MXPA00007959A - An iron-dextran compound for use as a component in a therapeutical composition for prophylaxis or treatment of iron-deficiency, a process for producing said iron-dextran compound and use of said compoundfor the preparation of a parenterally administrabl - Google Patents

Abstract

An iron-dextran compound for parenteral treatment of iron-deficiency anemia comprises hydrogenated dextran having a weight average molecular weight (Mw) between 700 and 1,400 Daltons, preferably approximately 1,000 Daltons, a number average molecular weight (Mn) of 400 to 1,400 Daltons and wherein 90%by weight of the dextran has molecular weights less than 2,700 Daltons and the Mw of the 10%by weight fraction of the dextran having the highest molecular weights is below 3,200 Daltons, said hydrogenated dextran having been subjected to purification by membrane processes having a cut-off value between 340 and 800 Daltons, in stable association with ferric oxyhydroxide. The compound is produced by using membrane processes to eliminate dextrans of higher molecular weights than approximately 2,700 Daltons and membrane processes to remove saccharides of molecular weights below approximately 340 Daltons from hydrogenated dextran before precipitating ferric hydroxide in the presence of said dextran followed by heat treatment and purification.

Description

AN IRON-DEXTRAN COMPOUND FOR USE AS A COMPONENT IN A THERAPEUTIC COMPOSITION FOR THE PROFILAXIS OR IRON DEFICIENCY TREATMENT, AN PROCESS FOR THE PRODUCTION OF SUCH COMPOSITE OF IRON-DEXTRINE AND THE USE OF THE COMPOUND FOR THE PREPARATION OF A THERAPEUTIC COMPOSITION PARENTALLY ADMINISTRABLE BACKGROUND OF THE PREVIOUS INVENTION AND TECHNIQUE Iron deficiency anemia has been described as one of the most common pathological functions - possibly the most common - among humans when observed on a global basis. Also in modern feeding in pig farms and other domestic animals, iron deficiency anemia is a problem unless adequate prophylactic measures are taken. Although iron deficiency anemia can often be prevented or cured by oral administration of iron-containing preparations, in many cases it is preferred to use parenterally administrable iron preparations to avoid variations in the bioavailability of oral administrations and to ensure effective administration. Therefore, preparations containing iron for parenteral use, which means subcutaneous, intramuscular or intravenous administration, have for many years been available to the veterinary or human medical practitioner. Although various iron-containing substances have been used or are also suggested as components in parenterally injectable preparations against iron-deficiency anemia, the most common preparations accepted today are those comprising a combined product of ferric oxyhydroxide (or ferric hydroxide). ) in association with dextran. Dextran is a polymeric carbohydrate produced by the microorganisms Leuconos t oc mesen teroi des. A preparation containing iron for parenteral injection must obviously satisfy various requirements, including the easy availability of iron for the synthesis of hemoglobin, the absence of local or general side effects and storage stability, enabling a satisfactory shelf life at room temperature. . Iron-dextran preparations for the treatment of anemia have been marketed for decades, and many variations in the manufacturing process and in the selection of starting materials have been suggested with a view to improving the stability of such preparations, and decreasing the amount of collateral effects obtained in its administration. As examples of patents having to do with these problems, the following may be cited: U.S. Patent No.

