CN104725402A - Method for continuously crystallizing 6-amino-penicillanic acid - Google Patents
Method for continuously crystallizing 6-amino-penicillanic acid Download PDFInfo
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- CN104725402A CN104725402A CN201510127394.1A CN201510127394A CN104725402A CN 104725402 A CN104725402 A CN 104725402A CN 201510127394 A CN201510127394 A CN 201510127394A CN 104725402 A CN104725402 A CN 104725402A
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- amino
- penicillanic acid
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- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 title claims abstract description 36
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 27
- 238000002425 crystallisation Methods 0.000 claims abstract description 29
- 230000008025 crystallization Effects 0.000 claims abstract description 23
- 239000000243 solution Substances 0.000 claims description 40
- 239000007788 liquid Substances 0.000 claims description 27
- 239000011549 crystallization solution Substances 0.000 claims description 22
- 238000001914 filtration Methods 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 14
- 239000006166 lysate Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 239000012065 filter cake Substances 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 7
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 5
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 230000007547 defect Effects 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000009795 derivation Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000004886 process control Methods 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- JXYKOZKEXNCSSR-UHFFFAOYSA-N C(C1=CC=CC=C1)[Na].N Chemical compound C(C1=CC=CC=C1)[Na].N JXYKOZKEXNCSSR-UHFFFAOYSA-N 0.000 description 1
- 108010073038 Penicillin Amidase Proteins 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000005238 degreasing Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/04—Preparation
- C07D499/18—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/42—Compounds with a free primary amino radical attached in position 6
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for continuously crystallizing 6-amino-penicillanic acid and relates to the technical field of medical intermediate synthesis. The method is used for overcoming the defect of great quality difference between different batches of products obtained by use of an intermittent split-phase crystallization method in the prior art by virtue of a continuous crystallization; and as a result, the uniformity of the products is greatly improved, and meanwhile, the automatic control is applied, the production efficiency is improved and the energy source is saved.
Description
Technical field
The invention belongs to medical art, relate to a kind of preparation method of medicine intermediate, be specifically related to a kind of method of 6-amino-penicillanic acid continuous crystallization.
Background technology
6-amino-penicillanic acid, be called for short 6-APA, structure is as follows:
6-APA can introduce different side chains, obtains the microbiotic of different drug effect, is the important intermediate of producing semi-synthetic penicillins microbiotic ammonia benzyl sodium and amoxycilline Trihydrate bp.
The conventional preparation techniques of 6-APA take penicillin fermentation liquid as starting raw material, through twice extraction phase-splitting, obtains the degreasing fluid containing penicillanic acid; through penicillin acylase cracking; obtain the lysate containing 6-APA, then add hcl as extraction agent phase-splitting, add ammoniacal liquor crystallization in aqueous phase and obtain 6-APA.The operation of this interim phase-splitting, crystallization is intermittent, unstable product quality, differences between batches can be caused comparatively large, and intermittent operation cannot realize Automated condtrol, needs the manpower of at substantial, increases manufacturing enterprise's cost.
Summary of the invention
The object of this invention is to provide a kind of method of 6-amino-penicillanic acid continuous crystallization, the method, by serialization extracting and separating, achieves the continuous crystallization of 6-APA, reduces the differences between batches of product, significantly improve production efficiency, reduce production cost.
In order to realize object of the present invention, inventor provide following technical scheme.
A method for 6-amino-penicillanic acid continuous crystallization, comprises following operation steps:
A. by the lysate containing 6-APA and butanols mixing, mixing solutions is obtained;
B. temperature control 5-10 DEG C, stirs, and what the mixing solutions obtained by step a at the uniform velocity continued adds in reaction vessel, and aqueous hydrochloric acid is added in reaction vessel the pH value controlling reaction solution is 0-0.5 simultaneously;
C. when in step b, the liquid level of reaction solution rises to setting height, what at the uniform velocity continued by lower floor's reaction solution passes in crystallisation vessel, and what at the uniform velocity continued by upper strata reaction solution passes in retrieving arrangement, keeps the constant liquid level of reaction solution in setting height simultaneously;
D. the pH value adding ammoniacal liquor control solution in crystallisation vessel while passing into lower floor's reaction solution is 4.0-4.5, obtains crystallization solution;
E., when the liquid level of crystallization solution rises to setting height, passing in filtration unit of at the uniform velocity being continued by crystallization solution is filtered, and obtains filter cake, keeps the constant liquid level of crystallization solution in setting height simultaneously;
F. the filter cake that step e obtains is washed, dry, namely obtain the amino clear mould alkanoic acid of 6-.
The method of above-mentioned 6-amino-penicillanic acid continuous crystallization, in lysate described in step a, the content of 6-APA is 22-28%.
The volume ratio of lysate described in step a and butanols is 5:1.
