CN103432066A - Compound mannitol injection and preparation method thereof - Google Patents
Compound mannitol injection and preparation method thereof Download PDFInfo
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- CN103432066A CN103432066A CN2013103119234A CN201310311923A CN103432066A CN 103432066 A CN103432066 A CN 103432066A CN 2013103119234 A CN2013103119234 A CN 2013103119234A CN 201310311923 A CN201310311923 A CN 201310311923A CN 103432066 A CN103432066 A CN 103432066A
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Abstract
The invention relates to a compound mannitol injection which is added with a small amount of propylene glycol based on a conventional compound mannitol injection. The invention also relates to a preparation method of the compound mannitol injection. The compound mannitol injection provided by the invention is substantially improved in stability, and has no crystallization even after long-term storage, and thus the injection is substantially improved in quality and extremely improved in pharmacy safety. The preparation method provided by the invention is mild in technological conditions and simple in operation, and is suitable for large-scale industrialized application.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of compound formula mannitol injection liquid and preparation method thereof.
Background technology
The compound preparation that compound formula mannitol injection liquid is mannitol, sodium chloride and anhydrous glucose, adjuvant is water for injection.Compound formula mannitol injection liquid can be used as clinically: (1) tissue dewatering medicine, be used for the treatment of the cerebral edema that a variety of causes causes, and reduce intracranial pressure, prevent cerebral hernia.(2) reduce intraocular pressure, can effectively reduce intraocular pressure, be applied to other and fall intraocular pressure and prepare when invalid or before intraocular surgery.(3) osmotic diuretic, the oliguria for differentiating that property diuresis factor before kidney or acute renal failure cause, also can be applicable to the acute tubular necrosis of preventing a variety of causes to cause.(4) as the complementary diuresis measure treatment nephrotic syndrome, cirrhotic ascites, especially when with hypoproteinemia.(5) to the some drugs amount of exceeding or toxic poisoning (as barbiturate, lithium, Salicylate and bromide etc.), can promote the excretion of above-mentioned substance, and prevent nephrotoxicity.
Main active mannitol in compound formula mannitol injection liquid is PEARLITOL 25C, and PEARLITOL 25C is a kind of application natural hexabasic alcohol very widely, has determined that at present it exists 3 kinds of crystal formation: β, δ and α.All there is certain difference in the mannitol of different crystal forms aspect the physicochemical properties such as dissolubility, stability, density, and the existence of these differences can affect its function and application to a certain extent.
Existing compound formula mannitol injection liquid preparation method mainly comprises mannitol, sodium chloride and anhydrous glucose is dissolved in water for injection, then adds activated carbon decolorizing, fill, sterilizing and get final product.In existing preparation method, due to the difference of process conditions, can bring the uncertain variation of crystal formation, make the compound formula mannitol injection liquid obtained that crystallization easily occur, so that affect drug safety.
Summary of the invention
The defect of crystallization, less stable easily occurs for overcoming existing compound formula mannitol injection liquid, the purpose of this invention is to provide a kind of compound formula mannitol injection liquid.
Another object of the present invention is to provide a kind of preparation method of compound formula mannitol injection liquid.
Compound formula mannitol injection liquid provided by the invention comprises following composition by weight:
PEARLITOL 25C: 120～170 parts;
Anhydrous glucose: 30～80 parts;
Sodium chloride: 3～6 parts;
Propylene glycol: 0.5～0.95 part.
Preferably, described compound formula mannitol injection liquid comprises following composition by weight:
PEARLITOL 25C: 150 parts;
Anhydrous glucose: 50 parts;
Sodium chloride: 4.5 parts;
Propylene glycol: 0.75 part;
Water for injection: 1000 parts.
