CN103360278B - Method for improving olsalazine sodium quality - Google Patents
Method for improving olsalazine sodium quality Download PDFInfo
- Publication number
- CN103360278B CN103360278B CN201310333249.XA CN201310333249A CN103360278B CN 103360278 B CN103360278 B CN 103360278B CN 201310333249 A CN201310333249 A CN 201310333249A CN 103360278 B CN103360278 B CN 103360278B
- Authority
- CN
- China
- Prior art keywords
- olsalazine sodium
- crude product
- olsalazine
- product quality
- quality
- 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
- ZHPBLHYKDKSZCQ-UHFFFAOYSA-N cyclooctylmethanol Chemical compound OCC1CCCCCCC1 ZHPBLHYKDKSZCQ-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 229960004364 olsalazine sodium Drugs 0.000 title claims abstract description 66
- 238000000034 method Methods 0.000 title claims abstract description 27
- 239000012043 crude product Substances 0.000 claims abstract description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000008139 complexing agent Substances 0.000 claims abstract description 13
- 238000010438 heat treatment Methods 0.000 claims abstract description 7
- 238000002425 crystallisation Methods 0.000 claims abstract description 3
- 230000008025 crystallization Effects 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- 239000012065 filter cake Substances 0.000 claims description 20
- 239000000706 filtrate Substances 0.000 claims description 18
- 239000000047 product Substances 0.000 claims description 14
- 238000009413 insulation Methods 0.000 claims description 12
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 claims description 7
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 2
- 239000008213 purified water Substances 0.000 claims description 2
- 235000015598 salt intake Nutrition 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 238000002791 soaking Methods 0.000 claims description 2
- 229910001385 heavy metal Inorganic materials 0.000 abstract description 35
- 239000003814 drug Substances 0.000 abstract description 10
- 150000002500 ions Chemical class 0.000 abstract description 4
- 238000004090 dissolution Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 238000007670 refining Methods 0.000 description 17
- 238000003756 stirring Methods 0.000 description 8
- 238000010792 warming Methods 0.000 description 8
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 4
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 4
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229960004110 olsalazine Drugs 0.000 description 4
- QQBDLJCYGRGAKP-FOCLMDBBSA-N olsalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=C(C(O)=CC=2)C(O)=O)=C1 QQBDLJCYGRGAKP-FOCLMDBBSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical class NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 3
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 2
- 230000000536 complexating effect Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 229960004963 mesalazine Drugs 0.000 description 2
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 2
- 229960001940 sulfasalazine Drugs 0.000 description 2
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000008951 colonic inflammation Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- MXUHMQZOATZRIK-UHFFFAOYSA-N methyl 5-amino-2-hydroxybenzoate Chemical class COC(=O)C1=CC(N)=CC=C1O MXUHMQZOATZRIK-UHFFFAOYSA-N 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 210000001711 oxyntic cell Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- GECHUMIMRBOMGK-UHFFFAOYSA-N sulfapyridine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=CC=CC=N1 GECHUMIMRBOMGK-UHFFFAOYSA-N 0.000 description 1
- 229960002211 sulfapyridine Drugs 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of drug chemosynthesis and relates to a method for improving olsalazine sodium quality. The method comprises the following steps of dissolving an olsalazine sodium crude product in a certain amount of water, adding an appropriate amount of a complexing agent into the solution, carrying out heating for dissolution and crystallization, and removing heavy metal ions. The method can improve olsalazine sodium appearance and realize heavy metal ion removal.
Description
Technical field
The invention belongs to the synthetic field of pharmaceutical chemistry, be specially a kind of method that improves Olsalazine sodium quality.
