CN101723934A - Method for refining fasudil hydrochloride - Google Patents
Method for refining fasudil hydrochloride Download PDFInfo
- Publication number
- CN101723934A CN101723934A CN 200910224197 CN200910224197A CN101723934A CN 101723934 A CN101723934 A CN 101723934A CN 200910224197 CN200910224197 CN 200910224197 CN 200910224197 A CN200910224197 A CN 200910224197A CN 101723934 A CN101723934 A CN 101723934A
- Authority
- CN
- China
- Prior art keywords
- water
- add
- propyl carbinol
- distillation
- oil phase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for refining fasudil hydrochloride. The method comprises the following steps: 1, discoloring, namely adding active carbon into fasudil after resin adsorption, fully mixing the active carbon and the fasudil, filtering the mixture, removing the active carbon, and collecting the filtered solution for later use; 2, washing, namely adding purified water into the discolored solution, fully mixing the solution, separating the solution to remove water phase, and collecting the oil phase for later use; 3, acidifying and salifying, namely adding the purified water into the oil phase, adjusting pH value of the solution by hydrochloric acid to fully acidify and salify the oil phase, and collecting the water phase for later use; and 4, crystallization, namely, adding n-butyl alcohol into the water phase, fully mixing the solution, then decompressing and azeotropic-crystallizing the solution, duly replenishing the n-butyl alcohol to keep the consistency of the solution, stopping crystallization till the moisture content in the mother solution is reduced to a certain value, and filtering and drying the crystals to obtain a refined fasudil hydrochloride product.
Description
Technical field:
The present invention relates to a kind of refining and extracting of bulk drug, particularly a kind of process for refining that is used for the medicine Fasudil Hydrochloride production of raw medicine process of the ischemic cerebrovascular doing well,improving that cerebral vasospasm after subarachnoid hemorrhage etc. causes.
Technical background:
Fasudil Hydrochloride; English name: Fasudil; chemical name: six hydrogen-1-(5-alkylsulfonyl isoquinoline 99.9)-1 (H)-1; 4-diazepine hydrochloride; be that a kind of kinases inhibitor is the intracellular calcium antagonist; be used for the treatment of ischemic encephalopathy; existing Fasudil Hydrochloride is produced and is generally adopted 5-sulfonic acid isoquinoline 99.9 through superchlorination in the process for refining; then with high piperazine generation substitution reaction; use the hcl acidifying salify after resin column absorption, crude product carries out recrystallizing and refining repeatedly, and some side reactions inevitably take place in the preparation process; the by product that side reaction produces because of and the main ingredient structural similitude, be difficult to remove.
In order effectively to control quality product, we improve existing refining fasudil hydrochloride extraction process, this method adopts the mode of decompression azeotropic crystalization to substitute existing solvent dilution crystallization process, and the impurity of organic phase and water carried out two-way rejecting, reach the purpose of effective removal impurity, simple to operate, the favorable reproducibility of this method, strong to the adaptability of raw material, can guarantee quality product " safety, homogeneous, stable, effective, controlled ".
The refining and extracting that the present invention relates to, simple good stability, good to the adaptability of raw material, can in big production, use.
Summary of the invention:
The invention provides a kind of process for purification of Fasudil Hydrochloride: this method may further comprise the steps:
Step 1, decolouring:
Fasudil after the resin absorption of learning from else's experience adds gac, behind the thorough mixing, filters, and removes gac, and filtrate is stand-by.
Step 2, washing:
Get the feed liquid after the decolouring, add purified water, behind the thorough mixing, separate, aqueous phase discarded, oil phase is stand-by.
Step 3, acidifying salify:
Get oil phase, add purified water, use the salt acid for adjusting pH value, make it abundant acidifying salify, it is stand-by to collect water
Step 4, crystallization:
The water intaking phase adds propyl carbinol, begins the azeotropic crystalization that reduces pressure behind the thorough mixing, adds propyl carbinol in good time, to keep the denseness of feed liquid, after moisture content is reduced to certain value in mother liquor, stops crystallization, filters, and drying gets the Fasudil Hydrochloride elaboration.Preferably, process for purification of the present invention: may further comprise the steps:
Step 1, decolouring:
Take the fasudil feed liquid behind the post away, add 1～5 ‰ (g/ml) gac, the thorough mixing after-filtration.
