CN103159817A - Preparation method for methylprednisolone succinate - Google Patents
Preparation method for methylprednisolone succinate Download PDFInfo
- Publication number
- CN103159817A CN103159817A CN2011104143231A CN201110414323A CN103159817A CN 103159817 A CN103159817 A CN 103159817A CN 2011104143231 A CN2011104143231 A CN 2011104143231A CN 201110414323 A CN201110414323 A CN 201110414323A CN 103159817 A CN103159817 A CN 103159817A
- Authority
- CN
- China
- Prior art keywords
- succsinic acid
- methylprednisolone
- preparation
- acid methylprednisolone
- acetone
- 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.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and mainly relates to a preparation method suitable for industrialized production of methylprednisolone succinate. Specifically, the invention relates to a crystallization purifying method for the methylprednisolone succinate. The method increases purity of the methylprednisolone succinate and reduces content of impurities by crystallization in a specific solvent and in specific conditions, thereby increasing security of clinic applications. More importantly, methylprednisolone sodium succinate lyophilized powder for injection prepared by the methylprednisolone succinate has quality superior to commercially available products, has stable and controllable quality, is safe and effective, and has good application prospects.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of preparation method who is applicable to the succsinic acid methylprednisolone of suitability for industrialized production.
Background technology
Methylprednisolone is succeeded in developing in late 1950s by the Upjohn pharmaceutical factory, and with the listing of succsinic acid methylprednisolone salt, the listing formulation is freeze-dried powder.
Succsinic acid methylprednisolone (Methylprednisolone succinate) is a kind of, not halogen-containing middle effect glucocorticoid medicine synthetic take methylprednisolone as precursor, is the medicine that developed country's pharmacopeia continues to record.The chemical name of succsinic acid methylprednisolone is: 11 β, 17 α, the pregnant steroid-Isosorbide-5-Nitrae of 21-trihydroxy--6 Alpha-Methyl-diene-3,20-diketone-21-succinate.Structural formula is as follows:
Molecular formula: C
26H
34O
8
Molecular weight: 474.55.
Methylprednisolone sodium succinate for inj is the sterile product that succsinic acid methylprednisolone, sodium bicarbonate and phosphate buffer etc. are made through lyophilize, have the effects such as powerful anti-inflammatory, antianaphylaxis, antishock, immunosuppression, be used for clinically urgent patient's acute phase and critical phase, and keep treatment after first aid, be widely used in: the rejection after respiratory tract disease, endocrine disturbance, rheumatism, collagen disease (premunity disease), anaphylaxis, nervous system disorders, gastrointestinal tract disease, tetter, organ transplantation etc.
Summary of the invention
The object of the present invention is to provide a kind of preparation method who is applicable to the succsinic acid methylprednisolone of suitability for industrialized production, particularly, the preparation method of succsinic acid methylprednisolone of the present invention comprises the following steps:
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) add the gac processing of decolouring in the boiling solution of succsinic acid methylprednisolone, then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, be drying to obtain.
Described succsinic acid methylprednisolone crude product can be the succsinic acid methylprednisolone crude product that obtains by the synthetic approach, can be also marketable material.
Described drying can be completed by well known to a person skilled in the art any drying means, comprises spraying drying, lyophilize, vacuum-drying, heat-wind circulate drying, fluidised bed drying, air stream drying etc.Drying is preferably carried out at 30-60 ℃.
In above-mentioned preparation method, the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone in described step (1) is 1: 1-1.5: 9-12.
In above-mentioned preparation method, the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone in described step (1) is 1: 1.5: 9.
In above-mentioned preparation method, the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone in described step (1) is 1: 1: 9.
In above-mentioned preparation method, the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone in described step (1) 1: 1: 12.
In above-mentioned preparation method, the addition of the gac in described step (2) is the 0.1-1% (g/ml) of overall solution volume.
In above-mentioned preparation method, the addition of the gac in described step (2) is the 0.1-0.5% (g/ml) of overall solution volume.
In above-mentioned preparation method, the addition of the gac in described step (2) is 0.3% (g/ml) of overall solution volume.
The preparation method of succsinic acid methylprednisolone provided by the present invention under specific solvent and condition, has improved the purity of succsinic acid methylprednisolone by the mode of crystallization, reduced foreign matter content, thereby strengthened the security of clinical application.
