WO2022118274A1 - Compositions destinées à être utilisées dans le traitement et/ou la prévention d'états ou de maladies de carence en fer - Google Patents

Compositions destinées à être utilisées dans le traitement et/ou la prévention d'états ou de maladies de carence en fer Download PDF

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Publication number
WO2022118274A1
WO2022118274A1 PCT/IB2021/061297 IB2021061297W WO2022118274A1 WO 2022118274 A1 WO2022118274 A1 WO 2022118274A1 IB 2021061297 W IB2021061297 W IB 2021061297W WO 2022118274 A1 WO2022118274 A1 WO 2022118274A1
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iron
nutraceutical
pharmaceutical composition
starch
ranging
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PCT/IB2021/061297
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English (en)
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Umberto DI MAIO
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Neilos S.r.l.
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Publication of WO2022118274A1 publication Critical patent/WO2022118274A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements

Definitions

  • the present invention relates to a nutraceutical or pharmaceutical composition of substances effective in the prevention and/or treatment of conditions and pathologies characterized by iron deficiency both in man and animals .
  • Iron is an essential oligo-element performing di f ferent vital functions in the human body and it is involved in several metabolic processes : it transports the oxygen through the bloodstream towards the body districts , it is a co- factor in the synthesis of DNA, of steroid hormones and of the bile acids , it transports the electrons in the mitochondrial transport chain and it detoxi fies the organism from foreign substances , since it belongs to p450 cytochrome . Iron is essential for several metabolic processes which occur at cellular level , also being able to be potentially dangerous , its biochemical ef fects and its levels are finely controlled by sophisticated mechanisms which regulate the homeostasis thereof at di f ferent levels .
  • the haemoglobin is a globular protein formed by four polypeptide chains , each one thereof includes a Heme group, consisting of one porphyrin ring surrounding and complexes one iron atom.
  • Each iron atom is capable of binding one oxygen molecule by allowing in this way the passage of the oxygen from the lungs to the bloodstream and its transportation to all districts of the organism .
  • the remaining percentage of iron existing in the organism is bound to other tissue enzymes , to transportation systems , such as trans ferrin, and to not-heme proteins such as ferritin .
  • the iron which the human organism succeeds in absorbing through feeding is of two types : heme iron, which does not create absorption problems , and non-heme iron, or inorganic iron, which instead has a very low bioavailability .
  • heme iron which does not create absorption problems
  • non-heme iron or inorganic iron, which instead has a very low bioavailability .
  • Even i f it constitutes the greatest source of iron in diet the inorganic iron is absorbed only when it is in the reduced state ( Fe 2 + ) , which represents the form favoured by the acid pH of the stomach and of the proximal duodenum . At physiological pH, the inorganic iron is instead quickly oxidi zed to Fe 3 + .
  • the human organism succeeds in maintaining the iron normal levels through a continuous recycling of the deposits existing in the cells and by avoiding the excretion thereof .
  • the amount of iron which the body eliminates every day is very low ( « 1 mg/die ) .
  • the iron elimination substantially takes place through exfoliation of the epithelial cells of the skin and mucous membranes of the genitourinary and gastrointestinal tract .
  • the subj ects at risk there are : - Children and adolescents : iron is fundamental for the correct body growth, therefore in the absence of adequate supplementation, it is one of the main factors which could cause a deficiency thereof ;
  • this category includes whoever suf fers from diseases characteri zed by malabsorption such as intestinal chronic inflammatory diseases , celiac disease or obesity .
  • the latter is a condition accompanied by a chronic inflammatory state and by high levels of hepcidin, a peptide hormone inhibiting ferroportin 1 on the basolateral membrane of enterocytes and macrophage ferroportin, by inhibiting both the intestinal absorption, and the release from the macrophages of the iron already existing in the organism.
  • an iron deficiency can appear with or without anaemia, but most iron deficit symptoms are, mainly, attributable to the anaemic picture.
  • anaemia a condition is meant characterized by alterations in the number of red blood cells or haemoglobin in blood going down to a lower level than the one required to the correct transportation of oxygen to all districts and body tissues.
