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Pemetrexed disodium for injection and preparation method thereof

A technique for pemetrexed disodium and injection, which is applied in the field of pemetrexed disodium for injection and its preparation, and can solve the problem of oxidation reduction in product quality and yield, poor stability of pemetrexed disodium, and 2.5 hydration Instability and other problems, to avoid infusion pain, ideal stability and curative effect, suitable for popularization of production

Active Publication Date: 2013-04-17
SHANXI PUDE PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The technical problems it solves are: the stability of pemetrexed disodium is relatively poor, it is easy to degrade under high temperature, oxidation and light conditions, and produces impurities that may cause toxic and side effects, the stability of the freeze-dried preparation is poor, and the compatible solution cannot be used in clinical use. Leave it for a long time
The technical problem it solves: the stability of pemetrexed disodium is poor
However, the 2.5 hydrate is unstable. Although the stability of the 3 hydrate is better than the former, it is difficult to control the amount of crystal water when drying, and 2.5 hydrate may appear.
The quality of the 7 hydrate is stable, but it is very easy to lose part of the crystallization water when stored under high temperature, low humidity or vacuum conditions, and the drying process of the hydrate also increases the process of treating with wet nitrogen flow and corresponding equipment, increasing cost of production
Technical problem to be solved: the current purification methods of pemetrexed disodium and pemetrexed all involve the process of heating and crystallizing with a mixed solvent. characteristics, so it is bound to accelerate their oxidation during the heating process to reduce the quality and yield of products
[0015] But above-mentioned technical method all can't really meet the high requirement that pemetrexed disodium raw material proposes in freeze-dried preparation itself and clinical application process, therefore, still remains to find a kind of ideal pemetrexed disodium compound, in order to further Obtained pemetrexed disodium for injection which is significantly better than the prior art in terms of stability and curative effect

Method used

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  • Pemetrexed disodium for injection and preparation method thereof
  • Pemetrexed disodium for injection and preparation method thereof
  • Pemetrexed disodium for injection and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0062] The preparation of embodiment 1 pemetrexed disodium compound

[0063] (1) Weigh 100g of crude pemetrexed disodium, dissolve 96g of it in water with a volume equivalent to 12 times the weight of the crude pemetrexed disodium (g / ml), stir well to obtain solution A.

[0064] (2) Fully dissolve the remaining 4g of pemetrexed disodium crude product in a mixture of acetone and isopropanol at 42°C with a stirring speed of 25rmp to form solution B. The volume of acetone and isopropanol in the mixture The ratio is 1:6; the volume of the mixed solution is 1.5 times that of solution A.

[0065] (3) Within 3 hours, add solution B dropwise to solution A at a constant speed, while controlling the temperature of solution A at 22°C, stirring at a low speed of 8rmp during the dropwise addition.

[0066] (4) After the dropwise addition, the temperature of the solution was lowered to 2°C, and the crystal was left to grow for 10 hours, filtered, the filter cake was washed with acetone, an...

Embodiment 2

[0068] The preparation of embodiment 2 pemetrexed disodium compound

[0069] (1) Weigh 100g of crude pemetrexed disodium, dissolve 98g of it in water whose volume is equivalent to 15 times the weight of the crude pemetrexed disodium, and stir evenly to obtain solution A;

[0070] (2) Dissolve the remaining 2g of crude pemetrexed disodium in a mixture of acetone and isopropanol at 40°C with a stirring speed of 20rmp to form solution B. The volume of acetone and isopropanol in the mixture is 1:3, the volume of the mixed solution is 0.8 times that of solution A;

[0071](3) Within 2 hours, add solution B dropwise to solution A at a constant speed, while controlling the temperature of solution A at 20°C, stirring at a low speed of 5rmp during the dropping process;

[0072] (4) After the dropwise addition, the temperature of the solution was lowered to 5°C, and the crystal was left to grow for 8 hours, filtered, the filter cake was washed with acetone, and dried at low temperature...

Embodiment 3

[0074] The preparation of embodiment 3 pemetrexed disodium compound

[0075] (1) Weigh 100g of pemetrexed disodium crude product, dissolve 94g of it in water whose volume is equivalent to 10-15 times the weight of pemetrexed disodium crude product, stir well to obtain solution A;

[0076] (2) Fully dissolve the remaining 6g of pemetrexed disodium crude product in the mixture of acetone and isopropanol at 45°C with a stirring speed of 30rmp to form solution B. The volume of acetone and isopropanol in the mixture 1:7, the volume of the mixed solution is twice that of solution A;

[0077] (3) Within 2-4 hours, add solution B dropwise to solution A at a constant speed, while controlling the temperature of solution A at 25°C, stirring at a low speed of 10rmp during the dropping process;

[0078] (4) After the dropwise addition, the temperature of the solution was lowered to 0°C, and the crystal was left to grow for 12 hours, filtered, the filter cake was washed with acetone, and d...

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Abstract

The invention discloses pemetrexed disodium for injection. The pemetrexed disodium for injection comprises the components in part by weight as follows: 50-60 parts of a pemetrexed disodium compound, 20-40 parts of mannitol and 2-4 parts of arginine. Besides, the invention further provides the pemetrexed disodium compound, the stability of the pemetrexed disodium compound is improved remarkably, the organic solvent residual volume is low, the quality can be controlled, and the pemetrexed disodium compound can be placed for a long time and cannot change easily, so that the medication safety for a patient is improved greatly.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to pemetrexed disodium for injection and a preparation method thereof. Background technique [0002] Pemetrexed disodium is a new anti-metabolite preparation of folic acid, which can inhibit the activity of various folic acid-dependent enzymes and exert its anticancer effect. On February 4, 2004, the FDA approved the combination of pemetrexed disodium and cisplatin for the treatment of malignant pleural mesothelioma. On August 19, 2004, FDA approved pemetrexed disodium as a second-line drug for locally advanced or metastatic non-small cell lung cancer (NSCLC). Since the product has many targets and relatively mild side effects, clinical trials on many types of tumors have been conducted internationally, showing the broad prospect of the product for anti-tumor. [0003] The prior art discloses a variety of pemetrexed disodium and related preparations, such as ...

Claims

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Application Information

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IPC IPC(8): A61K31/519A61K47/18A61K47/10A61P35/00C07D487/04
Inventor 李立忠王勇解晓荣李润宝苏志强姚荷云闫洁胡成伟
Owner SHANXI PUDE PHARMA CO LTD
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