Background technology
Olsalazine sodium is also Olsalazine (Olsalazine), has another name called Olsalazine, Di Botan, is by the medicine of Phar ma ci A B company of Switzerland exploitation, goes on the market first in 1989 in Denmark.Olsalazine splits into 2 molecule 5-aminosalicylic acids and acts on colonic inflammation mucous membrane under colon bacteria effect, suppress prostaglandin(PG) synthetic, the formation of inflammation-inhibiting medium leukotriene, reduce the permeability of intestines parietal cell film, alleviate intestinal mucosa oedema, therefore it has anti-inflammatory, increases immunity of organisms, reduces the effects such as inflammatory mediator generation.The clinical long term maintenance treatment that is used for the treatment of acute and chronic ulcerative colitis, clone disease, Crohn disease and alleviation thereof.This product substitutes the sulfapyridine of non-activity in sulfasalazine with activeconstituents 5-aminosalicylic acid, connect the 5-aminosalicylic acid of 2 molecules by azo bond, and with sulfasalazine comparison, curative effect improves, adverse reaction rate reduces.
Due to the feature of Olsalazine sodium self structure, be very easy in process of production the heavy metal ion in complexing raw material or conversion unit, cause Olsalazine sodium heavy metal content severe overweight, Quality Down, and do not take effective process for purification for the heavy metal wherein containing at present, cause quality product decline, and clothes for patients with after there is negative influence.
Summary of the invention
Main purpose of the present invention is to provide a kind of method that improves Olsalazine sodium quality, the method is by Olsalazine sodium crude product heating for dissolving, adopt complexing agent to carry out complexing, then filtration washing, step is simple, easy to operate, make heavy metal content drop to the following (inspection (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law of 20ppm by 1000ppm, must not cross 20/1000000ths containing heavy metal), outward appearance becomes glassy yellow from green-yellow, thereby reaches the specification of quality described in pharmacopeia.
The refining Olsalazine sodium crude product of the present invention is diazonium salt and the wintergreen oil coupling of preparing with 5-aminosalicylic acid methyl esters, and gained azo makes with sodium hydroxide hydrolysis again.
Technical scheme of the present invention:
A method that improves Olsalazine sodium quality, comprises the following steps:
(1) Olsalazine sodium crude product is heated to 80-105 DEG C, is dissolved in appropriate pure water, amount of purified water used is 5-15 times of Olsalazine sodium crude product quality;
(2) after heating for dissolving, add the complexing agent of Olsalazine sodium crude product quality 1-10%, at 80-105 DEG C of insulation 10-50min;
(3) at 80-100 DEG C, filter, cooling crystallization, filters, and by methanol wash twice, is 10% of Olsalazine sodium crude product quality at every turn, obtains glassy yellow product.
Described complexing agent is removed the heavy metal ion in Olsalazine sodium crude product, and complexing agent used is the one in nitrilotriacetic acid(NTA) sodium (NTA), disodium EDTA (EDTA), tetrasodium salt of EDTA (EDTA), diethylenetriamine pentacarboxylic acid salt (DTPA).
Described complexing agent consumption is the 2-10% of Olsalazine sodium crude product quality.
Described complexing agent disodium EDTA or tetrasodium salt of EDTA consumption are the 2-3% of Olsalazine sodium crude product quality.
Described complexing agent nitrilotriacetic acid(NTA) sodium consumption is the 7-8% of Olsalazine sodium crude product quality.
Described complexing agent diethylenetriamine pentacarboxylic acid salt consumption is the 9-10% of Olsalazine sodium crude product quality.
In step (1), pure water consumption is 8-10 times of Olsalazine sodium crude product quality.
In step (1), pure water consumption is 11 times of Olsalazine sodium crude product quality.
In step (2), soaking time is 10-15 minute.
Described step (3) is to filter at 80-100 DEG C, is cooled to 0-5 DEG C, leaves standstill insulation extremely dry by rejection filter after 24 hours, and methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn, and filtrate is reclaimed; Filter cake is dried 4～6 hours at 60～65 DEG C, obtains product.
Beneficial effect of the present invention is:
Refine for the heavy metal in Olsalazine sodium crude product, successful, step is simple, make Olsalazine sodium crude product heavy metal content drop to the following (inspection (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law of 20ppm by 1000ppm, must not cross 20/1000000ths containing heavy metal), outward appearance becomes glassy yellow from green-yellow, thereby reaches the specification of quality described in pharmacopeia, and concrete data are shown in detection table 1.
