US20180140570A1 - Product based on iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, formulations thereof, and pharmaceutical uses thereof - Google Patents

Product based on iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, formulations thereof, and pharmaceutical uses thereof Download PDF

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US20180140570A1
US20180140570A1 US15/575,278 US201615575278A US2018140570A1 US 20180140570 A1 US20180140570 A1 US 20180140570A1 US 201615575278 A US201615575278 A US 201615575278A US 2018140570 A1 US2018140570 A1 US 2018140570A1
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water
alginic acid
soluble salts
alginate
iron
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Massimo Baldacci
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Laboratori Baldacci SpA
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    • 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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/734—Alginic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics

Definitions

  • the object of the present invention is a product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, the use of said product for the prevention and/or treatment of anaemia, preferably sideropenic anaemia, in humans, the pharmaceutical formulations containing it, and the use of said formulations for the prevention and/or treatment of anaemia, preferably sideropenic anaemia, in humans.
  • Inorganic salts of divalent iron are generally used, which in most cases exhibit poor bioavailability and side effects in a high percentage of patients.
  • Iron bis-glycinate chelate has the following structural formula (I):
  • Iron bis-glycinate chelate is a rather soluble chelate complex characterised by a metal centre, Fe(II), tetracoordinated by two identical chelants (glycine).
  • the dative bond of the nitrogen atom contributes to stabilising the energy of the metal centre orbitals and the ligand geometry through the formation of a five-atom ring.
  • This compound is also known for its tolerability, safety and high bioavailability (Jeppsen R. B. Toxicology and safety of Ferrochel and other iron amino acids chelates, Arch. Latino Am. de Nutr., 2001, 51(1), 26-34; Opinion of the scientific Panel on Food additives, Flawouring Processing Aids and materials in contact with Food on a request from the Commision related to: Ferrous bisglycinate as a source of iron for use in the manufacturing of foods and in foods supplements, EFSA Journal, 2006, 299, 1-17).
  • iron bis-glycinate chelate does not show any interference with food or other active principles.
  • iron bis-glycinate chelate like other products containing iron, is found to have a very unpleasant taste, characteristic of the iron complex contained therein and, more generally, of all the products containing iron which, notoriously, are therefore not easy to administrate due to their low palatability.
  • anaemia comprises sideropenic anaemia, aplastic anaemia, vitamin and/or folate deficiency anaemia (such as, for example, pernicious anaemia), chronic disease anaemia (such, as for example, AIDS, cancer or hepatitis) and haemolytic anaemia; it preferably refers to sideropenic anaemia.
  • Sideropenic anaemia is a form of anaemia characterised by a significant decrease of haemoglobin in the circulating blood which is caused by iron deficiency.
  • Alginic acid is a copolymer composed of a series of polysaccharide polyanions formed by repeated units of ⁇ -D-mannuronic and ⁇ -L-glucuronic acid linked together by 1 ⁇ 4 bonds.
  • the product is isolated from various species of algae and has an average molecular weight which can vary from a few thousands Dalton (Da) up to 350,000 Da.
  • alginic acid The physical and chemical properties of alginic acid depend on the ratio between glucuronic acid and D-mannuronic acid.
  • the product is recognised by the FDA as a safe product from a toxicological point of view, i.e. it is defined as GRAS (Generally Referred as Safe), and it is used in therapy as the sodium salt in disorders related to acid secretion, gastroesophageal reflux, heartburns and acid regurgitation.
  • GRAS Generally Referred as Safe
  • Alginates are salts of the alginic acid.
  • the alginates of alkali metals, in particular sodium alginate, potassium alginate, and magnesium alginate are soluble in water, while calcium alginate is not water-soluble.
  • the product based on iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof object of the present invention is characterised by being obtained by a spray-drying process of an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or the water-soluble salts thereof.
  • the product thus obtained is characterised by a high surface area which allows its rapid absorption, with protective properties at the level of the gastrointestinal mucosa itself.
