WO2015033216A1 - Solid compositions based on minerals and orally disintegrating formulations containing the same. - Google Patents

Solid compositions based on minerals and orally disintegrating formulations containing the same. Download PDF

Info

Publication number
WO2015033216A1
WO2015033216A1 PCT/IB2014/001780 IB2014001780W WO2015033216A1 WO 2015033216 A1 WO2015033216 A1 WO 2015033216A1 IB 2014001780 W IB2014001780 W IB 2014001780W WO 2015033216 A1 WO2015033216 A1 WO 2015033216A1
Authority
WO
WIPO (PCT)
Prior art keywords
lecithin
weight
composition
comprised
solid
Prior art date
Application number
PCT/IB2014/001780
Other languages
French (fr)
Inventor
Andrea Lacorte
Germano Tarantino
Gianni LAZZARINI
Original Assignee
Alesco S.R.L.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alesco S.R.L. filed Critical Alesco S.R.L.
Priority to CA2925188A priority Critical patent/CA2925188C/en
Priority to US15/024,709 priority patent/US11813290B2/en
Priority to EP14792856.8A priority patent/EP3043872B1/en
Priority to RS20240841A priority patent/RS65812B1/en
Publication of WO2015033216A1 publication Critical patent/WO2015033216A1/en

Links

Classifications

    • 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
    • A61K33/42—Phosphorus; Compounds thereof
    • 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
    • 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
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • 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
    • A61K33/18—Iodine; Compounds thereof
    • 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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to solid compositions, preferably in powder or granule form, based on minerals (semifinished or raw material) and a process for preparing said solid compositions. Furthermore, the present invention relates to solid formulations (final products) and orally disintegrating formulations (final products) containing said solid compositions. Moreover, the present invention relates to a process for preparing said solid formulations and said orally disintegrating formulations. Finally, the present invention relates to the use of said solid compositions or said solid or orally disintegrating formulations in the treatment of disorders or diseases related to or derived from a deficiency of minerals such as magnesium (II), calcium (II), iron (III), zinc (II) and/or iodine. All the compositions or formulations of the present invention are suitable for pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly.
  • Solid compositions based on minerals such as for example magnesium, calcium and iron are known to be commercially available, which are used for preparing solid formulations (final products) for human use.
  • solid compositions and formulations containing said solid composition based on minerals, suitable for oral route have limits and contraindications which, at times, restrict the use thereof.
  • a first limit is that solid, orally disintegrating formulations based on minerals such as for example magnesium, calcium, iron, zinc, iodine and mixtures thereof are commercially unavailable.
  • a second limit is that oral solid formulations presently marketed often contain the mineral, for example iron or magnesium or zinc, in a chemical form resulting hardly or poorly absorbable by the body and, thus, not bioavailable for the body.
  • compositions based on minerals have to be administered between meals. I n this event the oral administration between meals of said minerals could lead to further drawbacks.
  • a third drawback is that the solid compositions or formulations containing said solid compositions are poor processable from an industrial point of view, since they suffer from external conditions and, at times, tend to pack and not flow causing problems of mineral titer reproducibility and can lead to granulometric changes, the manufacturing of the formulations as final products is thereby jeopardized.
  • formulations based on minerals in which the mineral, as mineral salt, is highly bioavailable are devoid of any limits or drawbacks from the organoleptic point of view (taste, smell, color, long-term stability).
  • solid or orally disintegrating formulations (final products) devoid of limits and drawbacks related to, for example, their hygroscopicity, particle agglomeration, color changing and their solubility.
  • the aim of the present invention is to provide solid compositions (semi-finished or raw material) based on minerals such as for example magnesium, calcium, iron, zinc, iodine and mixtures thereof in which said minerals, in the form of mineral salts, are made efficiently absorbable and bioavailable and are well-tolerated by the body in order to be administered, upon formulation in solid form and orally disintegrating form as final products, to pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly, even under fasting conditions.
  • Said solid and orally disintegrating formulations, containing said solid compositions based on minerals have a good palatability and are stable over the time from the chemical-physical and organoleptic point of views since they do not give rise to color, smell, flavor, taste and solubility changes.
  • compositions solid compositions (semi-finished or raw materials) based on minerals such as magnesium (II), calcium (II), iron (I II), zinc (I I), iodine and mixtures thereof, having the characteristics as disclosed in the appended claims.
  • All the formulations of the present invention are suitable for pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly.
  • the solid composition (semi-finished or raw material) based on minerals of the present invention is a composition which could exist in the form of granules or powder or aggregates having varying sizes and granulometry depending on the pharmaceutical form of the intended final formulation.
  • compositions of the present invention at solid state in the form of granules or powders or aggregates, have a bulk density (measured by equipment and methods known to the skilled in the field) comprised from 0.2 to 0.9 g/ml, preferably from 0.4 to 0.8 g/ml.
