CN1566097A - Purification process for 5-[pair-(2-pyridine sulfamic) benzene] azo salicylic acid - Google Patents
Purification process for 5-[pair-(2-pyridine sulfamic) benzene] azo salicylic acid Download PDFInfo
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- CN1566097A CN1566097A CN 03129670 CN03129670A CN1566097A CN 1566097 A CN1566097 A CN 1566097A CN 03129670 CN03129670 CN 03129670 CN 03129670 A CN03129670 A CN 03129670A CN 1566097 A CN1566097 A CN 1566097A
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 238000000746 purification Methods 0.000 title abstract description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Natural products OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 title abstract description 3
- -1 azo salicylic acid Chemical compound 0.000 title abstract description 3
- 229960004889 salicylic acid Drugs 0.000 title abstract description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 title abstract 2
- NCEXYHBECQHGNR-UHFFFAOYSA-N chembl421 Chemical compound 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 claims abstract description 43
- 239000000047 product Substances 0.000 claims abstract description 22
- 102100033717 Retroviral-like aspartic protease 1 Human genes 0.000 claims abstract description 21
- 101710188689 Small, acid-soluble spore protein 1 Proteins 0.000 claims abstract description 21
- 101710188693 Small, acid-soluble spore protein 2 Proteins 0.000 claims abstract description 21
- 101710166422 Small, acid-soluble spore protein A Proteins 0.000 claims abstract description 21
- 101710166404 Small, acid-soluble spore protein C Proteins 0.000 claims abstract description 21
- 101710174019 Small, acid-soluble spore protein C1 Proteins 0.000 claims abstract description 21
- 101710174017 Small, acid-soluble spore protein C2 Proteins 0.000 claims abstract description 21
- 101710174574 Small, acid-soluble spore protein gamma-type Proteins 0.000 claims abstract description 21
- 239000002253 acid Substances 0.000 claims abstract description 13
- 238000000926 separation method Methods 0.000 claims abstract description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 11
- 239000007787 solid Substances 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 8
- 238000004821 distillation Methods 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims 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 claims description 4
- 229960004110 olsalazine Drugs 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000012423 maintenance Methods 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 239000012535 impurity Substances 0.000 abstract description 25
- 230000000694 effects Effects 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract description 5
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- 101710166563 Small, acid-soluble spore protein I Proteins 0.000 description 8
- 239000012065 filter cake Substances 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 238000009413 insulation Methods 0.000 description 8
- 238000007670 refining Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000012467 final product Substances 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000005554 pickling Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- XNLWJFYYOIRPIO-UHFFFAOYSA-N 3-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C=CC=CC=2)=C1 XNLWJFYYOIRPIO-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 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 1
- WILKPBCVHVMTJO-UHFFFAOYSA-N OC1=C(C=C(C=C1)N=NC1=CC=C(C=C1)N1C(C=CC=C1)N)C(=O)O Chemical compound OC1=C(C=C(C=C1)N=NC1=CC=C(C=C1)N1C(C=CC=C1)N)C(=O)O WILKPBCVHVMTJO-UHFFFAOYSA-N 0.000 description 1
- SIWLKFXKWUUXNH-UHFFFAOYSA-N OC1=C(C=C(C=C1)N=NS(=O)(=O)C1=CC=CC=C1)C(=O)O Chemical compound OC1=C(C=C(C=C1)N=NS(=O)(=O)C1=CC=CC=C1)C(=O)O SIWLKFXKWUUXNH-UHFFFAOYSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation 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
- 238000006193 diazotization reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 159000000000 sodium salts Chemical class 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
- 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 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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Abstract
The invention relates to a purification process for 5-[pair-(2-pyridine sulfamic) benzene] azo salicylic acid, wherein a DMF hybrid solvent is utilized to dissolve the coarse product, and acid separation is employed to obtain the end product. The invention realizes simple operation, high yield, fine impurity removing effect and increased SASP quality.
Description
Technical field:
The present invention relates to the synthetic field of medicine, be specifically related to 5-[right-(2-pyridine sulfamic) benzene] purifying process of Olsalazine.
Background technology:
5-(right-(2-pyridine sulfamic) benzene) Olsalazine, general sulfasalazine by name (SASP) has following formula I structure
SASP is mainly used in the treatment nonspecific ulcerative colitis, and this product has special avidity to reticular tissue, and plays therapeutic action, the clinical rheumatic arthritis that also is used for the treatment of to discharge sulfapyridine and 5-aminosalicylic acid in the intestines wall.Although this product is an old product, the market requirement is still very big, and is especially more and more higher to its specification of quality.