No. 2,885,393 (1959) describes a basic process for the production of an iron-dextran complex in which the average molecular weight of dextran is ,000 to 80,000 Daltones or less. The ability to adapt these complexes for human therapy does not appear in this patent specification. US Re. 24,642 (1959) comprises a detailed explanation of the requirements for an iron solution designed for intramuscular injection, incorporated by reference herein. The patent concerns the substantially non-ionic complex of ferric hydroxide with a dextran having an average intrinsic viscosity at 25 ° C from about 0.025 to about 0.25, as well as a process for preparing such a complex by contacting a dextran. as described, with ferric hydroxide formed in itself by reaction between a ferric salt and an alkaline base. No information is given regarding the desired molecular weight of dextran, and no chemical modification of dextran is suggested, apart from a partial depolymerization. United States Patent No. 3,093,545 (1963). This patent describes some details such as temperatures and pH values in an improved method for the preparation of a product apparently very similar to one prepared in the aforementioned last patent. The British Patent GB 1, 200,902 (1970) teaches that in contrast to the preparation of the ferric hydroxide in itself it is advantageous to preform the ferric hydroxide under controlled conditions, since such ferric hydroxide will readily form complexes with dextrans. It is stated that not only the partially depolymerized dextran having a weight average molecular weight in the range for example from 500 to 50,000 Daltons, preferably in the range of 1,000 to 10,000 Daltons, but also the modified forms or dextran derivatives such as Hydrogenated dextrans or oxidized dextrans, or dextrans treated with alkali, come into consideration as theoretical possibilities. However, the only dextrans specifically mentioned are oxidized dextrans that have an average molecular weight of 3,000 and 5,000 Daltones, respectively. Ferric hydroxide is prepared before contact with dextran. This means that the resulting product consists of ferric oxyhydroxide on which the dextran forms a coating, in contrast to the more homogeneous products formed by the precipitation of ferric hydroxide in itself, which means in the presence of dextran. Danish Patent DK 117,730 (1970) has to do with a process in which the hydrogenated dextran having a molecular weight between 2,000 and 10,000 Daltons is reacted with ferric hydroxide in aqueous medium. The average molecular weight of the dextran used in the examples of the modality is not indicated. However, the intrinsic viscosity is set to be about 0.05, which could correspond to an average molecular weight of about 5,000 Daltons. Danish Patent DK 122,398 (1972) also describes the use of hydrogenated dextran for the preparation of complex compounds with ferric hydroxide, and it is explained that a substantially lower toxicity is obtained than when the non-hydrogenated dextran is used. The purpose of the patent is a process in which the wet ferric hydroxide is mixed with dry hydrogenated dextran, and after the optional addition of citric acid or citrate the mixture is heated or purified. U.S. Patent No. 3,697,502 (1972) describes a process for the production of an iron-dextran preparation in which the citric acid is added to the dextran and a simultaneous addition of alkali metal hydroxide solution and a ferric chloride solution. The average molecular weight of dextran is between 3,000 and 20,000 Daltones. The dextran used in the examples of the modality has a molecular weight of 7,000 and 10,00 Daltones, respectively. Danish Patent DK 129,353 (1974) is directed to an analogous process for the production of a ferric-dextran hydroxide derivative at an average molecular weight of dextran of at most 50,000 Daltones, and the terminal groups of the polymer chains thereof have have been modified to convert the terminal reducing anhydroglucose unit into a corresponding carboxylic acid group. Although the limits indicated for the molecular weight of dextran are very broad, namely from 500 to 50,000 Daltons, preferably from 1,000 to 10,000 Daltons, the only exemplified dextran has an average molecular weight of 5,000 Daltons. Danish Patent DK 129,942 (1974) has similarity to the Danish patent just mentioned and has to do with the manufacture of ferric hydroxide complexes with dextran-hepton acid or dextrin-hepton acid. Hepton acids are prepared by hydrolysis of the corresponding cyanhydrides. The Patents of the United States Nos. 4,827,945 (1989) and 5,102,652 (1992) both have to do with the superparamagnetic metal oxides such as iron oxides coated with or associated with polymeric materials such as dextran. The polymer is contacted with a mixture of metal oxides in two different oxidation states to produce a superparamagnetic combined product which is subsequently oxidized to transform all the metal oxide at the highest of the oxidation steps. The product is especially useful as a contrast agent in magnetic resonance imaging in medical diagnosis. However, it is also mentioned that these can be used for the treatment of iron deficiency anemia. The molecular weight of the polymers, including carbohydrates such as dextran, are preferably from 5,000 to 250,000 Daltons. British Patent 1,076,219 describes the production of an iron preparation, wherein the ferric hydroxide is linked to a complexing agent consisting of sorbitol, gluconic acid and an oligosaccharide in a certain proportion, where sorbitol is the dominant component. In one of the examples in the patent specification, a hydrogenated dextran with an average molecular weight of about 1,000 Daltons is used, such as the oligosaccharide. From the process described for the production of this dextran, it can be deduced that its contents of very low molecular weight components must be high. Even more important in connection with the present invention is, however, the following explanation, that at the time of complex formation a high amount of dextran hydrogenated monomer, eg, sorbitol, is present. Despite various attempts to improve iron-dextran preparations for the treatment of anemia, as reflected in the above patents, preparations prepared according to the state of the art still have some drawbacks. This is a result of the fact that in some patients the preparations may cause delayed hypersensitivity, or severe anaphylactic side effects, resulting in for example dyspnea, hypotension, shock and death. Other toxic reactions can also be observed. In addition, several of the prior art preparations are not available to meet current requirements regarding stability. The lack of stability can manifest itself as gelatinization of the liquid or precipitation of iron hydroxide or iron oxy-hydroxide.

