CN112028804B - Concentrating method of dienogest - Google Patents
Concentrating method of dienogest Download PDFInfo
- Publication number
- CN112028804B CN112028804B CN202010988290.0A CN202010988290A CN112028804B CN 112028804 B CN112028804 B CN 112028804B CN 202010988290 A CN202010988290 A CN 202010988290A CN 112028804 B CN112028804 B CN 112028804B
- Authority
- CN
- China
- Prior art keywords
- nanofiltration
- dienogest
- treatment
- ultrafiltration
- concentration
- 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.)
- Active
Links
- AZFLJNIPTRTECV-FUMNGEBKSA-N dienogest Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@](CC3)(O)CC#N)CC3)C3=C21 AZFLJNIPTRTECV-FUMNGEBKSA-N 0.000 title claims abstract description 31
- 229960003309 dienogest Drugs 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 28
- 238000001728 nano-filtration Methods 0.000 claims abstract description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 44
- 238000000108 ultra-filtration Methods 0.000 claims abstract description 44
- 239000012528 membrane Substances 0.000 claims abstract description 31
- 239000012466 permeate Substances 0.000 claims abstract description 26
- 238000006911 enzymatic reaction Methods 0.000 claims abstract description 13
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 10
- 238000001471 micro-filtration Methods 0.000 claims abstract description 8
- 238000000605 extraction Methods 0.000 claims abstract description 5
- 238000004090 dissolution Methods 0.000 claims abstract description 3
- 238000002390 rotary evaporation Methods 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- 239000000919 ceramic Substances 0.000 claims description 10
- 239000012510 hollow fiber Substances 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 238000010025 steaming Methods 0.000 abstract description 16
- 239000007788 liquid Substances 0.000 abstract description 14
- 239000012141 concentrate Substances 0.000 abstract description 12
- 238000011097 chromatography purification Methods 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 28
- 239000012074 organic phase Substances 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 5
- 229960002986 dinoprostone Drugs 0.000 description 5
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000000498 cooling water Substances 0.000 description 3
- 230000006837 decompression Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 230000010355 oscillation Effects 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000000916 dilatatory effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
- C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
- C07C405/0016—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing only hydroxy, etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- 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
Abstract
The invention discloses a concentrating method of dienogest, which relates to the technical field of biological pharmacy and comprises the following steps: sequentially carrying out microfiltration and ultrafiltration treatment on enzymatic reaction liquid of the dienogest to obtain ultrafiltration permeate; adding ethanol solution into the ultrafiltration permeate until the ethanol concentration in the ultrafiltration permeate is 17-22%, and then carrying out nanofiltration treatment to obtain nanofiltration concentrated solution; and (3) subjecting the nanofiltration concentrated solution to column passing, primary rotary steaming, extraction, secondary rotary steaming and re-dissolution treatment to obtain the concentrated solution of the dienogest. The invention adopts nanofiltration to concentrate the dienogest in the enzymatic reaction liquid to improve the concentration, reduces the volume of subsequent chromatographic purification treatment, improves the purification rate, and adds ethanol into the ultrafiltration permeate to adjust the concentration of the feed liquid, thereby effectively improving the multiple of nanofiltration concentration and being fast and efficient on the basis of not affecting the performance of the nanofiltration membrane.
Description
Technical Field
The invention relates to the technical field of biological pharmacy, in particular to a concentrating method of dienogest.
Background
The dienoprost, also called prostaglandin E2, is an important cell growth and regulation factor, is an arachidonic acid cyclooxygenase metabolite, and is an eicosaunsaturated fatty acid. Prostaglandin E2 has the effects of dilating blood vessel, increasing blood flow of organ, reducing peripheral resistance of blood vessel, lowering blood pressure, dilating bronchial smooth muscle, reducing airway resistance, inhibiting gastric acid secretion, and inhibiting immunity and inflammation.
Currently, dienoprost is often prepared by chemical synthesis. There are fewer methods for preparing dienoprost by enzymatic methods. The application document of CN201911326101.7 mentions that a reaction liquid is obtained by preparing prostaglandin E2 by an enzyme catalysis method, but a simple and effective method for preparing a prostaglandin E2 concentrated solution with high concentration by utilizing the enzyme catalysis reaction liquid does not exist, and prostaglandin E2 is easy to separate out in the concentration process by adopting a conventional method.
