CN103211757A - Edaravone injection and preparation method thereof - Google Patents
Edaravone injection and preparation method thereof Download PDFInfo
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- CN103211757A CN103211757A CN2013101445667A CN201310144566A CN103211757A CN 103211757 A CN103211757 A CN 103211757A CN 2013101445667 A CN2013101445667 A CN 2013101445667A CN 201310144566 A CN201310144566 A CN 201310144566A CN 103211757 A CN103211757 A CN 103211757A
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Abstract
The invention relates to the field of medicines, and particularly relates to an edaravone injection and a preparation method thereof. The invention adopts the following technical scheme: the edaravone injection comprises edaravone, sodium hydrogen sulfite, L-cysteine hydrochloride, sodium hydroxide, sodium chloride and water for injection. The daravone injection disclosed by the invention has the advantages that in the environments of high temperature, illumination, low temperature and freeze thawing, no foreign matter is produced, the osmotic pressure is stable, the shape and the properties of the solution remain unchanged, the performance of the edaravone injection is stable and the medical effect is guaranteed.
Description
Technical field
The present invention relates to field of medicaments, be meant a kind of Edaravone Injection and compound method thereof especially.
Background technology
Edaravone is a kind of cerebral protective agent (free radical scavenger).Clinical research prompting N-acetyl Aspartic Acid (NAA) is the sign of specific survival neurocyte, and cerebral infarction their early stage content sharply reduces.Acute period of cerebral infarction the patient give Edaravone, can suppress to block the minimizing of regional cerebral blood flow on every side, makes that NAA content obviously raises than the glycerol matched group in the 28th day brain in morbidity back.The preclinical study prompting, rat gives Edaravone at ischemia/ischemia-reperfusion posterior vein, can stop the progress of cerebral edema and cerebral infarction, and alleviates the nervous symptoms of being followed, and suppresses delayed neuronal death.Mechanism research prompting, Edaravone can be removed free radical, suppresses lipid peroxidation, thereby suppresses the oxidative damage of brain cell, vascular endothelial cell, neurocyte.
Wherein Edaravone is a kind of antioxidant of hydroxyl radical free radical scavenging action, has shown the remarkable antioxidation to the lipid peroxide of hydroxyl radical free radical and ion generation; Its chemistry 3-methyl isophthalic acid-phenyl by name-2-pyrazolin-5-one (3-methyl-1-phenyl-2-pyrazolin-5-one), its structural formula is:
Molecular formula: C
10H
10N
2O molecular weight: 174.19
Edaravone Injection is a kind of cerebral protective agent, is mainly used in symptom such as treatment acute cerebral infarction etc., and Edaravone can effectively alleviate nervous symptoms and the dysfunction that brain tissue impairment causes behind the cerebral infarction;
And the preparation of domestic existing Edaravone is got and is had following shortcoming: 1, principal agent Edaravone character instability in the Edaravone Injection, and easily oxidized, medical effect is not high; 2, domestic existing Edaravone Injection is little liquid drugs injection, needs during clinical administration to dilute then through intravenous drip with normal saline earlier, and requires to drip off in 30 minutes;
In sum, domestic existing Edaravone Injection just can be injected after with normal saline dilution compatibility because of need in the clinical administration process, not directly administration, and make the principal agent Edaravone be exposed in the air, unavoidably principal agent is oxidized, can't guarantee the safety of medical procedure.
Summary of the invention
Deficiency at prior art exists the object of the present invention is to provide a kind of stable performance, directly administration, is convenient to medical treatment and stable Edaravone Injection and the compound method thereof of medical effect.
A kind of Edaravone Injection of the present invention, this injection comprise Edaravone, sodium sulfite, L-cysteine hydrochloride, sodium hydroxide, sodium chloride and water for injection.
Sodium sulfite in the Edaravone Injection of the present invention and L-cysteine hydrochloride play the antioxidative effect as antioxidant, and sodium sulfite is soluble in water, also be slightly soluble in alcohol, water stability is stronger, very easily is absorbed, thereby has stronger antioxygenic property; And the L-cysteine hydrochloride has the strong acid flavor, and is very easily water-soluble, has strong antioxygenic property; Sodium chloride is very easily water-soluble, and the sodium ion in the sodium chloride and chloride ion major part are dissolved in extracellular fluid, the osmotic pressure of scalable extracellular fluid; Wherein sodium hydroxide is very easily water-soluble, and its aqueous solution is alkalescence, in injection the principal agent Edaravone is played the hydrotropy effect, can effectively regulate the pH value of Edaravone Injection, after these several compositions mix, has just improved the stability of solution greatly.
