CN106074366B - The injection and preparation method thereof for treating the disturbance of consciousness after brain trauma and brain surgery - Google Patents
The injection and preparation method thereof for treating the disturbance of consciousness after brain trauma and brain surgery Download PDFInfo
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- CN106074366B CN106074366B CN201610430919.3A CN201610430919A CN106074366B CN 106074366 B CN106074366 B CN 106074366B CN 201610430919 A CN201610430919 A CN 201610430919A CN 106074366 B CN106074366 B CN 106074366B
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- injection
- consciousness
- disturbance
- edaravone
- brain
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Abstract
The invention belongs to pharmaceutical technology fields, more particularly to a kind of injection and preparation method thereof for treating the disturbance of consciousness after brain trauma and brain surgery, mainly it is made of active constituent Edaravone, sodium chloride, cysteine hydrochloride, disodium glycyrrhizinate, methyl hydroxybenzoate, pH adjusting agent and water for injection.The foamless generation of preparation prepared by the present invention, foam is avoided in the adhesion of ampoule bottleneck, since medical fluid charing leads to the generation of visible foreign matters unqualified phenomenons during effective solution high temperature sealing, furthermore invention formulation quality is stablized, simple process investigates indices through long-term experiment and meets regulation.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of injection for treating the disturbance of consciousness after brain trauma and brain surgery
Liquid and preparation method thereof.
Background technique
Trauma Brain Infarct Were Analyzed (traumatic cerebral infarction TCI) is more serious concurrent of craniocerebral injury
The generation of one of disease, especially large area infraction will aggravate the damage of brain function, seriously affect the prognosis of patient.And for cranium brain
The patient of damage, because the disturbance of consciousness is serious, the symptom of primary lesion masks the sings and symptoms of cerebral infarction, so that TCI
Early detection is extremely difficult.Craniocerebral injury cerebral Infarction often hides morbidity, rapid progress, is easily covered by the symptom of primary wound, special
It is not that comatose patient is less susceptible to find, easily delay treatment.
The formation mechenism of Trauma Brain Infarct Were Analyzed mainly has several lower several points：
1. disturbances of blood coagulation
Brain tissue is destroyed, and thromboplastin largely discharges, and blood-brain barrier goes to pot, and activates extrinsic coagulation system, is produced
Sick rationality fibrin ferment, finally causes the thrombosis in the cerebrovascular.
2. hemodynamic responses
Cranium pressure is high, widely applies dehydrating agent, causes pachyemia, and blood viscosity increases.Massive blood loss, shock in operation draw
Encephalic Low perfusion is played, blood viscosity slows down significant raising with blood flow, causes the thrombosis of intracranial vessel.When patient is concurrent simultaneously high
When blood pressure, coronary heart disease, diabetes, it is easier to the complication for cerebral infarction occur.
3. blood supply area injury of blood vessel
Surgery locating depth tumour, Gigantic Meningioma, the normal adjacent blood vessel of easy damaged in cerebrovascular malformation art；Postoperative cerebral
Oedema, increased intracranial pressure cause cerebrovascular distortion, elongation and spasm；Because operation wound causes the stress reaction of body, cause complete
Body arteriolar spasm, dyshaemia induce thrombosis.
Edaravone is that Mitsubishi Tokyo drugmaker develops first, and on April 4th, 2001 is worked in Japan by medical treatment
Department of Welfare ratifies clinical use, which is liquid drugs injection in Japan's listing dosage form, and specification 30mg/20ml, auxiliary material is bisulfite
Sodium and cysteine hydrochloride are that each 30mg is dissolved in quiet in physiological saline or other dilutions 2 times a day usually using dosage
Arteries and veins instils, and general continuous use is no more than 14 days, for improving the various Spirit nerve symptoms of disease and various machines of acute period of cerebral infarction
It can obstacle.
Edaravone (Edaravone) is one of pyrazolone derivative, the entitled 3- methyl-1-phenyl-of chemistry
2- pyrazoles woods -5- ketone, molecular formula C10H10N2O, chemical structural formula are as follows：
Edaravone Injection easily aoxidizes during storage, and related substance increases, content decline.Antioxygen
Agent sodium hydrogensulfite, cysteine hydrochloride can increase the stability of Edaravone, in order to prevent active constituent Edaravone quilt
It aoxidizes, the antioxidant such as sodium hydrogensulfite, cysteine hydrochloride is added in commercial preparation, prescription is as follows
It is easily aoxidized during storage based on Edaravone Injection, related substance increases, under content
Drop.Current patent has carried out research and inquirement primarily with respect to problem above.