Disclosure of Invention
Based on the technical problems in the background technology, the invention provides a concentrating method of dienoprost ketone, which is characterized in that ethanol is added into feed liquid to adjust the concentration of the feed liquid, so that the multiple of nanofiltration concentration is effectively improved on the basis of not affecting the performance of nanofiltration membranes, and the concentrating method is rapid and efficient.
The invention provides a concentrating method of dienogest, which comprises the following steps:
s1, sequentially carrying out microfiltration and ultrafiltration treatment on enzymatic reaction liquid of dienogest to obtain ultrafiltration permeate;
s2, adding an ethanol solution into the ultrafiltration permeate until the concentration of ethanol in the ultrafiltration permeate is 17-22%, and then carrying out nanofiltration treatment to obtain nanofiltration concentrated solution;
and S3, subjecting the nanofiltration concentrated solution to column passing, primary rotary evaporation, extraction, secondary rotary evaporation and re-dissolution treatment to obtain the concentrated solution of the dienogest.
The above-mentioned "enzymatic reaction solution of dienoprost" refers to the reaction solution obtained in example 5 in the application document of application number CN 201911326101.7.
Preferably, ceramic membrane microfiltration is used; preferably, the pore size of the ceramic membrane is 100-500nm.
Preferably, ultrafiltration treatment is performed by using a hollow fiber ultrafiltration membrane; preferably, the hollow fiber ultrafiltration membrane has a molecular weight cut-off of 5000Da.
Preferably, nanofiltration membrane is used for nanofiltration treatment; preferably, the nanofiltration membrane has a molecular weight cut-off of 150Da.
Preferably, the nanofiltration process is carried out at a pressure of 0.5-0.8MPa.
Preferably, the process conditions of the primary rotary steaming and the secondary rotary steaming are as follows: the pressure is 14-18mbar, the rotating speed is 27-32rpm, and the temperature is 25-30 ℃.
Preferably, the extraction reagent is ethyl acetate.
The beneficial effects are that: the invention can concentrate the dienogest in the enzymatic reaction liquid by adopting nanofiltration to improve the concentration of the dienogest, reduce the volume of subsequent chromatographic purification treatment, improve the purification rate, and add ethanol into the ultrafiltration permeate to adjust the concentration of the liquid, thus effectively improving the multiple of nanofiltration concentration on the basis of not affecting the performance of the nanofiltration membrane, being fast and efficient, and effectively solving the problem that the sample precipitation and concentration multiple are low when the liquid without ethanol is concentrated to 1.2mg/ml of dienogest by nanofiltration.
Drawings
FIG. 1 is a high performance liquid chromatogram of an ultrafiltration permeate in a comparative example of the present invention after dilution by a factor of 2;
FIG. 2 is a high performance liquid chromatogram of a nanofiltration concentrate of the comparative example of the present invention diluted 5-fold;
FIG. 3 is a high performance liquid chromatogram of the ultrafiltration permeate of example 1 of the present invention;
FIG. 4 is a high performance liquid chromatogram of the nanofiltration concentrate of example 1 of the present invention diluted 2-fold.
Detailed Description
The technical scheme of the invention is described in detail through specific embodiments.
Example 1
A method for concentrating dienoprost, comprising the steps of:
s1, taking enzymatic reaction liquid of dienogest, sequentially carrying out microfiltration through a ceramic membrane with the aperture of 100nm and ultrafiltration through a hollow fiber ultrafiltration membrane with the molecular weight cutoff of 5000Da to obtain ultrafiltration permeate; in this step, most of impurities in the enzymatic reaction solution are removed by filtration through ceramic membranes and ultrafiltration membranes.
S2, adding 95% ethanol solution into the ultrafiltration permeate until the concentration of ethanol in the ultrafiltration permeate is 20%, and then adopting a nanofiltration membrane with a molecular weight cutoff of 150Da to carry out nanofiltration concentration treatment, wherein the pressure of the nanofiltration treatment is 0.65MPa, so as to obtain nanofiltration concentrate; in the step, the concentration of the dienogest is increased by nanofiltration concentration, the volume of the subsequent chromatographic purification treatment is reduced, and the purification rate is increased.