BRIEF DESCRIPTION OF THE INVENTION Based on the investigations, the tests and the medical experiences, it has now been found that the drawbacks now mentioned are associated with the presence of dextran relatively high molecular weight insufficiently hydrolyzed, although in smaller quantities, in the dextran used as the initial material , as well as the presence of low molecular weight saccharides in it. It is generally recognized that high molecular weight dextrans involve a higher risk for anaphylactic reactions than low molecular weight dextrans. Indeed, it is a current practice to reduce the risk for anaphylactic reactions when clinical dextrans are infused by pretreating the patient by injection of low molecular weight dextran such as a dextran having a weight average molecular weight (Mw) of approximately 1,000 Daltons. . The manufacture of the dextran usually involves acid hydrolysis of the higher molecular weight dextrans, followed by the isolation and purification operations including the precipitation of the dextran, for example from an aqueous solution by addition, for example of an alcohol. By such precipitation not only the desired fractions of the dextran precipitate will be precipitated, but also any dextran of higher molecular weight., for which reason the recovered dextran fraction frequently contains high molecular weight dextrans which have not been disintegrated in the preceding acid hydrolysis. Since even very small concentrations of high molecular weight dextrans are capable of causing unpredictable and often rather severe anaphylactic reactions, a feature of the present invention is that the presence of such dextrans should be avoided by replacing or supplementing conventional precipitation processes. by membrane processes capable of very efficiently removing the presence of high molecular weight dextrans before the desired dextran fraction is contacted with the iron compounds. However, it has been experienced that the removal of the higher molecular weight dextrans from the desired dextran fractions having a weight average molecular weight for example of 1,000 Daltons, does not ensure that the resulting iron-dextran will be non-toxic and stable. . It has also been revealed that the presence of low molecular weight carbohydrates such as monosaccharides resulting from the hydrolysis process creates difficulties. The presence of such saccharides has until now only been considered of minor importance. However, when the dextran containing such saccharides is reacted with iron, by precipitation of ferric hydroxide in a solution thereof, not only dextran-iron combination compounds are formed, but also the saccharides which combine with the iron to form iron. complexes or association compounds. However, these saccharide-based iron compounds are much less stable than the dextran-iron compounds, and in aqueous solution they give rise to a certain concentration of free ferric ions and low molecular weight saccharides, such as glucose. As is well known, free ferric ions exert a toxic action when present in preparations for parenteral administration. Furthermore, it has been found that not only the ferric ions, but also the low molecular weight saccharides cause instability of an aqueous solution of iron-dextran, due to precipitation and / or gel-forming reactions that possibly result in a Complete solidification of the solution within days or months. In addition, the presence of low molecular weight saccharides appears to increase the parenteral toxicity of an iron-dextran solution, apparently because the saccharides interfere with the binding of the iron compounds to the dextran, thereby forming free ferric ions or only weakly linked. Although the link between the low molecular weight saccharides and the iron compounds, as is apparent from the foregoing, is rather weak, it is sufficient to prevent efficient removal of saccharides and free iron compounds by the dialysis process. which is customary to fasten the iron-dextran solution to a post-treatment. Therefore, a further important feature of the invention is that the dextran fraction must be purified by membrane processes by removing the low molecular weight saccharides before it is used in the reaction where the association compounds or iron-containing complexes are formed . The present invention thus relates to the iron-dextran compounds which have an extremely low frequency of unwanted side effects and which are satisfactorily stable, also during sterilization and storage as aqueous solutions, whose iron-dextran compound it can be used as a component in a therapeutic composition for the prophylaxis or treatment of iron deficiency in animal or human subjects by parenteral administration, the iron-dextran compound being characterized in that it comprises hydrogenated dextran having a weight-average molecular weight ( Mw) between 700 and 1, 400 Daltons, preferably about 1,000 Daltons, a number average molecular weight (Mn) of 400 to 1,400 Daltons, and wherein 90% by weight of dextran has a molecular weight of less than 2,700 Daltons and the Mw of 10% by weight of the dextran fraction having the highest molecular weights is below 3,200 Daltones, said hydrogenated dextran has been subjected to purification by membrane processes having a cut-off value between 340 and 800 Daltons, in stable association with ferric oxy-hydroxide . In connection with the present invention, the "weight average molecular weight" and the "number average molecular weight" mean the respective average molecular weight at the time where the formation of the complexes takes place, based on all the dextran molecules that come from of the monomer and subsequently. It is believed that the reason why the dextrans of the molecular weight distribution defined above have not found commercial applicability in the manufacture of iron-dextran compounds, is because not enough attention has been paid to the presence of the low weight saccharides molecular, for which reason toxicity and inferior stability have been experienced, and because insufficient attention has been paid to the fact that dextrans of weight-average molecular weight around 1,000 Daltons are better tolerated by the human or animal organism than dextrans of higher molecular weight conventionally used in iron preparations.