The more important thing is, by the methylprednisolone sodium succinate for inj preparation of succsinic acid methylprednisolone preparation of the present invention, its quality is better than commercially available product, and stable and controllable for quality, and is safe and effective.
Embodiment
The present invention is described in further detail below in conjunction with specific embodiment and experimental example, but be not to be construed as limiting the scope of the invention.
Embodiment 1
1, the preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product (commercially available) is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1.5: 9, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.3%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 40 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
2, the preparation of methylprednisolone sodium succinate for inj
Preparation prescription (specification: the 0.125g/ bottle):
Preparation technology:
(1) get the water for injection of dosing total amount 70%, be cooled to below 45 ℃, add Sodium phosphate dibasic, sodium bicarbonate, stirring and dissolving.5% sodium dihydrogen phosphate that adds dosing total amount 2.5%, stirring and evenly mixing.Load weighted succsinic acid methylprednisolone of the present invention is slowly added in mentioned solution, stir while adding, fill nitrogen and be stirred to dissolving fully.
(2) regulate pH value to 6.9～7.2 with 5% sodium dihydrogen phosphate, add water for injection after stirring to the dosing total amount, add 0.25% (W/V) needle-use activated carbon, whip attachment 10 minutes, carbon removal, Sterile Filtration are sub-packed in the 10ml cillin bottle.
(3) lyophilize: shelf is lowered the temperature; make goods be down to-40 ℃ of left and right; constant temperature made goods freeze reality in 1～3 hour; start vacuum pump; shelf intensification goods begin distillation, after waterline disappears, shelf are warming up to 25 ℃ of constant temperature with the speed of 10 ℃ per hour, rise to 35 ℃ after goods are near shelf temperature again; constant temperature approximately 2～4 hours, shelf is down to 20 ℃ of shutdown.Shelf is lowered the temperature; make goods be down to-40 ℃ of left and right; constant temperature made goods freeze reality in 1～3 hour; start vacuum pump, shelf intensification goods begin distillation, heat up with suitable speed after waterline disappears; keep products temperature and shelf temperature to approach; and finally be warming up to 35 ℃, and constant temperature approximately 2～6 hours, shelf is down to 20 ℃ of shutdown.
(4) gland, sealing, packing, and get final product.
Embodiment 2
1, the preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1.5: 9, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.5%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 40 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
2, the preparation of methylprednisolone sodium succinate for inj
Preparation prescription (specification: the 0.125g/ bottle) and technique with embodiment 1.
Embodiment 3
1, the preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1.5: 9, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.1%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 40 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
2, the preparation of methylprednisolone sodium succinate for inj
Preparation prescription (specification: the 0.125g/ bottle) and technique with embodiment 1.
Embodiment 4
1, the preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1.5: 9, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 1%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 40 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
2, the preparation of methylprednisolone sodium succinate for inj
Preparation prescription (specification: the 40mg/ bottle):
Preparation technology:
(1) get the water for injection of dosing total amount 70%, be cooled to below 45 ℃, add Sodium phosphate dibasic, sodium bicarbonate, stirring and dissolving.5% sodium dihydrogen phosphate that adds dosing total amount 2.5%, stirring and evenly mixing.Load weighted succsinic acid methylprednisolone of the present invention is slowly added in mentioned solution, stir while adding, fill nitrogen and be stirred to dissolving fully.
(2) regulate pH value to 6.9～7.2 with 5% sodium dihydrogen phosphate, add water for injection after stirring to the dosing total amount, add 0.25% (W/V) needle-use activated carbon, whip attachment 10 minutes, carbon removal, Sterile Filtration are sub-packed in the 10ml cillin bottle.
(3) lyophilize: shelf is lowered the temperature; make goods be down to-40 ℃ of left and right; constant temperature made goods freeze reality in 1～3 hour; start vacuum pump; shelf intensification goods begin distillation, after waterline disappears, shelf are warming up to 25 ℃ of constant temperature with the speed of 10 ℃ per hour, rise to 35 ℃ after goods are near shelf temperature again; constant temperature approximately 2～4 hours, shelf is down to 20 ℃ of shutdown.Shelf is lowered the temperature; make goods be down to-40 ℃ of left and right; constant temperature made goods freeze reality in 1～3 hour; start vacuum pump, shelf intensification goods begin distillation, heat up with suitable speed after waterline disappears; keep products temperature and shelf temperature to approach; and finally be warming up to 35 ℃, and constant temperature approximately 2～6 hours, shelf is down to 20 ℃ of shutdown.