S3, passing the nanofiltration concentrated solution through a column to obtain a column purified solution; placing the purified solution after passing through the column into a rotary steaming bottle for one-time decompression rotary steaming, wherein the temperature of cooling water is-10 to-20 ℃, the rotating speed is 30rpm, the temperature is 25 ℃, and the pressure is 15mbar (the pressure is gradually reduced from 50mbar to 15mbar according to the boiling state of the solution); adding ethyl acetate into the feed liquid subjected to primary rotary evaporation to a separating funnel according to a proportion, uniformly mixing an organic phase with an aqueous phase through oscillation, standing for layering, taking an upper organic phase 1, and repeating the aqueous phase twice according to the method to obtain an organic phase 2 and an organic phase 3; mixing the organic phases 1, 2 and 3 uniformly, and performing secondary reduced pressure rotary evaporation treatment, wherein the rotary evaporation pressure is 30mbar (the rotary evaporation pressure slowly decreases from 100mbar to 30mbar according to the boiling state of the solution), and other conditions are the same as those of the primary reduced pressure rotary evaporation treatment; after the rotary steaming is completed, adding a small amount of 95% medicinal ethanol into a rotary steaming bottle, and redissolving the dienogest to obtain a concentrate of the dienogest.
Example 2
A method for concentrating dienoprost, comprising the steps of:
s1, taking enzymatic reaction liquid of dienogest, sequentially carrying out microfiltration through a ceramic membrane with the aperture of 500nm and ultrafiltration through a hollow fiber ultrafiltration membrane with the molecular weight cutoff of 5000Da to obtain ultrafiltration permeate; in this step, most of impurities in the enzymatic reaction solution are removed by filtration through ceramic membranes and ultrafiltration membranes.
S2, adding 95% ethanol solution into the ultrafiltration permeate until the ethanol concentration in the ultrafiltration permeate is 17%, and then adopting a nanofiltration membrane with a molecular weight cutoff of 150Da to carry out nanofiltration concentration treatment, wherein the pressure of the nanofiltration treatment is 0.5MPa, so as to obtain nanofiltration concentrate; in the step, the concentration of the dienogest is increased by nanofiltration concentration, the volume of the subsequent chromatographic purification treatment is reduced, and the purification rate is increased.
S3, passing the nanofiltration concentrated solution through a column to obtain a column purified solution; placing the purified solution after passing through the column into a rotary steaming bottle for one-time decompression rotary steaming, wherein the temperature of cooling water is-10 to-20 ℃, the rotating speed is 27rpm, the temperature is 25 ℃, and the pressure is 14mbar (the pressure is gradually reduced from 50mbar to 15mbar according to the boiling state of the solution); adding ethyl acetate into the feed liquid subjected to primary rotary evaporation to a separating funnel according to a proportion, uniformly mixing an organic phase with an aqueous phase through oscillation, standing for layering, taking an upper organic phase 1, and repeating the aqueous phase twice according to the method to obtain an organic phase 2 and an organic phase 3; mixing the organic phases 1, 2 and 3 uniformly, and performing secondary reduced pressure rotary evaporation, wherein the rotary evaporation pressure is 30mbar (the rotary evaporation pressure slowly decreases from 100mbar to 30mbar according to the boiling state of the solution), and other conditions are the same as those of the primary reduced pressure rotary evaporation; after the rotary steaming is completed, adding a small amount of 95% medicinal ethanol into a rotary steaming bottle, and redissolving the dienogest to obtain a concentrate of the dienogest.
Example 3
A method for concentrating dienoprost, comprising the steps of:
s1, taking enzymatic reaction liquid of dienogest, sequentially carrying out microfiltration through a ceramic membrane with the aperture of 200nm and ultrafiltration through a hollow fiber ultrafiltration membrane with the molecular weight cutoff of 5000Da to obtain ultrafiltration permeate; in this step, most of impurities in the enzymatic reaction solution are removed by filtration through ceramic membranes and ultrafiltration membranes.