When used for parenteral administration, the compound in question is dissolved or dispersed in an aqueous liquid, and this may be marketed as such, preferably having an iron content of 5 to 20% w / v. On the other hand, the compound is sufficiently stable to be dehydrated without deterioration in a conventional drying or dehydrating process such as spray drying, for which reason the compound can also be marketed as such or as a partial constituent of a dry powder. The iron content thereof will typically be from 15 to 45% w / w. In the relatively low molecular weight dextrans such as those which come into consideration according to the present invention, the influence of the terminal groups (partially hydrogenated aldehyde groups) on the polymer chains is substantially more pronounced than in the dextrans of higher molecular weight , since, on a weight basis, the number of functional end groups is higher. These terminal functional groups tend to increase instability by reactions involving Fe3 + and low molecular weight saccharides. Therefore, the absence of Fe3 + and low molecular weight saccharides is even more important than when it comes to dextrans of higher molecular weight. The invention also comprises a process for the production of an iron-dextran compound as described above, the process of which is characterized by the following steps: The molecular weight of the dextran is reduced by hydrolysis, and the dextran is hydrogenated to convert the terminal groups functional aldehyde in alcohol groups, the hydrogenated dextran as an aqueous solution is combined with at least one water-soluble ferric salt, base is added to the resulting solution to form ferric hydroxide, and the resulting mixture is heated to transform the ferric hydroxide into oxy ferric hydroxide as a compound in association with dextran, whose process is characterized in that, after hydrolysis but before being combined with the water-soluble ferric salt, dextran is purified by one or more membrane processes using a membrane having a suitable cut-off value to retain the molecular weight dextran by above 2,700 Daltones, possibly followed by additional hydrolysis, and followed by one or more membrane processes using membranes with a cut between 340 and 800 Daltones. A preferred embodiment of the process comprises the following: the preparation of an aqueous solution comprising hydrogenated dextran, purified, and at least one ferric salt soluble in water; adjusting the pH of the aqueous solution to a value above 10 by adding a base; heating the mixture to a temperature above 100 ° C until it becomes a black to dark brown colloidal solution, which can be filtered through a 0.45 μm filter; and further purification and stabilization using filtration, heating and membrane processes and addition of one or more stabilizers, and optionally drying the solution to obtain the desired iron-dextran compound as a stable powder. Liquids for injection can be produced by redissolving this powder, adjusting the pH, sterilizing by filtration and filling in ampoules or flasks. The sterilization can also be achieved by autoclaving the ampoules or the filled bottles. Alternatively, the drying operation is omitted, and a liquid for injection is produced from the purified solution without intermediate drying thereof. In a further preferred embodiment, the hydrogenation of the dextran is carried out by means of sodium borohydride in aqueous solution. The stabilization is suitably carried out by the addition of a salt of an organic hydroxy acid, preferably a citrate. The invention also comprises the use of a compound consisting of or containing a hydrogenated dextran having a weight average molecular weight of 700 to 1., 400 Daltons, preferably about 1,000 Daltons, a number average molecular weight (Mn) of 400 to 1,400 Daltons, and wherein 90% by weight of the dextran has average molecular weights less than 2,700 Daltons and the Mw of the 10% fraction by weight of the dextran having the highest molecular weights, is below 3,200 Daltones, in stable association with ferric oxyhydroxide, said hydroxyated dextran having been subjected to purification by membrane processes having a cut-off value between 340 and 800 Daltones, for the preparation of a therapeutic composition parenterally administrable for the prophylaxis or treatment of iron deficiency anemia in animal or human subjects. The invention is further illustrated by means of the following non-limiting examples.

