WO2024069644A1 - Carboxymaltose ferrique pharmaceutiquement acceptable et sa préparation - Google Patents

Carboxymaltose ferrique pharmaceutiquement acceptable et sa préparation Download PDF

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Publication number
WO2024069644A1
WO2024069644A1 PCT/IN2023/050843 IN2023050843W WO2024069644A1 WO 2024069644 A1 WO2024069644 A1 WO 2024069644A1 IN 2023050843 W IN2023050843 W IN 2023050843W WO 2024069644 A1 WO2024069644 A1 WO 2024069644A1
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Prior art keywords
carbohydrate
solution
iron
ferric
range
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PCT/IN2023/050843
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English (en)
Inventor
Sunil Kumar AGARWAL
Manoj Mukhopadhyay
Avijit Sehanobish
Subhrataa Guha
Saunak Sarbajna
Debasmita Choudhury
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West Bengal Chemical Industries Limited
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Publication of WO2024069644A1 publication Critical patent/WO2024069644A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B30/00—Preparation of starch, degraded or non-chemically modified starch, amylose, or amylopectin
    • C08B30/12—Degraded, destructured or non-chemically modified starch, e.g. mechanically, enzymatically or by irradiation; Bleaching of starch
    • C08B30/18—Dextrin, e.g. yellow canari, white dextrin, amylodextrin or maltodextrin; Methods of depolymerisation, e.g. by irradiation or mechanically
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/295—Iron group metal compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B31/00—Preparation of derivatives of starch
    • C08B31/18—Oxidised starch
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L3/00—Compositions of starch, amylose or amylopectin or of their derivatives or degradation products
    • C08L3/02—Starch; Degradation products thereof, e.g. dextrin

Definitions

  • the present invention relates to a pharmaceutically acceptable Ferric Carboxymaltose and preparation thereof.
  • the present invention relates an economically feasible, facile and robust route to prepare pharmaceutically acceptable Iron (III) Carbohydrate Complex, particularly, Ferric Carboxymaltose.
  • the present invention relates to pharmaceutical composition of Iron (III) Carbohydrate Complex which can be administered as intervenous (IV) dose as to allow better release of iron in the biological system to ensure less hypersensitivity, thus lowering the chances of anaphylactic shock with better patient compliance.
  • the iron deficiency anemia (IDA) is the most common hematological disease with potentially serious clinical consequences faced by a majority of worldwide population.
  • oral iron replacement theory was implemented to combat Iron Deficiency Anemia (IDA), however long term treatment was required to adequately replete iron stores. Further it was associated with gastrointestinal adverse side effect along with low intestinal absorption of iron.
  • US2018/0105609 Al discloses a process for the preparation of ferric carboxymaltose comprising oxidation of maltodextrins using organic hypo-halite in the presence of catalyst such as transition metal catalyst and phase transfer catalyst and subsequently reacting the obtained oxidized maltodextrin with ferric hydroxide to produce ferric carboxymaltose with inconsistence in the molecular weight.
  • the said process also involves usage of expensive reagents and also additional reagents in the process. This results in increase in the production cost and hence making the process uneconomical and not suggested for commercial scale.
  • IN3463/MUM/2011 discloses a process for the preparation of ferric carboxymaltose comprising oxidation of maltodextrin with sodium hypochlorite to provide oxidized maltodextrin followed by reacting with iron (III) salt to provide ferric carboxymaltose.
  • the said process involves addition of sodium hypochlorite at higher temperatures i.e.at 65-70°C which is not suggested. As sodium hypochlorite explodes on heating and hence the said process is not recommended for commercial scale.
  • US20120214986A1 discloses process for the preparation of ferric carboxymaltose comprising oxidation of maltodextrins using an aqueous sodium hypochlorite solution and subsequently reacting the obtained oxidized maltodextrin with ferric hydroxide to produce ferric carboxymaltose with inconsistent molecular weight.
  • the main objective of present invention is to provide a pharmaceutically acceptableferric carboxymaltose with increased stability and shelf life.
  • Another objective of the present invention is to provide Ferric carboxymaltose complex particularly Iron (III) carbohydrate complex having high purity, low endotoxin limit, with minimal labile iron content.
  • Yet another objective of the present invention is to provide Ferric carboxymaltose having average molecular weight in a minimized range so as to produce less toxic product which ensures control release of elemental iron into the biological system.