  • this product has an improved palatability compared to iron bis-glycinate chelate alone, which allows its use in buccal and chewable formulations, and in oral solutions, achieving an improved adherence to the medical scheme (compliance) by the patient.
  • the alginic acid and/or the water-soluble salts thereof preferably sodium alginate, potassium alginate, and/or magnesium alginate, particularly preferred for the spray-drying with iron bis-glycinate chelate has a low viscosity, with a molecular weight preferably comprised between 10,000 and 15,000 Da (for example, Protanal® LFR), but also alginic acid and/or water-soluble salts thereof with a molecular weight preferably comprised between 40,000 and 50,000 Da (for example, Protanal® LFR 5/60), comprised between 90,000 and 200,000 Da (for example, Protanal® CR 8133) or comprised between 250,000 and 350,000 Da (for example, Protanal® CR 8233) may be used.
  • a molecular weight preferably comprised between 10,000 and 15,000 Da (for example, Protanal® LFR)
  • alginic acid and/or water-soluble salts thereof with a molecular weight preferably comprised between 40,000
  • the molecular weight of the alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, usable for spray-drying the iron bis-glycinate chelate to obtain the product of the present invention is comprised between 10,000 and 350,000 Da, preferably between 10,000 and 250,000 Da, being the range between 10,000 and 15,000 Da the most preferred.
  • the preferred weight ratio between the iron bis-glycinate chelate and the alginic acid and/or the water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, in the product obtained by spray-drying are comprised in the range of 1-2:1-3, and they are preferably 1:1, 1:2 or 2:3.
  • the peculiarity of the spray-drying process of an aqueous solution comprising the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate is the obtainment of a dry powder in which the weight proportion present in the aqueous starting solution are maintained.
  • the preferred weight ratios between the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, in the aqueous solution used for spray drying are comprised in the range of 1-2:1-3, and preferably they are 1:1, 1:2, or 2:3.
  • a product obtained by spray-drying an aqueous solution containing iron bis-glycinate chelate and sodium alginate (Protanal® LFR), with a molecular weight comprised between 10,000 and 15,000 Da, wherein the weight ratio between the iron bis-glycinate chelate and the sodium alginate, is comprised in the range of 1-2:1-3, preferably it is 1:1, 1:2 or 2:3, and even more preferably it is 1:1.
  • the aqueous solution used for spray-drying is obtained by solution of iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, which preferably has a molecular weight comprised between 10,000 and 15,000 Da, in a weight ratio with water of 1:10 and 1:12, respectively.
  • the particle size of the product in powder form obtained after spray-drying the aqueous solution comprising the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, is less than 20 ⁇ .
  • the aqueous solution comprising the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof may comprise an antioxidant, preferably in an amount lower than 0.5% of the total weight of the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof, and even more preferably in an amount lower than 0.3%, where said percentages are referred to the total weight of the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof.
  • said antioxidant is ascorbic acid.
  • the residual moisture value in the product in dry powder form obtained after spray-drying the aqueous solution comprising the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, is comprised between 2.60% and 2.90%.
  • the density of the product in dry powder form obtained after spray-drying the aqueous solution comprising the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, was found to be comprised between 0.2 g/ml and 0.8 g/ml, preferably between 0.3 g/ml and 0.6 g/ml, and even more preferably between 0.4 g/ml and 0.5 g/ml.
  • An object of the present invention is, therefore, a product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, as indicated above, for use in the prevention and/or treatment of anaemia, preferably sideropenic anaemia, in humans.
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, as indicated above is administered orally, preferably formulated in a solid, semi-solid or liquid form, said solid form being selected from tablet, granulate, microgranulate or capsule, and said semi-solid or liquid form selected from suspension (aqueous or oily) or solution.
  • Objects of the present invention are, therefore, the oral pharmaceutical forms comprising the product obtainable by spray-drying an aqueous solution comprising the iron bis-glycinate chelate and the alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, as indicated above, optionally together with physiologically acceptable excipients.