The present invention further is set to: the concentration of described Edaravone in injection is 0.2-0.4mg/ml; Edaravone is a kind of cerebral protective agent (free radical scavenger); main medicament (principal agent) for Edaravone Injection among the present invention; clinical research prompting N-acetyl Aspartic Acid (NAA) is the sign of specific survival neurocyte; cerebral infarction their early stage content sharply reduces; acute period of cerebral infarction the patient give Edaravone; can suppress to block the minimizing of regional cerebral blood flow on every side; make that NAA content obviously raises than the glycerol matched group in the 28th day brain in morbidity back; concentration during this is provided with changes according to the demand of reality, usually between 0.2-0.4mg/ml.
The present invention further is set to: the concentration of described sodium sulfite in injection is 0.1-0.3mg/ml, the content of this scope all can make the solution non-oxidizability of Edaravone Injection strengthen, thereby make solution more stable, and the medical effect of maintenance solution the best, minimum is 0.1mg/ml, be up to 0.3mg/ml, the medical effect of this Edaravone Injection is along with the variation in wave shape of the consumption of sodium sulfite, when the concentration of sodium sulfite in injection is 0.2mg/ml, medical effect the best of Edaravone Injection, be in the 100ml water for injection, the content of sodium sulfite is 20mg.
The present invention further is set to: the concentration of described L-cysteine hydrochloride in injection is 0.05-0.2mg/ml; the L-cysteine hydrochloride also is a kind of antioxidant in the present invention; its effect is in order to make solution of the present invention more stable; the effect that certain L-cysteine hydrochloride also has drug effect to augment and protect; therefore the content of this scope all can be realized the medical effect of Edaravone Injection; minimum is 0.05mg/ml; be up to 0.2mg/ml; the medical effect of this Edaravone Injection is along with the variation in wave shape of the consumption of L-cysteine hydrochloride; when the concentration of L-cysteine hydrochloride in injection is 0.1mg/ml; medical effect the best of Edaravone Injection; be in the 100ml water for injection, the content of L-cysteine hydrochloride is 10mg.
The present invention further is set to: the concentration of described sodium hydroxide in injection is 0.06-0.26mg/ml, plays the effect of cosolvent in the present invention, increases the dissolubility of principal agent Edaravone.Sodium hydroxide also has the effect of regulating pH value, usually in solution of the present invention, when concentration sodium hydroxide reaches 0.06-0.26mg/ml, the pH value of solution is between 3.0～6.0, under the prerequisite of this PH, the drug effect of solution of the present invention keeps the most complete, the situation of mutation can not occur.
The present invention further is set to: the concentration of described sodium chloride in injection is 7.55-9.55mg/ml, the content of this scope all can be realized the medical effect of Edaravone Injection, minimum is 7.55mg/ml, be up to 9.55mg/ml, in the concentration range of this sodium chloride, satisfy various human body osmotic pressure demands, but best concentration is 8.55mg/ml, osmotic pressure reaches the degree of mating most with human body like this.
The present invention further is set to: the pH value of this injection is 3.0～6.0; When the pH value of injection was 3.5～4.5, Edaravone was the most stable in water for injection.
Another aspect of the present invention: the compound method of this Edaravone Injection, compound method is as follows:
(1) feeding nitrogen is saturated in dense preparing tank, injects the water for injection of preparing total amount 70% again in dense preparing tank, and temperature is 40 ℃～50 ℃;
(2) it is saturated to feed nitrogen again in the water for injection, drops into sodium sulfite, L-cysteine hydrochloride under condition of stirring, fully after the dissolving, drop into sodium hydroxide, treat to drop into Edaravone again after the dissolution of sodium hydroxide, treat to drop into sodium chloride again, stirring and dissolving after the Edaravone dissolving;
(3) solution in the dense preparing tank is injected dilute preparing tank, add the injection water to preparing 95% of total amount;
(4) regulate the pH value of above-mentioned solution with phosphoric acid,diluted or sodium hydroxide; In dilute preparing tank, add the injection water again to preparing total amount;
(5) the above-mentioned solution that makes is stirred, and adopt circulating pump that solution is circulated, through 0.22 ц m polypropylene microporous filter membrane fine straining.