Step 2, washing:
In filtrate, add after 5～10% purified water fully stir 10～15min, stop to stir standing demix, water phase separated and oil phase.
Step 3, acidifying salify:
Get oil phase, add 5～10% purified water, under whipped state, regulate material liquid pH=5.0～6.5 then, isolate water with hydrochloric acid, stand-by.
Step 4, crystallization:
The propyl carbinol that adds 2～5 times of volumes of water volume at aqueous phase, fully stir the back underpressure distillation, vacuum degree control is more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process is collected the propyl carbinol that distills out and the mixed solution of water, and distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 5～8%, stop distillation, filter, filter cake washes with propyl carbinol.
Step 5, drying:
The crystal that suction filtration is good is placed on and carries out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 5～10 hours time of drying.
The most preferred method of the present invention is listed in the embodiment of the invention.
The invention has the advantages that, simple to operate, favorable reproducibility, strong to the adaptability of raw material, can guarantee quality product " safety, homogeneous, stable, effective, controlled ", be applicable to big production.
Specific embodiments:
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1
1, takes feed liquid 500ml behind the post away, add 2.5 ‰ (g/ml) gac, the thorough mixing after-filtration.
2, after adding 7.5% purified water fully stirs (12.5min) in filtrate, stop to stir standing demix, water phase separated and oil phase.
3, get oil phase, add 7.5% purified water, under whipped state, regulate feed liquid PH=6.75 then, isolate water with hydrochloric acid, stand-by.
4, the aqueous phase that obtains in previous step adds the propyl carbinol of 3.5 times of volumes of water volume, begin underpressure distillation after fully stirring, vacuum degree control more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected.Distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 6.5%, stops distillation, filters, and filter cake washes with an amount of propyl carbinol.
5, crystal that suction filtration is good is placed on and carries out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 7.5 hours time
Detected result:
The dry vehement burning huge sum of money of sampling body clarification
Lot number output g yield % PH content is infrared
The weightless residue of long-pending ml degree belongs to
Scheme 1-1 500 35.50 98.61 5.80 qualified 0.11 0.06 99.5 is qualified
Scheme 1-2 500 36.10 100.27 5.76 qualified 0.62 0.05 99.5 is qualified
Embodiment 2
1, takes feed liquid 1000ml behind the post away, add 2 ‰ (g/ml) gac, the thorough mixing after-filtration.
2, after adding 7.5% purified water fully stirs in filtrate, stop to stir standing demix, water phase separated and oil phase.
3, get oil phase, add 7.5% purified water, under whipped state, regulate feed liquid PH=5.5 then, isolate water with 6M hydrochloric acid, stand-by.
4, the aqueous phase that obtains in previous step adds the propyl carbinol of 3.5 times of volumes of water volume, begin underpressure distillation after fully stirring, vacuum degree control more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected.Distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 6.5%, stops distillation, filters, and filter cake washes with an amount of propyl carbinol.
5, crystal that suction filtration is good is placed on and carries out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 7.5 hours time.
The dry vehement burning huge sum of money of sampling clarification
Lot number volumetric production g yield % PH content is infrared
Spending weightless residue belongs to
ml
Scheme 2-1 1,000 73.5 102.10 4.29 qualified 0.56 0.06 99.6 is qualified
Scheme 2-2 1,000 74.8 103.89 5.60 qualified 0.20 0.05 99.7 is qualified
Embodiment 3
1, takes feed liquid 500ml behind the post away, add 1 ‰ (g/ml) gac, the thorough mixing after-filtration.
2, after adding 5% purified water fully stirs (10min) in filtrate, stop to stir standing demix, water phase separated and oil phase.
3, get oil phase, add 5～10% purified water, under whipped state, regulate feed liquid PH=5.0 then, isolate water with hydrochloric acid, stand-by.
4, the aqueous phase that obtains in previous step adds the propyl carbinol of 2 times of volumes of water volume, begins underpressure distillation after fully stirring, vacuum degree control more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected.Distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 5%, stops distillation, filters, and filter cake washes with an amount of propyl carbinol.
5, crystal that suction filtration is good is placed on and carries out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 5 hours time
Embodiment 4
1, takes feed liquid 500ml behind the post away, add 5 ‰ (g/ml) gac, the thorough mixing after-filtration.
2, after adding 10% purified water fully stirs (15min) in filtrate, stop to stir standing demix, water phase separated and oil phase.
