CN102525898A - Edaravone composition injection and preparation method thereof - Google Patents
Edaravone composition injection and preparation method thereof Download PDFInfo
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- CN102525898A CN102525898A CN2012100140493A CN201210014049A CN102525898A CN 102525898 A CN102525898 A CN 102525898A CN 2012100140493 A CN2012100140493 A CN 2012100140493A CN 201210014049 A CN201210014049 A CN 201210014049A CN 102525898 A CN102525898 A CN 102525898A
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- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 title claims abstract description 54
- 229950009041 edaravone Drugs 0.000 title claims abstract description 51
- 238000002347 injection Methods 0.000 title claims abstract description 46
- 239000007924 injection Substances 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 239000000203 mixture Substances 0.000 title abstract 5
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 12
- 235000019445 benzyl alcohol Nutrition 0.000 claims abstract description 11
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229960001305 cysteine hydrochloride Drugs 0.000 claims abstract description 6
- 239000011780 sodium chloride Substances 0.000 claims abstract description 6
- 239000002131 composite material Substances 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000008215 water for injection Substances 0.000 claims description 7
- 235000010265 sodium sulphite Nutrition 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 230000001186 cumulative effect Effects 0.000 claims description 3
- 238000005262 decarbonization Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 230000001954 sterilising effect Effects 0.000 claims description 3
- 238000004659 sterilization and disinfection Methods 0.000 claims description 3
- 229960004217 benzyl alcohol Drugs 0.000 abstract description 9
- 150000003254 radicals Chemical class 0.000 abstract description 9
- 238000012360 testing method Methods 0.000 abstract description 9
- 206010008118 cerebral infarction Diseases 0.000 abstract description 5
- 230000000813 microbial effect Effects 0.000 abstract description 4
- 206010008111 Cerebral haemorrhage Diseases 0.000 abstract description 3
- 206010019196 Head injury Diseases 0.000 abstract description 2
- 208000026106 cerebrovascular disease Diseases 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 abstract 1
- 210000004556 brain Anatomy 0.000 abstract 1
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 230000035755 proliferation Effects 0.000 abstract 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 abstract 1
- 230000033228 biological regulation Effects 0.000 description 26
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 230000008859 change Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 230000002000 scavenging effect Effects 0.000 description 5
- 102000019197 Superoxide Dismutase Human genes 0.000 description 4
- 108010012715 Superoxide dismutase Proteins 0.000 description 4
- 238000011443 conventional therapy Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 201000006474 Brain Ischemia Diseases 0.000 description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- -1 Hydroxyl radical free radical Chemical class 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000007971 neurological deficit Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 206010048962 Brain oedema Diseases 0.000 description 1
- 208000026680 Metabolic Brain disease Diseases 0.000 description 1
- 206010062190 Metabolic encephalopathy Diseases 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medicine and discloses an edaravone composition injection and a preparation method thereof. Every liter of edaravone composition injection comprises 1.5mg of edaravone, 1mg of sodium bisulfite, 0.5mg of cysteine hydrochloride, 6.75mg of sodium chloride, 0.5 percent by volume of phenylcarbinol and the balance of water. The edaravone composition injection comprises 0.5 percent by volume of phenylcarbinol which can be used for relieving pain, suppressing microbial proliferation and enhancing the free radical clearing function of edaravone. As proved by a test, the edaravone composition injection disclosed by the invention has an enhanced free radical clearing function, an improved brain protection function and high stability, and can be widely applied to treatment of cerebral infarction, cerebral hemorrhage and craniocerebral trauma.
Description
Technical field
The present invention relates to medical technical field, relate to a kind of Edaravone composite injection and preparation method thereof specifically.
Background technology
Edaravone, chemistry 3-methyl isophthalic acid-phenyl by name-2-pyrazolin-5-one, molecular formula is C
10H
10N
2O, molecular weight are 174.20, and structural formula does
Edaravone is to obtain Japanese health ministry approval listing by the exploitation of Mitsubishi drugmaker and April calendar year 2001, and commodity are called Radicut.Go on the market in 2008 in China.
Edaravone has free radical and the effect that suppresses lipid peroxidation of removing; The peroxidation and delay neuronal death that can suppress brain cell; And can alleviate cerebral edema and the tissue injury that cerebral ischemia and cerebral ischemia cause, in various cerebral ischemic models, demonstrating has extraordinary protective effect to cerebral ischemia.Be widely used in the cerebral infarction treatment of acute stage clinically, and also be applied to the treatment of cerebral hemorrhage, craniocerebral trauma and some nutrition, metabolic encephalopathy gradually.