  • Yet another objective of the present invention is to provide hypersensitivity free ferric carboxymaltose.
  • Yet another objective of the present invention is to provide an economically feasible, facile and robust route to prepare pharmaceutically acceptableferric carboxymaltose without using any reagent.
  • Yet another objective of the present invention is tosynthesize ferric carboxymaltose from a novel oxidation route.
  • Yet another objective of the present invention is to provide a pharmaceutical composition of ferric carboxymaltose in which the ratio of divalent iron to trivalent iron is less than 1 % which ensures no oxidative stress induced in body.
  • the present invention relates to a pharmaceutical acceptable Ferric Carboxymaltose having improved characteristics prepared through a robust, economical and simple synthetic route.
  • the process comprises of electrolytic oxidation of carbohydrate followed by isolation of the oxidized carbohydrate. Further, the oxidized carbohydrate is reacted with freshly prepared ferric hydroxide cake under stirring condition at pH 6-7 and heating at 85-90°C for about a period of 4to 6 hours till clear reddish brown solution is obtained.
  • the solution is sequence filtered and spray dried and the product so obtained has a total iron content in the range of 30-34% w/w and the average molecular weight in the range of 80 kDa-250kDa.
  • the ratio of divalent to trivalent iron is found to be not more than 1 % wherein ferrous content is determined titrimetrically using potassium dichromate standard solution ensuring the ferrous content to be less than l%.
  • the ferric carboxymaltose has reduced content of dimer carbohydrate moiety to less than about 2% which indicates reduced toxicity profile.
  • the present invention also provides a pharmaceutical composition comprising ferric carboxymaltose which is improved with less or no side effects, low labile content and reduced toxicity.
  • Figure 1 illustrates Transmission Electron Microscope data of Ferric Carboxymaltose
  • Figure 2 illustrates Scanning Electron Microscope of Ferric Carboxymaltose
  • Figure 3 illustrate X-ray diffraction of Ferric Carboxymaltose
  • FIG. 1 illustrates Thermogravimetric Analysis (TGA) of Ferric Carboxymaltose.
  • the present invention relates to a pharmaceutically acceptable Iron (III) carbohydrate complex, particularly, ferric carboxymaltose with better characterisation for bio-available iron.
  • the pharmaceutically acceptable Iron (III) carbohydrate complex has reduced impurity profile which helps in a better intervenous administration of product in a single dose in the biological system.
  • the present invention relates to a pharmaceutically acceptable Iron (III) carbohydrate complex, particularly ferric carboxymaltose complex and a process of preparation thereof.
  • the present invention provides a process having the controlled oxidation step to minimize range of the average molecular weight of ferric carboxymaltose with reduced toxicity profile and improved characteristics, and which can be administered as intervenous (IV) dose so as to allow better release of iron in the biological system to ensure less hypersensitivity, thus lowering the chances of anaphylactic shock with better patient compliance.
  • the present invention provides a process for synthesizing a pure pharmaceutically acceptable ferric carboxymaltose.
  • the complex is prepared through organic free solvent route.
  • the process comprises of three major steps: a. Preparation of oxidized carbohydrate; b. Preparation of ferric hydroxide; and c. Preparation of ferric carboxymaltose.
  • the carbohydrate undergoes electrolytic oxidation in an electrolyzer in the presence of salt in an amount of 0.5- 1.5 equivalent, preferably in the range of 0.8- 1.2 equivalent of one aldehyde group per molecule of the carbohydrate to be oxidized. This ensures that the oxidation takes place at the terminal aldehyde group of the carbohydrate.
  • the salt for oxidation is selected from, but not limited to, sodium chloride, sodium bromide and potassium bromide.
  • the amount of salt is used in the range of 0.025-0.075% w/w.
  • the isolation of oxidized carbohydrate is done using the organic solvent is protic solvent selected from, such as, but not limited to, methanol and isopropanol.
  • the amount of organic solvent used in the present invention may vary depending on the amount of the oxidized carbohydrate that needs to be isolated. For instance, the amount of organic solvent used in the present invention is in a range of 1 -2 liters for isolating 100 gram of oxidized carbohydrate.
  • the oxidization of carbohydrates is carried out at different periods of times in order to obtain the complete oxidation of carbohydrates.
  • Period of oxidization ranges between 2 to 7 hours; preferably between 4 to 6 hours.