(6) under the environment of nitrogen the above-mentioned solution that makes is carried out embedding, adopt flowing steam sterilization, the time was controlled at 30 minutes, and temperature is controlled at 115 ℃.
In sum, in the water for injection of 100ml, the content of Edaravone is 30mg, the content of sodium sulfite is 20mg, the content of L-cysteine hydrochloride is 10mg, the content of sodium hydroxide is 16mg, the content of sodium chloride is 855mg, the pH value of injection is 3.5～4.5, owing to added sodium sulfite in the present invention, the L-cysteine hydrochloride has improved the stability of solution of the present invention as antioxidant, cooperates 3.5～4.5 pH value environment simultaneously, guarantee the stability of Edaravone Injection of the present invention, thereby make its medical effect remain in optimum state, this Edaravone Injection is at high temperature always, illumination, under the environment of low temperature and freeze thawing, be as good as deposits yields, and the character of osmotic pressure and solution remains unchanged, the stable performance of Edaravone Injection has guaranteed medical effect, and in this technology, adopt nitrogen that the oxygen barrier processing is carried out in preparation and storage, further guaranteed the stability of Edaravone Injection.
The specific embodiment
Below the technical scheme in the embodiment of the invention is clearly and completely described, obviously, described embodiment only is the present invention's part embodiment, rather than whole embodiment.Based on the embodiment among the present invention, those of ordinary skills belong to the scope of protection of the invention not making the every other embodiment that is obtained under the creative work prerequisite.
In the present embodiment, the prescription of the Edaravone Injection that provides is as follows:
The consumption that above-mentioned prescription is mentioned sodium hydroxide or phosphoric acid,diluted is to decide according to the pH value of solution, transfers to 3.5～4.5 up to the pH value with solution.
The above-mentioned recipe quantity of mentioning is best recipe quantity, and by the Edaravone Injection stable performance that this recipe quantity preparation obtains, non-oxidizability is stronger, and homeo-osmosis, is difficult for changing, and has guaranteed medical effect.
Certainly on it prescription proportioning optimum among the present invention, and in the present invention: the concentration of Edaravone in injection can change between 0.2-0.4mg/ml; The concentration of sodium sulfite in injection can change between 0.1-0.3mg/ml; The concentration of L-cysteine hydrochloride in injection can change in 0.05-0.2mg/ml scope; The concentration of sodium hydroxide in injection is between 0.06-0.26mg/ml; The concentration of sodium chloride in injection is that 7.55-9.55mg/ml regulates its concentration according to concrete application, reaches suitable osmotic pressure.
The relation that has the intersection proportioning between the content range of various compositions of the present invention, not for concerning one to one, when between 0.2-0.4mg/ml, changing such as the concentration of Edaravone in injection, other each components can be in its scope proportioning arbitrarily.
Compound method:
The invention discloses a kind of compound method of Edaravone Injection, compound method is as follows:
(1) it is saturated to feed nitrogen in dense preparing tank, and the time was controlled at 10 minutes at least, injects 70% the water for injection of preparing total amount 100ml again in the dense preparing tank, and temperature is controlled at 40 ℃～50 ℃;
(2) it is saturated to feed nitrogen again in the water for injection, under condition of stirring, drop into sodium sulfite 20mg, L-cysteine hydrochloride 10mg, fully after the dissolving, drop into sodium hydroxide 16mg, treat to drop into Edaravone 30mg again after the dissolution of sodium hydroxide, treat to drop into sodium chloride 855mg again, stirring and dissolving after the Edaravone dissolving;
(3) solution in the dense preparing tank is injected dilute preparing tank, add the injection water to 95ml;
(4) regulate pH value to 3.0～6.0 of above-mentioned solution with phosphoric acid,diluted or 1mol/l sodium hydroxide; In dilute preparing tank, add the injection water again to 100ml.
(5) the above-mentioned solution that makes is stirred, and adopt circulating pump to solution circulation 5 minutes, through 0.22 ц m polypropylene microporous filter membrane fine straining.
(6) under the environment of inflated with nitrogen the above-mentioned solution that makes is carried out embedding, adopt flowing steam sterilization, the time was controlled at 30 minutes, and temperature is controlled at 115 ℃.