Compound formula mannitol injection liquid preparation method provided by the invention comprises the following steps:
(1) dense joining
At the temperature of 40～60 ℃, PEARLITOL 25C, propylene glycol, anhydrous glucose and sodium chloride are mixed with the water for injection of 1/4～1/2 volume, add active carbon to be adsorbed, de-charcoal;
(2) rare joining
At the temperature of 40～60 ℃, will in step (1) gained solution, with residue water for injection, mix, then add active carbon to carry out second adsorption, de-charcoal, the pH value of adjusting gained solution is 4.5 ± 0.3;
(3) fill
Step (2) gained solution is filtered with 0.22 μ m filter, and fill becomes injection;
(4) sterilizing
By step (3) gained injection moist heat sterilization 30～50 minutes and get final product at the temperature of 110～130 ℃.
Wherein, described in described step (1), the addition of active carbon is 0.02%(W/V).
Wherein, described in described step (2), the addition of active carbon is 0.01%(W/V).
Wherein, described step (2) is used 0.45 μ m filter to be filtered after also comprising de-charcoal.
The inventor finds: mannitol is at different solvents, different temperature, and the conversion of crystal formation is not identical yet.According to this characteristic, technical solution of the present invention adopts water for injection and propylene glycol as solvent, and the modulation of injection (dense joining and rare step of joining) temperature is controlled as 40-60 ℃, can postpone δ-mannitol and be transformed into β-mannitol in aqueous solution.The compound formula mannitol injection liquid stability obtained thus is significantly improved, and under long storage time, does not also have crystallization to occur, thereby the quality of medicinal liquid also obtained obvious improvement, thereby drug safety is greatly improved.
Preparation method process conditions provided by the invention are gentle, simple to operate, the suitability for mass industrialized application.
The specific embodiment
Following examples are used for the present invention is described, but are not used for limiting the scope of the invention.
Embodiment 1
Formula (by weight):
PEARLITOL 25C: 150 parts;
Anhydrous glucose: 50 parts;
Sodium chloride: 4.5 parts;
Propylene glycol: 0.75 part;
Water for injection: 1000 parts.
Preparation process:
(1) dense joining:
Be about at the temperature of 50 ℃, first the raw material mannitol of accurate weighing and propylene glycol are dissolved to (consumption of water for injection gets final product for mannitol and propylene glycol are dissolved) with water for injection, solution after dissolving is carried out to ultrafiltration with the ultrafilter of 0.22 μ m, obtain the mannitol solution after ultrafiltration.
The about water for injection of 1/3 volume (for the total consumption of water for injection) is heated to temperature and is about 50 ℃, inject dense preparing tank, open and stir, by the mannitol solution after ultrafiltration, the anhydrous glucose of accurate weighing and sodium chloride join in above-mentioned dense preparing tank, stirring is fully dissolved it, add 0.02% active carbon (g active carbon/ml solution) to be adsorbed, clean and adjust charcoal bucket and scoop to steep without charcoal with a small amount of water for injection, merging washing liquid joins in dense preparing tank, stir 10 minutes, the solution temperature of controlling in dense preparing tank now is 50 ℃ of left and right, finally use titanium rod decarbonization filtering device to take off charcoal, solution after de-charcoal is sent in dilute preparing tank, dense preparing tank cleans 3 times with a small amount of water for injection, washing liquid merges delivers to dilute preparing tank, the solution temperature of controlling in dilute preparing tank in above whole process is 50 ℃ of left and right.
(2) rare joining
Add the approximately 1/2 volume (water for injection for the total consumption of water for injection in above-mentioned dilute preparing tank, add 0.01% active carbon (g active carbon/ml solution) to carry out second adsorption, clean and adjust charcoal bucket and scoop to steep without charcoal with a small amount of water for injection, merging washing liquid joins in dense preparing tank, stir 10 minutes, take off charcoal with titanium rod decarbonization filtering device, inject water until amount of preparation, gained solution in dilute preparing tank is returned to filter 20 minutes with 0.45 μ m filter, the pH value of adjusting solution is 4.5 ± 0.3, the solution temperature of controlling in dilute preparing tank in above whole process is 50 ℃ of left and right.
Then sampling, detect metronidazole content, sodium chloride content, pH value and visible foreign matters inspection wherein, qualified rear to be filled.
(3) fill
By step (2) gained medicinal liquid after 0.22 μ m filter filters fill to the transfusion flexible bag of required specification.