  • the solid compositions based on minerals of the present invention comprise minerals selected from the group comprising or, alternatively, consisting of magnesium, calcium, iron, zinc and iodine or mixtures thereof.
  • Minerals (or metal cations) are in the form of mineral salts.
  • the mineral or cation magnesium (II) is in said compositions as mineral salt magnesium oxide or, alternatively, as mineral salt magnesium hydroxide;
  • the mineral or cation calcium Ca (II) is in said compositions as mineral salt tricalcium phosphate E341 ;
  • the mineral or cation iron (II I) is in said compositions as mineral salt iron pyrophosphate;
  • the mineral or cation zinc (II) is in said compositions as mineral salt zinc oxide;
  • the mineral iodine is in said compositions as mineral salt sodium iodate; or alternatively said compositions may contain a mixture (two or three or four or five minerals) of said minerals.
  • the solid compositions (semi-finished or raw material) based on minerals of the present invention further comprise, besides one o more of the above-cited minerals in the form of mineral salt, acutester and a lecithin and also, preferably, a pregelatinized starch to obtain solid compositions as granules or powders or agglomerates (semi-finished or raw material).
  • compositions of the present invention can be in liquid form.
  • the liquid compositions (semi-finished or raw material) based on minerals such as magnesium, calcium, iron, zinc, iodine or mixtures thereof of the present invention further comprise, besides one or more of the above-cited minerals in the form of mineral salt, ahester and a lecithin and also, preferably, a guar gum and water to form liquid compositions (semi-finished or raw material).
  • solid compositions as granules or powder or agglomerates are then formulated with pharmacologically acceptable additives and excipients to obtain solid formulations (final products) such as for example a supplement product, a medical device or a pharmaceutical composition in the form of granules or powder or agglomerates, having a pharmaceutical form such as, for example packet, tablet, pastille or capsule.
  • compositions as granules or powder or agglomerates are formulated with pharmacologically acceptable additives and excipients to obtain orally disintegrating formulations (final products) such as for example a supplement product, a medical device or a pharmaceutical composition in the form of an orally disintegrating powder, said formulations having a pharmaceutical form of packet or stick.
  • the solid compositions as granules or powder or agglomerates are then formulated with sorbitol in an amount comprised from 40 to 90% by weight, preferably from 50 to 80% by weight, with maltodextrins in an amount comprised from 5 to 25% by weight, preferably from 9 to 20% by weight and citric acid in an amount comprised from 0.1 to 1 % by weight and other pharmacologically acceptable additives and excipients for obtaining a final product (a supplement product, a medical device or a pharmaceutical composition) in the form of orally disintegrating granules or powder or agglomerates, preferably as orally disintegrating granules, having a pharmaceutical form such as, for example a packet or stick.
  • sorbitol in an amount comprised from 40 to 90% by weight, preferably from 50 to 80% by weight
  • maltodextrins in an amount comprised from 5 to 25% by weight, preferably from 9 to 20% by weight
  • citric acid in an amount comprised from 0.1
  • the tablets being obtained can have various shapes among those known in the pharmaceutical form field, such as for example a cylindrical or spheroidal shape.
  • Tablets may have a weight comprised from 200 to 2000 mg.
  • a gel capsule may have a weight of 500 mg
  • a hard tablet may have a weight comprised from 800 to 1000 mg
  • a chewable tablet may have a weight comprised from 1000 to 2000 mg.
  • Capsules may consist of hard gelatin or soft gelatin or soft gel. Tablets can be coated or filmed with one or more coating layers or films capable to pass through the gastric barrier. The coating is prepared by using a beeswax solution or a sugar-based solution.
  • the solid compositions (semi-finished or raw material) of the present invention comprise at least a mineral selected from the group comprising or, alternatively, consisting of magnesium, calcium, iron, zinc and iodine or mixtures thereof in an amount comprised from 30 to 70%, preferably from 40 to 60%, even more preferably from 50 to 55% by weight.
  • the iron pyrophosphate being used ⁇ [Fe ⁇ CvJSxhbO], CAS 10058-44-3, dry molecular weight 745.22 ⁇ is preferably in micronized form and has an iron content comprised from 18 to 24%, preferably from 20 to 22% by weight.
  • the solid compositions (semi-finished or raw material) of the present invention further comprise, combined with at least a mineral, a lecithin.
  • Lecithin is a food additive -E322 (Directive 95/2/EC of 20.2.95 published on O.J. L61 of 18.3.95). Lecithin, due to its chemical-physical properties, primarily plays an emulsifying function and, being also rich in natural antioxidant substances, has a secondary antioxidant function as well. Directive 2008/84/EC of 27 August 2008 (published on European Community O.J. No.
  • L253 establishes the purity criteria that lecithin has to meet in order to be considered of food grade quality (E322): Acetone-insoluble (essentially the lecithin active part): 60% min.; Humidity: 2% max.; Acid number: 35 max.; Peroxide value: 10 max.; Toluene-insoluble (essentially impurities): 0.3% max.
