Stable large volume parenteral edaravone injection and preparation process thereof

A technology for edaravone and injection, which is applied to the field of large infusion edaravone injection and its preparation, and can solve the problems of being easily oxidized, not being directly administered, and unavoidable main drug oxidation, etc.

Inactive Publication Date: 2018-07-27
JIANGSU CHIA TAI FENGHAI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Summarize the following disadvantages in the existing Edaravone preparations in China: 1. The main drug Edaravone in Edaravone Injection is unstable in nature, easily oxidized, and the medical effect is not high; 2. The existing Edaravone in China Lavone injections are all small water injections, and clinical administration needs to be diluted with normal saline before intravenous infusion, and the infusion should be completed within 30 minutes
[0010] To sum up, the existing Edaravone injection in China needs to be diluted with normal saline before injection in the clinical administration process, and cannot be administered directly, so that Edaravone is exposed to the air, which is unavoidable. The main drug is oxidized, and the safety of the medical process cannot be guaranteed
[0011] For the above problems, the present invention has invented a kind of stable big transfusion specification (100ml: 30mg) Edaravone injection by changing the specification of Edaravone injection, can be directly used in clinical intravenous infusion, both solved The potential safety hazard caused by insoluble edaravone saves the trouble of clinical dilution and compatibility

Method used

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  • Stable large volume parenteral edaravone injection and preparation process thereof
  • Stable large volume parenteral edaravone injection and preparation process thereof
  • Stable large volume parenteral edaravone injection and preparation process thereof

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Effect test

Embodiment 1

[0031] Embodiment 1: Bulk drug dissolution rate under different temperature conditions

[0032] The research results of the solubility of raw materials show that the solubility of edaravone raw materials in water is poor, and the dissolution rate is relatively slow. It can be considered to increase the dissolution rate of raw materials by increasing the water temperature during dissolution. The specific operation is as follows: Add 30 mg of Edaravone into 100 ml of water at 25°C, 45°C, 55°C, 65°C, and 80°C, seal it, stir until it is completely dissolved, record the dissolution time, and detect related substances; See Table 1.

[0033] Table 1. The dissolution rate of raw materials and related substances at different temperatures

[0034]

[0035] It is known that the raw materials are easily oxidized, so the time for dissolving the raw materials should be reduced as much as possible, taking into account the changes in the related substances of the raw materials after disso...

Embodiment 2

[0036] Embodiment 2: pH value screening

[0037] For injections, the stability of the solution can only be guaranteed under suitable pH conditions, thereby ensuring the safety and effectiveness of the injections. Therefore, the choice of the pH range of the finished product for injection is particularly important and is one of its key quality attributes.

[0038] Table 2. Formulation of the formulation

[0039]

[0040]Preparation Process:

[0041] Dissolve the prescribed amount of sodium chloride with 20-40% water for injection, add 0.05% medicinal charcoal in total, heat to boil and keep boiling slightly for 15 minutes, then cool down to 60-70°C. Stand for 20min, decarbonize. Transfer the filtrate to 50-70% water for injection, boil, cool to 60-70°C, fill with high-purity nitrogen for full protection, add pH regulator, dissolution aid, antioxidant L-cysteine ​​hydrochloride, and the prescription amount in sequence After stirring the edaravone until it completely disso...

Embodiment 3

[0045] Embodiment 3: Screening of pH regulator

[0046] Table 4. Acid Regulator Screening Test Prescription

[0047]

[0048]

[0049] Table 5. Acid regulator screening test results

[0050]

[0051] Prescription 1 (phosphoric acid) and prescription 2 (hydrochloric acid), after sterilization and after 10 days of stability setting out, the appearance of the sample has no obvious change, and the related substances are at a low level, and there is no obvious difference. However, considering hydrochloric acid corrosion equipment, phosphoric acid is preferred.

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Abstract

The invention discloses a stable large volume parenteral edaravone injection and a preparation process thereof, and belongs to the field of medicine preparation. The edaravone injection includes a therapy active component raw material edaravone, an osmotic pressure regulator NaCl, and a pH regulator being a phosphate buffer solution composed of phosphoric acid and NaOH, in which the NaOH also serves as a solution additive, and an antioxidant L-cysteine hydrochloride and sodium hydrogen sulfite. The specification of the large volume parenteral edaravone injection is 100 ml, containing 0.03 g ofthe edaravone and 0.855 g of NaCl. The preparation method includes the steps of: 1) liquid preparation, 2) filtration, 3) fill packaging, and 4) sterilization, wherein in the steps 1-3, a system is filled with high-purity nitrogen gas for protection, water-for-injection is boiled for removing oxygen, and residual oxygen content in medicine liquids and content of related substances in the productare strictly controlled in order to guarantee the safety and efficacy of the product. Influence factor experiments prove that generation of related substances is relative low. The production has stable quality and is safe.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a large infusion edaravone injection with good stability and a preparation process thereof. Background technique [0002] Stroke is a common and frequently-occurring disease among middle-aged and elderly people. It is one of the three diseases with the highest human mortality rate, and it is also the disease with the fastest development, the slowest recovery, and the most deaths among the three major diseases. Stroke can be divided into ischemic stroke and hemorrhagic stroke according to the pathogenesis, and ischemic stroke includes brain blood test and brain check plug, and the latter two are collectively referred to as cerebral infarction clinically. At present, there are 2.5 million new cases of stroke in China every year, and about 1.5 million people die of stroke every year, and 3 / 4 of the survivors have disabilities of varying degrees. Therefore, reduc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/08A61K31/4152A61K47/20A61K47/02A61P9/10
CPCA61K9/08A61K9/0019A61K31/4152A61K47/02A61K47/20
Inventor 袁晓远
Owner JIANGSU CHIA TAI FENGHAI PHARMA
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