  • the complete oxidation is justified through the peaks obtained in the FTIR report ranging between 1630 cm' 1 to 1640cm 1 , preferably in the range of 1635-1638cm -1
  • the iron carbohydrate complex may be produced with various length of the carbohydrate moiety, preferably having the Dextrose Equivalent (DE) value ranging from 10-15.
  • DE Dextrose Equivalent
  • the apparent molecular weight of the carbohydrate is 5000-9000Da and preferably 6000-8000Da, and more preferably, 6500-9000Da.
  • the maltodextrin when carbohydrate is maltodextrin, the maltodextrin undergoes oxidation under controlled condition through electrolysis at room temperature followed by isolation, thereby reducing the need of oxidizing agent that may hinder the nascent ferric ion in further complexation reaction. The process continues until the reducing sugar concentration in the solution is in the range of 0.05 to 0.2 % which is close to nil. Samples are tested by standard methods such as Nelson-Somogyi method for monitoring the carbohydrate content which gives blue colour on detection of reducing sugar.
  • the apparent molecular weight of the oxidized maltodextrin is found in the range of 6500-9000Da while the viscosity of the liquid oxidized carbohydrate is checked which emphasizes on the reduced impurity of the starting material.
  • the variation in the molecular weight is minimized so as to stabilize the iron core interaction with the carbohydrate shell thus enhancing the bio-availability of the iron.
  • WFI Water for Injection
  • the amount of ferric chloride added in water in step (i) is in the range between 34-38%w/w.
  • the obtained cake of ferric hydroxide has the amount of sodium chloride in rinsed water not more than 45ppm and the chloride content of ferric hydroxide precipitate is not more than 2.5%w/w.
  • the amount of oxidized carbohydrate added in the freshly prepared ferric hydroxide cake is in a ratio of 1:0.6, preferably in the ratio of 1:0.55.
  • pH is maintained at 6-7and heated at a temperature of 85 to 90° C for a period of ranging between 1 to 6 hours; preferably 2 to 4 hours, more preferably 3.5 to 4 hours.
  • the pH is adjusted towards neutral in the range of 6-7 by adding mild mineral acid.
  • the mild mineral acid solution is selected from, but not limited to, citric acid and acetic acid.
  • the reaction is crucial in terms of temperature and pH.
  • the synthesis route of the present invention is so robust that altering the pH as well as the temperature in the desired range do not alter the inherent characteristics of the carbohydrate complex i.e. the apparent average molecular weight of the product.
  • alteration of temperature ⁇ 5 degrees does not affect purity or molecular weight range.
  • alternation of pH ⁇ 2 does not affect the quality of product (Table 2).
  • step (ii) After settling the solution obtained in step (ii) is sequentially filtered through the micron filter paper of 0.2 to 20pm, preferably filter papers are in series of 20 pm, 2.5 pm, 0.45 pm and 0.2 pm to remove any unwanted impurities, most preferably the solution is passed through 0.45 pm and 0.2 pm filter papers.
  • the ferric carboxymaltose after filtration is dried using an apparatus selected from, but not limited to, Vacuum Tray Dryer (VTD) and Spray dryer.
  • the ferric carboxymaltose is preferably dried using spray dryer according to the standard procedure.
  • the inlet temperature of the dryer is maintained at about 250-275°Cwhile the outlet temperature is about 95-115°Cso as to obtain a light brown ferric carboxymaltose powder with iron content not less than 25% and molecular weight of the powder being not less than 80kDa.
  • Molecular weight and polydispersity index of the ferric carboxymaltose obtained is analyzed at the different time periods using the Gel Permeable Chromatography (GPC) and illustrated in Table 1.
  • the molecular weight of the ferric carboxymaltose is in the range of 80kDa-200kDa, predominantly in the range of 85kDa-150kDa, while not exceedingbelowlOkDaas well as above 300kDa.
  • the polymer chains are uniformly distributed throughout the backbone of the present invention, thus the polydispersity index being not more than 2%.
  • Table 2 illustrates the change in the molecular weight by changing different parameters:
  • the ferric carboxymaltose having the physio-chemical properties characterisation for controlled release of iron in the biological system.
  • the obtained ferric carboxymaltose is stable and has iron content preferably in the range of 30-34% w/w with the Loss on Dry (LOD) so obtained not more than 3%.
  • LOD Loss on Dry
  • the endotoxin Limit of the ferric carboxymaltose complex is 0.35Eu/mg, which itself is concordant of the fact that additional sterilization process as a part of manufacturing is not required for Ferric carboxymaltose.