In a word, the present invention possesses outstanding substantive distinguishing features and significant progressive.
table 1 Olsalazine sodium is processed front and back quality examination table
embodiment
Below by specific embodiment, technical scheme of the present invention is described in detail.
Following detection method is two annex VIII H first methods of Chinese Pharmacopoeia version in 2010.
embodiment 1
In reactor, add 44kg pure water, 4.0kg Olsalazine sodium crude product, heating makes its dissolving, add Olsalazine sodium crude product quality 3% disodium EDTA, stirring is warming up to 100 DEG C, is incubated 10～15 minutes, filtered while hot, filtrate is cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn.Filtrate is reclaimed.Filter cake is dried 4～6 hours at 60～65 DEG C, the qualified product 3.80kg obtaining, yield 95%.
Before refining, heavy metal content has exceeded 1000ppm, outward appearance green-yellow, refining rear detection heavy metal is 10ppm, outward appearance glassy yellow, reach the required standard of medicine (check (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law, must not cross 20/1000000ths containing heavy metal).
embodiment 2
In reactor, add 44kg pure water, 4.0kg Olsalazine sodium crude product, heating makes its dissolving, add Olsalazine sodium crude product quality 8% NTA, stirring is warming up to 105 DEG C, is incubated 10～15 minutes, filtered while hot, filtrate is cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn.Filtrate is reclaimed.Filter cake is dried 6 hours at 60 DEG C, the qualified product 3.84kg obtaining, yield 96%.
Before refining, heavy metal content has exceeded 1000ppm, outward appearance green-yellow, refining rear heavy metal 9ppm, the outward appearance glassy yellow of detecting, reach the required standard of medicine (check (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law, must not cross 20/1000000ths containing heavy metal).
embodiment 3
In reactor, add 44kg pure water, 4.0kg Olsalazine sodium crude product, heating makes its dissolving, add Olsalazine sodium crude product quality 10% DTPA, stirring is warming up to 80 DEG C, is incubated 10～15 minutes, filtered while hot, filtrate is cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn.Filtrate is reclaimed.Filter cake is dried 4 hours at 65 DEG C, the qualified product 3.82kg obtaining, yield 95.5%.
Before refining, heavy metal content has exceeded 1000ppm, outward appearance green-yellow, refining rear heavy metal 11ppm, the outward appearance glassy yellow of detecting, reach the required standard of medicine (check (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law, must not cross 20/1000000ths containing heavy metal).
embodiment 4
In reactor, add 20kg pure water, 4.0kg Olsalazine sodium crude product, be heated to 80 DEG C and make its dissolving, add Olsalazine sodium crude product quality 9% DTPA, stirring is warming up to 100 DEG C, is incubated 50 minutes, filtered while hot, filtrate is cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn.Filtrate is reclaimed.Filter cake is dried 4 hours at 65 DEG C, the qualified product 3.70kg obtaining, yield 92.5%.
Before refining, heavy metal content has exceeded 1000ppm, outward appearance green-yellow, refining rear heavy metal 11ppm, the outward appearance glassy yellow of detecting, reach the required standard of medicine (check (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law, must not cross 20/1000000ths containing heavy metal).
embodiment 5
In reactor, add 60kg pure water, 4.0kg Olsalazine sodium crude product, be heated to 100 DEG C and make its dissolving, add Olsalazine sodium crude product quality 2% tetrasodium salt of EDTA, stirring is warming up to 103 DEG C, is incubated 10 minutes, filtered while hot, filtrate is cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn.Filtrate is reclaimed.Filter cake is dried 5 hours at 63 DEG C, the qualified product 3.68kg obtaining, yield 92.0%.
Before refining, heavy metal content has exceeded 1000ppm, outward appearance green-yellow, refining rear heavy metal 11ppm, the outward appearance glassy yellow of detecting, reach the required standard of medicine (check (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law, must not cross 20/1000000ths containing heavy metal).
embodiment 6
In reactor, add 32kg pure water, 4.0kg Olsalazine sodium crude product, be heated to 100 DEG C and make its dissolving, add Olsalazine sodium crude product quality 1% disodium EDTA, stirring is warming up to 105 DEG C, is incubated 30 minutes, filtered while hot, filtrate is cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn.Filtrate is reclaimed.Filter cake is dried 5 hours at 63 DEG C, the qualified product 3.76kg obtaining, yield 94%.