S2, adding 95% ethanol solution into the ultrafiltration permeate until the ethanol concentration in the ultrafiltration permeate is 22%, and then adopting a nanofiltration membrane with a molecular weight cutoff of 150Da to carry out nanofiltration concentration treatment, wherein the pressure of the nanofiltration treatment is 0.8MPa, so as to obtain nanofiltration concentrate; in the step, the concentration of the dienogest is increased by nanofiltration concentration, the volume of the subsequent chromatographic purification treatment is reduced, and the purification rate is increased.
S3, passing the nanofiltration concentrated solution through a column to obtain a column purified solution; placing the purified solution after passing through the column into a rotary steaming bottle for one-time decompression rotary steaming, wherein the temperature of cooling water is-10 to-20 ℃, the rotating speed is 32rpm, the temperature is 25 ℃, and the pressure is 18mbar (the pressure is gradually reduced from 50mbar to 15mbar according to the boiling state of the solution); adding ethyl acetate into the feed liquid subjected to primary rotary evaporation to a separating funnel according to a proportion, uniformly mixing an organic phase with an aqueous phase through oscillation, standing for layering, taking an upper organic phase 1, and repeating the aqueous phase twice according to the method to obtain an organic phase 2 and an organic phase 3; mixing the organic phases 1, 2 and 3 uniformly, and performing secondary reduced pressure rotary evaporation, wherein the rotary evaporation pressure is 30mbar (the rotary evaporation pressure slowly decreases from 100mbar to 30mbar according to the boiling state of the solution), and other conditions are the same as those of the primary reduced pressure rotary evaporation; after the rotary steaming is completed, adding a small amount of 95% medicinal ethanol into a rotary steaming bottle, and redissolving the dienogest to obtain a concentrate of the dienogest.
Comparative example
Compared with the example 1, the difference is that in S2, nanofiltration concentration treatment is carried out on ultrafiltration permeate by adopting a nanofiltration membrane with the molecular weight cut-off of 150Da, and ethanol is not added into the ultrafiltration permeate; the remainder were identical.
The concentration of dienogest in each step in the embodiment 1 of the present invention is tested, the detection result is shown in table 1, and the high-phase liquid chromatogram is shown in fig. 3-4; the high-phase liquid chromatogram in the comparative example is shown in fig. 1-2; the chromatographic conditions in the high-phase liquid chromatography in fig. 1 and 2 are as follows:
| time min | Acetonitrile% | 10mmol ammonium acetate (ph=4.0))% | Flow rate ml/ |
| 0 | 30 | 70 | 1 |
| 12 | 95 | 5 | 1 |
| 12.01 | 95 | 5 | 1.2 |
| 14 | 95 | 5 | 1.2 |
| 15 | 30 | 70 | 1.2 |
| 19 | 30 | 70 | 1.2 |
Sample injection amount: 20ul; detection wavelength: 210nm.
The conditions of the high performance liquid chromatography in fig. 3-4 are:
mobile phase: acetonitrile: 17mmol phosphoric acid = 40:60, PH2.11; flow rate: 1.3ml/min (isocratic); sample injection amount: 20ul; detection wavelength: 210nm.
Other conditions of the HPLC in FIGS. 1-2 and 3-4 are identical.
TABLE 1 concentration of PEG2 in Ultrafiltration permeate and nanofiltration concentrate
As can be seen from Table 1 and FIGS. 1 to 4, it is difficult to concentrate the ultrafiltration permeate without ethanol by nanofiltration, and the concentration ratio is effectively increased after ethanol is added.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.
Claims (7)
1. A method for concentrating dienoprost, comprising the steps of:
s1, sequentially carrying out microfiltration and ultrafiltration treatment on enzymatic reaction liquid of dienogest to obtain ultrafiltration permeate;
s2, adding an ethanol solution into the ultrafiltration permeate until the concentration of ethanol in the ultrafiltration permeate is 17-22%, and then carrying out nanofiltration treatment to obtain nanofiltration concentrated solution;
and S3, subjecting the nanofiltration concentrated solution to column passing, primary rotary evaporation, extraction, secondary rotary evaporation and re-dissolution treatment to obtain the concentrated solution of the dienogest.