3, get oil phase, add 5～10% purified water, under whipped state, regulate feed liquid PH=6.5 then, isolate water with hydrochloric acid, stand-by.
4, the aqueous phase that obtains in previous step adds the propyl carbinol of 5 times of volumes of water volume, begins underpressure distillation after fully stirring, vacuum degree control more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected.Distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 8%, stops distillation, filters, and filter cake washes with an amount of propyl carbinol.
5, crystal that suction filtration is good is placed on and carries out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 10 hours time
Embodiment 5
1, takes feed liquid 1000ml behind the post away, add 1 ‰ (g/ml) gac, the thorough mixing after-filtration.
2, after adding 5% purified water fully stirs in filtrate, stop to stir standing demix, water phase separated and oil phase.
3, get oil phase, add 5% purified water, under whipped state, regulate feed liquid PH=5.0 then, isolate water with 6M hydrochloric acid, stand-by.
4, the aqueous phase that obtains in previous step adds the propyl carbinol of 2 times of volumes of water volume, begins underpressure distillation after fully stirring, vacuum degree control more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected.Distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 5%, stops distillation, filters, and filter cake washes with an amount of propyl carbinol.
5, crystal that suction filtration is good is placed on and carries out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 5 hours time.
Embodiment 6
1, takes feed liquid 1000ml behind the post away, add 3 ‰ (g/ml) gac, the thorough mixing after-filtration.
2, after adding 10% purified water fully stirs in filtrate, stop to stir standing demix, water phase separated and oil phase.
3, get oil phase, add 10% purified water, under whipped state, regulate feed liquid PH=6.0 then, isolate water with 6M hydrochloric acid, stand-by.
4, the aqueous phase that obtains in previous step adds the propyl carbinol of 5 times of volumes of water volume, begins underpressure distillation after fully stirring, vacuum degree control more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected.Distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 8%, stops distillation, filters, and filter cake washes with an amount of propyl carbinol.
5, crystal that suction filtration is good is placed on and carries out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 10 hours time.
Claims (8)
1. a method for refining fasudil hydrochloride is characterized in that, this method may further comprise the steps:
Step 1, decolouring:
Fasudil after the resin absorption of learning from else's experience adds gac, behind the thorough mixing, filters, and removes gac, and filtrate is stand-by;
Step 2, washing:
Get the feed liquid after the decolouring, add purified water, behind the thorough mixing, separate, aqueous phase discarded, oil phase is stand-by;
Step 3, acidifying salify:
Get oil phase, add purified water, use the salt acid for adjusting pH value, make it abundant acidifying salify, it is stand-by to collect water;
Step 4, crystallization:
The water intaking phase adds propyl carbinol, begins the azeotropic crystalization that reduces pressure behind the thorough mixing, adds propyl carbinol in good time, to keep the denseness of feed liquid, after moisture content is reduced to certain value in mother liquor, stops crystallization, filters, and drying gets the Fasudil Hydrochloride elaboration.
2. the process for purification of claim 1 is characterized in that, may further comprise the steps:
Step 1, decolouring:
Take the fasudil feed liquid behind the post away, add 1～5 ‰ (g/ml) gac, the thorough mixing after-filtration;
Step 2, washing:
In filtrate, add after 5～10% purified water fully stir 10～15min, stop to stir standing demix, water phase separated and oil phase;
Step 3, acidifying salify:
Get oil phase, add 5～10% purified water, under whipped state, regulate material liquid pH=5.0～6.5 then, isolate water with hydrochloric acid, stand-by;
Step 4, crystallization:
The propyl carbinol that adds 2～5 times of volumes of water volume at aqueous phase, fully stir the back underpressure distillation, vacuum degree control is more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process is collected the propyl carbinol that distills out and the mixed solution of water, and distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 5～8%, stop distillation, filter, filter cake washes with propyl carbinol;
Step 5, drying:
The crystal that suction filtration is good is placed on and carries out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 5～10 hours time of drying.