  • the iron deficiency anaemia is defined "sideropenic anaemia" and it can appear in the subjects which do not succeed in reaching adequate levels of such essential element through the diet, or in subjects affected by morbid states characterized by chronic losses of blood (such as gastric ulcers, colon or uterine cancer, intestinal polyps and haemorrhoids) , pregnant women and obese subjects.
  • the main symptoms characterizing an iron deficiency anaemia include: feeling of tiredness, weakness and reduced resistance; concentration difficulty and reduced physical and mental performances; pallor; shortness of breath; difficulty in maintaining an adequate body temperature (in particular at the ends which appear cool) ; during pregnancy it can lead to an increase in the risk of preterm birth .
  • more serious deficiencies symptoms can appear such as : glossitis ( inflammation of the tongue which appears reddened, swollen and painful ) ; chapped lips ; neurological symptoms such as pica (need for eating substances such as dirt , ice and paints ) .
  • the iron percentage absorbed through feeding is very low, therefore , under determined conditions or li fe phases , it is essential to have to recourse to a supplementation .
  • This last strategy is not always easy to be implemented since the inorganic iron has several vehiculation problems .
  • any iron salt has a characteristic rust odour and taste resulting extremely unpleasant by invalidating the compliance of any supplement including inorganic iron .
  • Another important problem correlated to its vehiculation is the modest absorption which, as mentioned, is influenced by the iron redox state . The only form which can be absorbed at intestinal level is the reduced one ( Fe 2 + ) .
  • the reduced state is favoured by acid pH values which can be found in the stomach and in the proximal duodenum . Therefore , the intestinal absorption of the inorganic iron is limited to this tract , considering that the pancreatic j uices , existing in the portion of remaining intestine , favour instead the oxidi zed state ( Fe 3 + ) .
  • Some iron salts such as pyrophosphate , have a very bad suspensibility and a high tendency to sediment . This feature makes that , in contact with the gastric mucosa, on one side the iron is oxidi zed due to the contact with the basic mucus and, on the other side , it irritates the mucosa itsel f .
  • the oral administration of iron in most patients , causes unwished ef fects at gastro-intestinal level , such as abdominal pain, diarrhoea or constipation, nausea and vomit .
  • the purpose of the present invention is then to make available a nutraceutical or pharmaceutical composition apt to vehiculate iron to re-integrate the levels thereof in subj ects having a deficiency of such element .
  • the iron pyrophosphate is one of the salts most used in the iron-based supplements .
  • the pyrophosphate is a substance which participates in the energy cycle and it is produced by the hydrolysis of adenosine triphosphate . When it is combined with multivalent cations , it is capable of forming complexes insoluble in water which are characteri zed by a considerable chemical and structural complexity . This feature makes that pyrophosphate is among the most used compounds in chemical and biomedical industries .
  • the selection of the most suitable inorganic salt is performed by taking into consideration several factors , the first thereamong is ef fectiveness .
  • Many clinical studies have highlighted that the iron pyrophosphate is among the salts which provide best results , even in case of most serious deficiency .
  • the iron deficiency i s among the most common nutritional deficits and it can be a secondary ef fect caused by the increase in erythropoiesis , by the decrease in the intestinal absorption capability, by the increase in the blood losses or in chronic bleeding, by the increased exfoliation of the gastrointestinal epithelial cells .
  • iron inorganic salts (II) soluble in water such as iron sulphate
  • iron pyrophosphate results to be extremely advantageous since it does not alter the colour of the supplements in which it is inserted.
  • the iron salts (III) such as indeed the iron pyrophosphate, have the disadvantage of being less soluble in water and less bioavailable with respect to the iron salts
  • (III) is correlated to their moderate solubility in the diluted acids, such as those existing in the gastric juices.
  • nutraceutical or pharmaceutical composition characteri zed in that it comprises iron pyrophosphate as active principle and a combination of functional excipients , that i s beta-cyclodextrin and starch, capable of providing properties of gastro-resistance and of increasing iron bioavailability .
  • the nutraceutical or pharmaceutical composition of the invention is particularly ef fective in the treatment and prevention of conditions and pathologies , including the related symptomatic states , caused by iron deficiency .
  • the iron deficiency can be due to a reduced intake with diet or to an increased requirement .