Before refining, heavy metal content has exceeded 1000ppm, outward appearance green-yellow, refining rear heavy metal 11ppm, the outward appearance glassy yellow of detecting, reach the required standard of medicine (check (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law, must not cross 20/1000000ths containing heavy metal).
embodiment 7
In reactor, add 40kg pure water, 4.0kg Olsalazine sodium crude product, be heated to 80 DEG C and make its dissolving, add Olsalazine sodium crude product quality 9% DTPA, stirring is warming up to 90 DEG C, is incubated 20 minutes, filtered while hot, filtrate is cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn.Filtrate is reclaimed.Filter cake is dried 6 hours at 60 DEG C, the qualified product 3.82kg obtaining, yield 95.5%.
Before refining, heavy metal content has exceeded 1000ppm, outward appearance green-yellow, refining rear heavy metal 11ppm, the outward appearance glassy yellow of detecting, reach the required standard of medicine (check (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law, must not cross 20/1000000ths containing heavy metal).
embodiment 8
In reactor, add 44kg pure water, 4.0kg Olsalazine sodium crude product, be heated to 90 DEG C and make its dissolving, add Olsalazine sodium crude product quality 7% NTA, stirring is warming up to 105 DEG C, is incubated 15 minutes, filtered while hot, filtrate is cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn.Filtrate is reclaimed.Filter cake is dried 4 hours at 60 DEG C, the qualified product 3.84kg obtaining, yield 96%.
Before refining, heavy metal content has exceeded 1000ppm, outward appearance green-yellow, refining rear heavy metal 11ppm, the outward appearance glassy yellow of detecting, reach the required standard of medicine (check (two annex VIII H first methods of Chinese Pharmacopoeia version in 2010) in accordance with the law, must not cross 20/1000000ths containing heavy metal).
Detailed introduction to the embodiment of the present invention above, for one of ordinary skill in the art, according to the thought of the embodiment of the present invention, all will change in specific embodiments and applications, in sum, this description should not be construed as limitation of the present invention.
Claims (5)
1. a method that improves Olsalazine sodium quality, comprises the following steps:
(1) Olsalazine sodium crude product is heated to 80-105 DEG C, is dissolved in appropriate pure water, amount of purified water used is 5-15 times of Olsalazine sodium crude product quality;
(2) after heating for dissolving, add the complexing agent of Olsalazine sodium crude product quality 1-10%, at 80-105 DEG C of insulation 10-50min; Described complexing agent is the one in nitrilotriacetic acid(NTA) sodium, diethylenetriamine pentacarboxylic acid salt; Described complexing agent nitrilotriacetic acid(NTA) sodium consumption is the 7-8% of Olsalazine sodium crude product quality; Described complexing agent diethylenetriamine pentacarboxylic acid salt consumption is the 9-10% of Olsalazine sodium crude product quality;
(3) at 80-100 DEG C, filter, cooling crystallization, filters, and by methanol wash twice, is 10% of Olsalazine sodium crude product quality at every turn, obtains glassy yellow product.
2. the method for raising Olsalazine sodium quality according to claim 1, is characterized in that, in step (1), pure water consumption is 8-10 times of Olsalazine sodium crude product quality.
3. the method for raising Olsalazine sodium quality according to claim 1, is characterized in that, in step (1), pure water consumption is 11 times of Olsalazine sodium crude product quality.
4. the method for raising Olsalazine sodium quality according to claim 1, is characterized in that, in step (2), soaking time is 10-15 minute.