3. the process for purification of claim 1 is characterized in that, may further comprise the steps:
Step 1, take the feed liquid 500ml behind the post away, add 2.5 ‰ (g/ml) gac, the thorough mixing after-filtration;
Step 2, in filtrate, add after 7.5% purified water fully stirs 12.5min, stop to stir standing demix, water phase separated and oil phase;
Step 3, get oil phase, add 7.5% purified water, under whipped state, regulate feed liquid PH=6.75 then, isolate water with hydrochloric acid, stand-by;
Step 4, the aqueous phase that obtains in previous step add the propyl carbinol of 3.5 times of volumes of water volume, begin underpressure distillation after fully stirring, vacuum degree control is more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected, and distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 6.5%, stop distillation, filter, filter cake washes with an amount of propyl carbinol;
Step 5, the crystal that suction filtration is good are placed on and carry out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 7.5 hours time.
4. the process for purification of claim 1 is characterized in that, may further comprise the steps:
Step 1, take the feed liquid 1000ml behind the post away, add 2 ‰ (g/ml) gac, the thorough mixing after-filtration;
Step 2, in filtrate, add after 7.5% purified water fully stirs, stop to stir standing demix, water phase separated and oil phase;
Step 3, get oil phase, add 7.5% purified water, under whipped state, regulate feed liquid PH=5.5 then, isolate water with 6M hydrochloric acid, stand-by;
Step 4, the aqueous phase that obtains in previous step add the propyl carbinol of 3.5 times of volumes of water volume, begin underpressure distillation after fully stirring, vacuum degree control is more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected, and distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 6.5%, stop distillation, filter, filter cake washes with an amount of propyl carbinol;
Step 5, the crystal that suction filtration is good are placed on and carry out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 7.5 hours time.
5. the process for purification of claim 1 is characterized in that, may further comprise the steps:
Step 1, take the feed liquid 500ml behind the post away, add 1 ‰ (g/ml) gac, the thorough mixing after-filtration;
Step 2, in filtrate, add after 5% purified water fully stirs (10min), stop to stir standing demix, water phase separated and oil phase;
Step 3, get oil phase, add 5～10% purified water, under whipped state, regulate feed liquid PH=5.0 then, isolate water with hydrochloric acid, stand-by;
Step 4, the aqueous phase that obtains in previous step add the propyl carbinol of 2 times of volumes of water volume, begin underpressure distillation after fully stirring, vacuum degree control is more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected, and distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 5%, stop distillation, filter, filter cake washes with an amount of propyl carbinol;
Step 5, the crystal that suction filtration is good are placed on and carry out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 5 hours time.
6. the process for purification of claim 1 is characterized in that, may further comprise the steps:
Step 1, take the feed liquid 500ml behind the post away, add 5 ‰ (g/ml) gac, the thorough mixing after-filtration;
Step 2, in filtrate, add after 10% purified water fully stirs (15min), stop to stir standing demix, water phase separated and oil phase;
Step 3, get oil phase, add 5～10% purified water, under whipped state, regulate feed liquid PH=6.5 then, isolate water with hydrochloric acid, stand-by;
Step 4, the aqueous phase that obtains in previous step add the propyl carbinol of 5 times of volumes of water volume, begin underpressure distillation after fully stirring, vacuum degree control is more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected, and distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 8%, stop distillation, filter, filter cake washes with an amount of propyl carbinol;
Step 5, the crystal that suction filtration is good are placed on and carry out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 10 hours time.
7. the process for purification of claim 1 is characterized in that, may further comprise the steps:
Step 1, take the feed liquid 1000ml behind the post away, add 1 ‰ (g/ml) gac, the thorough mixing after-filtration;
Step 2, in filtrate, add after 5% purified water fully stirs, stop to stir standing demix, water phase separated and oil phase;
Step 3, get oil phase, add 5% purified water, under whipped state, regulate feed liquid PH=5.0 then, isolate water with 6M hydrochloric acid, stand-by;
Step 4, the aqueous phase that obtains in previous step add the propyl carbinol of 2 times of volumes of water volume, begin underpressure distillation after fully stirring, vacuum degree control is more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected, and distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 5%, stop distillation, filter, filter cake washes with an amount of propyl carbinol;
Step 5, the crystal that suction filtration is good are placed on and carry out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 5 hours time.
