CN103751104A - Edaravone injection and preparation method thereof - Google Patents
Edaravone injection and preparation method thereof Download PDFInfo
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- CN103751104A CN103751104A CN201410031230.4A CN201410031230A CN103751104A CN 103751104 A CN103751104 A CN 103751104A CN 201410031230 A CN201410031230 A CN 201410031230A CN 103751104 A CN103751104 A CN 103751104A
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Abstract
The invention relates to edaravone injection and a preparation method thereof. The injection comprises edaravone, cysteine hydrochloride, sodium bisulfite and water for injection. The edaravone injection provided by the invention has stable properties, and the preparation process can effectively control the content of dimers of related substance, so as to improve the safety of clinical use.
Description
Technical field
The invention belongs to technical field of medicine, relate to a kind of stable Edaravone Injection and preparation technology thereof.
Background technology
Edaravone (Edaravone) is a kind of in pyrazolone derivative, its chemistry 3-methyl isophthalic acid-phenyl-2-pyrazoles woods-5-ketone by name, molecular formula C
10h
10n
2o, chemical structural formula is as follows:
Edaravone is that first Mitsubishi Tokyo drugmaker develops, and April 4 calendar year 2001, Japan was ratified clinical use, trade name by medical workfare portion
this medicine is aqueous injection in Japan's listing dosage form, specification is 30mg/20ml, adjuvant is sodium sulfite and cysteine hydrochloride, conventionally using dosage is each 30mg, every day 2 times, be dissolved in normal saline or other diluent iv drip, general continuous use is no more than 14 days, for improving various Spirit nerve symptoms of diseases and the various malfunction of acute period of cerebral infarction.
Because Edaravone Injection is easily oxidized and easily produces dimer impurity in preparation process, affecting drug activity also may increase the untoward reaction of medicine, has brought difficulty to production and clinical use.
Summary of the invention
In order to reduce the content of dimer impurity in Edaravone Injection preparation, anti-oxidation, the invention provides a kind of Edaravone Injection, this injection has good clinical safety.
The present invention provides the preparation method of above-mentioned Edaravone Injection simultaneously; the method by adding antioxidant and cosolvent and obtain solution and embedding process all to operate under nitrogen protection in solution; with sodium hydroxide, regulate pH value, guarantee preparation steady quality in process of production.
Concrete technical scheme of the present invention is as follows:
The Edaravone Injection the present invention relates to, is characterized in that this injection is by active component Edaravone, antioxidant sodium sulfite, cosolvent cysteine hydrochloride, water for injection with for regulating the sodium hydroxide of pH value to form.
Described bisulfite sodium content is 0.5～20.0mg/ml, is preferably 0.5～12.0mg/ml.
Described CYSTEAMINE HCL acid content is 0.5～50.0mg/ml, is preferably 0.5～40.0mg/ml.
The Edaravone Injection the present invention relates to, wherein the pH value of pH adjusting agent regulator solution is 3.0～5.0, preferably pH value is 4.0～5.0.
The present invention also provides a kind of preparation method of Edaravone Injection: the Edaravone of moistening, pre-molten cysteine hydrochloride and sodium sulfite are mixed to dissolving, add active carbon, filter decarburization, with sodium hydroxide, regulating pH value is 3.0～5.0, ultrafiltration, standardize solution, fill, 121 ℃ of sterilizing 15min of flowing steam, leak detection, obtains finished product.
The preparation method of above-mentioned Edaravone Injection, the configuration of its herb liquid and pouring process all complete under nitrogen filled protection.
The preparation method of above-mentioned Edaravone Injection, medicinal liquid configures to fill and finishes to complete in 6h, preferably in 4h, completes.
The present invention compared to existing technology tool has the following advantages:
A kind of Edaravone Injection the present invention relates to, is guaranteeing, under the prerequisite of Edaravone stability, compared with prior art to have good clinical safety.