  • the pharmaceutical product or a food supplement comprising the nutraceutical or pharmaceutical composition according to the invention .
  • the pharmaceutical product or food supplement of the invention can optionally include active principles and functional excipients which are easily selected by the person skilled in the art based upon the case needs . Even the selection of the vehicles, excipients and/or diluents required for the formulation of the pharmaceutical product or food supplement in an appropriate dosage form lies within the usual capabilities of the person skilled in the art .
  • nutraceutical or pharmaceutical composition according to the invention is as defined in the enclosed claim 1 .
  • the nutraceutical or pharmaceutical composition of the present invention comprises iron pyrophosphate as active principle and a combination of functional excipients which provide to the composition properties of gastro-resistance and increase the iron bioavailability .
  • Such combination of functional excipients includes beta- cyclodextrin and starch .
  • the nutraceutical or pharmaceutical composition of the invention is then particularly effective for the vehiculation and supplementation of iron in contrasting the typical symptomatology of the iron- deficiency states and to provide high levels of such element in periods of reduced intake with diet or of increased iron requirement .
  • Examples of such conditions and pathologies are anaemia, sideropenia, pregnancy, breastfeeding, loss of appetite , asthenia, menstruation, haemorrhages , menopause , intestinal inflammatory diseases , celiac disease , obesity, gastric ulcers , colon or uterine cancer, intestinal polyps , haemorrhoids .
  • the starch is an organic compound of polysaccharide nature consisting of the repetition of glucose units bound by a-glycosidic bonds . It consists of two types of polymers : amylose , which generally is equal to about 20% , and amylopectin, which generally is equal to about 80% .
  • amylose constitutes the central portion of the starch granules , it is soluble in very hot water and it consists of molecules of glucose bound by a- 1 , 4 glycosidic bonds .
  • the amylopectin is a polymer with a high degree of branching forming the external portion of the granules .
  • the monomeric units constituting it are j oined, in the branching points , by a- 1 , 6 glycosidic bonds .
  • a- 1 , 6 glycosidic bonds In nature it forms in the green portions of plants , to be then accumulated in the reserve elements , such as tubers , seeds and roots .
  • the reserve elements such as tubers , seeds and roots .
  • the starch is particularly important in food industry, which uses it as thickening agent and in the production of sweeteners such as maltitol and sorbitol . Thanks to its gluing properties it is also used in the production of paper and glues , under the form of solid starch . In the pharmaceutical industry the starch has always been used as excipient and for the formation of coatings , thanks to its binding properties .
  • the starch is also used in its natural form, the interest of the firms is mainly directed to the modi fied starches , that is starch molecules suitably modi fied to meet the needs of the various productive processes in which the starch is used .
  • modi fied starches can be obtained by using as source plants which mutated genetically naturally or induced and which then produce starches with altered features.
  • Another strategy is that of modifying the starch, generally deriving from maize, tapioca and rice, by chemical treatments (addition of functional groups, treatment with acids and bases, physical treatments (gelatinization) or enzymatic treatments (partial hydrolysis) .
  • Dextrins are an example of modified starches obtained by hydrolysis and repolymerization.
  • Such reactions can be made by simple thermal degradation or by means of acid catalysis. The result is to obtain molecules characterized by shorter chains and then partially or wholly soluble in water.
  • dextrins are cyclodextrins and maltodextrins, excipients widely used in nutraceutical and pharmaceutical field .
  • HAS high amylose modified starches
  • a starch in order to be defined as such, must have a percentage of amylose equal to at least 50%.
  • the high amylose starch can be obtained from genetically modified plants or by enriching with amylose starches which have low percentages thereof.
  • the strategies used by several firms provide the use of HAS for the preparation of solid pharmaceutical forms or in the coating processes .
  • HAS have several advantages with respect to other types of starch, for example a better consistency, a greater thermal stability and a greater resistance to humidity and adhesion phenomena . Di f ferent strategies were put into practice to exploit HAS advantages in the most suitable way .
  • di f ferent types of starch can be used .
  • a not chemically modi fied starch of pregelatini zed mai ze or a starch of pregelatini zed acetylated mai ze with a high content of amylose which, in the specific case, can reach up to 90% by weight.