8. the process for purification of claim 1 is characterized in that, may further comprise the steps:
Step 1, take the feed liquid 1000ml behind the post away, add 3 ‰ (g/ml) gac, the thorough mixing after-filtration;
Step 2, in filtrate, add after 10% purified water fully stirs, stop to stir standing demix, water phase separated and oil phase;
Step 3, get oil phase, add 10% purified water, under whipped state, regulate feed liquid PH=6.0 then, isolate water with 6M hydrochloric acid, stand-by;
Step 4, the aqueous phase that obtains in previous step add the propyl carbinol of 5 times of volumes of water volume, begin underpressure distillation after fully stirring, vacuum degree control is more than 0.008Mpa, the suitable propyl carbinol of adding in the still-process, the propyl carbinol that distills out and the mixed solution of water are collected, and distillation has crystal and begin to separate out mid-term, when the water content of reaction solution drops to 8%, stop distillation, filter, filter cake washes with an amount of propyl carbinol;
Step 5, the crystal that suction filtration is good are placed on and carry out drying in the vacuum drying oven, and vacuum degree control is more than 0.085Mpa, and 70 ℃ of temperature, obtain the Fasudil Hydrochloride crystallization at 10 hours time.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910224197 CN101723934B (en) | 2009-11-27 | 2009-11-27 | Method for refining fasudil hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910224197 CN101723934B (en) | 2009-11-27 | 2009-11-27 | Method for refining fasudil hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101723934A true CN101723934A (en) | 2010-06-09 |
| CN101723934B CN101723934B (en) | 2013-04-10 |
Family
ID=42445557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200910224197 Active CN101723934B (en) | 2009-11-27 | 2009-11-27 | Method for refining fasudil hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101723934B (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101863880A (en) * | 2010-06-12 | 2010-10-20 | 陶灵刚 | Fasudil hydrochloride compound and novel method thereof |
| CN101962379A (en) * | 2010-09-28 | 2011-02-02 | 山西普德药业有限公司 | Method for refining sulfonyl isoquinoline derivative |
| CN101973981A (en) * | 2010-10-09 | 2011-02-16 | 南京新港医药有限公司 | Refining method of 1-(5-isoquinoline sulfonyl) homopiperazine hydrochloride |
| CN101985444A (en) * | 2010-08-20 | 2011-03-16 | 天津红日药业股份有限公司 | V crystal form of Fasudil hydrochloride and preparation method and application thereof |
| CN102060844A (en) * | 2010-12-28 | 2011-05-18 | 天津红日药业股份有限公司 | Fasudil crystal formation IV as well as preparation method and application thereof |
| CN102060845A (en) * | 2010-12-28 | 2011-05-18 | 天津红日药业股份有限公司 | Fasudil crystal formation III as well as preparation method and application thereof |
| CN102199123A (en) * | 2010-03-24 | 2011-09-28 | 天津红日药业股份有限公司 | New crystal form and pharmaceutical application of fasudil |
| CN102229601A (en) * | 2011-05-12 | 2011-11-02 | 天津市汉康医药生物技术有限公司 | Hexahydro-1-(5-isoquinoline sulfonyl)-1 (H)-1, 4- diazepine hydrochloride amorphous compound |
| CN102775387A (en) * | 2011-05-13 | 2012-11-14 | 深圳海王药业有限公司 | Method for refining fasudil hydrochloride |
| CN102924436A (en) * | 2012-11-30 | 2013-02-13 | 南京正大天晴制药有限公司 | Refining method of fasudil hydrochloride |
-
2009
- 2009-11-27 CN CN 200910224197 patent/CN101723934B/en active Active
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102199123A (en) * | 2010-03-24 | 2011-09-28 | 天津红日药业股份有限公司 | New crystal form and pharmaceutical application of fasudil |
| CN102199123B (en) * | 2010-03-24 | 2014-09-03 | 天津红日药业股份有限公司 | New crystal form and pharmaceutical application of fasudil |
| CN101863880A (en) * | 2010-06-12 | 2010-10-20 | 陶灵刚 | Fasudil hydrochloride compound and novel method thereof |
| CN101863880B (en) * | 2010-06-12 | 2012-08-01 | 陶灵刚 | Fasudil hydrochloride compound and novel method thereof |
| CN101985444B (en) * | 2010-08-20 | 2013-04-24 | 天津红日药业股份有限公司 | V crystal form of Fasudil hydrochloride and preparation method and application thereof |
