Synthesis of the starting material of the iron sucrose injection complex to increase the reaction efficiency

Abstract

Iron deficiency is a common nutritional deficiency that occurs when the body does not have enough of the mineral iron. Iron is used by the body to make hemoglobin, the protein in red blood cells that enables them to carry oxygen throughout the body. While iron deficiency is most often associated with low levels of hemoglobin in the blood, iron deficiency can also lead to symptoms such as fatigue and lack of energy. Iron deficiency without anemia is often treated with oral iron, which is taken orally as iron tablets. However, oral iron is likely to cause side effects, is not effective for certain types of iron deficiency, and takes time to fully work. In addition, newer iron products, such as intravenous iron, are more stable, have fewer side effects, and show maximum benefit in a shorter period of time. For this purpose, in this project, an attempt has been made to synthesize the starting material of the iron sucrose complex in the final stages of precipitation, achieving the optimal reaction point, which has resulted in an increase in the reaction efficiency and also in the formation of the complex at a lower temperature.

Description

Description of the invention Title of the invention Synthesis of the starting material of the injectable iron sucrose complex to increase the reaction efficiency Technical background of the relevant invention Medicinal chemistry Technical problem and stating the objectives of the invention Anemia is a common problem in society that can affect people's health and quality of life. One of the essential factors in preventing and treating anemia is ensuring and consuming sufficient amounts of iron in the body. Iron is an important element for the production of hemoglobin - a protein that transports oxygen in the blood from the lungs to various organs of the body. When faced with anemia, doctors prescribe anemia medications such as iron injections. Iron sucrose is used to treat iron deficiency (anemia) in people with long-term kidney disease, who may need extra iron due to blood loss during kidney dialysis. If you are taking the drug erythropoietin to help make new red blood cells, your body may also need more iron. Iron is an important part of your red blood cells and is needed to transport oxygen around the body. Many patients with kidney disease cannot get enough iron from food and need injections. Iron sucrose is a type II complex with two oxygen atoms attached to each iron atom. When used for medicinal purposes, the iron complex polymerizes and the sucrose molecules combine to form a larger polysaccharide. The synthesis of the starting material for the preparation of the iron sucrose injectable complex reduces the efficiency of the reaction due to the lack of an optimal pH point in the final stages of precipitation. Precipitation in the final stages of synthesis due to the lack of an optimal pH point causes a waste of starting material and ultimately reduces the overall efficiency of the reaction, which is achieved by utilizing knowledge of medicinal chemistry and chemical reactions to find the optimal point and increase the efficiency of the reaction. The formation of iron and sucrose complexes requires appropriate temperature regulation to increase complex formation, otherwise it will cause unreacted precipitates in the vessel, ultimately reducing efficiency and making precipitation difficult. Also, the purification of the starting materials of the Tair reaction is of great importance in the final analysis of the product, because impurities will cause errors in the reaction calculations. In this plan, all the problems mentioned in the synthesis have been resolved. A description of the state of the prior art and the history of developments related to the claimed invention. Iron sucrose complexes and their preparation method US Patent 767478 A process is provided for preparing iron sucrose complexes, substantially free of by-products, for preparing iron sucrose complexes with sucrose, and for preparing iron sucrose complexes in aqueous solution. Synthesis of high molecular weight iron-saccharide complexes US Patent 8691776 A process for preparing injectable iron-saccharide complexes, and the complexes produced, comprising: (1) providing an aqueous solution or dispersion comprising (i) Fe(III) and (OH)- ions and (2) at least one saccharide, to form a reaction mixture, wherein the molar ratio of (i):(ii) is about 30:1 to about 1:30. and the temperature and pH of the mixture are at or above the complex assembly point (CAP). and (2) maintaining the temperature and pH at or above the CAP for a time sufficient to form an iron-saccharide complex having a molecular weight of about 25,000 daltons or greater. Controlling the temperature and pH effectively produces a high molecular weight complex. The complex can be isolated by precipitation, dialysis and / or column fractionation and optionally dried, e.g., lyophilization or spray drying. This process can controllably synthesize complexes with different molecular weight and / or chemical composition, in particular sodium ferric gluconate and iron hydroxide-sucrose. Method for producing pure hematinic iron-saccharide complex and the produced product US Patent 6939715 A method for the isolation and purification of active hematinic species present in iron-saccharide complexes including iron sodium gluconate complex in sucrose, ferric hydroxide-sucrose complex and ferric saccharate complex and other similar forms and functions, based on the separation of the iron-saccharide complex. From one or more by-products and preferably lyophilization. Isolation of the iron-saccharide complex allows for its analytical quantification. Further concentration or purification as a new and useful product; preparation of redesigned formulations for new and useful drugs; and / or lyophilization. The ability to isolate the iron-saccharide complex responsible for the hematinic function, including its lyophilized form, also provides a means for the preparation of analytical materials for the purpose of verifying and validating the pharmaceutical integrity, patient safety and clinical performance, as well as its analytical monitoring, standardization and quality. Inspection of the control of hematinic manufacturing processes and the establishment of standards for its use Process for preparing iron