EXAMPLE 1 i) Hydrolysis and hydrogenation of dextran 2,522 kg of hydrolyzed dextran collected as permeate from a membrane having a cut-off value of less than 5,000 Daltons, is hydrolyzed at pH 1.5 at a temperature of 95 ° C. The hydrolysis is periodically checked chromatographically using gel permeation chromatography (GPC), and terminated by cooling when the molecular weight of the material that is hydrolyzed is estimated to have reached the desired value, eg, a weight average molecular weight. from 700 to 1,400 Daltones. Low-molecular-weight dextran is produced by hydrolysis, but glucose is also formed. After cooling and neutralization, the amount of glucose and the very low molecular weight oligomers is reduced by membrane processes having a cut-off value of 340 to 800 Daltons. After this process, it is determined that the content of dextran by optical rotation (D u-200) is 1.976 kg, and the amount of reducing sugar is determined by the use of the Somogy reagent, as of 36.8%. The reducing capacity is decreased by treatment with sodium borohydride. For the 1,976 kg of dextran, 57 kg of sodium borohydride are added at basic pH. After treatment with sodium borohydride, the reducing capacity is determined as 1.5%. After this the solution is neutralized to pH less than 7.0, and subsequently it is deionized. The average molecular weights and the molecular weight distribution are determined chromatographically. Chromatography also reveals that the above conditions are met, namely that 99% by weight of the dextran has molecular weights of less than 2,700 Daltons and that the weight average molecular weight (Mw) of 10% by the weight fraction of the dextran having the highest molecular weights, is less than 3,200 Daltones. It is found that Mw is 1,217 and Mn is 845 Daltones. The final amount of dextran after de-ionization is 1,320 kg-determined by optical rotation. ii) Iron-dextran synthesis 120 kg of dextran, produced as described above, is as an 18% solution mixed with 150 kg of ferric chloride hexahydrate. To the stirred mixture is added 93 kg of sodium carbonate as a saturated aqueous solution, and, thereafter, the pH is raised to 10.5 using 24 liters of concentrated aqueous sodium hydroxide (27% w / v). The mixture obtained in this way is heated above 100 ° C until it becomes a black to dark brown colloidal solution, which can be filtered through a 0.45 μm filter and subsequently cooled. After cooling, the solution is neutralized using 12 liters of concentrated hydrochloric acid to obtain a pH of 5.80 and purified using membrane processes until the chloride content in the solution is less than 0.68%, calculated on the basis of a solution containing 5% w / v of iron. If the chloride content of the solution is lower than desired to obtain an isotonic solution, sodium chloride is added and the pH is finally adjusted to 5.6 and the solution is filtered through a 0.45 μm membrane filter (or alternatively 0.2 μm). The solution is spray-dried and the iron-dextran powder is ready for commercialization or for further processing. As an alternative to spray drying, the solution can be used for the direct production of injection liquids having an iron content of, for example, 5%, as described above. When the iron-dextran powder is used for the production of injection or infusion liquids, the powder is redissolved in an aqueous medium, the pH is verified, and, if necessary, it is adjusted and the solution is filled in ampoules or flasks after being sterilized by filtration. Alternatively, the sterilization can take place by heating in an autoclave after being filled in ampoules or flasks.