Because Edaravone is very easily oxidized and easily forms insoluble matter Edaravone dimer, increase adverse effect probability.Edaravone Injection of the present invention; antioxidant and cosolvent in composition, have been added; medicinal liquid configures to fill and finishes to complete in 6h simultaneously; the strict control time; configuration and pouring process all carry out under nitrogen filled protection condition simultaneously; can reduce the generation of dimer impurity, reduce the untoward reaction of medicine.
The preparation technology of Edaravone Injection of the present invention is simple, and adjuvant is common adjuvant, is suitable for industrialized mass.
In Edaravone Injection preparation technology of the present invention, after adjusting pH value, adopt ultrafiltration, can effectively isolate microorganism, improve sterilizing efficiency, shorten sterilization time, guarantee the stability of Edaravone.
In Edaravone Injection preparation technology of the present invention, sterilizing adopts 121 ℃ of sterilizing 15min of flowing steam, and this sterilising conditions is killing microorganisms effectively, and sterilization time is shorter simultaneously, also can guarantee the stability of Edaravone.
A kind of Edaravone Injection the present invention relates to, can be used for improving various Spirit nerve symptoms of diseases and the various malfunction of acute period of cerebral infarction.
The specific embodiment
Adopt some specific embodiments to further describe the present invention below, but protection scope of the present invention is not limited in following examples.
Embodiment 1:
Formula (specification: 5ml:10mg)
The Edaravone of the moistening of recipe quantity, pre-molten cysteine hydrochloride and sodium sulfite are mixed to dissolving, add active carbon, filter decarburization, with sodium hydroxide, regulating pH value is 5.0, ultrafiltration, standardize solution, fill, 121 ℃ of sterilizing 15min of flowing steam, leak detection, obtains finished product.Wherein, medicinal liquid configures to fill and finishes to complete in 6h, and configuration and pouring process all carry out under nitrogen filled protection condition simultaneously.
Embodiment 2:
Formula (specification: 5ml:10mg)
The Edaravone of the moistening of recipe quantity, pre-molten cysteine hydrochloride and sodium sulfite are mixed to dissolving, add active carbon, filter decarburization, with sodium hydroxide, regulating pH value is 4.0, ultrafiltration, standardize solution, fill, 121 ℃ of sterilizing 15min of flowing steam, leak detection, obtains finished product.Wherein, medicinal liquid configures to fill and finishes to complete in 6h, and configuration and pouring process all carry out under nitrogen filled protection condition simultaneously.
Embodiment 3:
Formula (specification: 5ml:10mg)
The Edaravone of the moistening of recipe quantity, pre-molten cysteine hydrochloride and sodium sulfite are mixed to dissolving, add active carbon, filter decarburization, with sodium hydroxide, regulating pH value is 3.0, ultrafiltration, standardize solution, fill, 121 ℃ of sterilizing 15min of flowing steam, leak detection, obtains finished product.Wherein, medicinal liquid configures to fill and finishes to complete in 6h, and configuration and pouring process all carry out under nitrogen filled protection condition simultaneously.
Three batches of examination and test of products results that embodiment 1～3 produces are as follows:
According to two guidelines about stability experiment of < < Chinese Pharmacopoeia > > version in 2010, carry out Accelerated stability test.The three batches of products that embodiment 1～3 is produced and commercially available product
(Edaravone, specification: 5mg:10ml) put into climatic chamber, be controlled under the condition of 40 ℃ and relative humidity 75%, respectively at 0,1,2,3 and several point in time sampling of 6 months, by investigation project Observe and measure, experimental result is as follows:
Result shows, Edaravone Injection prepared by the present invention is more stable, and especially the dimeric content of Edaravone is low, and the stability of embodiment 2 is better than other embodiment.This embodiment key process parameter is that described bisulfite sodium content is 20.0mg/ml, and CYSTEAMINE HCL acid content is 50.0mg/ml, and the pH value of pH adjusting agent regulator solution is 4.0.Except public technology scheme, this patent relates to all technical schemes all can guarantee that the Edaravone Injection of preparing has good stability.