(4) sterilizing
The injection that step (3) is obtained sterilizing 35 minutes at the temperature of 115 ℃.
By influence factor's test, accelerated test, long term test data (data are in Table 1-4), analyze, the mannitol content in above-mentioned injection is all between 95.0%-105.0%; Glucose content is all between 90.0%-110.0%; Sodium chloride content is all between 95.0%-105.0%, and every detection index such as visible foreign matters is all " in the acceptability limit of Chinese pharmacopoeia.
The hot test result of table 1 embodiment 1 compound formula mannitol injection liquid (experimental condition: 60 ℃)
Exposure experiments to light result (the experimental condition: 4500LX ± 500LX) of table 2 embodiment 1 compound formula mannitol injection liquid
The accelerated test of table 3 embodiment 1 compound formula mannitol injection liquid is investigated result
(experimental condition: 40 ℃ ± 2 ℃ of temperature, relative humidity 25% ± 5%)
The investigation result that keeps sample for a long time of table 4 embodiment 1 compound formula mannitol injection liquid
(experimental condition: 25 ℃ ± 2 ℃ of temperature, relative humidity 40% ± 5%)
Embodiment 2
Formula (by weight):
PEARLITOL 25C: 170 parts;
Anhydrous glucose: 80 parts;
Sodium chloride: 6.0 parts;
Propylene glycol: 0.5 part;
Water for injection: 1000 parts.
Preparation process:
(1) dense joining:
Being about at the temperature of 50 ℃, first raw material mannitol and the propylene glycol of accurate weighing are dissolved with water for injection, the solution after dissolving is carried out to ultrafiltration with the ultrafilter of 0.22 μ m, obtain the mannitol solution after ultrafiltration.
The about water for injection of 1/4 volume (for the total consumption of water for injection) is heated to temperature and is about 50 ℃, inject dense preparing tank, open and stir, by the mannitol solution after ultrafiltration, the anhydrous glucose of accurate weighing and sodium chloride join in above-mentioned dense preparing tank, stirring is fully dissolved it, add 0.02% active carbon (g active carbon/ml solution) to be adsorbed, clean and adjust charcoal bucket and scoop to steep without charcoal with a small amount of water for injection, merging washing liquid joins in dense preparing tank, stir 12 minutes, the solution temperature of controlling in dense preparing tank now is 50 ℃ of left and right, finally use titanium rod decarbonization filtering device to take off charcoal, solution after de-charcoal is sent in dilute preparing tank, dense preparing tank cleans 3 times with a small amount of water for injection, washing liquid merges delivers to dilute preparing tank, the solution temperature of controlling in dilute preparing tank in above whole process is 50 ℃ of left and right.
(2) rare joining
Add the approximately 1/2 volume (water for injection for the total consumption of water for injection in above-mentioned dilute preparing tank, add 0.01% active carbon (g active carbon/ml solution) to carry out second adsorption, clean and adjust charcoal bucket and scoop to steep without charcoal with a small amount of water for injection, merging washing liquid joins in dense preparing tank, stir 10 minutes, take off charcoal with titanium rod decarbonization filtering device, inject water until amount of preparation, gained solution in dilute preparing tank is returned to filter 15 minutes with 0.45 μ m filter, the pH value of adjusting solution is 4.5 ± 0.3, the solution temperature of controlling in dilute preparing tank in above whole process is 50 ℃ of left and right.
Then sampling, detect metronidazole content, sodium chloride content, pH value and visible foreign matters inspection wherein, qualified rear to be filled.
(3) fill
By step (2) gained medicinal liquid after 0.22 μ m filter filters fill to the transfusion flexible bag of required specification.
(4) sterilizing
The injection that step (3) is obtained sterilizing 30 minutes at the temperature of 120 ℃.
By influence factor's test, accelerated test, long term test data analysis, the mannitol content in above-mentioned injection is all between 95.0%-105.0%; Glucose content is all between 90.0%-110.0%; Sodium chloride content is all between 95.0%-105.0%, and every detection index such as visible foreign matters is all " in the acceptability limit of Chinese pharmacopoeia.