  • lecithin is a mixture of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides and phospholipids.
  • Phospholipids represent the main components thereof; they are derived from the triglyceride structure, wherein a fatty acid is replaced by a phosphate group, which confers a negative charge, and thus, polarity to the molecule; said molecule has the generic name of phosphatide.
  • a more complex organic molecule usually serine, choline, ethanolamine, inositol or a single hydrogen atom is bound through an ester bond to the phosphate group, giving rise to a phospholipid named phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol or phosphatidic acid, respectively.
  • phosphatidylcholine In a more strict sense of lecithin, phosphatidylcholine is often designated. Phospholipids are characterized by a polar, water-soluble head, well- dissolving in water, whereas the two saturated fatty acids represent the two non polar, not water-soluble but lipophilic tails. Such a kind of molecules is called amphipathic and in the presence of water and fat they arrange themselves between the fatty and water molecules emulsifying them. Lecithin is a natural emulsifier.
  • All the solid compositions of the present invention are for oral use and do not contain neither a hydrolyzed lecithin nor an enzymatically hydrolyzed lecithin.
  • the lecithin being used is a powdery non-hydrolyzed lecithin and can be selected from sunflower or maize or soya lecithin.
  • the lecithin being used is a powdery lecithin having a water content comprised from 1.5 to 4.5%, preferably from 2 to 4%, even more preferably from 2.5 to 3.5%.
  • the lecithin being used is a powdery sunflower lecithin.
  • the sunflower lecithin has a glucose amount comprised from 20 to 60%, preferably from 30 to 50%, for example about 45% by weight, such as in the product Lecico Sun CG 450 from Lecico GmbH Company- Germany.
  • a sunflower lecithin usable in the context of the present invention may have the following composition by weight (chemical-physical analysis): sunflower lecithin from 40 to 50%, carbohydrates from 40 to 50% (for example about 42%), proteins from 6 to 10%, ashes from 3 to 8%, humidity from 2 to 5% and a glidant others from 0.5 to 1 .5%.
  • lecithin is in an amount comprised from 0.1 to 1 .5%, preferably from 0.4 to 1 .0%, even more preferably from 0.50 to 0.8% by weight.
  • the solid composition of the present invention comprises or, alternatively, consists of a magnesium (I I) salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight.
  • the mineral or cation magnesium (II) is magnesium oxide or, alternatively, magnesium hydroxide and lecithin is from sunflower and/or maize.
  • the solid composition of the present invention comprises or, alternatively, consists of a calcium (II) salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight.
  • the mineral or cation calcium (II) is tricalcium phosphate E341 and lecithin is from sunflower and/or maize.
  • the solid composition of the present invention comprises or, alternatively, consists of an iron (III) salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight.
  • the mineral or cation iron (II I) is iron pyrophosphate and lecithin is from sunflower and/or maize.
  • the solid composition of the present invention comprises or, alternatively, consists of a zinc (II) salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight.
  • the mineral or cation zinc (II) is zinc oxide and lecithin is from sunflower and/or maize.
  • the solid composition of the present invention comprises or, alternatively, consists of an iodine salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight.
  • the mineral iodine is sodium iodate and lecithin is from sunflower and/or maize.
  • compositions of the present invention further comprise, combined with a lecithin disclosed above, a sucrose ester oriser.
  • Sucresters are obtained by fatty acid esterification or transesterification of fatty acid methyl esters with carbohydrates, generally sucrose and other polysaccharides, for this reason they are also referred to as fatty acid sucrose esters.
  • the chemical-physical properties of these compounds depend on the number and kind of esterified fatty acids.
  • the abbreviation E473 means that Atsters are food additives permitted by the European Union legislation and regulated by ministerial decree (M. D. 1996). They are essentially emulsifiers and added in order to obtain a better stabilization between an aqueous phase and a fatty phase.
  • Sucrose esters are are withsters (E473) and used in the composition of the present invention at a HLB value of about 14-18, advantageously a HLB value of about 15 or 16, and used as emulsifiers.
  • Atauric and palmitic contains 70% of monoesters, being obtained by sucrose esterification with vegetable fatty acids (stearic and palmitic).
  • Aerster usable in the context of the present invention may have the following composition by weight: total ester content at least 90%; free fatty acids (such as oleic acid) content not greater than 3%; free sucrose content not greater than 2%; humidity not greater than 4%; acid value not greater than 5.
  • free fatty acids such as oleic acid
  • free sucrose content not greater than 2%
  • humidity not greater than 4%
  • acid value not greater than 5.
  • Sucrose esters orisers are in the solid composition in an amount comprised from 10 to 20%, preferably from
  • the solid compositions of the present invention do not contain a diglycerol fatty acid ester.
  • compositions of the present invention comprise or, alternatively, consist of at least a mineral, a lecithin
  • sucrose esters orisers E473 in an amount by weight as specified above.