Such as：Chinese Patent Application No.：03116418.8 discloses a kind of pharmaceutical composition of cerebral protective agent, main medicine
Managing active constituent is Edaravone.The preparation method of the pharmaceutical composition is by Edaravone and the different alkali pharmaceutically allowed
Property substance is prepared, and clear solution is made, is then freeze-dried according to lyophilized technique, Edaravone freeze-dried powder is made
Agent.
Chinese Patent Application No.：201010022006.0 a kind of injection containing Edaravone is disclosed, it is of the invention
High concentration injection containing Edaravone, by the Edaravone of 1~5% (w/v), the 1,2-PD of 5~25% (v/v), 5
The ethyl alcohol and water for injection of~15% (v/v) forms, and pH value is 4.5~5.5.Edaravone Injection of the invention makes in clinic
Used time is added in sodium chloride infusion to patient's intravenous drip, increases the patient population for being suitble to use, is suitable for more Patients With Acute Cerebral Infarctions
Patient uses.
Chinese Patent Application No.：201010216022.3 disclosing a kind of Edaravone Injection of stable safety, the note
Liquid Edaravone Injection is penetrated, includes Edaravone and pharmaceutically acceptable auxiliary material, it is characterised in that the injection contains phosphorus
The antioxidant and pH adjusting agent of acid, L-cysteine hydrochloride and sodium hydrogensulfite composition.In matching for Edaravone Injection
Using rapid cooling method after whole nitrogen charging deoxygenation method and sterilizing in system and potting process, the stabilization of Edaravone Injection is improved
Property, it substantially reduces in relation to substance-dimer content, the Edaravone Injection for stablizing safety is provided for clinical application.
Chinese Patent Application No.：201110086709.4 disclose a kind of pharmaceutical composition containing edaravone compound and
Preparation method, the pharmaceutical composition is by Edaravone, L-cysteine hydrochloride, anhydrous sodium sulfite, sodium chloride and injection
It is formed with water.Pharmaceutical composition property provided by the invention containing edaravone compound is stablized.
Chinese Patent Application No.：201310035122.X disclose a kind of Edaravone Injection that antioxidant is not added and its
Preparation method.The object of the present invention is to provide a kind of impurity is few, prepare that the time is short, Edaravone without adding antioxidant is injected
Liquid, it contains following components：Edaravone, pH adjusting agent, water for injection；Preparation method step is：A, match liquid；B, it filters；
C, filling；D, it sterilizes；The nitrogen charging gas shielded in preceding 3 steps, and remaining oxygen and product impurity content in strict control water guarantee
It is in the safe and effective of clinical use.
Chinese Patent Application No.：201310299714.2 disclosing a kind of Edaravone Injection and preparation method thereof, institute
Contain vitamin C and glutathione in the Edaravone Injection stated, in the Edaravone Injection, Edaravone it is dense
Degree is 0.1%-0.2% (W/V), and ascorbic concentration is 0.1%-0.5% (W/V), and the concentration of glutathione is 1.0%-
10.0% (W/V).The present invention has the advantages that compared with prior art：The present invention is by Edaravone, vitamin C, paddy
The rational proportion of the sweet peptide of Guang, makes three act synergistically, and plays its good anti-oxidation characteristics, has to cerebral injury and its complication good
Good therapeutic effect, and stability is high.
But inventor, in actual production inventors have found that in the pouring process of medical fluid, medical fluid can generate largely
Bubble, bubble hangs over to fill and can not eliminate in time on needle, to adhere to bottleneck, Edaravone Injection is filled using ampoule bottle
Dress will cause the medical fluid charing of adhesion during high temperature sealing, cause visible foreign matters are underproof to happen.
Summary of the invention
Against the above deficiency, the present invention provides it is a kind of treat after brain trauma and brain surgery the injection of the disturbance of consciousness and its
Preparation method, inventor have found that disodium glycyrrhizinate equally has the effect for inhibiting its oxidation to Edaravone in actual test
Fruit, while can be avoided Edaravone Injection under disodium glycyrrhizinate and methyl hydroxybenzoate synergistic effect and steeping in process of production
Foam, therefore injection provided by the invention is mainly by active constituent Edaravone, sodium chloride, cysteine hydrochloride, glycyrrhizic acid two
Sodium, methyl hydroxybenzoate, pH adjusting agent and water for injection composition.
