A (en) * | 2017-11-06 | 2018-02-23 | 西安近代化学研究所 | A kind of nitroguanidine is engineered production technology |
| CN109232324A (en) * | 2018-11-15 | 2019-01-18 | 宁夏宁杭循环科技股份有限公司 | A kind of novel purification guanidine hydrochloride is synthetically prepared production technology |
| CN110204461A (en) * | 2019-05-15 | 2019-09-06 | 西安万德能源化学股份有限公司 | The microchannel crystallization processes and device of a kind of nitroguanidine crystal and nitroguanidine |
-
2020
- 2020-03-18 CN CN202010192916.7A patent/CN111302977B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4542240A (en) * | 1980-02-28 | 1985-09-17 | Degussa Aktiengesellschaft | Process for the production of guanidine hydrochloride |
| CN1385419A (en) * | 2002-06-14 | 2002-12-18 | 方建文 | Process for preparing guanidine hydrochloride |
| CN103951591A (en) * | 2014-05-19 | 2014-07-30 | 宁夏贝利特化工有限公司 | Production technique of guanidine hydrochloride |
| CN104860849A (en) * | 2015-06-04 | 2015-08-26 | 西安近代化学研究所 | Continuous crystallization process for preparing nitroguanidine through nitric acid method |
| CN107721884A (en) * | 2017-11-06 | 2018-02-23 | 西安近代化学研究所 | A kind of nitroguanidine is engineered production technology |
| CN109232324A (en) * | 2018-11-15 | 2019-01-18 | 宁夏宁杭循环科技股份有限公司 | A kind of novel purification guanidine hydrochloride is synthetically prepared production technology |
| CN110204461A (en) * | 2019-05-15 | 2019-09-06 | 西安万德能源化学股份有限公司 | The microchannel crystallization processes and device of a kind of nitroguanidine crystal and nitroguanidine |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113754567A (en) * | 2021-10-13 | 2021-12-07 | 宁夏蓝白黑循环科技有限公司 | Novel preparation process of refined guanidine carbonate |
| CN113754567B (en) * | 2021-10-13 | 2024-02-20 | 宁夏蓝白黑循环科技有限公司 | Preparation process of novel refined guanidine carbonate |
| CN115286538A (en) * | 2022-07-12 | 2022-11-04 | 烟台三鼎化工有限公司 | Antibacterial guanidine hydrochloride efficient crystallization drying process |
| CN116283830A (en) * | 2023-01-08 | 2023-06-23 | 湖南吴赣药业有限公司 | Preparation method of high-purity 3-morpholinopropane sulfonic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111302977B (en) | 2022-05-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111302977B (en) | Purification method of pharmaceutical grade guanidine hydrochloride | |
| CN107935846B (en) | Device and method for continuously producing environment-friendly plasticizer | |
| CN101293849B (en) | Process for preparing glutamic acid crystallization | |
| CN101671324B (en) | Production method of glucolactone | |
| CN210419601U (en) | Desulfurization waste water resourceful treatment system | |
| CN110732154A (en) | internal circulation reaction crystallizer | |
| CN103910651B (en) | Iminodiacetonitrile continuous crystallisation technique | |
| CN108530291B (en) | Continuous acidolysis method of calcium hydrogen citrate | |
| CN115465991B (en) | Ferric phosphate mother liquor wastewater treatment method and system | |
| CN110655547A (en) | Adenosine extraction method for reducing content of single related impurities | |
| CN108191868B (en) | A kind of processing method of the molten refinement mother liquor of riboflavin acid | |
| CN109665683A (en) | A method of recycling nitrogen phosphorus prepares high-purity phosphoric acid ammonium magnesium from cultivation waste | |
| CN111518119B (en) | Continuous amoxicillin crystallization process | |
| CN214654256U (en) | Waste alkali lye resourceful treatment system | |
| CN217092171U (en) | Device for reducing scale formation of phosphoric acid purification extraction tank | |
| CN110306041B (en) | Continuous preparation device for rare earth compound precipitate | |
| CN210419812U (en) | Threonine crystallization extraction system | |
| CN213077544U (en) | Concentrated three-section crystallization device of purification syrup | |
| CN103739145A (en) | High fructose syrup production wastewater treatment technology | |
| CN220788618U (en) | D-chiro-inositol's apparatus for producing | |
| CN221027731U (en) | System for preparing sodium nitrate, magnesium sulfate and gypsum by utilizing calcium-magnesium concentrated solution | |
| CN214142138U (en) | A device for producing water-soluble fertile of hemispherical medium element | |
| CN213060875U (en) | Preparation system of acrylamide | |
| CN220351733U (en) | Device for separating oxalate in sodium aluminate solution | |
| CN204569617U (en) | Heavily flocculate carrier waste disposal plant |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A purification method of pharmaceutical grade guanidine hydrochloride Effective date of registration: 20230112 Granted publication date: 20220517 Pledgee: Agricultural Bank of China Limited Changsha Wangcheng District sub branch Pledgor: Hunan Wugan Pharmaceutical Co.,Ltd. Registration number: Y2023430000003 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20220517 Pledgee: Agricultural Bank of China Limited Changsha Wangcheng District sub branch Pledgor: Hunan Wugan Pharmaceutical Co.,Ltd. Registration number: Y2023430000003 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A purification method for pharmaceutical grade guanidine hydrochloride Granted publication date: 20220517 Pledgee: Agricultural Bank of China Limited Changsha Wangcheng District sub branch Pledgor: Hunan Wugan Pharmaceutical Co.,Ltd. Registration number: Y2024980004057 |