  • the solid composition of the present invention comprises or, alternatively, consists of a magnesium (II) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers in the above-cited amounts by weight.
  • the mineral or cation magnesium (II) is magnesium oxide or, alternatively, magnesium hydroxide, lecithin is from sunflower and/or maize and the excessivester is E473.
  • the solid composition of the present invention comprises or, alternatively, consists of a calcium (II) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers in the above-cited amounts by weight.
  • the mineral or cation calcium (II) is tricalcium phosphate E341
  • lecithin is from sunflower and/or maize and the
  • the excessivester is E473.
  • the solid composition of the present invention comprises or, alternatively, consists of an iron (III) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers E473 in the above-cited amounts by weight.
  • the mineral or cation iron (II I) is iron pyrophosphate
  • lecithin is from sunflower and/or maize
  • the excessivester is E473.
  • the solid composition of the present invention comprises or, alternatively, consists of a zinc (I I) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers E473 in the above-cited amounts by weight.
  • the mineral or cation zinc (II) is zinc oxide
  • lecithin is from sunflower and/or maize
  • theentar is E473.
  • the solid composition of the present invention comprises or, alternatively, consists of an iodine salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers E473 in the above-cited amounts by weight.
  • the mineral iodine is sodium iodate
  • lecithin is from sunflower and/or maize andiser is E473.
  • the solid compositions of the present invention can further comprise, combined with a lecithin and a sucrose ester oriser, a vegetable starch.
  • the vegetable starch is selected from rice (Oryza sativa) starches or maize starches.
  • the starch is rice starch.
  • the rice starch is a gelatinized or pregelatinized native rice starch.
  • a pregelatinized rice starch usable in the context of the present invention may have the following chemical-physical characteristics: humidity not greater than 7%; protein content not greater than 1 %; ash content not greater than 1 %; pH (10% solution) comprised from 5.5 to 7.5, density 0.40-0.48 g/cm 3 ; minimum starch content 97% and fats not greater than 0.1 %.
  • An example of starch is given by the pregelatinized rice starch AX-FG-P from Reire Sri Company -Italy.
  • the gelatinized or pregelatinized vegetable starch is in the solid compositions in an amount comprised from 15 to 40%, preferably from 20 to 35, even more preferably from 25 to 30 by weight.
  • the solid compositions of the present invention comprise or, alternatively, consist of at least a mineral, as mineral salt, a lecithin E322 (neither non-hydrolyzed nor enzymatically hydrolyzed), sucrose esters orisers E473 and a vegetable starch, in the above-cited amounts by weight.
  • said vegetable starch is a rice (Oryza sativa) starch or a pregelatinized rice (Oryza sativa) starch.
  • the solid composition of the present invention comprises or, alternatively, consists of a magnesium (II) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed), sucrose esters orisers in the above-cited amounts by weight.
  • the mineral or cation magnesium (II) is magnesium oxide or, alternatively, magnesium hydroxide, lecithin is from sunflower and/or maize, the
  • theiser is E473 and the starch is a pregelatinized vegetable starch.
  • the solid composition of the present invention comprises or, alternatively, consists of a calcium (II) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers in the above-cited amounts by weight.
  • the mineral or cation calcium (II) is tricalcium phosphate E341
  • lecithin is from sunflower and/or maize
  • tercithin is from sunflower and/or maize
  • the starch is a pregelatinized vegetable starch.
  • the solid composition of the present invention comprises or, alternatively, consists of an iron (III) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers E473 in the above-cited amounts by weight.
  • the mineral or cation iron (II I) is iron pyrophosphate
  • lecithin is from sunflower and/or maize
  • the starch is a pregelatinized vegetable starch.
  • the solid composition of the present invention comprises or, alternatively, consists of a zinc (I I) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers E473 in the above-cited amounts by weight.
  • the mineral or cation zinc (II) is zinc oxide
  • lecithin is from sunflower and/or maize
  • the starch is a pregelatinized vegetable starch.
  • the solid composition of the present invention comprises or, alternatively, consists of an iodine salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters orisers E473 in the above-cited amounts by weight.
  • the mineral iodine is sodium iodate
  • lecithin is from sunflower and/or maize
  • theentar is E473
  • the starch is a pregelatinized vegetable starch.
  • Said first method of the present invention is for preparing a solid composition
  • a solid composition comprising or, alternatively, consisting of a mineral, in the form of mineral salt, a lecithin, a sucrose ester oriser and, preferably, a vegetable starch, according to the above-cited embodiments.
  • Said first method does not contemplate the addition of solvents or water since it is a method in which all the individual components existing in the solid composition are mixed at solid state as powders or granules and in no case in aqueous solution or in the presence of solvents.