(4) gland, packing, sealing, and get final product.
Embodiment 5
1, the preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1: 9, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.3%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 45 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
2, the preparation of methylprednisolone sodium succinate for inj
Preparation prescription (specification: the 40mg/ bottle) and technique with embodiment 4.
Embodiment 6
1, the preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1: 9, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.5%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 45 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
2, the preparation of methylprednisolone sodium succinate for inj
Preparation prescription (specification: the 40mg/ bottle) and technique with embodiment 4.
Embodiment 7
The preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1: 9, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.1%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 45 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
Embodiment 8
The preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1: 9, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 1.0%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 45 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
Embodiment 9
The preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1: 12, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.3%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 50 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
Embodiment 10
The preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1: 12, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.5%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 50 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
Embodiment 11
The preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1: 12, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 0.1%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 50 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
Embodiment 12
The preparation of succsinic acid methylprednisolone of the present invention
(1) succsinic acid methylprednisolone crude product is added in the mixing solutions of entry and acetone, wherein the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone is 1: 1: 12, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) adding addition in the boiling solution of succsinic acid methylprednisolone is the processing of decolouring of the gac of overall solution volume 1.0%, and then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, 50 ℃ of vacuum-dryings, namely get succsinic acid methylprednisolone of the present invention.
Experimental example
One, compare by the content before and after method crystallization purifying of the present invention and impurity
Measure embodiment 1-12 by content and the impurity situation of the succsinic acid methylprednisolone before and after method crystallization purifying of the present invention by the HPLC method, the results are shown in Table 1.
Content before and after table 1 purifying and impurity are relatively
Above experimental result shows, method of the present invention can improve the content of succsinic acid methylprednisolone effectively, reduces its impurity, thus the security when strengthening clinical application.The following further advantage that method of the present invention relatively is described and the practicality thereof by preparation.
Two, the mass ratio of methylprednisolone sodium succinate for inj of the present invention and commercially available prod
Get the methylprednisolone sodium succinate for inj of embodiment 1-6 preparation, [(pfizer produces R05204 with commercially available methylprednisolone sodium succinate for inj, 0.5g specification), (pfizer produces S05856, the 40mg specification), 201101211 (Tianjin TianAn Medicine Industry Co., Ltd's productions, the 40mg specification)] carry out the quality contrast, the results are shown in Table 2.
The mass ratio of table 2 the present invention and commercially available prod
Above experimental result shows, methylprednisolone sodium succinate for inj and commercially available product by amber methylprednisolone preparation of the present invention compare, its free methylprednisolone and other foreign matter content are starkly lower than commercially available product, all other index no significant differences, show that its quality is better than commercially available product, method of the present invention is worth of widely use.
Three, the stability test of methylprednisolone sodium succinate for inj of the present invention
1, accelerated test
To simulate the commercially available back sample and be placed in 40 ℃ ± 2 ℃ of temperature, under relative humidity 75% ± 5% condition, lucifuge was placed 6 months.In the 1st, 2,3, take a sample once June, detects indices.The results are shown in Table 3～4.
2, test of long duration
To simulate the commercially available back sample and be placed in lucifuge placement under 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% condition, in the 3rd, 6,9,12,18,24, the 36 month indices of taking a sample to check, now keep sample 6 months, and investigate and the results are shown in Table 5～6.
Accelerated test result (the specification: 0.125g) of table 3 methylprednisolone sodium succinate for inj
Accelerated test result (the specification: 40mg) of table 4 methylprednisolone sodium succinate for inj of the present invention
Long-term test results (the specification: 0.125g) of table 5 methylprednisolone sodium succinate for inj of the present invention
Long-term test results (the specification: 40mg) of table 6 methylprednisolone sodium succinate for inj of the present invention
3, the stability test conclusion of methylprednisolone sodium succinate for inj of the present invention
Accelerated test is investigated result and is shown: press commercially available back, lucifuge was placed 6 months under 40 ℃ ± 2 ℃, relative humidity 75% ± 5% condition, compared with 0 month, except free methylprednisolone amount increases to some extent, outside related substance slightly increases, other every Index for examinations such as content have no significant change, and all indexs are all in acceptability limit.
Long-term stable experiment is investigated result and shown: press commercially available back, lucifuge was placed 6 months under 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% condition, and every Index for examination has no significant change, and shows that this product is more stable.