The synthetic of SAPA normally is that starting raw material obtains intermediate SP (II) through amination and condensation with the pyridine, reaches and the Acidum Salicylicum coupling by diazotization then, obtains finished product SASP (I), and reaction formula is formula as follows:
Through above-mentioned reaction, the impurity that has in the finished product crude product is a lot, and the impurity of known structure has nine, comprising:
A, 4,4 '-[(4-hydroxyl-1,3-phenylene) two (diazenediyls)] two [N-(pyridine-2-yl) benzsulfamide.
B, 2-hydroxyl-3,5-two [2-(4-(pyridine-2-base sulfoamido) phenyl) diazenyl] phenylformic acid.
C, 2-hydroxyl-5-[2-[4-(2 aminopyridine-1 (2H)-yl) phenyl] diazenyl] phenylformic acid:
D, 4-[2-(2-hydroxy phenyl) diazenyl]-N-(pyridine-2 base) benzsulfamide:
E, 2-hydroxyl-4 '-(pyridine-2-base sulfoamido)-5-[2-[4-(pyridine-2-base sulfoamido) phenyl] diazenyl] phenylbenzene-3-carboxylic acid:
F, 2-hydroxyl-3-[2-[4-(pyridine-2-base sulfoamido) phenyl] diazenyl] phenylformic acid
G, 5-[2-[4 ', 5 two (pyridine-2-base sulfoamido) phenylbenzene-2-yl] diazenyl]-2 hydroxybenzoic acid:
H, Whitfield's ointment
I, 2-hydroxyl-5-[2-(4-benzenesulfonyl) diazenyl] phenylformic acid:
Be B, E, F wherein, in treating process, be difficult to remove to the most similar impurity of finished product character.
Reaching conventional process for purification according to the literature is the SASP crude product to be refluxed with Glacial acetic acid remove alkaline impurities, after the centrifugation, is dissolved in alkaline solution again, the acquisition finished product of saltouing after the decolouring.Used acid, the alkali number of this method is big, and yield is low, and equipment corrosion is serious, and the three wastes are difficult to handle, and final product quality is difficult to reach the regulation of European Pharmacopoeia.
Summary of the invention:
Technical problem to be solved by this invention is to improve existing SASP process for purification, and a kind of economy, easy is provided, and removes the more effective significant method of impurity.
SASP purification process disclosed by the invention comprises the following steps:
(1) in the SASP crude product, add 2～6 times 15～70% the DMF aqueous solution, heated and stirred slowly adds alkali, to all dissolvings;
(2) drip acid in above-mentioned solution, maintenance pH is 1-3,60～95 ℃ of temperature, and fully centrifuging promptly gets half highly finished product behind the acid out;
(3) above-mentioned half highly finished product are added alkali dissolution in the aqueous solution, add heat decoloring, filter, filtrate is adjusted to pH1-3 with acid, filters, and is drying to obtain;
(4) the DMF solution behind step (2) the separation finished product is applied mechanically after underpressure distillation is handled.
Alkali of the present invention and acid are acid or alkali such as industrial nitric acid, hydrochloric acid and industrial solid sodium hydroxide or liquid sodium hydroxide commonly used.
The present invention has carried out a series of groping to SASP crude product refining method:
(1) the nitration mixture pickling refluxes and carries highly acid pH value, can play certain effect to removing impurity, but undesirable, can't reach the specification of quality of EP4 version.
(2) add elutriation with the neat solvent dissolving and go out, cold filtration is refining, and the result separates out impurity simultaneously, and it is not obvious to remove impurity; If the filtered while hot yield is low, it is big to reclaim quantity of solvent simultaneously, and neat solvent must be gone up column distillation, and energy consumption is big, and production schedule is slow, and yield is on the low side.
(3) mixed solvent refluxes to wash and can only remove less impurity, mainly is the complete molten process of none, and this method is also inadvisable.
Adopt the thin plate layer analysis method to detect, the impurity spot of SASP mainly is that two significantly big impurity spots are being arranged on the point of sample and under the principal spot, with the Glacial acetic acid reflow method mainly is the impurity spot of removing on the point of sample, i.e. diamino-pyridine impurity (impurity numbering C).With becoming the sodium salt method mainly to remove impurity spot principal spot under, i.e. Whitfield's ointment impurity, effect is relatively good, and the impurity spot effect that Glacial acetic acid is washed is not remarkable.
With the method for DMF mixed solvent of the present invention, can remove above-mentioned two major impurities simultaneously, and can remove other impurity in a small amount.Its major cause is at first crude product to be dissolved fully, according to the character of product, the product acid out is come out again, and the impurity that is wrapped in the crude product solid is fully separated.To compare effect obvious with methods such as former pickling.
Adopt process for purification of the present invention, have following distinguishing feature:
1, it is obvious to remove impurity, and final product quality meets the requirement of Chinese Pharmacopoeia 2000 editions, BP2000 version, Ph.Eur.4 version fully, and the T degree requires can satisfy various requirement simultaneously, accomplishes fluently solid foundation for pharmacopeia from now on rises version.Just contrasting as can be seen from the stratographic analysis figure (Fig. 1) that improves the back finished product stratographic analysis figure (Fig. 2) that produces and original finished product, 9 impurity obviously reduce.