  • Said first method of the present invention comprises or, alternatively, consists of a series of processing steps through which the mineral salt selected from the group comprising magnesium (I I) salts, preferably magnesium oxide or magnesium hydroxide; or calcium (II) salts, preferably tricalcium phosphate; or iron (III) salts, preferably iron pyrophosphate; or zinc salt, preferably zinc oxide; or iodine salts, preferably sodium iodate; or mixtures thereof is coated or enveloped or encapsulated with said lecithin and/or said sucrose ester orollister, depending on the adopted addition order, and with said vegetable starch, if any.
  • the mineral salt at solid state is firstly contacted with said lecithin and then, secondly, with said sucrose ester orollister and/or said vegetable starch.
  • the mineral salt at solid state as powder or granules has a water content of less than 5%, preferably of less than 3% by weight.
  • the mineral salt containing the mineral magnesium (I I) or calcium (II) or iron (III) or zinc (II) or iodine is used in an amount comprised from 50 to 90%, preferably from 60 to 80%, even more preferably from 70 to 75% by weight.
  • the lecithin being used has the characteristics as described above.
  • the contact time between mineral salt and lecithin is comprised from 1 to 60 minutes, preferably from 10 to 50, even more preferably from 20 to 40 minutes.
  • the lecithin being used can be selected from a sunflower or maize or soya lecithin.
  • the lecithin being used is a powdery lecithin having a water content comprised from 1 .5 to 4.5%, preferably from 2 to 4%, even more preferably from 2.5 to 3.5%.
  • the lecithin used in said first method is a powdery, sunflower lecithin E322.
  • Lecithin is in the solid compositions of the present invention in an amount comprised from 0.1 to 1 %, preferably from 0.4 to 0.8%, even more preferably from 0.50 to 0.6% by weight.
  • Lecithin when contacted with said mineral salt, arranges itself uniformly over said salt and, thus, over the mineral magnesium (I I) or calcium (II) or iron (II I) or zinc (II) or iodine as well.
  • the gelatinized or pregelatinized vegetable starch is selected from a rice starch or maize starch.
  • the starch is rice starch.
  • the rice starch is a gelatinized or pregelatinized native rice starch.
  • the vegetable starch has the characteristics as described above.
  • the starch is in the solid compositions of the present invention in an amount comprised from 15 to 40%, preferably from 20 to 35%, even more preferably from 25 to 30% by weight.
  • the starch in the form of gelatinized or pregelatinized starch is advantageously more fluid and flowable and can be carefully dosed without causing errors or weight variations. Furthermore, it arranges itself in a more even and homogeneous manner. Finally, the pregelatinized starch enhances the bioavailability of the mineral salt and thus, of the mineral (cation contained within said mineral salt) as the obtained compound is better dissolved at temperatures comprised from 15 to 30°C (pressure 1 atmosphere), preferably from 20 to 25°C, even more preferably from 18 to 23°C.
  • the solid compositions as powder or granules or agglomerates of the present invention are obtained, which comprise or, alternatively, consist of mineral salts, a sucrose ester oriser, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and, preferably, a pregelatinized vegetable starch, in the above-cited amounts by weight.
  • the solid compositions of the present invention are obtained, which comprise or, alternatively, consist of a mineral salt, a sunflower lecithin E322 (neither non-hydrolyzed nor enzymatically hydrolyzed), a sucrose ester oriser E473 and a pregelatinized rice starch, in the above-cited amounts by weight.
  • the Applicant found that in order to further enhance the bioavailability of the mineral salt and thus, of the mineral (cation contained within said mineral salt), the amount by weight of lecithin to be used in the process for preparing the solid compositions of the present invention has to be reduced as much as possible.
  • the non-hydrolyzed lecithin is in an amount of less than 1 % by weight, relative to the weight of the solid composition; in an embodiment the non-hydrolyzed lecithin is in an amount of less than 0.8% by weight, preferably of less than 0.6% by weight.
  • the Applicant found that in order to further enhance the bioavailability of the mineral salt and, thus, of the mineral (cation contained within said mineral salt), it is important to use a specific amount by weight of sucrose esters or at least one of sucrose esters or at least one of sucrose esters or at least one of sucrose esters or at least one of sucrose esters or at least one of sucrose esters or at least one of sucrose esters or at least one of sucrose esters orasters in association with a reduced amount by weight of lecithin.
  • sucrose ester or auxiliaryster to lecithin ratio is comprised from 30: 1 to 25: 1.
  • said ratio is comprised from 20: 1 to 15: 1 .
  • Said second method of the present invention is for preparing the solid compositions comprising or, alternatively, consisting of a mineral salt, sucrose esters orisers, a lecithin and a gelatinized or pregelatinized starch.
  • Said second method does not contemplate the addition of solvents or water since it is a method in which all the individual components existing in the solid composition are mixed at solid state as powders or granules and in no case in aqueous solution or in the presence of solvents.
  • Said second method of the present invention comprises or, alternatively, consists of a technology developed in order to create a coating or encapsulation around the mineral salt so that to improve the stability and bioavailability of the mineral salt and, thus, of the mineral (cation) therein contained as well.