Flow velocity when mixing solutions described in step b adds reaction vessel is every 100 liters of reaction vessel 24-36L/min.
The 1/2-2/3 place using the bottom of stirring rake to be positioned at reaction solution liquid level is stirred described in step b.
Setting height described in step c is the 60-80% of reaction vessel height.
The concentration of aqueous hydrochloric acid described in step b is 20%.
The concentration of ammoniacal liquor described in steps d is 20%.
Filtration unit described in step e is preferably many covers, passes into the crystallization solution of same volume, carries out filter operation respectively, can ensure that crystallization solution can filters in every sets filtering device.
The solvent of use is washed for acetone described in step e.
Temperature dry described in step f is 40-50 DEG C, and the dry time is 40-60min.
The lysate containing 6-APA that the method for the invention obtains for traditional method is all applicable.
The method of continuous crystallization provided by the present invention, layering is there is immediately after lysate containing 6-APA in step a adds hydrochloric acid, upper strata is the butanols organic phase of toluylic acid, lower floor is the aqueous phase containing 6-APA, stir the middle and upper part being positioned at reaction vessel in the process, add speed at restriction lysate simultaneously, under limiting the condition of liquid level, upper organic phase continues derivation and conventionally recycles accordingly, lower layer of water continues derivation mutually and enters crystallisation vessel, both ensure that fully carrying out of acidification reaction, fully being separated of organic phase and aqueous phase can not be affected again, and stable reaction conditions in process, good basis determined by stable pad for quality product, the process of crystallization, by controlling liquid level, ensure that the constant of crystallization time, thus can obtain the homogeneous product of quality, filtration step can use one or more sets filtration units according to actual needs, and crystallization solution can continually pass in filtration unit, reduces because intermittent operation causes the fluctuation of quality product.Whole pass continuous operation, thus can adopt Automated condtrol, controls the key operation such as material flow, valve opening time more accurately, avoids the error that manual operation causes.
The advantage of the method for 6-amino-penicillanic acid continuous crystallization of the present invention is:
1, can continuous mass production be realized, reduce operation, increase work efficiency, reduce production cost, for manufacturing enterprise creates objective economic benefit.
2, the realization of continuous prodution, overcome traditional batch and produce the unstable product quality caused, the problem that differences between batches are large, the homogeneity of product is better.
3, the realization of continuous prodution, makes Automated condtrol be applied, and further ensure that the homogeneity of quality product.
4, the realization of continuous prodution, effectively reduces the generation of odd powder, reduces because odd powder reclaims the wasting of resources caused.
Embodiment
Below in conjunction with specific embodiment, content of the present invention is described in further detail.
Embodiment 1
Retort volume is 100L, and in retort, the setting height of liquid level is 60% of retort height, and the lowermost end of stirring rake is positioned at 2/3 place of setting liquid level.
Crystallizer volume is 100L, and in crystallizer, the setting height of liquid level is 60% of crystallizer height.
Filtration unit is five covers.
A. by 6-APA content be 22% lysate with the flow velocity of 20L/min at the uniform velocity continue pass in line mixer, meanwhile by butanols with the flow velocity of 4L/min at the uniform velocity continue pass in line mixer, the two mixing, obtain mixing solutions;
B. retort temperature control 10 DEG C, opens and stirs, and what at the uniform velocity continued with the flow velocity of 24L/min by the mixing solutions in line mixer passes in retort, and the aqueous hydrochloric acid of 20% is added the pH value automatically controlling reaction solution in retort is 0 simultaneously;
C. when in retort, the liquid level of reaction solution rises to setting height, what at the uniform velocity continued with the speed of 28L/min by lower floor's reaction solution passes in crystallizer, what at the uniform velocity continued with the speed of 6L/min by upper strata reaction solution passes in withdrawing can, and whole process controls the constant liquid level of reaction solution all the time in setting height;
D. crystallizer is opened and is stirred, and the pH value adding 20% ammoniacal liquor control solution while lower floor's reaction solution passes into is 4.0, obtains crystallization solution;
E. when the liquid level of crystallization solution rises to setting height, what at the uniform velocity continued with the speed of 31L/min by crystallization solution passes in filtration unit, the crystallization solution of 825L is passed in every sets filtering device, five sets filtering devices are continual to carry out successively, vacuum filtration, obtain filter cake, in crystallizer, the constant liquid level of crystallization solution is in setting height;
F. obtain five filter cakes are divided by proper amount of acetone respectively and wash for three times, dry 40min under 40-50 DEG C of condition subsequently, obtain five batches of 6-amino-penicillanic acids, respectively heavy 101.2kg, 101.2kg, 101.1kg, 101.0kg, 101.3kg, average yield 91.03%.