  • the percentage of acetylic groups ranges from 0.5% to 2.5%.
  • the acetylation is performed with acetic anhydride which guarantees to reach a percentage of acetylic groups higher than 0.5% but not higher than 2.5%.
  • the starch pre-gelatinization treatment consists in dispersing the acetylated starch in water and in subjecting the so-obtained dispersion at temperatures ranging from 100 to 130 degrees and high pressures.
  • the starch granules subjected to such procedure blow up and form a gel with a humidity content ranging from 5 and 10%.
  • the thus obtained modified starch can be used in the processes for coating stiff, soft capsules and microgranules and it guarantees to obtain a coating which results resistant and adequately viscous at the same time, which is capable of masking unpleasant odours and tastes and which can be used even when one wants to obtain e a gastro-resistant pharmaceutical form or a form with modified release.
  • the features of the pharmaceutical form can be modulated by modifying the amount of starch used in the coating.
  • Tests performed by using the above-mentioned starch showed the gastro-resistant action, the action of protecting against humidity and the capability of releasing the active principle after few minutes in intestinal environment .
  • the other functional excipient present in the nutraceutical or pharmaceutical composition of the invention is beta-cyclodextrin .
  • Cyclodextrins ( CD) are cyclic oligosaccharides which are produced by the starch or by starch derivatives by using the cyclodextrin glycosyltrans ferase enzyme . These compounds are used as pharmaceutical excipients as they can form inclusion complexes by binding in a not covalent way (host -guest complexes ) several drugs in solution or in the solid state .
  • cyclodextrins include units of a-D-glucopyranose with (a- 1-4 ) bond, having a central lyophile cavity and a hydrophile external surface ; from the spatial and three-dimensional point of view they have a truncated-conical shape or a donut-like shape .
  • Cyclodextrins are used in the pharmaceutical industry for several purposes , such as : improving the aqueous solubility, the dissolution and the bioavailability of drugs , increasing the chemical- physical stability of the drug and improving the shel f-li fe of the drugs , modi fying the release , reducing to the minimum adverse reactions such as gastrointestinal and ocular irritation, reducing or removing unpleasant taste and odour, preventing drug-drug or drug-excipient interactions , converting liquid drugs into microcrystalline or amorphous powders .
  • betacyclodextrins al f a-cyclodextrins and gammacyclodextrins .
  • p-CDs and their derivatives from chemical modi fications are the ones most used by the pharmaceutical industry in the field of the controlled release of active principles .
  • Hydrophobic ( diethyl- p -CD and triacetyl- p -CD) and ioni zable derivatives of p-CDs are used in the formulation of tablets with prolonged release and with delayed release , respectively .
  • O-carboxymethyl-O-ethyl- p-CD causes a delayed dissolution of the included substances , not thanks to the presence of the ioni zable carboxymethyl groups but due to the presence of the ethylic hydrophobic groups .
  • the ef fect of the CD complexes on the chemical stability of drugs was examined and it was highlighted that the complexation with CD can hinder hydrolysis , oxidation, photodegradation, isomeri zation and degradation catalyzed by enzymes of drugs dissolved in aqueous solution .
  • the addition of p-CD as excipient to Limaprost-based tablets improved the stability of the derivative of El prostaglandin .
  • CDs An additional application of CDs relates to their use with the purpose of masking the unpleasant taste of possible substances , the complexation of drugs with CDs constituting a coating method ( formation of a physical barrier ) or chemical modi fication .
  • a coating method formation of a physical barrier
  • chemical modi fication a coating method
  • Aceclofenac a non-steroidal antiinflammatory drug
  • CDs then, are used to reduce to the minimum the side ef fects of the drugs such as gastric, intestinal , nasal and ocular irritation .
  • Naprossene for example has poor solubility in water and problems of gastrointestinal toxicity and ulceration i f administered by oral route , in order to overcome these critical issues coated tablets were developed containing Nanoprossene/HP-p-CD inclusion complexes to vehiculate the drug to the colon .
  • CDs were used in the formulation of tablets as filler for the direct compression (p -CD) , disintegrating agents (polymers of CDs) , binding agents (p -CD) and osmotic pump agents (for example, SBE-p-CD) .