2, improve 15% by the refining yield of process modification.
3, easy and simple to handle, easy to control with novel process, low to equipment corrosion, shorten the production cycle and reduced labour intensity, the labour protection aspect is had more reasonableness.
4, the solvent employing is applied mechanically in the improvement technology, deals impurity simultaneously and also can focus on solid form, and the three wastes obviously reduce.
Description of drawings:
The former explained hereafter of Fig. 1 obtains the HPLC collection of illustrative plates of SASP
Fig. 2 obtains the HPLC collection of illustrative plates of SASP with explained hereafter of the present invention
Wherein I, C, G, B, A are impurity peaks.
Embodiment:
SASP crude product 30g and 60g70%DMF solution are dropped in the 250ml reaction flask, open and stir, heating, add solid NaOH, regulate pH to 7.5～8.5 in 60 ℃, complete molten after, insulation, drip HCL to pH2.0～2.5, filter, the filter cake hot wash is drained, get SASP-I, mother liquor DMF recovery set after underpressure distillation is handled is used.SASP-I is dropped in the deionized water of 20 times of amounts, add NaOH, heating for dissolving is regulated pH to 7.5～8.5, add proper amount of active carbon after molten entirely in 70 ± 2 ℃ of insulation decolourings, filter, filtrate is adjusted to pH2.0～2.5 with hydrochloric acid, filters, the filter cake hot wash, dry the SASP finished product, refining yield 80.33%, the gained final product quality meets EP4.(seeing collection of illustrative plates 2)
SASP crude product 30g and 120g15%DMF solution are dropped in the 250ml reaction flask, open and stir, heating, add solid NaOH, with 80 ℃ regulate pH to 7.5～8.5, complete molten after, insulation, drip HCL to pH2.0～2.5, filter, the filter cake hot wash is drained, get SASP-I, mother liquor DMF recovery set after underpressure distillation is handled is used.SASP-I is dropped in the deionized water of 20 times of amounts, add NaOH, heating for dissolving is regulated pH to 7.5～8.5, add proper amount of active carbon after molten entirely in 70 ± 2 ℃ of insulation decolourings, filter, filtrate is adjusted to pH2.0～2.5 with hydrochloric acid, filters, the filter cake hot wash, dry the SASP finished product, refining yield 81.66%, the gained final product quality meets EP4.
SASP crude product 30g and 150G45%DMF solution are dropped in the 250ml reaction flask, open and stir, heating, add solid NaOH, with 60 ℃ regulate pH to 7.5～8.5, complete molten after, insulation, drip HCL to pH2.0～2.5, filter, the filter cake hot wash is drained, get SASP-I, mother liquor DMF recovery set after underpressure distillation is handled is used.SASP-I is dropped in the deionized water of 20 times of amounts, add NaOH, heating for dissolving is regulated pH to 7.5～8.5, add proper amount of active carbon after molten entirely in 70 ± 2 ℃ of insulation decolourings, filter, filtrate is adjusted to pH2.0～2.5 with hydrochloric acid, filters, the filter cake hot wash, dry the SASP finished product, refining yield 79.33%, the gained final product quality meets EP4.
SASP crude product 30g and 180g30%DMF solution are dropped in the 250ml reaction flask, open and stir, heating, add solid NaOH, with 65 ℃ regulate pH to 7.5～8.5, complete molten after, insulation, drip HCL to pH2.0～2.5, filter, the filter cake hot wash is drained, get SASP-I, mother liquor DMF recovery set after underpressure distillation is handled is used.SASP-I is dropped in the deionized water of 20 times of amounts, add NaOH, heating for dissolving is regulated pH to 7.5～8.5, add proper amount of active carbon after molten entirely in 70 ± 2 ℃ of insulation decolourings, filter, filtrate is adjusted to pH2.0～2.5 with hydrochloric acid, filters, the filter cake hot wash, dry the SASP finished product, refining yield 80.33%, the gained final product quality meets EP4.
Claims (3)
1,5-[right-(2-pyridine sulfamic) benzene] the Olsalazine purifying process, it is characterized in that this method comprises the following steps:
(1) in the SASP crude product, add 2～6 times 15～70% the DMF aqueous solution, heated and stirred slowly adds alkali, to all dissolvings;
(2) drip acid in above-mentioned solution, maintenance pH is 1-3,60～95 ℃ of temperature, treat abundant acid out after centrifuging promptly;
(3) above-mentioned half highly finished product are added alkali dissolution in the aqueous solution, add heat decoloring, filter, filtrate is adjusted to pH1-3 with acid, filters, and is drying to obtain;
(4) the DMF solution behind step (2) the separation finished product is applied mechanically after underpressure distillation is handled.