Claims (7)
1. an Edaravone Injection, it is characterized in that: this injection is by active component Edaravone, antioxidant sodium sulfite, cosolvent cysteine hydrochloride, water for injection with for regulating the sodium hydroxide of pH value to form, the pH value of this injection is 3.0 ~ 5.0, preparation technology adopts and fills nitrogen dosing and fill, and Edaravone content is 1.0 ~ 20.0mg/ml; Described antioxidant content is 0.5 ~ 20.0mg/ml; Described cosolvent content is 0.5 ~ 50.0mg/ml.
2. Edaravone Injection according to claim 1, is characterized in that: described antioxidant bisulfite sodium content is 0.5 ~ 5.0mg/ml.
3. Edaravone Injection according to claim 1, is characterized in that: described cosolvent CYSTEAMINE HCL acid content is 0.5 ~ 30.0mg/ml.
4. the preparation method of one of any described Edaravone Injection of claim 1 ~ 3, it is characterized in that: during preparation, Edaravone, cysteine hydrochloride and sodium sulfite are dissolved in to water for injection, are stirred to completely and add active carbon after dissolving, filtering decarbonization, with sodium hydroxide, regulate pH value, ultrafiltration, standardize solution, fill, 121 ℃ of sterilizing 15min of flowing steam, leak detection, obtains finished product.
5. the preparation method of Edaravone Injection according to claim 4, is characterized in that: above-mentioned configuration and pouring process all complete under nitrogen filled protection.
6. the preparation method of Edaravone Injection according to claim 4, is characterized in that: above-mentioned medicinal liquid configures to fill finishing control and completes in 6h.
7. the preparation method of Edaravone Injection according to claim 6, is characterized in that: above-mentioned medicinal liquid configures to fill finishing control and completes in 4h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410031230.4A CN103751104A (en) | 2014-01-23 | 2014-01-23 | Edaravone injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410031230.4A CN103751104A (en) | 2014-01-23 | 2014-01-23 | Edaravone injection and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104784111A (en) * | 2015-03-28 | 2015-07-22 | 河北仁合益康药业有限公司 | Edaravone injection composition and preparation method thereof |
| CN107823128A (en) * | 2017-11-21 | 2018-03-23 | 扬子江药业集团上海海尼药业有限公司 | A kind of preparation method of Edaravone Injection |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63132833A (en) * | 1986-11-25 | 1988-06-04 | Mitsubishi Kasei Corp | Stable injection containing 3-methyl-1-phenyl-2-pyrazolon-5-one |
| CN102119920A (en) * | 2010-07-13 | 2011-07-13 | 福建天泉药业股份有限公司 | Edaravone injection and preparation method thereof |
-
2014
- 2014-01-23 CN CN201410031230.4A patent/CN103751104A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63132833A (en) * | 1986-11-25 | 1988-06-04 | Mitsubishi Kasei Corp | Stable injection containing 3-methyl-1-phenyl-2-pyrazolon-5-one |
| CN102119920A (en) * | 2010-07-13 | 2011-07-13 | 福建天泉药业股份有限公司 | Edaravone injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 方国民等: "依达拉奉注射液的制备工艺研究", 《中国药业》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104784111A (en) * | 2015-03-28 | 2015-07-22 | 河北仁合益康药业有限公司 | Edaravone injection composition and preparation method thereof |
| CN107823128A (en) * | 2017-11-21 | 2018-03-23 | 扬子江药业集团上海海尼药业有限公司 | A kind of preparation method of Edaravone Injection |
| CN107823128B (en) * | 2017-11-21 | 2018-11-09 | 扬子江药业集团上海海尼药业有限公司 | A kind of preparation method of Edaravone Injection |
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Application publication date: 20140430 |