  • physiologically acceptable excipient means a substance devoid of any pharmacological effect of its own, and that does not produce adverse reactions when administered to a mammal, preferably a human being.
  • the tablet, granulate and microgranulate may be in coated, non-coated and/or effervescent and/or buccal and/or chewable form, preferably in the form of an effervescent tablet, buccal tablet, or chewable tablet.
  • effervescent means a form that is able to develop carbon dioxide when in contact with water and/or with the buccal environment, in the presence of saliva.
  • bi-carboxylic acids In order to obtain the effervescent form of the invention, bi-carboxylic acids, tri-carboxylic acids, or a mixture thereof are preferably used.
  • the effervescent compositions according to the invention are formulated with sodium citrate dihydrate and monohydrate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, citric acid, tartaric acid, adipic acid, monosodium phosphate, alginic acid, magnesium hydroxycarbonate, or a mixture thereof.
  • the capsules comprising the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, as indicated above, may be coated.
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate according to the invention in a ratio of 1:1 is contained in an amount ranging from about 10 mg to about 400 mg of iron bis-glycinate chelate and alginic acid polymer (tolerance of about 0.5% by weight) (corresponding to from about 1 mg to about 40 mg of iron ion), preferably from about 20 mg to about 350 mg (i.e. corresponding to from about 2 mg to about 35 mg of iron ion), more preferably from about 100 mg to about 300 mg (corresponding to from about 10 mg to about 30 mg of iron ion).
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate according to the invention in a ratio of 1:2 is contained in an amount ranging from about 20 mg to about 800 mg of iron bis-glycinate chelate and alginic acid polymer (tolerance of about 0.5% by weight) (corresponding to from about 1 mg to about 40 mg of iron ion), preferably from about 40 mg to about 750 mg (i.e. corresponding to from about 2 mg to about 35 mg of iron ion), more preferably from about 200 mg to about 600 mg (corresponding to from about 10 mg to about 30 mg of iron ion).
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate according to the invention in a ratio of 2:3 is contained in an amount ranging from about 15 mg to about 600 mg of iron bis-glycinate chelate and alginic acid polymer di (tolerance of about 0.5% by weight) (corresponding to from about 1 mg to about 40 mg of iron ion), preferably from about 30 mg to about 525 mg (i.e. corresponding to from about 2 mg to about 35 mg of iron ion), more preferably from about 150 mg to about 450 mg (corresponding to from about 10 mg to about 30 mg of iron ion).
  • said solid oral form is a tablet, more preferably an effervescent tablet, or a buccal or chewable tablet.
  • said solid oral form is a capsule.
  • Preferred capsules of the invention may comprise bulking agents, such as for example dicalcium phosphate, coating agents, such as for example hydroxypropyl methylcellulose, anti-caking agents, such as for example silicon dioxide, agglomerating agents, such as for example magnesium salts of fatty acids, and colourants, such as for example titanium dioxide.
  • bulking agents such as for example dicalcium phosphate
  • coating agents such as for example hydroxypropyl methylcellulose
  • anti-caking agents such as for example silicon dioxide
  • agglomerating agents such as for example magnesium salts of fatty acids
  • colourants such as for example titanium dioxide.
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate according to the invention is contained in a quantity ranging from 1 to 10 g/100 ml of solution/suspension (corresponding to from 2 to 20 mg of iron ion/ml).
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, according to the invention may also be formulated in association with at least one sweetener and/or flavour.
  • Said at least one sweetener and/or flavour according to the invention may preferably be selected from acesulfame K, sucralose, sorbitol, sucrose, fructose, orange flavour, lemon flavour, mandarin flavour, caramel flavour, or a mixture thereof.
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, according to the invention is preferably formulated in association with a mixture comprising acesulfame K, sucralose, sorbitol and flavour, where the weight ratio between acesulfame K : sucralose : sorbitol : flavour is of about 1:0.30-0.50:0.12-0.24:3.00-3.40 by weight, respectively.
  • said weight ratio is preferably of about 1:0.40:0.18:3.20 by weight.
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, according to the invention may also be formulated in association with additional physiologically acceptable excipients and/or additives, such as for example acidifiers and/or preservatives (ascorbic acid, parabens).
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate of the invention may be administered in association with one or more additional active principles.