2, purifying process according to claim 1 is characterized in that wherein said alkali and acid are selected from solid sodium hydroxide, the liquid sodium hydroxide of industrial nitric acid, hydrochloric acid and technical grade respectively.
3, purifying process according to claim 1 is characterized in that the DMF solution behind wherein said separation half highly finished product, applies mechanically after underpressure distillation is handled.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 03129670 CN1261413C (en) | 2003-07-01 | 2003-07-01 | Purification process for 5-[pair-(2-pyridine sulfamic) benzene] azo salicylic acid |
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| CN 03129670 CN1261413C (en) | 2003-07-01 | 2003-07-01 | Purification process for 5-[pair-(2-pyridine sulfamic) benzene] azo salicylic acid |
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| CN1566097A true CN1566097A (en) | 2005-01-19 |
| CN1261413C CN1261413C (en) | 2006-06-28 |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044323A (en) * | 2012-12-27 | 2013-04-17 | 浙江九洲药业股份有限公司 | Method for purifying salazosulfapyridine |
| CN103709098A (en) * | 2013-12-27 | 2014-04-09 | 浙江九洲药业股份有限公司 | Salazosulfapyridine crystal form and preparation method thereof |
| CN104130186A (en) * | 2014-06-30 | 2014-11-05 | 江苏瑞克医药科技有限公司 | Method for improving salicylazosulfapyridine refining production efficiency |
| CN105330599A (en) * | 2015-11-26 | 2016-02-17 | 苏州统华药品有限公司 | Method for synthesizing salazosulfapyridine by utilizing 2-aminopyridine as raw material |
| CN105348184A (en) * | 2015-11-26 | 2016-02-24 | 苏州统华药品有限公司 | Preparation method for sulfasalazine |
| CN105367488A (en) * | 2015-11-26 | 2016-03-02 | 苏州统华药品有限公司 | Purification method for salazosulfapyridine |
| CN105367489A (en) * | 2015-11-26 | 2016-03-02 | 苏州统华药品有限公司 | Method for synthesizing salazosulfapyridine using pyridazol as raw material |
| CN106032357A (en) * | 2015-03-11 | 2016-10-19 | 浙江九洲药物科技有限公司 | Sulfasalazine impurities and preparation method thereof |
| CN106279008A (en) * | 2015-05-19 | 2017-01-04 | 浙江九洲药业股份有限公司 | A kind of purifying process of sulfasalazine |
| CN108264481A (en) * | 2017-01-03 | 2018-07-10 | 江苏瑞科医药科技有限公司 | Salazosulfapyridine crystal form and preparation method thereof |
-
2003
- 2003-07-01 CN CN 03129670 patent/CN1261413C/en not_active Expired - Lifetime
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044323A (en) * | 2012-12-27 | 2013-04-17 | 浙江九洲药业股份有限公司 | Method for purifying salazosulfapyridine |
| CN103044323B (en) * | 2012-12-27 | 2017-12-19 | 浙江九洲药业股份有限公司 | A kind of purification process of SASP |
| CN103709098A (en) * | 2013-12-27 | 2014-04-09 | 浙江九洲药业股份有限公司 | Salazosulfapyridine crystal form and preparation method thereof |
| CN104130186A (en) * | 2014-06-30 | 2014-11-05 | 江苏瑞克医药科技有限公司 | Method for improving salicylazosulfapyridine refining production efficiency |
| CN106032357A (en) * | 2015-03-11 | 2016-10-19 | 浙江九洲药物科技有限公司 | Sulfasalazine impurities and preparation method thereof |
| CN106279008A (en) * | 2015-05-19 | 2017-01-04 | 浙江九洲药业股份有限公司 | A kind of purifying process of sulfasalazine |
| CN105330599A (en) * | 2015-11-26 | 2016-02-17 | 苏州统华药品有限公司 | Method for synthesizing salazosulfapyridine by utilizing 2-aminopyridine as raw material |
| CN105348184A (en) * | 2015-11-26 | 2016-02-24 | 苏州统华药品有限公司 | Preparation method for sulfasalazine |
| CN105367488A (en) * | 2015-11-26 | 2016-03-02 | 苏州统华药品有限公司 | Purification method for salazosulfapyridine |
| CN105367489A (en) * | 2015-11-26 | 2016-03-02 | 苏州统华药品有限公司 | Method for synthesizing salazosulfapyridine using pyridazol as raw material |
| CN105348184B (en) * | 2015-11-26 | 2020-12-29 | 苏州统华药品有限公司 | Preparation method of sulfasalazine |
| CN108264481A (en) * | 2017-01-03 | 2018-07-10 | 江苏瑞科医药科技有限公司 | Salazosulfapyridine crystal form and preparation method thereof |
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