EXAMPLE 2 i) Hydrolysis and hydrogenation of dextran This portion of the synthesis is carried out as described under subparagraph (i) in Example 1 above, apart from the fact that 54 kg of sodium borohydride are used and the reducing capacity is thereby reduced to 3.0%. ii) Synthesis of iron-dextran 120 kg of the aforementioned dextran as in an 18% solution are mixed with 300 kg of ferric chloride hexahydrate (FeCl3 * 6H20). To the stirred mixture is added 180 kg of sodium carbonate as a saturated aqueous solution, and thereafter the pH of the mixture is raised to pH 11.5 using 38 liters of concentrated aqueous sodium hydroxide (27% w / v). The mixture obtained in this way is heated above 100 ° C until it becomes a black to dark brown colloidal solution and can be filtered through a 0.45 μm filter after which it is cooled. The cooled solution is neutralized, using 25 liters of concentrated hydrochloric acid, to a pH of 5.60 and purified using membrane processes until the chloride content is less than 1.1% calculated based on a solution containing 10% w / v of iron. After this, a hydroxy acid in the form of 6 kg of citric acid is added, and the pH is adjusted to a pH above 8.0 using sodium hydroxide, and the solution is stabilized by raising the temperature above 100 ° C for 60 minutes. Subsequently, the pH is adjusted by means of concentrated hydrochloric acid to pH 5.6. In the case where the chloride content of the solution is lower than desired, it is adjusted by the addition of sodium chloride. After this, the solution is filtered through a membrane filter of 0.45 μm (or 0.2 μm). The solution is spray-dried and the iron-dextran powder is thus finished.

This powder is suitable for the production of a liquid iron-dextran preparation containing approximately 10% w / v iron.

EXAMPLE 3 i) Hydrolysis and hydrogenation of dextran This portion of the synthesis is carried out as in Example 2 above. ii) Synthesis of iron-dextran 80 kg of the above dextran as a 10% aqueous solution is mixed with 400 kg of ferric chloride hexahydrate (FeCl3 * 6 H20). To the stirred mixture is added 232 kg of sodium carbonate as a saturated aqueous solution, and thereafter the pH of the mixture is raised to 11.5 using 60 liters of concentrated aqueous sodium hydroxide (27% w / v). The aforementioned mixture is heated above 100 ° C until it turns into a black to dark brown colloidal solution and can then be filtered through a 0.45 μm filter, after which it is cooled. The cold solution is neutralized using 15 liters of concentrated hydrochloric acid at pH 5.60, and purified using membrane processes until the chloride content is less than 1.8%, calculated based on a solution containing 20% w / v iron. After this the hydroxy acid, consisting of 8 ~ kg of citric acid, is added and the pH is adjusted with sodium hydroxide to a value above 8.0, after which the solution is stabilized by raising the temperature above 100. ° C for 60 minutes. After this the pH is adjusted with concentrated hydrochloric acid to 5.6. In the event that the chloride content of the solution is lower than desired, the chloride content is adjusted by the addition of sodium chloride. The solution is filtered through a membrane filter of 0.45 μm (or 0.2 μm). The solution is spray-dried and the iron-dextran powder is finished. This powder is suitable for the production of a liquid preparation containing 20% w / v of iron.

In all three examples, the iron-dextran powder yield is greater than 95%, calculated based on the iron used in the process.