  • the endotoxin Limit is obtained as per the BET White Paper
  • the labile iron content as obtained is ⁇ 0.98%, which is determined by spiking ferric carboxymaltose in serum and measuring the labile iron content spectrophotometrically by ferrozine.
  • the ferric carboxymaltose having an iron core surrounded by carbohydrate shell established by the Transmission Electron Microscopy. Dark, electron dense, beadlike structures confirms the cores of the iron oxide complexes, which are surrounded by a less electron dense matrix contributing to the carbohydrate fraction.
  • TEM analysis in Figure 1 provides the clear understanding of the well dispersed, isolated iron core particles of the present invention.
  • the mean iron core of the iron carbohydrate complex as measured by TEM Analysis is suitably not greater than about 72 nm and usually in the range of about 10 nm to no greater than 72 nm such as at least 14 nm but not much greater than 67 nm and preferably at least falls in the range of 15 nm-44 nm.
  • Thermogravimetric Analysis is conducted in order to identify the mass loss due to oxidative decomposition. As shown in the Figure 4, there are three distinct thermal events, which indicates at temperature 355.80°C, mass loss of 44.83% obtained.
  • the ferrous iron content of ferric carboxymaltose is minimized in order to reduce the oxidative stress that can be induced from ferrous iron, thus enhancing the quality of the product as a medicament for parenteral administration.
  • the ratio of divalent to trivalent iron is found to be not more than 1% wherein ferrous content is determined titrimetrically using potassium dichromate standard solution ensuring the ferrous content to be less than 1%.
  • the ferric carboxymaltose complex obtained in the present invention has reduced content of dimer carbohydrate moiety to less than about 2%. This reduction in dimer content results in enhanced stability based on accelerated stability analysis as well as reduced toxicity. Further, the monomer content of ferric carboxymaltose complex is found to be practically nil thus emphasizing on the reduced toxicity.
  • Table 3 illustrates stability data ferric carboxymaltose complex
  • the present invention provides pharmaceutical composition comprising elemental iron of ferric carboxymaltose and water for injection in the specific range percentage.
  • the pharmaceutical composition comprising 50 mg of elemental iron of ferric carboxymaltoseandl ml water for injection.
  • the Ferric carboxymaltose powder is present in a concentration of 50mg/ml of water.
  • the pharmaceutical composition may be formulated as a liquid formulation 10 selected from, but not limited to liquid formulations using isotonic solution such as NaCl solution.
  • composition comprising elemental iron of ferric carboxymaltose is being able to adjust the iron concentration of preferably in the range of 100-150 mg in 1 ml of water for injection for administering dose flexibility.
  • the pharmaceutical composition is suitable to be dissolved in suitable liquid for preparation of a medicament that can be administered parenterally.
  • Example 3 4001iters of WFI water was added to 100kg maltodextrin of dextrose equivalent 10-15 taken in a reactor at 25-30°C and stirred for 1 hour at the same temperature till clear aqueous solution of maltodextrin is obtained.
  • the obtained aqueous solution of maltodextrin oxidized by Electrolysis using an electrolyzer. To it a catalytic amount of sodium halide (1.2 eq.) is added and reaction is carried out at 30°C for 4.5 hours. 2 ml of the oxidized maltodextrin is collected in a test tube and added to 1 ml of Fehling’s solution. The same is heated in water bath, no red precipitate was found. Finally solution is isolated in an organic solvent, preferably methanol and dried under vacuum to obtain oxidized maltodextrin in solid form.
  • an organic solvent preferably methanol
  • ferric chloride 34% w/w ferric chloride is taken and added to 6001iters of WFI water; taken in a reactor and further the solution is cooled to 15°C. The solution transmission is checked and the clarity of the solution is justified to ensure no insoluble matters are present emphasizing good quality raw material.
  • Sodium carbonate solution (20%w/w) is added slowly to ferric chloride solution under stirring until the pH was 4.0.
  • 30001iters of water is further added to the mixture and the ferric hydroxide precipitate is allowed to settle for 8 hours and then decanted the upper layer of water and the precipitate is transferred to the filter assembly.
  • the ferric hydroxide precipitate is thoroughly washed with water until the sodium chloride in the rinsed water is not more than 45ppm and the chloride content of ferric hydroxide precipitate is not more than 2.5%w/w.