  • Additional active principles according to the present invention may preferably be selected from vitamins and/or mineral salts.
  • Said vitamins may preferably be selected from vitamin B9 (folic acid), vitamin B12 and/or vitamin B6.
  • Said mineral salts may preferably be selected from potassium, magnesium, iodine, zinc salts.
  • the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate, according to the present invention may be administered as the sole therapy, or following a conventional therapy, both oral and parenteral (for example, iron sulphate).
  • Objects of the present invention are also the oral pharmaceutical forms comprising the product obtainable by spray-drying an aqueous solution comprising iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, preferably sodium alginate, potassium alginate and/or magnesium alginate as indicated above, for use in the prevention and/or treatment of anaemia, preferably sideropenic anaemia, in humans.
  • FIG. 1 Photograph of the powder obtained in Example 1, showing the product obtained by spray-drying iron bis-glycinate chelate and alginic acid (Protanal® LFR) in a ratio of 1:1. The photograph was taken with a stereomicroscope Wild Heerbrugg Makroskop M420 connected to an OPTIKAM MICROSCOPY DIGITAL USB CAMERA.
  • FIG. 2 Photograph of the powder obtained in Example 1, showing the product obtained by spray-drying iron bis-glycinate chelate and alginic acid (Protanal® LFR) in a ratio of 1:1. The photograph was taken with an optical microscope LEITZ DIAPLAN with a NIKON DIGITAL SIGHT DS-U1 camera.
  • the weight ratio between the iron bis-glycinate chelate and the alginic acid was 1:1.
  • the solution was placed in a mixer until dissolution was complete, then it was spray-dried by means of a spray-drying apparatus from BUchi company, using the following parameters:
  • the analysis carried out on the dried powder confirmed the total recovery of the iron in the product (97.21%) with a residual moisture value of 2.80%, while the density of the powder was found to be 0.5 g/ml and the particle size thereof was found to be less than 20 ⁇ .
  • FIGS. 1 and 2 images of the powder obtained by the method described above are shown, obtained, respectively, with a stereomicroscope and an optical microscope, connected to a digital camera, from which it is possible to infer the formation of a product by spray-drying of iron bis-glycinate chelate and alginic acid.
  • Example 2 A product based on iron bis-glycinate chelate sodium alginate with the same starting materials and the same equipment of Example 1 was obtained, wherein the only differences consisted in the weight ratio between the iron bis-glycinate chelate and the alginic acid, which in the present Example is 1:2, and in the amount of ascorbic acid, which was added herein in a percentage of 0.285% with respect to the total weight of the iron bis-glycinate chelate and the sodium alginate.
  • the analysis carried out on the dry powder confirmed the total recovery of the iron in the product (100.04%) with a residual moisture value of 2.87%, while the density of the powder was found to be 0.5 g/m, and the particle size thereof was found to be less than 20 ⁇ .
  • Example 2 A product based on iron bis-glycinate chelate sodium alginate with the same starting materials and the same equipment of Example 1 was obtained, wherein the only differences consisted in the weight ratio between the iron bis-glycinate chelate and the alginic acid, which in the present Example is 2:3, and the amount of ascorbic acid, which was added herein in a percentage of 0.256% with respect to the total weight of the iron bis-glycinate chelate and the sodium alginate.
  • the analysis carried out on the dry powder confirmed the total recovery of the iron in the product (97.00%) with a residual moisture value of 2.63%, while the density of the powder was found to be 0.4 g/ml, and the particle size thereof was found to be less than 20 ⁇ .
  • the iron bis-glycinate chelate sodium alginate obtained according to Example 1 (1:1 ratio) was formulated in capsules for oral administration with the following formulation:
  • a capsule formulation for comparison was also prepared, whose formulation is shown in Table 2 below, containing the same excipients of the formulation according to the invention, but containing iron bis-glycinate chelate instead of iron bis-glycinate chelate sodium alginate.
  • the daily dose obtained by administration of capsules containing iron bis-glycinate chelate sodium alginate according to Table 1 and capsules containing iron bis-glycinate chelate according to Table 2 is the same, i.e. 30 mg of iron in total (Fe-ion namely Fe++, determined by an atomic absorption spectrophotometer).
  • the two groups were fully superimposable for haemoglobin values.
  • each subject of each group was sampled in order to assess the serum levels of iron-ion.