Claims (12)

1. An iron-dextran compound for use as a component in a therapeutic composition for the prophylaxis or treatment of iron deficiency in animal or human subjects, by parenteral administration, comprising hydrogenated dextran having a weight-average molecular weight (Mw) between 700 and 1,400 Daltons, preferably about 1,000 Daltons, a number average molecular weight (Mn) of 400 to 1,400 Daltons and wherein 90% by weight of dextran has molecular weights less than 2,700 Daltons and the Mw of the 10% fraction by weight of the dextran that has the highest molecular weights, is less than 3,200 Daltones, the hydrogenated dextran has been subjected to purification by membrane processes that have a cut-off value between 340 and 800 Daltons, in stable association with ferric oxy-hydroxide .

2. A compound according to claim 1, characterized in that it is the sole or partial constituent of a dry powder.

3. A compound according to claim 2, characterized in that the powder of which the compound is a single or partial constituent, has an iron content of 15-45% w / w.

4. A compound according to claim 1, characterized in that it is dissolved or dispersed in an aqueous liquid.

5. A compound according to claim 4, characterized in that it is dissolved or dispersed in the aqueous liquid in an amount such that the content of iron in the resulting solution or dispersion is from 5 to 20% w / v.

6. A process for producing an iron-dextran compound as defined in claim 1, wherein the molecular weight of the dextran is reduced by hydrolysis and the dextran is hydrogenated to convert the terminal functional groups aldehyde to alcohol groups; the hydrogenated dextran as an aqueous solution is combined with at least one ferric salt soluble in water; base is added to the resulting solution to form ferric hydroxide, and the resulting mixture is heated to transform the ferric hydroxide into ferric oxyhydroxide as an association compound with dextran, characterized because after hydrolysis, but before it is combined With water-soluble ferric salt, dextran is purified by one or more membrane processes having an adequate cut-off value to retain dextran of molecular weight greater than 2,700 Daltones, possibly followed by subsequent hydrolysis, and followed by one or more membrane processes that have a cut-off value between 340 and 800 Daltones.

7. A process according to claim 6, characterized by the following steps: the preparation of an aqueous solution comprising the resulting hydrogenated dextran and at least one ferric salt soluble in water; adjusting the pH of the aqueous solution to a value greater than 10 by adding a base; heating the mixture to a temperature above 100 ° C until it becomes a black colloidal solution to dark coffee and is filterable through a 0.45 μm filter; and purification and stabilization of the solution using filtration, heating and membrane processes, and the addition of one or more stabilizers, and, optionally, drying the solution to obtain the desired iron-dextran compound as a stable powder.

8. A process according to claim 6, characterized in that the hydrogenation of the dextrans is carried out by means of sodium borohydride in aqueous solution.

9. A process according to claim 7, characterized in that the stabilization comprises the addition of at least one salt of an organic hydroxy acid, preferably selected from the citrates.

10. The use of a compound comprising hydrogenated dextran having a weight average molecular weight (Mw) between 700 and 1,400 Daltons, preferably about 1,000 Daltons, a number average molecular weight (Mn) of 400 to 1, 400 Daltons and where 90% by weight of dextran has molecular weights less than 2,700 Daltons, and the Mw of the 10% dextran fraction having the highest molecular weights, is less than 3,200 Daltons, said dextran having been subject hydrogenated to purification by membrane processes having a cut-off value between 340 and 800 Daltons, in stable association with ferric oxyhydroxide for the preparation of a parenterally administerable therapeutic composition, for the prophylaxis or treatment of iron deficiency anemia in animal or human subjects.

11. A process for the production of an injection liquid containing a compound according to claim 1, characterized in that the compound is dissolved as a dry powder in an aqueous medium, the pH is adjusted, if necessary, stabilizer is optionally added, and the liquid is sterilized by filtration before filling it into vials or flasks, or by autoclaving after filling such vials or flasks.

12. A process for the production of an injection liquid containing a compound according to claim 1, characterized in that a liquid resulting from the process of claim 6 is purified, adjusted for the iron content and the pH value, stabilized and sterilized by filtration before being filled in ampoules or flasks, or by autoclaving after being filled in ampoules or flasks.