  • a solution of oxidized maltodextrin is prepared and added to the ferric hydroxide cake obtained.
  • the pH was adjusted to 6-7 using sodium citrate and heated to 85-90°C for 2 hours giving a reddish black colored solution of ferric carboxymaltose.
  • the product obtained was analyzed for its molecular weight and PDI using Gel Permeable Chromatography (GPC).
  • Apparent molecular weight is predominantly 1 lOKDa while other less prominent peaks showing 265KDaand 7500 Da.
  • ferric chloride 34% w/w ferric chloride is taken and added to 6001iters of WFI Water; taken in a reactor and further the solution is cooled to 15°C. The solution transmission is checked and the clarity of the solution is justified to ensure no insoluble matters are present emphasizing good quality raw material.
  • Sodium carbonate solution (20%w/w) is added slowly to ferric chloride solution under stirring until the pH was 4.0.
  • 30001iters of water is further added to the mixture and the ferric hydroxide precipitate is allowed to settle for 8 hours and then decanted the upper layer of water and the precipitate is transferred to the filter assembly.
  • the ferric hydroxide precipitate is thoroughly washed with water until the sodium chloride in the rinsed water is not more than 45ppm and the chloride content of ferric hydroxide precipitate is not more than 2.5%w/w.
  • a solution of oxidized maltodextrin is prepared and added to the ferric hydroxide cake obtained.
  • the pH was adjusted to 6-7 using sodium citrate and heated to 85-90°C for 3 hours giving a reddish black colored solution of ferric carboxymaltose.
  • the product obtained is analyzed for its molecular weight and PDI using Gel Permeable Chromatography (GPC).
  • ferric chloride 34% w/w ferric chloride is taken and added to 6001iters of WFI water; taken in a reactor and further the solution is cooled to 15°C. The solution transmission is checked and the clarity of the solution is justified to ensure no insoluble matters are present emphasizing good quality raw material.
  • Sodium carbonate solution (20%w/w) is added slowly to ferric chloride solution under stirring until the pH was 4.0.
  • 30001iters of water is further added to the mixture and the ferric hydroxide precipitate is allowed to settle for 8 hours and then decanted the upper layer of water and the precipitate is transferred to the filter assembly.
  • the ferric hydroxide precipitate is thoroughly washed with water until the sodium chloride in the rinsed water is not more than 45ppm and the chloride content of ferric hydroxide precipitate is not more than 2.5%w/w.
  • a solution of oxidized maltodextrin is prepared and added to the ferric hydroxide cake obtained.
  • the pH is adjusted to 6-7 using sodium citrate and heated to 85-90°C for 3.5 hours giving a reddish black colored solution of ferric carboxymaltose.
  • the product obtained is analyzed for its molecular weight and PDI using Gel Permeable Chromatography (GPC). Apparent molecular weight is predominantly 132KDawhile other less prominent peaks showing 265KDa and 5200 Da.
  • ferric chloride 34% w/w ferric chloride is taken and added to 6001iters of WFI water; taken in a reactor and further the solution is cooled to 15°C. The solution transmission is checked and the clarity of the solution is justified to ensure no insoluble matters are present emphasizing good quality raw material.
  • Sodium carbonate solution (20%w/w) is added slowly to ferric chloride solution under stirring until the pH was 4.0.
  • 30001iters of water is further added to the mixture and the ferric hydroxide precipitate is allowed to settle for 8 hours and then decanted the upper layer of water and the precipitate is transferred to the filter assembly.
  • the ferric hydroxide precipitate is thoroughly washed with water until the sodium chloride in the rinsed water is not more than 45ppm and the chloride content of ferric hydroxide precipitate is not more than 2.5%w/w.
  • a solution of oxidized maltodextrin is prepared and added to the ferric hydroxide cake obtained.
  • the pH is adjusted to 6-7 using sodium citrate and heated to 85-90°C for 4 hours giving a reddish black colored solution of ferric carboxymaltose.
  • the product obtained is analyzed for its molecular weight and PDI using Gel Permeable Chromatography (GPC).
  • Solubility 120 mg in 1 ml of water
  • ferric hydroxide precipitate is thoroughly washed with water until the sodium chloride in the rinsed water is not more than 45ppm and the chloride content of ferric hydroxide precipitate is not more than 2.5% w/w.
  • a solution of oxidized maltodextrin is prepared and added to the ferric hydroxide cake obtained.