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IT102015000035481 2015-07-17
ITUB2015A002290A ITUB20152290A1 (it) 2015-07-17 2015-07-17 Prodotto a base di ferro bisglicinato chelato e acido alginico e/o suoi sali idrosolubili, sue formulazioni ed suoi usi farmaceutici
PCT/IB2016/054199 WO2017013542A1 (en) 2015-07-17 2016-07-14 Product based on iron bis-glycinate chelate and alginic acid and/or water-soluble salts thereof, formulations thereof, and pharmaceutical uses thereof

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3886565A4 (en) * 2018-11-30 2022-11-09 Balchem Corporation COMPOSITIONS OF METAL COMPLEXES OR METAL CHELATES COMPRISING MINIMAL NANOPARTICLES

Families Citing this family (2)

* Cited by examiner, † Cited by third party
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IT201800002625A1 (it) * 2018-02-13 2019-08-13 Drugs Minerals And Generics Italia S R L In Forma Abbreviata D M G Italia S R L Composizione in forma solida per uso nel trattamento dei sintomi extra-esofagei del reflusso gastrico
IT202100018989A1 (it) 2021-07-19 2023-01-19 Laboratori Baldacci Spa Prodotto a base di ferro bis-glicinato chelato e acido alginico e/o suoi sali nel trattamento dello scompenso cardiaco

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2754924A (en) * 1953-06-15 1956-07-17 Gemmer Mfg Co Manual and hydraulic power actuated steering gear
US6455052B1 (en) * 1996-06-06 2002-09-24 Bifodan A/S Enteric coating, comprising alginic acid, for an oral preparation
EP2799074A1 (en) * 2009-12-16 2014-11-05 Laboratori Baldacci S.P.A. Iron bis-glycinate chelate for use in the oral treatment of anemia in patients with celiac disease

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030190355A1 (en) * 2002-04-05 2003-10-09 Hermelin Marc S. Modified release minerals
CN1280260C (zh) * 2004-11-02 2006-10-18 江南大学 一种食品营养强化剂甘氨酸亚铁螯合物的制备方法
CN100344326C (zh) * 2005-09-30 2007-10-24 北京康比特威创体育新技术发展有限公司 一种补铁制剂
CN100558257C (zh) * 2006-11-04 2009-11-11 江南大学 一种水溶性甘氨酸螯合铁的喷雾干燥方法
JP5416716B2 (ja) 2007-12-28 2014-02-12 アジェンデ・キミケ・リウニテ・アンジェリニ・フランチェスコ・ア・チ・エレ・ア・エフェ・ソシエタ・ペル・アチオニ グリコーゲンおよびアルギン酸塩の会合体に基づく徐放性製剤
CN101322778B (zh) * 2008-07-22 2011-04-06 北京康比特体育科技股份有限公司 一种补铁双层缓释片及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2754924A (en) * 1953-06-15 1956-07-17 Gemmer Mfg Co Manual and hydraulic power actuated steering gear
US6455052B1 (en) * 1996-06-06 2002-09-24 Bifodan A/S Enteric coating, comprising alginic acid, for an oral preparation
EP2799074A1 (en) * 2009-12-16 2014-11-05 Laboratori Baldacci S.P.A. Iron bis-glycinate chelate for use in the oral treatment of anemia in patients with celiac disease

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3886565A4 (en) * 2018-11-30 2022-11-09 Balchem Corporation COMPOSITIONS OF METAL COMPLEXES OR METAL CHELATES COMPRISING MINIMAL NANOPARTICLES

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CA2988524A1 (en) 2017-01-26
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CN107787228A (zh) 2018-03-09
ES2788138T3 (es) 2020-10-20
PT3236949T (pt) 2020-05-07
EP3236949A1 (en) 2017-11-01
RU2018101220A (ru) 2019-08-19
RU2018101220A3 (ru) 2019-10-22
US11213505B2 (en) 2022-01-04
HUE049790T2 (hu) 2020-10-28
LT3236949T (lt) 2020-06-10
US20200206181A1 (en) 2020-07-02
EP3236949B1 (en) 2020-02-19
RU2725743C2 (ru) 2020-07-03
WO2017013542A1 (en) 2017-01-26
ITUB20152290A1 (it) 2017-01-17

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