2. The concentrating method of dienogest according to claim 1, characterized in that a ceramic membrane microfiltration process is used; the pore diameter of the ceramic membrane is 100-500nm.
3. The concentrating method of dienogest according to claim 1, characterized in that ultrafiltration treatment is performed by using a hollow fiber ultrafiltration membrane; the molecular weight cut-off of the hollow fiber ultrafiltration membrane is 5000Da.
4. The concentrating method of dienogest according to claim 1, characterized in that nanofiltration treatment is carried out with nanofiltration membranes; the molecular weight cut-off of the nanofiltration membrane was 150Da.
5. The method for concentrating dienoprost according to claim 1, wherein the nanofiltration is carried out at a pressure of 0.5-0.8MPa.
6. The method for concentrating dienoprost according to claim 1, wherein the process conditions of the primary rotary evaporation and the secondary rotary evaporation are as follows: the pressure is 14-18mbar, the rotating speed is 27-32rpm, and the temperature is 25-30 ℃.
7. The method for concentrating dienoprost according to claim 1, wherein the extraction reagent is ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010988290.0A CN112028804B (en) | 2020-09-18 | 2020-09-18 | Concentrating method of dienogest |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010988290.0A CN112028804B (en) | 2020-09-18 | 2020-09-18 | Concentrating method of dienogest |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112028804A CN112028804A (en) | 2020-12-04 |
| CN112028804B true CN112028804B (en) | 2023-05-26 |
Family
ID=73575328
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010988290.0A Active CN112028804B (en) | 2020-09-18 | 2020-09-18 | Concentrating method of dienogest |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112028804B (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3992413A (en) * | 1975-07-25 | 1976-11-16 | Merck & Co., Inc. | Intermediates in the synthesis of prostaglandins |
| JPH04112866A (en) * | 1990-09-03 | 1992-04-14 | Lion Corp | Method for purifying prostaglandin |
| CN1064105A (en) * | 1991-02-08 | 1992-09-02 | 吉林大学 | Immobilized enzyme method is produced PGE 1, E 2 |
| CN1160766A (en) * | 1996-03-21 | 1997-10-01 | 江西鹿迪制药有限公司 | Prostaglandin E1 medicine material and its production technology |
| CN101120916A (en) * | 2006-08-08 | 2008-02-13 | 北京儒展生化药物研究中心 | Prostaglandin E2 injection and manufacturing method thereof |
| CN103373947A (en) * | 2012-04-27 | 2013-10-30 | 张家港九木科技有限公司 | Green synthesis method for dinoprostone (prostaglandin PGE2) |
| CN110951814A (en) * | 2019-12-30 | 2020-04-03 | 长春理工大学 | Method for preparing prostaglandin E1 by using genetically engineered cyclooxygenase-1 and genetically engineered prostaglandin E synthetase-1 |
| CN112479962A (en) * | 2020-11-23 | 2021-03-12 | 苏州纳微科技股份有限公司 | High-yield separation and purification method of prostaglandin E2 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001057225A1 (en) * | 2000-02-03 | 2001-08-09 | Chugai Seiyaku Kabushiki Kaisha | Protein having pge2 synthase activity and use thereof |
-
2020
- 2020-09-18 CN CN202010988290.0A patent/CN112028804B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3992413A (en) * | 1975-07-25 | 1976-11-16 | Merck & Co., Inc. | Intermediates in the synthesis of prostaglandins |
| JPH04112866A (en) * | 1990-09-03 | 1992-04-14 | Lion Corp | Method for purifying prostaglandin |
| CN1064105A (en) * | 1991-02-08 | 1992-09-02 | 吉林大学 | Immobilized enzyme method is produced PGE 1, E 2 |
| CN1160766A (en) * | 1996-03-21 | 1997-10-01 | 江西鹿迪制药有限公司 | Prostaglandin E1 medicine material and its production technology |
| CN101120916A (en) * | 2006-08-08 | 2008-02-13 | 北京儒展生化药物研究中心 | Prostaglandin E2 injection and manufacturing method thereof |
| CN103373947A (en) * | 2012-04-27 | 2013-10-30 | 张家港九木科技有限公司 | Green synthesis method for dinoprostone (prostaglandin PGE2) |