The pH value of this Edaravone Injection is 3.0～6.0.Adopt phosphoric acid,diluted or 1mol/l sodium hydroxide to regulate the pH value of Edaravone Injection among the present invention, when pH value was 3.5～4.5, Edaravone was the most stable in water for injection.
In sum, this Edaravone Injection is under the environment of high temperature, illumination, low temperature and freeze thawing, be as good as deposits yields, and the character of osmotic pressure and solution remains unchanged, the stable performance of Edaravone Injection, and every index is all up to specification, guaranteed medical effect, and in this technology, adopt nitrogen that the oxygen barrier processing is carried out in preparation and storage, further guaranteed the stability of Edaravone Injection.
The above only is preferred embodiment of the present invention, and is in order to restriction the present invention, within the spirit and principles in the present invention not all, any modification of being done, is equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (8)
1. Edaravone Injection, it is characterized in that: this injection comprises Edaravone, sodium sulfite, L-cysteine hydrochloride, sodium hydroxide, sodium chloride and water for injection.
2. Edaravone Injection according to claim 1 is characterized in that: the concentration of described Edaravone in injection is 0.2-0.4mg/ml.
3. Edaravone Injection according to claim 2 is characterized in that: the concentration of described sodium sulfite in injection is 0.1-0.3mg/ml.
4. Edaravone Injection according to claim 3 is characterized in that: the concentration of described L-cysteine hydrochloride in injection is 0.05-0.2mg/ml.
5. Edaravone Injection according to claim 4 is characterized in that: the concentration of described sodium hydroxide in injection is 0.06-0.26mg/ml.
6. Edaravone Injection according to claim 5 is characterized in that: the concentration of described sodium chloride in injection is 7.55-9.55mg/ml.
7. according to arbitrary described Edaravone Injection in the claim 1, it is characterized in that: the pH value of this injection is 3.0～6.0.
8. according to the compound method of arbitrary described Edaravone Injection in the claim 1 to 7, compound method is as follows:
(1) feeding nitrogen is saturated in dense preparing tank, injects the water for injection of preparing total amount 70% again in dense preparing tank, and temperature is 40 ℃～50 ℃;
(2) it is saturated to feed nitrogen again in the water for injection, drops into sodium sulfite, L-cysteine hydrochloride under condition of stirring, fully after the dissolving, drop into sodium hydroxide, treat to drop into Edaravone again after the dissolution of sodium hydroxide, treat to drop into sodium chloride again, stirring and dissolving after the Edaravone dissolving;
(3) solution in the dense preparing tank is injected dilute preparing tank, add the injection water to preparing 95% of total amount;
(4) regulate the pH value of above-mentioned solution with phosphoric acid,diluted or sodium hydroxide; In dilute preparing tank, add the injection water again to preparing total amount;
(5) the above-mentioned solution that makes is stirred, and adopt circulating pump that solution is circulated, through 0.22 ц m polypropylene microporous filter membrane fine straining.
(6) under the environment of nitrogen the above-mentioned solution that makes is carried out embedding, adopt flowing steam sterilization, the time was controlled at 30 minutes, and temperature is controlled at 115 ℃.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2013101445667A CN103211757A (en) | 2013-04-23 | 2013-04-23 | Edaravone injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2013101445667A CN103211757A (en) | 2013-04-23 | 2013-04-23 | Edaravone injection and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110090225A (en) * | 2019-04-19 | 2019-08-06 | 济南康和医药科技有限公司 | A kind of Edaravone sodium chloride injection and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1449754A (en) * | 2003-04-16 | 2003-10-22 | 浙江震元制药有限公司 | Edaravone medicine composition and preparation thereof |
-
2013
- 2013-04-23 CN CN2013101445667A patent/CN103211757A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1449754A (en) * | 2003-04-16 | 2003-10-22 | 浙江震元制药有限公司 | Edaravone medicine composition and preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| 郭涛等: "依达拉奉氯化钠注射液的制备和稳定性考察", 《沈阳部队医药》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110090225A (en) * | 2019-04-19 | 2019-08-06 | 济南康和医药科技有限公司 | A kind of Edaravone sodium chloride injection and preparation method thereof |
| CN110090225B (en) * | 2019-04-19 | 2021-07-16 | 济南康和医药科技有限公司 | Edaravone sodium chloride injection and preparation method thereof |
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Application publication date: 20130724 |