Injection provided by the invention：The active constituent Edaravone concentration is 1.0~4.0mg/ml.
Injection provided by the invention：The sodium chloride is isotonic regulator, and the addition of quantity is with injection etc.
It seeps and foundation is added for it.
Injection provided by the invention：The CYSTEAMINE HCL acid concentration is 0.2~0.4mg/ml.
Injection provided by the invention：The disodium glycyrrhizinate concentration is 0.8~1.2mg/ml.
Injection provided by the invention：The methyl hydroxybenzoate concentration is 0.1~0.3mg/ml.
Injection provided by the invention：, the active constituent Edaravone concentration is 1.5mg/ml, the hydrochloric acid half
Cystine concentration is 0.3mg/ml, and the disodium glycyrrhizinate concentration is 1.0mg/ml, and the methyl hydroxybenzoate concentration is
0.2mg/ml。
Injection provided by the invention：The pH adjusting agent is in sodium hydroxide, sodium phosphate, sodium acetate and sodium citrate
It is a kind of or several, pH range be 4.6~5.2.
Injection provided by the invention：The injection is sodium hydroxide, pH 4.9.
Invention further provides a kind of preparation method for treating the injection of the disturbance of consciousness after brain trauma and brain surgery,
It mainly includes the following steps that：The cysteine hydrochloride and disodium glycyrrhizinate that weigh recipe quantity are dissolved in 70~90% water for injection
In, the Edaravone of recipe quantity is added in stirring and dissolving, and stirring and dissolving adjusts pH value with pH adjusting agent, and pH value adjusting finishes,
The methyl hydroxybenzoate and sodium chloride of recipe quantity is added, stirring and dissolving adjusts pH value with pH adjusting agent again, and pH value adjusting finishes,
It is settled to total amount with water for injection, is stirred and evenly mixed, is filtered, filling, sterilizing, visual inspection is got product.
The preparation method of injection provided by the invention, further preferably following steps：Weigh the hydrochloric acid half of recipe quantity
Cystine and disodium glycyrrhizinate are dissolved in 80% water for injection, stirring and dissolving, and the Edaravone of recipe quantity is added, and are stirred molten
Solution adjusts pH value with the sodium hydroxide solution of 0.1mol/L, and pH value adjusting finishes, and methyl hydroxybenzoate and the chlorination of recipe quantity is added
Sodium, stirring and dissolving adjust pH value with the sodium hydroxide solution of 0.1mol/L again, and pH value adjusting finishes, with water for injection constant volume
It to total amount, stirs and evenly mixs, filters, filling, sterilizing, visual inspection is got product.
Above-mentioned injection of the present invention has the following advantages that compared with prior art：Preparation prepared by the present invention is still
The generation of foam, avoid foam in the adhesion of ampoule bottleneck, since medical fluid charing is led during effective solution high temperature sealing
The generation of the unqualified phenomenon of visible foreign matters is caused, furthermore invention formulation quality is stablized, simple process is investigated every through long-term experiment
Index meets regulation.
Specific embodiment
Embodiment 1：
Prescription
Preparation process
The cysteine hydrochloride and disodium glycyrrhizinate for weighing recipe quantity are dissolved in suitable water for injection, and stirring and dissolving adds
Enter the Edaravone of recipe quantity, stirring and dissolving adjusts pH value with pH adjusting agent, methyl hydroxybenzoate and the chlorination of recipe quantity is added
Sodium, stirring and dissolving adjust pH value with pH adjusting agent again, and pH value adjusting finishes, and are settled to total amount with water for injection, stirring is mixed
Even, filtering is filling, and sterilizing, visual inspection is got product.
Embodiment 2：
Prescription
Preparation process：With embodiment 1
Embodiment 3：
Prescription
Preparation process：With embodiment 1
Embodiment 4
Prescription
Preparation process：With embodiment 1
Embodiment 5
Prescription
Preparation process：With embodiment 1
Comparative example 1：
Prescription
Preparation process
The cysteine hydrochloride for weighing recipe quantity is dissolved in suitable water for injection, stirring and dissolving, be added recipe quantity according to
Da Lafeng, stirring and dissolving adjust pH value with pH adjusting agent, are added the methyl hydroxybenzoate and sodium chloride of recipe quantity, stirring and dissolving, then
Secondary to adjust pH value with pH adjusting agent, pH value adjusting finishes, is settled to total amount with water for injection, stirs and evenly mixs, filters, filling,
Sterilizing, visual inspection are got product.