The prescription of the Edaravone Injection of approval listing at present is:
Summary of the invention
The invention provides a kind of Edaravone composite injection and preparation method thereof, said Edaravone composite injection cerebral protection strengthens, good stability.
The present invention adopts following technical scheme:
A kind of Edaravone composite injection, every milliliter contains:
Edaravone 1.5mg;
Sodium sulfite 1mg;
Cysteine hydrochloride 0.5mg;
Sodium chloride 6.75mg;
Benzyl alcohol 0.5v/v%;
Sodium hydroxide is transferred pH to 3.2～3.8
Surplus is a water for injection.
Benzyl alcohol has another name called benzylalcohol, is one of the simplest aromatic alcohol, has easing the pain, suppresses the effect of microbial reproduction.Researcher of the present invention is found the inhibition microbial reproduction that not only can ease the pain behind a certain amount of benzyl alcohol of adding in the prescription through a large amount of tests; And strengthened Edaravone the effect of removing free radical; And stability and safety change little, reach safety, the effectiveness of medication.
The present invention also provides a kind of method for preparing of Edaravone composite injection, for getting the water for injection of total amount about 80%, under nitrogen protection, adds sodium sulfite, cysteine hydrochloride, sodium chloride and the benzyl alcohol stirring and dissolving of recipe quantity; Temperature control adds Edaravone at 60～70 ℃, and stirring and dissolving is regulated pH value to 3.2～3.8 with the 0.1mol/L sodium hydroxide solution; By g/mL, add the active carbon of cumulative volume 0.01%, stirring and adsorbing 15min; Filtering decarbonization adds to the full amount of water for injection, and stirs; Through 0.22 μ m filter membrane fine straining, fill nitrogen embedding sterilization and promptly get.
Can find out from above-mentioned technical scheme; Edaravone composite injection provided by the invention comprises that volume ratio is 0.5% benzyl alcohol; Benzyl alcohol not only can ease the pain, suppress microbial reproduction, and has strengthened the removing free radical effect of Edaravone Injection.
Description of drawings
Fig. 1 shows the scavenging action to DPPH of embodiment 2 Edaravone composite injections according to the invention and existing Edaravone group injection; Wherein
shows the scavenging action of existing Edaravone group injection to DPPH, and
shows the scavenging action of Edaravone composite injection according to the invention to DPPH.
The specific embodiment
The embodiment of the invention discloses a kind of Edaravone composite injection and preparation method thereof.Those skilled in the art can use for reference this paper content, suitably improve technological parameter and realize.Special needs to be pointed out is that all similarly replace and change apparent to those skilled in the art, they all are regarded as and are included in the present invention.Product of the present invention and method are described through preferred embodiment, and the related personnel obviously can change or suitably change and combination method as herein described in not breaking away from content of the present invention, spirit and scope, realizes and use technology of the present invention.
In order further to understand the present invention, the present invention is elaborated below in conjunction with embodiment.
Embodiment 1: Edaravone composite injection according to the invention
Method for preparing: get the water for injection of total amount of preparation about 80%, under nitrogen protection, add 1.0g sodium sulfite, 0.5g cysteine hydrochloride, 6.75g sodium chloride and 5mL benzyl alcohol stirring and dissolving, temperature control adds the 1.5g Edaravone at 60～70 ℃; Stirring and dissolving is regulated pH value to 3.2～3.8 with the 0.1mol/L sodium hydroxide solution, adds the active carbon of cumulative volume 0.01% (g/mL); Stirring and adsorbing 15min, filtering decarbonization adds the injection water to 1000mL; Stir,, fill the nitrogen embedding through 0.22 μ m filter membrane fine straining; 121 ℃ of moist heat sterilization 20min promptly get the Edaravone composite injection.
Embodiment 2: Edaravone composite injection according to the invention is removed the free radical effect
The orthophenanthroline solution 1mL that gets 0.75mmol/L adds people 2mL0.2mmol/L PBS buffer (pH 7.4), 1mL 0.75mmol/L FeSO successively in 10mL tool plug test tube
4Solution is mixing immediately, adds the Edaravone composite injection and the existing Edaravone Injection sample solution of the embodiment of the invention 1 preparation of 1mL variable concentrations respectively, adds 1mL 0.01% H behind the mixing
2O
2, using the deionized water standardize solution, 37 ℃ of water-bath 60min measure its absorbance at the 510nm place, calculate the clearance rate of hydroxy radical, and the result sees table 1.Wherein the computing formula to the clearance rate of hydroxy radical is: clearance rate=[(A
1-A
0)/(A
2-A
0)] * 100% formula in A
1For adding H
2O
2Absorbance during with sample; A
0For adding H
2O
2But absorbance when not adding sample; A
2Be H
2O
2With sample absorbance of added-time not.