| CN101985444A (en) * | 2010-08-20 | 2011-03-16 | 天津红日药业股份有限公司 | V crystal form of Fasudil hydrochloride and preparation method and application thereof |
| CN101962379B (en) * | 2010-09-28 | 2013-02-27 | 山西普德药业股份有限公司 | Method for refining sulfonyl isoquinoline derivative |
| CN101962379A (en) * | 2010-09-28 | 2011-02-02 | 山西普德药业有限公司 | Method for refining sulfonyl isoquinoline derivative |
| CN101973981B (en) * | 2010-10-09 | 2013-01-02 | 南京优科制药有限公司 | Refining method of 1-(5-isoquinoline sulfonyl) homopiperazine hydrochloride |
| CN101973981A (en) * | 2010-10-09 | 2011-02-16 | 南京新港医药有限公司 | Refining method of 1-(5-isoquinoline sulfonyl) homopiperazine hydrochloride |
| CN102060845A (en) * | 2010-12-28 | 2011-05-18 | 天津红日药业股份有限公司 | Fasudil crystal formation III as well as preparation method and application thereof |
| CN102060844A (en) * | 2010-12-28 | 2011-05-18 | 天津红日药业股份有限公司 | Fasudil crystal formation IV as well as preparation method and application thereof |
| CN102060844B (en) * | 2010-12-28 | 2014-05-28 | 天津红日药业股份有限公司 | Fasudil crystal formation IV as well as preparation method and application thereof |
| CN102229601A (en) * | 2011-05-12 | 2011-11-02 | 天津市汉康医药生物技术有限公司 | Hexahydro-1-(5-isoquinoline sulfonyl)-1 (H)-1, 4- diazepine hydrochloride amorphous compound |
| CN102229601B (en) * | 2011-05-12 | 2013-07-03 | 天津市汉康医药生物技术有限公司 | Hexahydro-1-(5-isoquinoline sulfonyl)-1 (H)-1, 4- diazepine hydrochloride amorphous compound |
| CN102775387A (en) * | 2011-05-13 | 2012-11-14 | 深圳海王药业有限公司 | Method for refining fasudil hydrochloride |
| CN102775387B (en) * | 2011-05-13 | 2014-08-20 | 深圳海王药业有限公司 | Method for refining fasudil hydrochloride |
| CN102924436A (en) * | 2012-11-30 | 2013-02-13 | 南京正大天晴制药有限公司 | Refining method of fasudil hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101723934B (en) | 2013-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101723934B (en) | Method for refining fasudil hydrochloride | |
| CN101628924B (en) | Process for extracting rebaudioside C in stevioside | |
| CN102050855B (en) | Method for comprehensively extracting synephrine and hesperidine from immature bitter orange raw material | |
| CN101486669A (en) | Method for synthesizing taurine | |
| CN104177370B (en) | A kind of method preparing high-load sesamin from sesame seed meal | |
| CN103204800B (en) | A kind of extracting method of 1 DNJ | |
| CN101891781A (en) | Method for preparing high-purity gardenoside | |
| CN104445290A (en) | Method for preparing high-purity anhydrous sodium carbonate by using membrane method | |
| CN102775387B (en) | Method for refining fasudil hydrochloride | |
| CN101962379A (en) | Method for refining sulfonyl isoquinoline derivative | |
| CN101768163B (en) | Method for separating purified nitidine chloride by using cation exchange resin | |
| EP4215538A1 (en) | Method for purifying sucralose | |
| WO2021212535A1 (en) | Method for refining benzhexol hydrochloride | |
| CN102321143A (en) | Method for preparing high-purity betulin | |
| CN101560188B (en) | Method for separating and purifying 2-methylimidazole crystal impurity | |
| CN102174052A (en) | Method for extracting and refining ginkgolide | |
| CN102432575A (en) | Method for extracting high-purity hesperetin from immature bitter orange | |
| CN110105195A (en) | A method of extracting dihydroartemisinic acid from sweet wormwood wax oil | |
| CN103755661A (en) | Separating and refining method of 2-chloro-5-chloromethylthiazole | |
| CN110698488B (en) | A method for extracting and separating morphine from pericarpium Papaveris | |
| CN104710492A (en) | Method for extracting androstenedione in bi-liquid phases system | |
| CN102952165A (en) | Method for extracting L-arabinose from xylose mother liquid | |
| CN102206185B (en) | Process for refining bendazac lysine and analogs thereof | |
| CN110862429A (en) | Preparation method of sodium aescinate | |
| CN109134562A (en) | A kind of aesculin purification process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |