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CN-121991256-A - Preparation method of ferric carboxymaltose

CN121991256ACN 121991256 ACN121991256 ACN 121991256ACN-121991256-A

Abstract

The invention discloses a preparation method of ferric carboxymaltose, which comprises the steps of firstly mixing ferric carboxymaltose solution with absolute ethyl alcohol for alcohol precipitation, centrifugally filtering to obtain a ferric carboxymaltose wet product, adding a small amount of absolute ethyl alcohol after the ferric carboxymaltose wet product is dissolved in water to obtain a compound solution, directly spray-drying the compound solution to obtain a powdered ferric carboxymaltose finished product, wherein the dosage of the absolute ethyl alcohol for alcohol precipitation is 70-100% w/w of the weight of the ferric carboxymaltose solution, the times of alcohol precipitation are 1, the ferric carboxymaltose wet product is added with 250-350% w/w of water for dissolution, and then 10-20% w/w of absolute ethyl alcohol of the weight of the ferric carboxymaltose wet product is added to obtain the compound solution. The method is simple, obviously simplifies the process steps, shortens the production period, obviously reduces the energy and material consumption, reduces the organic waste liquid, is beneficial to environmental protection and reduces the overall production cost.

Inventors

  • WAN HUI
  • PENG JIN
  • LI JIAN
  • WU YUNDENG
  • XU XIANGYANG
  • ZHANG QINGXIAO
  • ZHOU HONGYAN
  • WANG HUI
  • LIN CHEN

Assignees

  • 金陵药业股份有限公司

Dates

Publication Date
20260508
Application Date
20251231

Claims (10)

  1. 1. The preparation method of the ferric carboxymaltose is characterized by comprising the steps of firstly mixing a ferric carboxymaltose solution with absolute ethyl alcohol for alcohol precipitation, centrifugally filtering to obtain a ferric carboxymaltose wet product, adding a small amount of absolute ethyl alcohol after the ferric carboxymaltose wet product is dissolved in water to obtain a compound solution, and directly spray-drying the compound solution to obtain a finished product of the ferric carboxymaltose powder.
  2. 2. The method for preparing ferric carboxymaltose according to claim 1, wherein the amount of the ethanol used for precipitating the absolute ethyl alcohol is 70% -100% w/w of the weight of the ferric carboxymaltose aqueous solution.
  3. 3. The method for preparing iron carboxyl maltose according to claim 1, wherein the temperature of the alcohol precipitation is 0-30 ℃.
  4. 4. The method for preparing iron carboxyl maltose according to claim 1, wherein the number of times of alcohol precipitation is 1.
  5. 5. The method for preparing the ferric carboxymaltose according to claim 1, wherein the ferric carboxymaltose is dissolved by adding water accounting for 250-350% of the weight of the ferric carboxymaltose, and then the anhydrous ethanol accounting for 10-20% of the weight of the ferric carboxymaltose is added to obtain the compound solution.
  6. 6. The method for preparing the ferric carboxymaltose according to claim 1 or 5, wherein the ferric carboxymaltose is dissolved by adding water accounting for 290-320% of the weight of the ferric carboxymaltose, and absolute ethyl alcohol accounting for 14-16% of the weight of the ferric carboxymaltose is added to obtain a compound solution.
  7. 7. The method for preparing ferric carboxymaltose according to claim 1, wherein the temperature of the complex solution is 60-70 ℃.
  8. 8. The method for preparing iron carboxyl maltose according to claim 1, wherein the complex solution is spray-dried by a spray dryer.
  9. 9. The method for preparing iron carboxyl maltose according to claim 8, wherein the air inlet temperature of the drying chamber of the spray dryer is 150-200 ℃ and the air outlet temperature is 80-100 ℃.
  10. 10. A process for producing iron carboxyl maltose according to claim 1, wherein the process comprises the following steps: Mixing the carboxyl maltose molten iron solution with absolute ethyl alcohol according to the weight of the absolute ethyl alcohol being 70% -100% (w/w) of the carboxyl maltose molten iron solution, firstly stirring for 5-15 minutes at the temperature of 0-30 ℃, then standing for alcohol precipitation for 1.5-2.0 hours, and centrifugally filtering to obtain a carboxyl maltose molten iron tide product; adding water accounting for 250-350% of the weight of the iron carboxyl maltose wet product into the iron carboxyl maltose wet product for dissolution, adding absolute ethyl alcohol accounting for 10-20% of the weight of the iron carboxyl maltose wet product, stirring for 30-60 minutes at the temperature of 0-30 ℃, and heating to 60-70 ℃ to obtain a compound solution; and (3) maintaining the temperature of the compound solution at 60-70 ℃, pumping the compound solution into a spray dryer for spray drying, adjusting the air inlet temperature in the drying chamber at 150-200 ℃, and maintaining the air outlet temperature at 80-100 ℃ to obtain the finished product of the ferric carboxymaltose.

Description

Preparation method of ferric carboxymaltose Technical Field The invention belongs to the field of pharmaceutical chemical industry, and relates to a preparation method of ferric carboxymaltose. Background Iron deficiency anemia is a common nutritional disorder that occurs because the storage of iron in the body is not able to meet the needs of normal erythropoiesis. Currently, about 20 hundred million people worldwide suffer from anemia, of which more than 90% are iron deficiency anemia from a clinical statistical perspective. Iron deficiency anemia is most commonly treated by oral administration or injection of iron. Because of its effectiveness, low cost and safety, the oral iron preparation is often used as the first choice for iron deficiency anemia, and the oral iron preparation is still the main one in China. However, oral iron is often associated with significant gastrointestinal discomfort symptoms, and patients experience discontinuation of treatment due to intolerance. In addition, oral iron agents are also affected by the interference of food ingredients and iron reserves in the body, especially in many chronic diseases and tumor patients, inflammatory mediators in the body are increased, and the inflammatory mediators can induce the liver to synthesize iron regulatory proteins which down regulate the expression of the iron transport proteins on the gastrointestinal tract and the surface membrane of iron storage cells in the body, so that the iron absorption and utilization are affected, and the effect of the oral iron agents is often poor or ineffective at all. In addition, in gastrointestinal diseases, when the iron reservoir needs to be quickly restored and the oral administration is insufficient to supplement the human needs, intravenous iron supplement is needed under the conditions that the oral iron agent cannot be tolerated and cannot be complied with. Iron in the ferric carboxymaltose injection is complexed with carbohydrate polymers in a stable ferric iron state to release available iron to in-vivo iron transport and storage proteins (ferritin and transferrin), and the ferric carboxymaltose injection is a novel polysaccharide intravenous iron injection and becomes a representative medicament of the novel intravenous iron injection. The synthesis of the carboxyl maltodextrin iron takes maltodextrin as a starting material, and the carboxyl maltodextrin is obtained after oxidation and then is subjected to complexation reaction with a material containing ferric ions to generate the carboxyl maltodextrin iron. The related patent CN106977621A, CN108129582A, CN1705682A relates to the process and refining of the ferric carboxymaltose, but the preparation method of the ferric carboxymaltose has larger expression difference, the drying of the final material generally adopts a vacuum drying method, the effect is not ideal, and the molecular weight of the material is easy to change greatly. The refining of CN106977621A is complicated, the pH value of the carboxyl maltose molten iron solution obtained by the reaction is continuously regulated in the alcohol precipitation process, the carboxyl maltose molten iron solution is dried after being washed for a plurality of times by using the glacial ethanol, water is added again for dissolution, the absolute ethanol is used for alcohol precipitation, the processes of the glacial ethanol washing and the pH value regulation are repeated on filter cakes, and finally, the carboxyl maltose molten iron solution is dried in vacuum, so that the water content in the whole process is complex and does not meet the industrial requirements. CN108129582A, CN1705682a is not involved in the drying process. Disclosure of Invention The synthesis of the carboxyl maltodextrin iron takes maltodextrin as a starting material, and the carboxyl maltodextrin is obtained after oxidation and then is subjected to complexation reaction with a material containing ferric ions to generate the carboxyl maltodextrin iron. The inventor adopts the following technical scheme to prepare carboxyl maltodextrin iron with specific molecular weight, specifically, maltodextrin is dissolved by water with the weight ratio of 1-2 times of that of maltodextrin, sodium bromide with the weight of 1-2% of that of maltodextrin is used as a catalyst, the pH value of the maltodextrin is regulated to 9.0-11.0 by 30% sodium hydroxide solution, the temperature is controlled to 25-40 ℃, 10% sodium hypochlorite solution with the weight of 0.8-1 times of that of maltodextrin is added under the stirring condition to obtain carboxyl maltodextrin solution, the ferric trichloride hexahydrate and the maltodextrin are weighed according to the weight ratio of 1:2.2, the ferric trichloride hexahydrate and the sodium carbonate with the weight ratio of 2:1-3:1, ferric trichloride solution with the concentration of 70-80% w/w and sodium carbonate solution with the concentration of 20-35% w/w are respectively prepared, the car