The scavenging action of table 1 pair hydroxy radical
Get the Edaravone composite injection and the existing Edaravone Injection sample solution 2mL of the embodiment of the invention 1 preparation of variable concentrations; Add 2mL 0.1mmol/L 1; 1-diphenyl-2-trinitrophenyl-hydrazine (DPPH) solution mixing; Behind the lucifuge reaction 30min, measure absorbance A in 517 nm places; Blank control group replaces DPPH solution with the equal-volume distilled water, and matched group replaces sample solution with the equal-volume distilled water.Calculate clearance rate, the result sees Fig. 1, and wherein the computing formula to the clearance rate of hydroxy radical is:
Clearance rate=[1-(A
1-A
0)/A
2] * 100%
A in the formula
1Be sample sets absorbance, A
0Be blank control group absorbance, A
2Be the matched group absorbance.
Hydroxyl radical free radical is the active oxygen of tool offensiveness in the organism, it can be in several ways with organism in molecular action.Can know that by table 1 under variable concentrations, the clearance rate of Edaravone composite injection according to the invention all significantly is better than existing Edaravone Injection (P＜0.05).DPPH is a kind of free radical of very stable nitrogen center, and sample has reflected it to the DPPH measured by esr technique passs H
+Ability.Visible by Fig. 1, Edaravone Injection of the present invention to the scavenging action of DPPH, all significantly is better than existing Edaravone Injection (P＜0.05), and strengthens with concentration in the variable concentrations scope.In sum, show that the effect of the existing Edaravone group injection removing of Edaravone composite injection according to the invention free radical strengthens.
Embodiment 3: Edaravone composite injection according to the invention is removed free radical effect clinical research
114 routine patients with cerebral hemorrhage are divided into treatment A group (57), treatment B group (57) at random.Treatment group A gives existing Edaravone Injection on the basis of conventional therapy; Treatment group B gives the Edaravone composite injection of the embodiment of the invention 1 preparation on the basis of conventional therapy; Be total to 19d; In 19d each group is carried out neurological deficits score, establish normal control group 30 people simultaneously.Treatment A group and treatment B group morning, venous blood collection detected nitric oxide (NO), superoxide dismutase (SOD), lipid peroxide (LPO), glutathion peroxidase (GSHPX) level on an empty stomach, blood sampling before treatment and treatment back 5,19d carry out.The result sees table 2～6.
The clinical research of table 2 neurologic impairment
| Treatment A group | Treatment B group | |
| Neurologic impairment | 9.6±6.3 | 8.5±5.7 |
| Obvious effective rate | 48.3％ | 58.7％ |
| Effective percentage | 86.2％ | 90.3％ |
Table 3 different time points serum NO level value
| Group | Matched group | Treatment A group | Treatment B group |
| Before the treatment | 340.2±30.6 | 421.6±36.8 | 422.3±35.7 |
| Treatment back 5d | - | 445.5±37.1 | 399.3±35.4* |
| Treatment back 19d | - | 383.5±27.2 | 386.4±29.9 |
* compare P＜0.05 with treatment A group
Table 4 different time points Serum LPO value
| Group | Matched group | Treatment A group | Treatment B group |
| Before the treatment | 9.88±0.6 | 12.4±1.2 | 12.6±1.1 |
| Treatment back 5d | - | 14.3±1.1 | 11.4±0.9* |
| Treatment back 19d | - | 11.6±1.2 | 11.5±1.0 |
* compare P＜0.05 with treatment A group
Table 5 different time points SOD in serum value
| Group | Matched group | Treatment A group | Treatment B group |
| Before the treatment | 29.6±8.5 | 24.5±8.2 | 23.6±8.8 |
| Treatment back 5d | - | 23.6±9.0 | 27.7±10.0* |
| Treatment back 19d | - | 27.5±10.2 | 26.8±9.5 |
* compare P＜0.05 with treatment A group
Table 6 different time points serum GSH-Px value
| Group | Matched group | Treatment A group | Treatment B group |
| Before the treatment | 29.6±8.5 | 24.4±1.3 | 23.9±1.2 |
| Treatment back 5d | - | 23.7±1.2 | 27.1±1.4* |
| Treatment back 19d | - | 24.7±1.5 | 24.5±1.2 |
* compare P＜0.05 with treatment A group
Visible by table 2～6 results; Treatment group patient neurological deficits score all is starkly lower than matched group; Treatment obvious effective rate and effective percentage are significantly higher than matched group; And treatment B group is that Edaravone composite injection group obvious effective rate according to the invention and effective percentage promptly have Edaravone Injection now apparently higher than treatment A group, shows that Edaravone composite injection according to the invention can alleviate neurologic impairment, and cerebral protection is high.5d treatment B group NO, LPO are lower than the conventional therapy group behind the observation comparison patient treatment in addition, and SOD, GSH-Px are higher than the conventional therapy group, and difference has statistical significance (P＜0.05).