  • Literature shows the development of a new multifunctional excipient, to be used in the production of tablets through direct compression, based upon citric acid and p -CD, in its forms insoluble (PCD-I) and soluble (PCD-S) in water.
  • Other excipients such as binders, lubricants or disintegrating agents were not added.
  • This project highlighted the multifunctional properties of this polymeric excipient, such as good flowing properties, compressibility, absence of toxicity and modular disintegration time.
  • the present invention then allows to obtain :
  • the present invention is a ready and valid intervention to contrast symptoms typical of the iron-deficiency states and to provide adequate levels of such element in periods of reduced intake with diet or of increased requirement .
  • Such ef fect is ascribed to the combined action of the substances constituting it .
  • the starch used in the present invention allows to mask the unpleasant taste which can be found in the iron-based supplements , as well as to protect iron from acid pH in the stomach, by guaranteeing the release at intestinal level .
  • Beta-cyclodextrin thanks to the peculiar chemical structure is capable of incorporating iron pyrophosphate and favouring the bioavailability thereof by improving the solubility and stability thereof .
  • the ef fectiveness of the nutraceutical or pharmaceutical composition of the present invention is evaluated by means of the experimental protocol described hereinafter .
  • a disintegration test is performed, as provided by Pharmacopeia .
  • a sample of the pharmaceutical form to be tested is placed in suitable instrument containing hydrochloric acid 0 . 1 N .
  • the gastro-resistant pharmaceutical form in contact with the buf fer at pH 2 for two hours is not subj ected to disintegration .
  • the sample is trans ferred into a buf fer at pH 6 . 8 wherein it disintegrates within ten minutes .
  • the gastro-resistance can be evaluated even by means of a dissolution test by Pharmacopeia according thereto the pharmaceutical form is put in contact with a solution of 0 . 1 N-hydrochloric acid and for 2 hours .
  • an in-vitro test is performed on Caco- 2 cells of human derivation .
  • the cells put in culture , are prepared by using a suitable growth means (for example containing FBS , fetal bovine serum) and kept under controlled conditions (for example of 37 ° C, in an atmosphere having 5% of CO 2 and 100% of humidity) . After several passages the cells are washed and pre-incubated with PBS . After the treatment with the formulations of interest the collected samples are subj ected to analysis in order to quantify iron.
  • a suitable growth means for example containing FBS , fetal bovine serum
  • controlled conditions for example of 37 ° C, in an atmosphere having 5% of CO 2 and 100% of humidity
  • a variant discussed by way of example of the above-mentioned in vitro test provides that the Caco-2 cells are incubated under the same conditions of temperature, CO 2 and humidity. After sucking the means the cells are washed twice with suitable buffer (for example 50 mM HEPES, 130 mM NaCl, 10 mM KC1, 5 mM glucose, 1 mM MgS0 4 , pH 7) and, subsequently, treated with the samples to be tested for one hour. At the end of the treatment the monolayer of cells is washed with a buffer which removes iron and it is dissolved in suitable means (for example Triton-X 2%) in order to be sonificated. The protein concentration is calculated by suitable method (for example of the bicinchoninic acid) . The iron concentration is obtained by atomic absorption and the uptake is expressed as pg of iron for mg of proteins.
  • suitable buffer for example 50 mM HEPES, 130 mM NaCl, 10 mM KC1, 5 mM glucose, 1
  • TEER transepithelial electric resistance
  • the solution containing the composition, the present invention relates to , which is subj ected to gastric and intestinal digestion is then applied ( at the concentrations selected based upon the results of the preliminary cytotoxicity) from the apical side of the transwell (which in the model represents the intestinal lumen) .
  • the apical side of the transwell which in the model represents the intestinal lumen
  • the liquid is collected on the baso- lateral side which will be subsequently analysed for the iron pyrophosphate dosage by means of TCP or other accredited method .
  • the iron uptake can be evaluated on still on Caco-2 cell model by evaluation after treatment with the samples of ferritin in cell .
  • the percentage of ferritin is directly proportional to the iron amount inside the cell .
  • the ef fectiveness of the present invention can be evaluated even by means of an in vi vo test on experiment animals in line with the directives of the European Community and of the Ministry of Health by an Ethical Committee .