Embodiment 2
Retort volume is 100L, and in setting retort, the height of liquid level is 80% of retort height, and the lowermost end of stirring rake is positioned at 1/2 place of setting liquid level.
Crystallizer volume is 100L, and in crystallizer, the setting height of liquid level is 80% of crystallizer height.
Filtration unit is three covers.
A. by 6-APA content be 28% lysate with the flow velocity of 30L/min at the uniform velocity continue pass in line mixer, meanwhile by butanols with the flow velocity of 6L/min at the uniform velocity continue pass in line mixer, the two mixing, obtain mixing solutions;
B. retort temperature control 5 DEG C, opens and stirs, and what at the uniform velocity continued with the flow velocity of 36L/min by the mixing solutions in line mixer passes in retort, and the aqueous hydrochloric acid of 20% is added in retort the pH value controlling reaction solution is 0.5 simultaneously;
C. when in retort, the liquid level of reaction solution rises to setting height, what at the uniform velocity continued with the speed of 46L/min by lower floor's reaction solution passes in crystallizer, what at the uniform velocity continued with 9L/min by upper strata reaction solution passes in withdrawing can, and whole process controls the constant liquid level of reaction solution all the time in setting height;
D. crystallizer is opened and is stirred, and the pH value adding 20% ammoniacal liquor control solution while lower floor's reaction solution passes into is 4.0, obtains crystallization solution;
E. when in crystallizer, the liquid level of crystallization solution rises to setting height, what at the uniform velocity continued with the speed of 49L/min by crystallization solution passes in filtration unit, the crystallization solution of 795L is passed in every sets filtering device, three sets filtering devices are continual to carry out successively, vacuum filtration, obtain filter cake, in crystallizer, the constant liquid level of crystallization solution is in setting height;
F. three filter cakes obtained by step e divide by proper amount of acetone respectively and wash for three times, and dry 60min under 40-50 DEG C of condition subsequently, obtains three batches of 6-amino-penicillanic acids, respectively heavy 126.2kg, 125.9kg, 126.1kg, average yield 92.47%.
Embodiment 3
Contriver has carried out quality examination to the 6-amino-penicillanic acid that embodiment 1-2 obtains, and result is as shown in table 1, table 2.
Table 1
| Sample | Content | Single assorted | Total assorted | Look level | Moisture |
| Embodiment 1-1 | 99.5％ | 0.21％ | 0.53％ | 2# | 0.3％ |
| Embodiment 1-2 | 99.4％ | 0.32％ | 0.54％ | 2# | 0.3％ |
| Embodiment 1-3 | 99.3％ | 0.31％ | 0.51％ | 2# | 0.2％ |
| Embodiment 1-4 | 99.5％ | 0.24％ | 0.49％ | 2# | 0.2％ |
| Embodiment 1-5 | 99.2％ | 0.23％ | 0.55％ | 2# | 0.3％ |
Table 2
| Sample | Content | Single assorted | Total assorted | Look level | Moisture |
| Embodiment 2-1 | 99.5％ | 0.23％ | 0.58％ | 2# | 0.2％ |
| Embodiment 2-2 | 99.5％ | 0.30％ | 0.60％ | 2# | 0.2％ |
| Embodiment 2-3 | 99.3％ | 0.24％ | 0.62％ | 2# | 0.2％ |
Embodiment 4
Contriver has carried out study on the stability to the 6-amino-penicillanic acid that embodiment 1-2 obtains, and result is as shown in table 3, table 4.
Experiment condition: temperature 45 C, humidity 60%, accelerates 4 hours.
Table 3
| Sample | Content | Single assorted | Total assorted | Look level | Moisture |
| Embodiment 1-1 | 99.2％ | 0.29％ | 0.67％ | 3# | 0.4％ |
| Embodiment 1-2 | 99.2％ | 0.42％ | 0.69％ | 3# | 0.3％ |
| Embodiment 1-3 | 99.1％ | 0.38％ | 0.66％ | 2# | 0.3％ |
| Embodiment 1-4 | 99.2％ | 0.34％ | 0.63％ | 3# | 0.3％ |
| Embodiment 1-5 | 99.1％ | 0.33％ | 0.68％ | 2# | 0.4％ |
Table 4
| Sample | Content | Single assorted | Total assorted | Look level | Moisture |
| Embodiment 2-1 | 99.5％ | 0.34％ | 0.58％ | 3# | 0.3％ |
| Embodiment 2-2 | 99.5％ | 0.39％ | 0.59％ | 3# | 0.3％ |
| Embodiment 2-3 | 99.3％ | 0.31％ | 0.61％ | 3# | 0.3％ |
Claims (10)
1. a method for 6-amino-penicillanic acid continuous crystallization, is characterized in that, comprises following operation steps:
A. by the lysate containing 6-APA and butanols mixing, mixing solutions is obtained;
B. temperature control 5-10 DEG C, stirs, and what the mixing solutions obtained by step a at the uniform velocity continued adds in reaction vessel, and aqueous hydrochloric acid is added in reaction vessel the pH value controlling reaction solution is 0-0.5 simultaneously;
C. when in step b, the liquid level of reaction solution rises to setting height, what at the uniform velocity continued by lower floor's reaction solution passes in crystallisation vessel, and what at the uniform velocity continued by upper strata reaction solution passes in retrieving arrangement, keeps the constant liquid level of reaction solution in setting height simultaneously;
D. the pH value adding ammoniacal liquor control solution in crystallisation vessel while passing into lower floor's reaction solution is 4.0-4.5, obtains crystallization solution;
E., when the liquid level of crystallization solution rises to setting height, passing in filtration unit of at the uniform velocity being continued by crystallization solution is filtered, and obtains filter cake, keeps the constant liquid level of crystallization solution in setting height simultaneously;