Embodiment 4: Edaravone composite injection stability study according to the invention
With the embodiment of the invention 1 prepared injection is object of study, carries out comprehensive study on the stability, comprising: influence factor's test, accelerated test, long-time stability.Each study on the stability experimental condition and visible foreign matters inspection method all with reference to " relevant regulations in the Chinese pharmacopoeia appendix, the influence factor tests and investigates 10 days, accelerated test is investigated 6 months, long-time stability were investigated to 24 months, the result sees table 7～9.
Table 7 influence factor test
Annotate: injection is not investigated super-humid conditions, and content was in 100% in 0 day.
Table 8 accelerated test
| Time | Outward appearance | Visible foreign matters | Related substance | PH value | Content (%) |
| 0 month | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.8 | 99.85 |
| January | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.5 | 99.77 |
| February | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.7 | 99.73 |
| March | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.6 | 99.71 |
| June | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.8 | 99.65 |
Annotate: 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%
Table 9 long-term stable experiment
| Outward appearance | Visible foreign matters | Related substance | PH value | Content (%) | |
| 0 month | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.8 | 99.89 |
| March | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.7 | 99.86 |
| June | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.6 | 99.78 |
| JIUYUE | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.7 | 99.81 |
| December | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.7 | 99.85 |
| 18 months | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.8 | 99.79 |
| 24 months | The clear and bright solution of light brown | Meet " Chinese pharmacopoeia regulation | Meet the quality standard regulation | 3.6 | 99.76 |
Annotate: 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%
Can know by table 7～9 results; The prepared Edaravone composite injection of the embodiment of the invention 1 more violent high temperature, strong illumination condition held 10 days, at 40 ℃, is investigated 6 months under the acceleration environment of relative humidity 75% by relevant regulations; At 25 ± 2 ℃; Investigate 24 months under relative humidity 60 ± 10% conditions, main quality index does not have significant change, shows that Edaravone composite injection according to the invention is stable and controllable for quality.
The explanation of above embodiment just is used for helping to understand method of the present invention and core concept thereof.Should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention, can also carry out some improvement and modification to the present invention, these improvement and modification also fall in the protection domain of claim of the present invention.
Claims (2)
1. an Edaravone composite injection is characterized in that, every milliliter contains:
Edaravone 1.5mg;
Sodium sulfite 1mg;
Cysteine hydrochloride 0.5mg;
Sodium chloride 6.75mg;
Benzyl alcohol 0.5v/v%;
Surplus is a water for injection.
2. the method for preparing of the said injection of claim 1 is characterized in that, gets the water for injection of total amount about 80%; Under nitrogen protection, add sodium sulfite, cysteine hydrochloride, sodium chloride and the benzyl alcohol stirring and dissolving of recipe quantity, temperature control adds Edaravone, stirring and dissolving at 60～70 ℃; Regulate pH value to 3.2～3.8 with the 0.1mol/L sodium hydroxide solution,, add the active carbon of cumulative volume 0.01% by g/mL; Stirring and adsorbing 15min, filtering decarbonization adds to the full amount of water for injection; Stir,, fill nitrogen embedding sterilization and promptly get through 0.22 μ m filter membrane fine straining.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103263384A (en) * | 2013-05-20 | 2013-08-28 | 山东罗欣药业股份有限公司 | Edaravone composition injection and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1440749A (en) * | 2003-03-24 | 2003-09-10 | 南昌弘益科技有限公司 | Edaravone injection for treating acute cerebral thrombus and its prepn |
| CN102091028A (en) * | 2009-12-15 | 2011-06-15 | 南京长澳医药科技有限公司 | Edaravone injection and preparation method thereof |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1440749A (en) * | 2003-03-24 | 2003-09-10 | 南昌弘益科技有限公司 | Edaravone injection for treating acute cerebral thrombus and its prepn |
| CN102091028A (en) * | 2009-12-15 | 2011-06-15 | 南京长澳医药科技有限公司 | Edaravone injection and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103263384A (en) * | 2013-05-20 | 2013-08-28 | 山东罗欣药业股份有限公司 | Edaravone composition injection and preparation method thereof |
| CN103263384B (en) * | 2013-05-20 | 2014-09-17 | 山东罗欣药业集团股份有限公司 | Edaravone composition injection and preparation method thereof |
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Application publication date: 20120704 |