Embodiment 3
Formula (by weight):
PEARLITOL 25C: 120 parts;
Anhydrous glucose: 40 parts;
Sodium chloride: 4 parts;
Propylene glycol: 0.5 part;
Water for injection: 1000 parts.
Preparation process is with embodiment 1.
By influence factor's test, accelerated test, long term test data analysis, the mannitol content in above-mentioned injection is all between 95.0%-105.0%; Glucose content is all between 90.0%-110.0%; Sodium chloride content is all between 95.0%-105.0%, and every detection index such as visible foreign matters is all " in the acceptability limit of Chinese pharmacopoeia.
Although above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements, all belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (6)
1. a compound formula mannitol injection liquid, is characterized in that, comprises by weight following composition:
PEARLITOL 25C: 120～170 parts;
Anhydrous glucose: 30～80 parts;
Sodium chloride: 3～6 parts;
Propylene glycol: 0.5～0.95 part;
Water for injection: 1000 parts.
2. injection according to claim 1, is characterized in that, comprises by weight following composition:
PEARLITOL 25C: 150 parts;
Anhydrous glucose: 50 parts;
Sodium chloride: 4.5 parts;
Propylene glycol: 0.75 part;
Water for injection: 1000 parts.
3. the preparation method of claim 1 or 2 described compound formula mannitol injection liquid, is characterized in that, comprises the following steps:
(1) dense joining
At the temperature of 40～60 ℃, PEARLITOL 25C, propylene glycol, anhydrous glucose and sodium chloride are mixed with the water for injection of 1/4～1/2 volume, add active carbon to be adsorbed, de-charcoal;
(2) rare joining
At the temperature of 40～60 ℃, will in step (1) gained solution, with residue water for injection, mix, then add active carbon to carry out second adsorption, de-charcoal, the pH value of adjusting gained solution is 4.5 ± 0.3;
(3) fill
Step (2) gained solution is filtered with 0.22 μ m filter, and fill becomes injection;
(4) sterilizing
By step (3) gained injection moist heat sterilization 30～50 minutes and get final product at the temperature of 110～130 ℃.
4. preparation method according to claim 3, is characterized in that, described in step (1), the addition of active carbon is 0.02%(W/V).
5. preparation method according to claim 3, is characterized in that, described in described step (2), the addition of active carbon is 0.01%(W/V).
6. preparation method according to claim 3, is characterized in that, described step (2) is used 0.45 μ m filter to be filtered after also comprising de-charcoal.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105147602A (en) * | 2015-10-23 | 2015-12-16 | 广西裕源药业有限公司 | Mannitol injection |
| CN105147600A (en) * | 2015-10-23 | 2015-12-16 | 广西裕源药业有限公司 | Compound mannitol injection |
| CN105287368A (en) * | 2015-10-23 | 2016-02-03 | 广西裕源药业有限公司 | Mannitol injection |
| CN106074372A (en) * | 2016-08-11 | 2016-11-09 | 安徽环球药业股份有限公司 | The preparation method of formula mannitol injection liquid |
| CN106389324A (en) * | 2016-11-08 | 2017-02-15 | 江西科伦药业有限公司 | Production and preparation process capable of lowering mannitol injection crystallization |
| CN106551901A (en) * | 2017-01-02 | 2017-04-05 | 江苏恒丰强生物技术有限公司 | Animal compound formula mannitol injection liquid |
| CN116983258A (en) * | 2023-07-25 | 2023-11-03 | 河南双鹤华利药业有限公司 | Preparation process of mannitol injection not easy to crystallize |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1156587A (en) * | 1996-12-13 | 1997-08-13 | 孙旭光 | Non-crystal mannitol injection and preparing process thereof |