F. the filter cake that step e obtains is washed, dry, namely obtain the amino clear mould alkanoic acid of 6-.
2. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, in lysate described in step a, the content of 6-APA is 22-28%.
3. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, the volume ratio of lysate described in step a and butanols is 5:1.
4. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, flow velocity when mixing solutions described in step b adds reaction vessel is every 100 liters of reaction vessel 24-36L/min.
5. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, stirs the 1/2-2/3 place using the bottom of stirring rake to be positioned at reaction solution liquid level described in step b.
6. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, setting height described in step c is the 60-80% of reaction vessel height.
7. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, the concentration of aqueous hydrochloric acid described in step b is 20%.
8. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, the concentration of ammoniacal liquor described in steps d is 20%.
9. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, filtration unit described in step e is many covers, passes into the crystallization solution of same volume, carry out filter operation respectively in every sets filtering device.
10. the method for a kind of 6-amino-penicillanic acid continuous crystallization according to claim 1, is characterized in that, washs the solvent of use for acetone described in step f.
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| CN201510127394.1A CN104725402B (en) | 2015-03-23 | 2015-03-23 | A kind of method of 6 aminopenicillanic acid continuous crystallization |
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| CN201510127394.1A CN104725402B (en) | 2015-03-23 | 2015-03-23 | A kind of method of 6 aminopenicillanic acid continuous crystallization |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105693747A (en) * | 2016-03-07 | 2016-06-22 | 内蒙古常盛制药有限公司 | Solvent-free washing and drying technology for 6-APA (6-aminopenicillanic acid) |
| CN108218893A (en) * | 2017-12-18 | 2018-06-29 | 伊犁川宁生物技术有限公司 | A kind of method that 6-APA is recycled in the crystalline mother solution from 6-APA |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0950660A1 (en) * | 1998-03-20 | 1999-10-20 | Gist-Brocades B.V. | A process for recovery of 6-aminopenicillanic acid from a mother liquor |
| CN101735243A (en) * | 2008-11-11 | 2010-06-16 | 华北制药股份有限公司 | Process for preparing straight-through 6-aminopenicillanic acid |
| CN102925526A (en) * | 2012-11-23 | 2013-02-13 | 华北制药河北华民药业有限责任公司 | Preparation method for 6-amino penicillanic acid |
-
2015
- 2015-03-23 CN CN201510127394.1A patent/CN104725402B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0950660A1 (en) * | 1998-03-20 | 1999-10-20 | Gist-Brocades B.V. | A process for recovery of 6-aminopenicillanic acid from a mother liquor |
| CN101735243A (en) * | 2008-11-11 | 2010-06-16 | 华北制药股份有限公司 | Process for preparing straight-through 6-aminopenicillanic acid |
| CN102925526A (en) * | 2012-11-23 | 2013-02-13 | 华北制药河北华民药业有限责任公司 | Preparation method for 6-amino penicillanic acid |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105693747A (en) * | 2016-03-07 | 2016-06-22 | 内蒙古常盛制药有限公司 | Solvent-free washing and drying technology for 6-APA (6-aminopenicillanic acid) |
| CN105693747B (en) * | 2016-03-07 | 2018-02-06 | 内蒙古常盛制药有限公司 | A kind of 6 APA is without the dry technology of solvent washing |
| CN108218893A (en) * | 2017-12-18 | 2018-06-29 | 伊犁川宁生物技术有限公司 | A kind of method that 6-APA is recycled in the crystalline mother solution from 6-APA |
| CN108218893B (en) * | 2017-12-18 | 2021-02-23 | 伊犁川宁生物技术有限公司 | Method for recovering 6-APA from 6-APA crystallization mother liquor |
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| CN104725402B (en) | 2017-03-15 |
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