  • said second method contemplates the formation of agglomerates or granules comprising the mineral salt, sucrose esters orisers, lecithin and a gelatinized or pregelatinized starch. All of these components have the characteristics as specified above.
  • sucrose esters or Atcithin act by enhancing the absorption of the mineral salt and, accordingly, of the mineral (cation contained within said mineral salt).
  • the admixture with lecithin and starch gives rise to the formation of "chimeric" agglomerates capable to protect and shield the cation contained within said mineral salt from the gastric acid.
  • the mineral salt containing the mineral (cation) is used in an amount comprised from 30 to 70%, preferably from 40 to 60%, even more preferably from 50 to 55% by weight.
  • the mineral salt being used has the characteristics as described above.
  • the processing time is comprised from 1 to 60 minutes, preferably from 10 to 50, even more preferably from 20 to 40 minutes.
  • sucrose esters oresters are in an amount comprised from 10 to 30%, preferably from 15 to 25%, even more preferably from 16 to 20% by weight.
  • the lecithin being used is a maize or sunflower or soya lecithin.
  • the lecithin being used is a powdery lecithin having a water content comprised from 1 .5 to 4.5%, preferably from 2 to 4%, even more preferably from 2.5 to 3.5%.
  • the lecithin being used is a powdery sunflower lecithin.
  • the lecithin being used has the characteristics as specified above.
  • the lecithin being used is neither a hydrolyzed lecithin nor an enzymatically hydrolyzed lecithin.
  • Lecithin is in an amount comprised from 0.1 to 1 %, preferably from 0.4 to 0.8% even more preferably from 0.5 to 0.6% by weight.
  • Lecithin arranges itself over the outer surface of granules or powders of the mineral salts when directly added to said mineral salts, or arranges itself over the outer surface of granules or powders comprising the mineral salt andender, when added subsequently tohenster.
  • a gelatinized or pregelatinized vegetable starch selected from a rice starch or maize starch is used.
  • the starch is a rice starch.
  • the rice starch is a gelatinized or pregelatinized native rice starch.
  • the starch (Oryza sativa) being used has the characteristics as specified above.
  • the starch is in the solid compositions of the present invention in an amount comprised from 15 to 40%, preferably from 20 to 35%, even more preferably from 25 to 30% by weight.
  • the gelatinized or pregelatinized starch is prepared according to the equipment and techniques known to the person skilled in the field.
  • the gelatinization process of rice flour aims to modify its technological properties bringing about a molecular rearrangement of the starchy component: said changes allow to providing a greater plasticity and viscosity to the mixtures and improving several characteristics of the products in which they are used.
  • the properties obtained by gelatinization and subsequent structural change of native starches contained in rice allow the process to confer a faster hydration and a higher viscosity to flours.
  • the gelatinized starch strongly binds the water to the starchy matrix itself, thereby becoming less available. Accordingly, a longer storage time and a lower effect of chemical and enzymatic degradation phenomena are obtained.
  • Pregelatinization is a physical technique (thus it does not contemplate the addition of other components) that modifies the starch properties and is based on cooking and subsequently drying an aqueous native starch suspension (namely "rough" flour).
  • the pregelatinized starches display the pivotal functional property of adsorbing a high water amount, thus they are used as thickeners and gelling agents in several food formulations, especially when (and this is the case of rice or maize flours) the gluten protein fraction is absent.
  • the cooking-extrusion namely a short treatment at high temperatures and pressures
  • drying carried out on cylinders represent the most common method for obtaining pregelatinization.
  • Pregelatinized starch-based products show, among others, good storage characteristics.
  • lecithin is used in an amount comprised from 0.48 to 0.62% by weight, while sucrose esters orisers are used in an amount comprised from 16.5 to 18.5% by weight, relative to the weight of the final solid composition of the present invention.
  • the solid compositions (semi-finished or raw material) of the present invention are obtained, which comprise or, alternatively, consist of at least a mineral, in the form of mineral salt, sucrose esters orisers, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and a pregelatinized vegetable starch, in the amounts by weight disclosed above.
  • the solid compositions (semi-finished or raw material) of the present invention are obtained, which comprise or, alternatively, consist of magnesium (II), preferably magnesium oxide or magnesium hydroxide; or calcium (II), preferably tricalcium phosphate; or iron (III), preferably iron pyrophosphate; or zinc (I I), preferably zinc oxide; or iodine, preferably sodium iodate mineral salts; or mixtures thereof, sucrose esters or Atsters E473, a sunflower lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and a pregelatinized rice starch, in the amounts by weight disclosed above.
  • magnesium (II) preferably magnesium oxide or magnesium hydroxide
  • calcium (II) preferably tricalcium phosphate
  • iron (III) preferably iron pyrophosphate
  • zinc (I I) preferably zinc oxide
  • iodine preferably sodium iodate mineral salts
  • the solid compositions (semi-finished or raw material) of the present invention have a granulometry (that is understood as average granulometry measured by available equipment and techniques) comprised from 5 to 20 microns, preferably from 8 to 15 microns, even more preferably from 1 1 to 13 microns.