sucrose complex US Patent Application 20080167266 The process of preparing iron-sucrose complex in which a) An iron salt in aqueous solution is mixed with sucrose and an inorganic base simultaneously or in any order at low temperature, such that the reaction mixture has an acidity (pH) in the range of 12-3 and the reaction mixture remains at this acidity until all the iron salt is converted to iron oxyhydroxide, in which case when using an alkali metal hydroxide, sucrose is always introduced at the beginning of the reaction or added to the reaction mixture simultaneously with the alkali metal hydroxide; (b) The acidity of the reaction mixture is then increased to a value in the range of pH 12 and the reaction mixture is heated until the desired iron-sucrose complex is completely formed and the iron-sucrose complex formed is then precipitated. By mixing with a suitable water-miscible solvent, the iron-sucrose complex is purified by removing the anions present and any excess base, before or after precipitation. The iron-sucrose complex thus prepared. Use thereof for the preparation of medicaments; and medicaments containing such an iron-sucrose complex Method for producing pure hematinic iron-saccharide complex and the produced product US Patent Application 20040220141 A method for the isolation and purification of active hematinic species present in iron-saccharide complexes including iron sodium gluconate complex in sucrose, ferric hydroxide-sucrose complex and ferric saccharate complex and other similar forms and functions, based on the separation of the iron-saccharide complex. From one or more by-products and preferably lyophilization. Isolation of the iron-saccharide complex allows for its analytical quantification. Further concentration or purification as a new and useful product; preparation of redesigned formulations for new and useful drugs; and / or lyophilization. The ability to isolate the iron-saccharide complex responsible for the hematinic function, including its lyophilized form, also provides a means for the preparation of analytical materials for the purpose of verifying and validating the pharmaceutical integrity, patient safety and clinical performance, as well as its analytical monitoring, standardization and quality. Inspection of the control of hematinic manufacturing processes and the establishment of standards for its use Providing a solution to an existing technical problem along with an accurate, sufficient, and integrated description of the invention Iron supplementation by intravenous injection is preferred in various clinical conditions (such as patients with low intestinal iron absorption, failure to respond to oral iron therapy, need for rapid iron deficiency compensation, chronic kidney disease, active inflammatory gastrointestinal diseases, cancer, severe or chronic blood loss, etc.). One type of iron salt is iron sucrose, which is used as a source of iron in patients with severe iron deficiency and chronic kidney problems (dialysis or non-dialysis), with the approval of the US Food and Drug Administration. Iron sucrose injection (off-label) is also possible in other eligible individuals and patients with iron deficiency caused by chemotherapy. Iron supplementation is also used in patients with restless legs syndrome (RLS) associated with low ferritin levels (full off-label use). However, the American Academy of Neurology guidelines consider the evidence and information insufficient to recommend the use of iron sucrose in these cases.Iron sucrose acts as a source of iron, which is essential for the function and formation of vital factors such as hemoglobin, myoglobin, and numerous enzymes. The presented plan is the synthesis of the starting material of the injectable iron sucrose complex. First, 15 g of anhydrous FeCl3 is gradually added to 30 ml of distilled water over 5-10 minutes, and the reaction vessel is mixed for 20 minutes with the help of a rotating magnetic magnet. Then, 1 g of activated carbon is slowly added and the temperature is raised to about 30-40 degrees, and then stirred for 20-30 minutes. Then, the reaction vessel is kept at room temperature for 10 minutes, and the reaction solution is filtered using Celite 545, and gradually added with a 30% w / v sodium carbonate solution until the optimal pH is 4.9-5.1 (room temperature). Then, it is filtered and the formed clot is washed with 40 ml of distilled water. In the next step, 135 g of sucrose is dissolved in 50 ml of distilled water and stirred for 1 hour. Then, the clot from the previous step (solution) is added. (Add 5 ml of water every 5 minutes, observing the time interval.) At this stage, we gradually increase the temperature to 50 degrees. Then, we add a 30% weight-volume NaOH solution and adjust the pH to 11.5-10.6 and the mixture is stirred for 10 minutes, then the temperature is raised to 90-95 degrees and the pH is adjusted to 9.30-8.75 with 35% HCl. It is stirred at this temperature for 4 hours and 1 gram of activated charcoal is added and after 30 minutes it is filtered. The pH is adjusted to 11.3-11.2 with sodium hydroxide and concentrated under vacuum. In a separate container, 450 ml of ethanol and acetone are poured in a ratio of (2 to 1) and the solution from the previous step is added to the resulting solvent and then washed. Explanation of shapes, maps and diagrams Figure 1: Synthesis process of the starting material of iron sucrose complex A clear and precise statement of the advantages of the claimed invention over prior inventions. 1. Higher reaction efficiency 2. The need for lower temperatures for complex formation by creating specific reaction conditions 3. Optimal and convenient precipitation with a higher molecular size than the sediment 4. Economical cost price and lower than similar foreign models Description of at least one implementation method for implementing the invention Iron Sucrose Ampoule exerts its beneficial effects in the treatment of iron deficiency anemia by replacing the body's iron stores and can improve anemia symptoms such as fatigue, lethargy, headache, and dizziness by helping to produce red blood cells. Iron Sucrose is produced in the form of an injection vial for intravenous injection. Explicit mention of the industrial application of the invention Iron sucrose is used for anemia, hyperphosphatemia, and iron deficiency anemia, and can be used in all medical and health centers for all people with iron deficiency.