| CN1692916A (en) * | 2004-05-09 | 2005-11-09 | 北京奇源益德药物研究所 | Pharmaceutical prepn. of compound mannite, and its prepn. method |
| WO2008110374A2 (en) * | 2007-03-13 | 2008-09-18 | Add Advanced Drug Delivery Technologies Ltd. | Pellets containing a pharmaceutical substance, method for the production thereof and use of the same |
| CN101732287A (en) * | 2009-12-23 | 2010-06-16 | 北京圣方达隆医药科技发展有限责任公司 | Injection of mannite and glycerol and preparation method thereof |
| CN102120026A (en) * | 2011-03-03 | 2011-07-13 | 天津市炜杰科技有限公司 | 21(S) argatroban intravenous injection with alcohol as solubilizer |
-
2013
- 2013-07-23 CN CN2013103119234A patent/CN103432066A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1156587A (en) * | 1996-12-13 | 1997-08-13 | 孙旭光 | Non-crystal mannitol injection and preparing process thereof |
| CN1692916A (en) * | 2004-05-09 | 2005-11-09 | 北京奇源益德药物研究所 | Pharmaceutical prepn. of compound mannite, and its prepn. method |
| WO2008110374A2 (en) * | 2007-03-13 | 2008-09-18 | Add Advanced Drug Delivery Technologies Ltd. | Pellets containing a pharmaceutical substance, method for the production thereof and use of the same |
| CN101732287A (en) * | 2009-12-23 | 2010-06-16 | 北京圣方达隆医药科技发展有限责任公司 | Injection of mannite and glycerol and preparation method thereof |
| CN102120026A (en) * | 2011-03-03 | 2011-07-13 | 天津市炜杰科技有限公司 | 21(S) argatroban intravenous injection with alcohol as solubilizer |
Non-Patent Citations (3)
| Title |
|---|
| 其他溶媒: "《药剂学》", 31 May 1980, article "全国中等卫生学校试用教材《药剂学》编写组", pages: 230 * |
| 张锋: "新复方甘露醇注射液的稳定性研究", 《浙江中西医结合杂志》, vol. 13, no. 11, 31 December 2003 (2003-12-31) * |
| 薛金春等: "20%甘露醇注射液配制中应注意的问题", 《海峡药学》, vol. 10, no. 3, 31 December 1998 (1998-12-31) * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105147602A (en) * | 2015-10-23 | 2015-12-16 | 广西裕源药业有限公司 | Mannitol injection |
| CN105147600A (en) * | 2015-10-23 | 2015-12-16 | 广西裕源药业有限公司 | Compound mannitol injection |
| CN105287368A (en) * | 2015-10-23 | 2016-02-03 | 广西裕源药业有限公司 | Mannitol injection |
| CN105147602B (en) * | 2015-10-23 | 2018-06-29 | 广西裕源药业有限公司 | Formula mannitol injection liquid |
| CN105287368B (en) * | 2015-10-23 | 2018-06-29 | 广西裕源药业有限公司 | A kind of formula mannitol injection liquid |
| CN105147600B (en) * | 2015-10-23 | 2018-06-29 | 广西裕源药业有限公司 | A kind of compound formula mannitol injection liquid |
| CN106074372A (en) * | 2016-08-11 | 2016-11-09 | 安徽环球药业股份有限公司 | The preparation method of formula mannitol injection liquid |
| CN106389324A (en) * | 2016-11-08 | 2017-02-15 | 江西科伦药业有限公司 | Production and preparation process capable of lowering mannitol injection crystallization |
| CN106389324B (en) * | 2016-11-08 | 2019-05-03 | 江西科伦药业有限公司 | A kind of process for producing reducing formula mannitol injection liquid crystallization |
| CN106551901A (en) * | 2017-01-02 | 2017-04-05 | 江苏恒丰强生物技术有限公司 | Animal compound formula mannitol injection liquid |
| CN116983258A (en) * | 2023-07-25 | 2023-11-03 | 河南双鹤华利药业有限公司 | Preparation process of mannitol injection not easy to crystallize |
| CN116983258B (en) * | 2023-07-25 | 2024-03-22 | 河南双鹤华利药业有限公司 | Preparation process of mannitol injection not easy to crystallize |
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Application publication date: 20131211 |