  • the solid compositions (semi-finished or raw material) of the present invention obtained through said first and second methods have a content of:
  • magnesium oxide salt if present as magnesium oxide salt, comprised from 250 to 450 mg/g, preferably from 300 to 400 mg/g of composition,
  • magnesium hydroxide salt if present as magnesium hydroxide salt, comprised from 150 to 300 mg/g, preferably from 200 to 250 mg/g of composition,
  • iron (III) if present as iron pyrophosphate salt, comprised from 60 mg/g to 140 mg/g, preferably from 80 mg/g to 120 mg/g, even more preferably from 90 to 1 10 mg/g,
  • - zinc (II), if present as zinc oxide salt comprised from 350 to 600 mg/g, preferably from 400 to 550 mg/g of composition,
  • - iodine if present as sodium iodate salt, comprised from 5 to 20 mg/g, preferably from 8 to 15 mg/g of composition.
  • the solid compositions as granules or powder or agglomerates (semi-finished or raw materials), obtained by said first and second methods, are formulated with pharmacologically acceptable additives and excipients to obtain the formulations (final products) of the present invention in solid form such as powder or granules or agglomerates or solid, orally disintegrating powders.
  • the solid compositions (semi-finished or raw material) obtained as granules or powder or agglomerates are then formulated, by mixing, with sorbitol in an amount comprised from 40 to 90% by weight, preferably from 50 to 80% by weight, with maltodextrins in an amount comprised from 5 to 25% by weight, preferably from 9 to 20% by weight and citric acid in an amount comprised from 0.1 to 1 % by weight and with other pharmacologically acceptable additives and excipients to obtain a final product (a supplement product, a medical device or a pharmaceutical composition) in the form of orally disintegrating granules or powder or agglomerates, preferably orally disintegrating granules, having a pharmaceutical form such as, for example a packet or stick.
  • sorbitol in an amount comprised from 40 to 90% by weight, preferably from 50 to 80% by weight
  • maltodextrins in an amount comprised from 5 to 25% by weight, preferably from 9 to 20%
  • All the solid formulations (final products) are used in conditions of complete or partial deficiency of minerals such as magnesium (II) or calcium (II) or iron (I II) or zinc (II) or iodine, in particular they are for use in the treatment of disorders or diseases related to or derived from a deficiency of one or more of said minerals. Furthermore, all the formulations (final products) object of the present invention are successfully used in the treatment of (i) a proper cognitive development, for example in adolescents; (ii) an adequate red blood cell and hemoglobin production; (iii) a reduction of tiredness and physical fatigue in an individual.
  • minerals such as magnesium (II) or calcium (II) or iron (I II) or zinc (II) or iodine
  • the solid formulations (final products) containing said solid compositions (semi-finished or raw material) prepared by the method disclosed above (said first and second methods) are such that the mineral salt and, thus, the mineral (magnesium (II) or calcium (II) or iron (III) or zinc (II) or iodine or mixtures thereof) is readily absorbable and bioavailable in an affective manner.
  • the mineral is able to pass the gastric environment and, accordingly, can be directly absorbed at intestinal level thereby avoiding possible discomforts caused at gastric level. Therefore, said formulations shown to be well-tolerated by the body.
  • the solid formulations of the present invention can be administered, even under fasting conditions, to all the subject categories and have a good payability, a high long-term stability from the chemical-physical point of view and optimum organoleptic properties namely, when subjected to stability tests, the mineral salts did not bring about color, smell, flavor and/or taste changes.
  • the liquid compositions (semi-finished or raw material) based on minerals of the present invention further comprise, besides one or more of the above-cited minerals in the form of mineral salt, ahester and a lecithin and, preferably, also a guar gum and water for obtaining liquid compositions (semi-finished or raw material).
  • liquid compositions can be formulated with pharmacologically acceptable additives and excipients to obtain liquid formulations for oral use as suspension or syrup form.
  • liquid formulations (final products) of the present invention are for oral use and suitable as supplement product, medical device or pharmaceutical composition (briefly the liquid compositions of the present invention, for the sake of brevity).
  • the liquid formulations (final products) of the present invention are suitable in conditions of complete or partial deficiency of minerals such as magnesium (II) or calcium (II) or iron (I II) or zinc (II) or iodine, in particular they are for use in the treatment of disorders or diseases related to or derived from a deficiency of one or more of said minerals.
  • the liquid compositions (semi-finished or raw material) of the present invention comprise or, alternatively, consist of water, mineral salts, a lecithin as disclosed above, sucrose esters orisers as disclosed above and a guar gum. All of these components have the characteristics and chemical-physical properties, as specified above.
  • liquid compositions (semi-finished or raw material) of the present invention do not contain neither a hydrolyzed lecithin nor an enzymatically hydrolyzed lecithin.
  • liquid compositions (semi-finished or raw material) of the present invention do not contain a diglycerol fatty acid ester.