The preparation method of succsinic acid methylprednisolone provided by the invention under specific solvent and condition, has improved the purity of succsinic acid methylprednisolone by the mode of crystallization, reduced foreign matter content, thereby strengthened the security of clinical application.The more important thing is, with the methylprednisolone sodium succinate for inj lyophilized injectable powder of succsinic acid methylprednisolone preparation of the present invention, its quality is better than the commercially available prod, and stable and controllable for quality, and is safe and effective.
Claims (8)
1. the preparation method of a succsinic acid methylprednisolone is characterized in that comprising the following steps:
(1) succsinic acid methylprednisolone crude product is added in the mixed solvent of entry and acetone, to dissolving, obtain the boiling solution of succsinic acid methylprednisolone 35-40 ℃ of heated and stirred;
(2) add the gac processing of decolouring in the boiling solution of succsinic acid methylprednisolone, then filtered while hot, obtain destainer;
(3) destainer is cooled to 0-5 ℃, and at 0-5 ℃ of thermostatical crystallization, filters, be drying to obtain.
2. preparation method according to claim 1, is characterized in that, the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone in described step (1) is 1: 1-1.5: 9-12.
3. preparation method according to claim 1, is characterized in that, the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone in described step (1) is 1: 1.5: 9.
4. preparation method according to claim 1, is characterized in that, the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone in described step (1) is 1: 1: 9.
5. preparation method according to claim 1, is characterized in that, the weight part ratio of succsinic acid methylprednisolone crude product, water and acetone in described step (1) is 1: 1: 12.
6. preparation method according to claim 1, is characterized in that, the addition of the gac in described step (2) is the 0.1-1% of overall solution volume.
7. preparation method according to claim 1, is characterized in that, the addition of the gac in described step (2) is the 0.1-0.5% of overall solution volume.
8. preparation method according to claim 1, is characterized in that, the addition of the gac in described step (2) is 0.3% of overall solution volume.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104143231A CN103159817A (en) | 2011-12-13 | 2011-12-13 | Preparation method for methylprednisolone succinate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104143231A CN103159817A (en) | 2011-12-13 | 2011-12-13 | Preparation method for methylprednisolone succinate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103159817A true CN103159817A (en) | 2013-06-19 |
Family
ID=48583381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011104143231A Pending CN103159817A (en) | 2011-12-13 | 2011-12-13 | Preparation method for methylprednisolone succinate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103159817A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319559A (en) * | 2013-06-21 | 2013-09-25 | 辽宁海思科制药有限公司 | Methylprednisolone succinate compound |
| CN104650172A (en) * | 2015-03-25 | 2015-05-27 | 浙江仙琚制药股份有限公司 | Method for preparing methylprednisolone hemisuccinate |
| CN108498468A (en) * | 2018-05-25 | 2018-09-07 | 福安药业集团湖北人民制药有限公司 | Methylprednisolone sodium succinate for injection |
| CN109678919A (en) * | 2018-12-27 | 2019-04-26 | 重庆华邦胜凯制药有限公司 | A kind of preparation method of Methylprednisolone succinate impurity |
| CN116396347A (en) * | 2023-04-12 | 2023-07-07 | 河南利华制药有限公司 | Preparation method of high-standard prednisolone succinate |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5225335A (en) * | 1987-03-12 | 1993-07-06 | The Upjohn Company | 1,2-dehydrogenation of steroidal 21-esters with Arthrobacter simplex or Bacterium cyclooxydans |
| WO2003082251A2 (en) * | 2002-03-29 | 2003-10-09 | Hemofarm Koncern A.D. Pharmaceutical And Chemical Industry | THE EFFERVESCENT PHARMACEUTICAL DOSAGE FORM OF ESTERS AND ESTER SALTS OF 6 α METHYLPREDNISOLONE SUCCINATE, PROCEDURE FOR ITS OBTAINING AND APPLICATION |
| US20090240049A1 (en) * | 2008-03-18 | 2009-09-24 | Marco Villa | Purification of air sensitive steroids |