  • the test is performed on male mice , for example Sprague-Dawley, having an average weight of about 250-300 g .
  • the iron level is evaluated after one single administration of the formulation under examination .
  • the levels of plasmatic iron are measured by means of atomic absorption or other analytic technique suitable on blood samples collected at time zero and at determined time intervals after administration .
  • the levels of plasmatic iron are evaluated after daily administration of the above- mentioned formulation for a prolonged period of time and, at the end of the treatment , the blood levels of iron, haemoglobin, trans ferrin and ferritin are evaluated .
  • the ef fectiveness of the composition, the present invention relates to can be evaluated even by means of a clinical study on man by monitoring after a determined period of time the way in which the blood levels of iron, haemoglobin, trans ferrin, ferritin vary before and after administration of the formulation the present invention relates to .
  • All mentioned experimental models represent only not limitative examples ; even variants thereof or other types of experimental models known to the person skilled in the art could be used with the purpose of evaluating the synergic action of the composition the present invention relates to .
  • the nutraceutical or pharmaceutical composition of the present invention is particularly ef fective in contrasting the iron deficiency states thanks to the synergic action of its components .
  • nutraceutical or pharmaceutical composition of the present invention is inserted within a pharmaceutical product or food supplement , which is formulated in a suitable dosage form, the composition and preparation thereof lies within the capability of the person skilled in the art .
  • the iron pyrophosphate in the nutraceutical or pharmaceutical composition of the invention is present in an amount ranging from 0 . 1 and 90% , preferably between 1 and 80% , still more preferably between 5 and 70% , with respect to the total weight of the above-mentioned combination .
  • additional percentages of iron pyrophosphate which can be used in the composition of the invention are : 2 % , 3% , 4 % , 6% , 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, or 85%.
  • the starch in the nutraceutical or pharmaceutical composition of the invention is present in an amount ranging from 0.1 to 90%, preferably from 1 to 80%, still more preferably from 10 to 70% with respect to the total weight of the above-mentioned combination.
  • additional percentage of starch which can be used in the composition of the invention are: 2%, 3%, 4%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, or 85%.
  • betacyclodextrin in the nutraceutical or pharmaceutical composition of the invention is present in an amount ranging from 0.01 to 90%, preferably from 0.05 to 70%, still more preferably from 0.1 to 50% with respect to the total weight of the above- mentioned combination.
  • additional percentages of beta cyclodextrin which can be used in the composition of the invention are: 0.02%, 0.03%, 0.04%, 0.06%, 0.07%, 0.08%, 0.09%, 0.2%, 0.3%, 0.4%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 15%, 20%, 25%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75 o 85%.
  • the pharmaceutical product or food supplement comprising the pharmaceutical or nutraceutical composition of the invention, is formulated in a, preferably oral, pharmaceutical form which can be solid, half-solid or liquid.
  • a powder, an orosoluble powder, a granulate, a hard capsule, a soft-gel capsule, a tablet, a sachet, a solution, a suspension or an emulsion can be mentioned.
  • nutraceutical or pharmaceutical compositions are formulated as pharmaceutical products or food supplements and administered in a suitable form of oral dosage, in case divided into one or more dosage units, such as for example, a capsule, a tablet or a sachet.
  • the working process consists in the following steps : a) Mixing:
  • the raw materials previously loaded in the granulator basket are subjected to a first mixing phase on fluid bed, with process air having a pre- established temperature (for example of 80-90°C) , until obtaining a mixture having an average temperature for example of 44 °C.
  • process air having a pre- established temperature (for example of 80-90°C)
  • a homogeneous bulk from the point of view of the composition and of the temperature, pre-requirement necessary for the optimum course of the subsequent granulation phase.
  • b) Granulation The granulation phase provides to graft an aqueous solution of a suitably selected binding or granulation agent , by means of direct nebuli zation on the bulk premixed and fluidi f ied on fluid bed .
  • process air at 90 ° C is used by suitably selecting the speed for inletting the binding solution to obtain a granular structured according to expectations ( granulometry, bulk density, smoothness ) and homogeneous .
  • the water content of the preformed granular is basically brought back to the conditions of the mixture of the starting raw materials .