  • the pH is adjusted to 8-9using sodium citrate and heated to 85-90°Cfor 4 hours giving a reddish black colored solution of ferric carboxymaltose.
  • the product obtained is analyzed for its molecular weight and PDI using Gel Permeable Chromatography (GPC).
  • Apparent molecular weight is predominantly 154792 Da while other less prominent peaks showing 275KDa and 3565 Da.
  • ferric chloride 34% w/w ferric chloride is taken and added to 6001iters of WFI water; taken in a reactor and further the solution is cooled to 15°C. The solution transmission is checked and the clarity of the solution is justified to ensure no insoluble matters are present emphasizing good quality raw material.
  • Sodium carbonate solution (20%w/w) is added slowly to ferric chloride solution under stirring until the pH was 4.0.
  • 30001iters of water is further added to the mixture and the ferric hydroxide precipitate is allowed to settle for 8 hours and then decanted the upper layer of water and the precipitate is transferred to the filter assembly.
  • the ferric hydroxide precipitate is thoroughly washed with water until the sodium chloride in the rinsed water is not more than 45ppm and the chloride content of ferric hydroxide precipitate is not more than 2.5%w/w.
  • a solution of oxidized maltodextrin is prepared and added to the ferric hydroxide cake obtained.
  • the pH is adjusted to 6-7 using sodium citrate and heated to 75-80°C for 4 hours giving a reddish black colored solution ferric carboxymaltose.
  • the product obtained is analyzed for its molecular weight and PDI using Gel Permeable Chromatography (GPC).
  • Apparent molecular weight is predominantly 178922 Da while other less prominent peaks showing 215KDa and 2653 Da.

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Abstract

La présente invention concerne un carboxymaltose ferrique pharmaceutiquement acceptable présentant une meilleure caractérisation pour le fer biodisponible et son procédé de préparation. Le procédé comprend une étape d'oxydation contrôlée pour réduire au minimum la plage du poids moléculaire moyen du complexe glucidique du fer (III), ce qui permet d'obtenir du carboxymaltose ferrique ayant un profil de toxicité réduit et des caractéristiques améliorées. La présente invention concerne également une composition pharmaceutique de carboxymaltose ferrique qui est améliorée présentant moins ou pas d'effets secondaires, une faible teneur labile et une toxicité réduite.
PCT/IN2023/050843 2022-09-30 2023-09-07 Carboxymaltose ferrique pharmaceutiquement acceptable et sa préparation WO2024069644A1 (fr)

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IN202231056102 2022-09-30

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060205691A1 (en) * 2002-10-23 2006-09-14 Peter Geisser Water-soluble iron-carbohydrate complexes, production thereof, and medicaments containing said complexes
WO2016151367A1 (fr) * 2015-03-23 2016-09-29 Suven Life Sciences Limited Préparation de complexes d'hydrates de carbone ferriques trivalents solubles dans l'eau
IN201731011640A (fr) * 2017-03-30 2017-05-05
US20190135947A1 (en) * 2009-03-25 2019-05-09 Pharmacosmos Holding A/S Stable iron oligosaccharide compound
WO2019193608A1 (fr) * 2018-04-05 2019-10-10 Msn Laboratories Private Limited, R&D Center Procédé amélioré pour la préparation de carboxymaltose ferrique
WO2020176894A1 (fr) * 2019-02-28 2020-09-03 Renibus Therapeutics, Inc. Nouvelles compositions de fer ett leurs procédés de préparation et d'utilisation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060205691A1 (en) * 2002-10-23 2006-09-14 Peter Geisser Water-soluble iron-carbohydrate complexes, production thereof, and medicaments containing said complexes
US20190135947A1 (en) * 2009-03-25 2019-05-09 Pharmacosmos Holding A/S Stable iron oligosaccharide compound
WO2016151367A1 (fr) * 2015-03-23 2016-09-29 Suven Life Sciences Limited Préparation de complexes d'hydrates de carbone ferriques trivalents solubles dans l'eau
IN201731011640A (fr) * 2017-03-30 2017-05-05
WO2019193608A1 (fr) * 2018-04-05 2019-10-10 Msn Laboratories Private Limited, R&D Center Procédé amélioré pour la préparation de carboxymaltose ferrique
WO2020176894A1 (fr) * 2019-02-28 2020-09-03 Renibus Therapeutics, Inc. Nouvelles compositions de fer ett leurs procédés de préparation et d'utilisation

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