| CN101805387A (en) * | 2010-04-20 | 2010-08-18 | 天津金耀集团有限公司 | Methylprednisolone aceponate new crystal form and preparation method thereof |
-
2011
- 2011-12-13 CN CN2011104143231A patent/CN103159817A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5225335A (en) * | 1987-03-12 | 1993-07-06 | The Upjohn Company | 1,2-dehydrogenation of steroidal 21-esters with Arthrobacter simplex or Bacterium cyclooxydans |
| WO2003082251A2 (en) * | 2002-03-29 | 2003-10-09 | Hemofarm Koncern A.D. Pharmaceutical And Chemical Industry | THE EFFERVESCENT PHARMACEUTICAL DOSAGE FORM OF ESTERS AND ESTER SALTS OF 6 α METHYLPREDNISOLONE SUCCINATE, PROCEDURE FOR ITS OBTAINING AND APPLICATION |
| US20090240049A1 (en) * | 2008-03-18 | 2009-09-24 | Marco Villa | Purification of air sensitive steroids |
| CN101805387A (en) * | 2010-04-20 | 2010-08-18 | 天津金耀集团有限公司 | Methylprednisolone aceponate new crystal form and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 陈建新: "氢化可的松结晶过程研究", 《中国优秀博硕士学位论文全文数据库（博士）工程科技辑》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319559A (en) * | 2013-06-21 | 2013-09-25 | 辽宁海思科制药有限公司 | Methylprednisolone succinate compound |
| CN103319559B (en) * | 2013-06-21 | 2015-09-30 | 辽宁海思科制药有限公司 | A kind of Methylprednisolone succinate compound |
| CN104650172A (en) * | 2015-03-25 | 2015-05-27 | 浙江仙琚制药股份有限公司 | Method for preparing methylprednisolone hemisuccinate |
| CN108498468A (en) * | 2018-05-25 | 2018-09-07 | 福安药业集团湖北人民制药有限公司 | Methylprednisolone sodium succinate for injection |
| CN109678919A (en) * | 2018-12-27 | 2019-04-26 | 重庆华邦胜凯制药有限公司 | A kind of preparation method of Methylprednisolone succinate impurity |
| CN116396347A (en) * | 2023-04-12 | 2023-07-07 | 河南利华制药有限公司 | Preparation method of high-standard prednisolone succinate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103159817A (en) | Preparation method for methylprednisolone succinate | |
| CN103054863B (en) | Pharmaceutical composition of omeprazole sodium, and preparation method of pharmaceutical composition | |
| CN102525963A (en) | Netilmicin sulfate lyophiled powder injection and preparation method thereof | |
| CN102302461A (en) | Dantrolene sodium freeze-dried powder injection for injection and preparation method thereof | |
| CN102796078B (en) | Pantoprazole compound, preparation methods and pharmaceutical preparations thereof | |
| CN111955632A (en) | Sialic acid-containing beverage and preparation method thereof | |
| WO2016045530A1 (en) | Chlorogenic acid lyophilised powder for injection having high resolubility and high stability | |
| CN103006553A (en) | Luteolin solution composition | |
| CN103040855A (en) | Pharmaceutical composition of fludarabine phosphate and preparation method thereof | |
| CN103232395B (en) | Sodium ozagrel compound, preparation method and drug composition thereof | |
| CN102670524B (en) | Pantoprazole sodium freeze-dried preparation for injection and preparation method thereof | |
| CN102698253B (en) | Adenosine disodium triphosphate composition | |
| CN102311432B (en) | Stable vinpocetine compound and pharmaceutical composition thereof | |
| CN104856964B (en) | Alanyl glutamine freeze-dried preparation and preparation method thereof | |
| CN109620804B (en) | Ceftriaxone sodium powder injection preparation for injection and preparation method thereof | |
| CN109044969B (en) | Preparation method of paclitaxel injection | |
| CN103304424A (en) | Diisopropylamine dichloroacetate compound and compound medicine composition injection thereof | |
| CN105037195B (en) | Aceglutamide and its parenteral solution and preparation method | |
| CN101129374B (en) | Vinflunine pharmaceutical composition and method of producing the same and application of the same | |
| CN104109128A (en) | Cabozantinib malate and preparation method thereof | |
| CN103655490A (en) | Idarubicin hydrochloride pharmaceutical composition and preparation method thereof | |
| CN105726495B (en) | A kind of short-acting benzodiazepine salt pharmaceutical composition of injection and preparation method thereof | |
| CN102600143B (en) | Vinpocetine medicament composition and preparation method thereof | |
| CN103585119A (en) | Stabilization preparation containing epoprostenol and medical salt of epoprostenol and preparation method of stabilization preparation | |
| CN103059000A (en) | Novel omeprazole compound and pharmaceutical composition thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130619 |