5. the method for raising Olsalazine sodium quality according to claim 1, it is characterized in that, described step (3) is to filter at 80-100 DEG C, be cooled to 0-5 DEG C, leave standstill insulation extremely dry by rejection filter after 24 hours, methanol wash twice for filter cake is 10% of Olsalazine sodium crude product quality at every turn, and filtrate is reclaimed; Filter cake is dried 4～6 hours at 60～65 DEG C, obtains product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310333249.XA CN103360278B (en) | 2013-08-02 | 2013-08-02 | Method for improving olsalazine sodium quality |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310333249.XA CN103360278B (en) | 2013-08-02 | 2013-08-02 | Method for improving olsalazine sodium quality |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103360278A CN103360278A (en) | 2013-10-23 |
| CN103360278B true CN103360278B (en) | 2014-11-05 |
Family
ID=49362634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310333249.XA Active CN103360278B (en) | 2013-08-02 | 2013-08-02 | Method for improving olsalazine sodium quality |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103360278B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101786964A (en) * | 2010-03-16 | 2010-07-28 | 天津力生制药股份有限公司 | Improved synthetic method of Olsalazine sodium |
-
2013
- 2013-08-02 CN CN201310333249.XA patent/CN103360278B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101786964A (en) * | 2010-03-16 | 2010-07-28 | 天津力生制药股份有限公司 | Improved synthetic method of Olsalazine sodium |
Non-Patent Citations (3)
| Title |
|---|
| 超声波作用下合成奥沙拉秦;陈小全;《超声波作用下合成奥沙拉秦》;20081231;第17卷;858-860 * |
| 郑爱玲.络合滴定法.《化学基础与分析检验》.中国计量出版社,2003,136-138. * |
| 陈小全.超声波作用下合成奥沙拉秦.《超声波作用下合成奥沙拉秦》.2008,第17卷858-860. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103360278A (en) | 2013-10-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106397630B (en) | A method of Sodium Hyaluronate is extracted using membrane separation technique | |
| CN101831002B (en) | Preparation method of sodium alginate for tissue engineering | |
| CN103232558B (en) | Preparation method of high-quality low-molecular weight dalteparin sodium | |
| CN102863519A (en) | Refining method for vancomycin hydrochloride | |
| CN102070727A (en) | Extraction method of sodium heparin | |
| CN106831894B (en) | A kind of method of deacetylation Coupling Adsorption separation D-Glucosamine Hydrochloride | |
| CN104448043B (en) | The production of a kind of Enoxaparin Sodium and purification process | |
| CN103360278B (en) | Method for improving olsalazine sodium quality | |
| CN104610385A (en) | Refining method of D-glucosamine hydrochloride | |
| CN107488129B (en) | Method for purifying L-valine from L-valine compound | |
| CN102863497B (en) | Hyodeoxycholic acid refining method | |
| CN101942039A (en) | Parnaparin production method | |
| CN104974157A (en) | Istradefylline synthesis process | |
| CN105218390A (en) | A kind of Propacetamol Hydrochloride preparation technology of improvement | |
| CN102432645B (en) | A kind of purification process of Etimicin sulfate | |
| CN111217934A (en) | Method for removing endotoxin in pectin and pectin for removing endotoxin | |
| CN110922506A (en) | High-clarity heparin sodium | |
| CN102382072A (en) | Method for refining D-cycloserine | |
| CN104558251B (en) | A kind of preparation method of liquaemin | |
| CN107674131A (en) | A kind of method of the extraction purification hyaluronic acid from zymotic fluid | |
| CN102351775B (en) | Preparation method of levo-5-hydroxytryptophan | |
| CN104650165B (en) | A kind of preparation method of scutelloside | |
| CN111574576B (en) | Refining method of diquafosol sodium | |
| CN103923230A (en) | Heparin sodium refinement method | |
| CN102367255B (en) | Method for extracting riboflavin from riboflavin fermentation liquor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhou Yanming Inventor after: Luo Hongyu Inventor before: Liu Huaizhen |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: LIU HUAIZHEN TO: ZHOU YANMING LUO HONGYU |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160629 Address after: 252022 north of the Mount Lu, Liaocheng economic and Technological Development Zone, Shandong Patentee after: SHANDONG CHUANCHENG PHARMACEUTICAL CO., LTD. Address before: 250132, Sichuan Province, Ji'nan Shandong high tech Zone martyrs Road No. 15, Sichuan Pharmaceutical Science and Technology Development Co., Ltd. Patentee before: Liu Huaizhen |