Comparative example 2：
Prescription
Preparation process
The cysteine hydrochloride and disodium glycyrrhizinate for weighing recipe quantity are dissolved in suitable water for injection, and stirring and dissolving adds
Entering the Edaravone of recipe quantity, stirring and dissolving adjusts pH value with pH adjusting agent, it is added the sodium chloride of recipe quantity, stirring and dissolving,
PH value is adjusted with pH adjusting agent again, pH value adjusting finishes, is settled to total amount with water for injection, stirs and evenly mixs, filter, fills
Dress, sterilizing, visual inspection are got product.
Comparative example 3：
Prescription
Preparation process
The cysteine hydrochloride and disodium glycyrrhizinate for weighing recipe quantity are dissolved in suitable water for injection, and stirring and dissolving adds
Enter the Edaravone of recipe quantity, stirring and dissolving adjusts pH value with pH adjusting agent, methyl hydroxybenzoate and the chlorination of recipe quantity is added
Sodium, stirring and dissolving adjust pH value with pH adjusting agent again, and pH value adjusting finishes, and are settled to total amount with water for injection, stirring is mixed
Even, filtering is filling, and sterilizing, visual inspection is got product.
Comparative example 4：
Prescription
Preparation process
The cysteine hydrochloride and sodium hydrogensulfite for weighing recipe quantity are dissolved in suitable water for injection, and stirring and dissolving adds
Entering the Edaravone of recipe quantity, stirring and dissolving adjusts pH value with pH adjusting agent, it is added the sodium chloride of recipe quantity, stirring and dissolving,
PH value is adjusted with pH adjusting agent again, pH value adjusting finishes, is settled to total amount with water for injection, stirs and evenly mixs, filter, fills
Dress, sterilizing, visual inspection are got product.
Comparative example 5：
Prescription
Preparation process
The 1,2-PD and ethyl alcohol for weighing recipe quantity are added to 50~60 DEG C of 30% water for injection of full dose, and stirring is mixed
It is even, the Edaravone of recipe quantity and sodium pyrosulfite are added into above-mentioned solution, it is after mixing evenly, quantitative with water for injection
To full dose, with hydrochloric acid tune pH value to 4.5~5.5, filtering is filling, and sterilizing, visual inspection is got product.
Comparative example 6：
Prescription
Preparation process
The Edaravone of recipe quantity is weighed, 90~100 DEG C of water for injection of 1/2~1/3 recipe quantity is added, stirring is complete
Dissolution, obtains Edaravone solution；Weigh the vitamin C of recipe quantity, glutathione is added to above-mentioned solution, stir evenly, add
Water for injection is cooled to 70-80 DEG C, obtains mixed solution to the 80% of recipe quantity；Doctor is added into the mixed solution
With active carbon, the additional amount of the medical activated carbon is that 0.3% (W/V) is stirred 15 minutes, be filtered while hot processing make it is above-mentioned
Mixed solution takes off charcoal, obtains filtrate；It adds to the full amount of water for injection into the filtrate, then with 1M dilute hydrochloric acid or 1M sodium hydroxide
It is 4.0~4.5 that test solution, which adjusts pH value, is uniformly mixed, and is filtered, filling, and sterilizing, visual inspection is got product.
Verify embodiment
1. product yield compares
The embodiment of the present invention 1~5 and 1~6 gained finished product preparation final amt of comparative example are summarized, yield
It the results are shown in Table 1
1 Examples 1 to 5 of table and 1~4 preparation yield of comparative example compare
From experiment investigation result：Yield of the embodiment of the present invention will be substantially better than comparative example 1,2,4,5,6, simultaneously
It has also been discovered that the adjusting of pH value does not influence its yield.
2. long term test
By Examples 1 to 5 and comparison implement 3 obtained by preparation be put into 25 DEG C, in RH60% climatic chamber, respectively at
0,6, sampling in December, investigate its appearance character, it is seen that foreign matter, pH, the situation of change in relation to substance and content the results are shown in Table 2.