  • the temperature of the process air of the granulate at the end of the phase is suitably evaluated in the pilot testing phase depending upon such obj ective .
  • the hal f- finished product obtained from the previous phase is trans ferred from the fluid bed granulator to a swinging granulator where it is calibrated through a sieve for reducing the particle si ze of the granules and of the agglomerates with coarser structure .

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Abstract

La présente invention concerne une composition de substances efficace dans la prévention et/ou le traitement d'états et de maladies caractérisés par une déficience en fer. La composition de l'invention comprend du pyrophosphate de fer, de la bêta-cyclodextrine et de l'amidon. Cette formulation confère aux compositions des propriétés de gastro-résistance et une biodisponibilité élevée du principe actif de pyrophosphate de fer. La composition de l'invention est préparée sous la forme d'un dosage pharmaceutique solide, semi-solide ou liquide, de préférence pour une administration orale.
PCT/IB2021/061297 2020-12-03 2021-12-03 Compositions destinées à être utilisées dans le traitement et/ou la prévention d'états ou de maladies de carence en fer WO2022118274A1 (fr)

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Publication number Priority date Publication date Assignee Title
US20070065521A1 (en) * 2005-09-19 2007-03-22 Bala Venkataraman Composition and method for treating iron deficiency anemia
US20170112178A1 (en) * 2011-07-07 2017-04-27 Chemo S.A. France Compositions, kits and methods for nutrition supplementation
US20190105393A1 (en) * 2012-07-31 2019-04-11 Alesco S.R.L. Solid composition comprising iron for use in iron deficient conditions
WO2019171236A1 (fr) * 2018-03-09 2019-09-12 Frimline Private Limited Composition pharmaceutique pour l'anémie

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070065521A1 (en) * 2005-09-19 2007-03-22 Bala Venkataraman Composition and method for treating iron deficiency anemia
US20170112178A1 (en) * 2011-07-07 2017-04-27 Chemo S.A. France Compositions, kits and methods for nutrition supplementation
US20190105393A1 (en) * 2012-07-31 2019-04-11 Alesco S.R.L. Solid composition comprising iron for use in iron deficient conditions
WO2019171236A1 (fr) * 2018-03-09 2019-09-12 Frimline Private Limited Composition pharmaceutique pour l'anémie

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DATABASE GNPD [online] MINTEL; 12 May 2020 (2020-05-12), ANONYMOUS: "Iron & Multivitamin Supplement", XP055824782, retrieved from https://www.gnpd.com/sinatra/recordpage/7612483/ Database accession no. 7612483 *
DATABASE GNPD [online] MINTEL; 20 July 2020 (2020-07-20), ANONYMOUS: "Tropical Flavour Chewable Multivitamin & Mineral Food Supplement Tablets", XP055824781, retrieved from https://www.gnpd.com/sinatra/recordpage/7961093/ Database accession no. 7961093 *
DATABASE GNPD [online] MINTEL; 22 February 2017 (2017-02-22), ANONYMOUS: "Ferro Vital+ Dietary Supplement", XP055824788, retrieved from https://www.gnpd.com/sinatra/recordpage/4636435/ Database accession no. 4636435 *
DATABASE GNPD [online] MINTEL; 3 April 2018 (2018-04-03), ANONYMOUS: "Dietary Supplement for Pregnancy", XP055824786, retrieved from https://www.gnpd.com/sinatra/recordpage/5557275/ Database accession no. 5557275 *
DATABASE GNPD [online] MINTEL; 9 March 2020 (2020-03-09), ANONYMOUS: "Food Supplement with Sucrosomial Iron and Vitamin C", XP055824784, retrieved from https://www.gnpd.com/sinatra/recordpage/7423655/ Database accession no. 7423655 *
RAVIKIRAN PANAKANTI ET AL: "Impact of Excipient Interactions on Drug Bioavailability from Solid Dosage Forms", PHARMACEUTICAL RESEARCH, KLUWER ACADEMIC PUBLISHERS-PLENUM PUBLISHERS, NL, vol. 29, no. 10, 19 May 2012 (2012-05-19), pages 2639 - 2659, XP035111456, ISSN: 1573-904X, DOI: 10.1007/S11095-012-0767-8 *

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