Claims

Claims What is claimed: Claim 1) Synthesis of the starting material of the iron sucrose injection complex, which leads to the formation of the complex at a lower temperature and also finds an optimum point in the final stages of precipitation, increasing the efficiency of the reaction. The materials used in this synthesis include: anhydrous FeCl3, distilled water, activated carbon, Celite 545, sodium carbonate, sucrose, NaOH, HCl, activated carbon, ethanol and acetone. Claim 2) According to claim 1, the synthesis steps are as follows: First, 15 grams of anhydrous FeCl3 is gradually added to 30 ml of distilled water over 5-10 minutes, and the reaction container is mixed for 20 minutes with the help of a rotating magnetic magnet, then 1 gram of activated carbon is slowly added, and the temperature is raised to about 30-40 degrees, and then stirred for 20-30 minutes. Then, the reaction container is kept at room temperature for 10 minutes, and the reaction solution is filtered using Celite 545, and gradually added with a 30% w / v sodium carbonate solution until the optimal pH is 4.9-5.1 (room temperature). Then, it is filtered and the formed clot is washed with 40 ml of distilled water. Claim 3) According to claim 2, in the next step, 135 grams of sucrose is dissolved in 50 ml of distilled water and stirred for 1 hour. 5 ml is added to the clot of the previous step (dissolved in 70 ml of water) at an interval of 5 minutes. In this step, the temperature is gradually raised to 50 degrees. Then, a 30% NaOH solution is added and the pH is adjusted to 11.5-10.

6. The mixture is stirred for 10 minutes. Then, the temperature is raised to 90-95 degrees. The pH is adjusted to 9.30-8.75 with 35% HCl. It is stirred for 4 hours at this temperature, 1 gram of activated charcoal is added, and after 30 minutes, it is filtered. The pH is adjusted to 11.3-11.2 with sodium hydroxide and concentrated under vacuum. In a separate container, pour 450 ml of ethanol and acetone in a ratio of (2 to 1), add the solution from the previous step to the resulting solvent, and then wash.

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