2 Examples 1 to 5 of table and comparison implement 3 preparation long term tests and investigate result
From experiment investigation result：Preparation indices obtained by the embodiment of the present invention 1~5 meet regulation, and right
Than preparation obtained by embodiment 3, with the extension of standing time, its related substance becomes larger, and content reduces, and comprehensively considers, this hair
Bright high income, safety is good, and quality is stablized, and is made and promotes in production.
Claims (9)
1. a kind of injection for treating the disturbance of consciousness after brain trauma and brain surgery, which is characterized in that the injection by activity at
Divide Edaravone, sodium chloride, cysteine hydrochloride, disodium glycyrrhizinate, methyl hydroxybenzoate, pH adjusting agent and water for injection composition；Institute
The pH adjusting agent stated is that one of sodium hydroxide, sodium phosphate, sodium acetate and sodium citrate are either several, and pH range is 4.6
~5.2.
2. the injection of the disturbance of consciousness after treatment brain trauma according to claim 1 and brain surgery, which is characterized in that described
Active constituent Edaravone concentration be 1.0~4.0mg/ml.
3. the injection of the disturbance of consciousness after treatment brain trauma according to claim 1 and brain surgery, which is characterized in that described
CYSTEAMINE HCL acid concentration be 0.2~0.4mg/ml.
4. the injection of the disturbance of consciousness after treatment brain trauma according to claim 1 and brain surgery, which is characterized in that described
Disodium glycyrrhizinate concentration be 0.8~1.2mg/ml.
5. the injection of the disturbance of consciousness after treatment brain trauma according to claim 1 and brain surgery, which is characterized in that described
Methyl hydroxybenzoate concentration be 0.1~0.3mg/ml.
6. the injection of the disturbance of consciousness after treatment brain trauma according to claim 1 and brain surgery, which is characterized in that described
Active constituent Edaravone concentration be 1.5mg/ml, the CYSTEAMINE HCL acid concentration be 0.3mg/ml, the Radix Glycyrrhizae
Acid disodium concentration is 1.0mg/ml, and the methyl hydroxybenzoate concentration is 0.2mg/ml.
7. the injection of the disturbance of consciousness after treatment brain trauma according to claim 1 and brain surgery, which is characterized in that described
Injection pH regulator be sodium hydroxide, pH 4.9.
8. according to claim 1 in -7 after treatment brain trauma and brain surgery described in any claim the disturbance of consciousness injection
Liquid, which is characterized in that preparation method includes the following steps：The cysteine hydrochloride and disodium glycyrrhizinate for weighing recipe quantity are dissolved in
In 70~90% water for injection, the Edaravone of recipe quantity is added in stirring and dissolving, and stirring and dissolving is adjusted with pH adjusting agent
PH value, pH value adjusting finish, and the methyl hydroxybenzoate and sodium chloride of recipe quantity are added, stirring and dissolving is adjusted with pH adjusting agent again
PH value, pH value adjusting finishes, is settled to total amount with water for injection, stirs and evenly mixs, filters, filling, and sterilizing, visual inspection is got product.
9. the injection of the disturbance of consciousness after treatment brain trauma according to claim 8 and brain surgery, which is characterized in that it is made
Preparation Method is specially following steps：The cysteine hydrochloride and disodium glycyrrhizinate that weigh recipe quantity are dissolved in 80% water for injection
In, the Edaravone of recipe quantity is added in stirring and dissolving, and stirring and dissolving adjusts pH value, pH with the sodium hydroxide solution of 0.1mol/L
Value adjusting finishes, and the methyl hydroxybenzoate and sodium chloride of recipe quantity is added, and stirring and dissolving uses the sodium hydroxide solution of 0.1mol/L again
Adjust pH value, pH value adjusting finish, be settled to total amount with water for injection, stir and evenly mix, filter, it is filling, sterilizing, visual inspection up at
Product.
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| CN201610430919.3A CN106074366B (en) | 2016-06-16 | 2016-06-16 | The injection and preparation method thereof for treating the disturbance of consciousness after brain trauma and brain surgery |
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| 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 |
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| 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 |
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| Title |
|---|
| 依达拉奉氯化钠注射液的制备和稳定性考察;郭涛，等;《沈阳部队医药》;20030531;第16卷(第3期);第206-208页 * |
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