| CN110951814A (en) * | 2019-12-30 | 2020-04-03 | 长春理工大学 | Method for preparing prostaglandin E1 by using genetically engineered cyclooxygenase-1 and genetically engineered prostaglandin E synthetase-1 |
| CN112479962A (en) * | 2020-11-23 | 2021-03-12 | 苏州纳微科技股份有限公司 | High-yield separation and purification method of prostaglandin E2 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112028804A (en) | 2020-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104529755B (en) | A kind of method being separated α-ketoglutaric acid from conversion fluid | |
| Jackowski et al. | Non-alcoholic beer production–an overview | |
| CN112028804B (en) | Concentrating method of dienogest | |
| CN102838624B (en) | Method for purifying clavulanic acid from fermentation liquor | |
| CN107383135A (en) | The method that β thymidines are isolated and purified from zymotic fluid | |
| CN103130664A (en) | Process method of extracting gamma-aminobutyric acid through membrane separation technique | |
| CN111548380A (en) | Preparation method of monotropein in morinda officinalis | |
| CN106496022B (en) | A method of extracting pyruvic acid from microbial fermentation solution or enzymatic conversion liquid | |
| CN105439847A (en) | Separation purification method for natural abscisic acid | |
| CN107473979A (en) | A kind of processing method of film extraction theanine | |
| CN107629096A (en) | Using the method for β thymidines in ultrafiltration and ion exchange technique refining fermenting liquid | |
| CN107778357B (en) | Extraction and purification method of pneumocandin B0 | |
| CN111574639B (en) | Method for separating and purifying nitraria tangutorum bobr polysaccharide | |
| CN107056814A (en) | A kind of preparation method of the crude tacrolimus of low stain | |
| CN104356140A (en) | Method for separating and preparing high-purity Moxidectin membrane | |
| CN101780134B (en) | Membrane separation process for extracting solution of south dodder seed | |
| CN109705174B (en) | Method for extracting tobramycin | |
| CN104004091B (en) | A kind of preparation technology of human normal immunoglobulin | |
| CN112745368A (en) | Purification process of doxorubicin | |
| CN107904267B (en) | Method for synthesizing p-hydroxybenzaldehyde by adopting microbial transformation | |
| CN105420293A (en) | Method for separating and purifying resveratrol from traditional Chinese medicine polygonum cuspidatum extraction solution | |
| CN216321130U (en) | Extraction and concentration device for clavulanic acid fermentation liquor | |
| CN102018819A (en) | Radix rehmanniae extract membrane treatment process | |
| CN110787210A (en) | Method for preparing desmodium styracifolium total glycosides based on membrane separation technology | |
| CN215049775U (en) | Extraction and concentration device for 1, 3-propylene glycol fermentation liquor |
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 | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wang Kanglin Inventor after: Jin Yonghong Inventor after: Pu Kun Inventor after: Pan Liying Inventor after: Lin Zirong Inventor after: Wang Zhongwei Inventor after: Li Jun Inventor before: Wang Kanglin Inventor before: Jin Yonghong Inventor before: Pu Kun Inventor before: Pan Liying Inventor before: Lin Zirong |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 475000 66 south section of Jinming Road, Kaifeng, Henan Patentee after: KAIFENG KANGNUO PHARMACEUTICAL Co.,Ltd. Patentee after: Hefei Kangnuo Biopharmaceutical Co.,Ltd. Address before: 475000 66 south section of Jinming Road, Kaifeng, Henan Patentee before: KAIFENG KANGNUO PHARMACEUTICAL Co.,Ltd. Patentee before: Hefei Kangnuo biopharmaceutical Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 475000 66 south section of Jinming Road, Kaifeng, Henan Patentee after: KAIFENG KANGNUO PHARMACEUTICAL Co.,Ltd. Patentee after: Kangnuo Biopharmaceutical Co.,Ltd. Address before: 475000 66 south section of Jinming Road, Kaifeng, Henan Patentee before: KAIFENG KANGNUO PHARMACEUTICAL Co.,Ltd. Patentee before: Hefei Kangnuo Biopharmaceutical Co.,Ltd. |