  • the liquid compositions (semi-finished or raw material) of the present invention have a viscosity (measured under standard conditions and by known equipment and techniques) comprised from 1 .01 to 1 .15 g/ml, preferably from 1.02 to 1.12 g/ml, even more preferably from 1.03 to 1.10 g/ml.
  • the liquid compositions of the present invention comprise the minerals, as mineral salts, magnesium (I I) or calcium (II) or iron (II I) or zinc (II) or iodine;
  • the mineral magnesium (II) can be magnesium oxide or magnesium hydroxide;
  • the mineral calcium can be tricalcium phosphate E473;
  • the mineral iron (III) can be iron pyrophosphate;
  • the mineral zinc (II) can be zinc oxide and iodine can be sodium iodate.
  • the liquid compositions (semi-finished or raw material) of the present invention contain at least a mineral salt in an amount comprised from 1 to 10%, preferably from 2 to 8%, even more preferably from 4 to 6% by weight, relative to the weight of the liquid composition.
  • liquid compositions (semi-finished or raw material) of the present invention further comprise sucrose esters oresters, having the characteristics as disclosed above.
  • Sucrose esters or Atsters E473 are in said liquid composition of the present invention in an amount comprised from 0.10 to 5%, preferably from 0.5 to 4%, even more preferably from 1 to 3% by weight, relative to the weight of the liquid composition.
  • liquid compositions (semi-finished or raw material) of the present invention further comprise a lecithin, having the characteristics as disclosed above.
  • the lecithin E322 being used can be selected from a sunflower or maize or soya lecithin.
  • the lecithin being used is a sunflower lecithin.
  • the sunflower lecithin contains a glucose amount comprised from 20 to 60%, preferably from 30 to 50%, for example 45% by weight such as in the product Lecico Sun CG 450 from Lecico GmbH Company-Germany.
  • a sunflower lecithin usable in the context of the present invention can have the following composition by weight (chemical-physical analysis): sunflower lecithin from 40 to 50%, carbohydrates from 40 to 50% (for example, carbohydrates 42%), proteins from 6 to 10%, ashes from 3 to 8%, humidity from 2 to 5% and a glidant others from 0.5 to 1 .5%.
  • Lecithin is in said liquid compositions in an amount comprised from 0.1 to 4%, preferably from 0.5 to 3.5%, even more preferably from 1.5 to 2.5% by weight, relative to the weight of the liquid composition.
  • liquid compositions (semi-finished or raw material) of the present invention further comprise a guar gum.
  • the guar gum is in said liquid compositions in an amount comprised from 0.1 to 5%, preferably from 0.2 to 4%, even more preferably from 0.4 to 2% by weight, relative to the weight of the liquid composition.
  • the guar gum is selected from those commercially available and has a viscosity (cPs, 2 hours) comprised from 3000-4500, preferably from 3500 to 4000; starch-free; with a content of acid-insoluble substances comprised from 5 to 9, preferably from 6 to 8, for example 7; with a R.U.A comprised from 2.5 to 4%, preferably from 3 to 3.5% and a granulometry comprised from 100 to 300, preferably from 150 to 250, for example 200.
  • a viscosity cPs, 2 hours
  • a viscosity comprised from 3000-4500, preferably from 3500 to 4000
  • starch-free with a content of acid-insoluble substances comprised from 5 to 9, preferably from 6 to 8, for example 7
  • a R.U.A comprised from 2.5 to 4%, preferably from 3 to 3.5%
  • a granulometry comprised from 100 to 300, preferably from 150 to 250, for example 200.
  • It is an object of the present invention a process for preparing said liquid composition which comprises or, alternatively, consists of a technology capable to yield a time-stable composition or emulsion or suspension depending on the operating conditions being used.
  • the process provides the liquid compositions devoid of deposit (precipitates or agglomerates in suspension) and having an even and sustained concentration over the time.
  • water is in an amount of 90%, or 92%, or 94% by weight. Water is kept under stirring at a temperature comprised from 15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C.
  • sucrose esters oresters, lecithin, guar gum and iron (III) salts are added in the amounts specified below.
  • Sucrose esters oresters are in an amount comprised from 0.10 to 5%, preferably from 0.5 to 4%, even more preferably from 1 to 3% by weight, relative to the weight of the liquid composition.
  • Water and sucrose esters orisers form a clear solution/suspension at a temperature comprised from 15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C.
  • the processing time is comprised from 1 to 60 minutes, preferably from 10 to 50 minutes, even more preferably from 20 to 40 minutes.
  • Lecithin (having the characteristics as disclosed above) is used in an amount comprised from 0.1 to 4%, preferably from 0.5 to 3.5%, even more preferably from 1 .5 to 2.5% by weight, relative to the weight of the liquid composition.
  • the guar gum (having the characteristics as disclosed above) is used in an amount comprised from 0.1 to 5%, preferably from 0.2 to 4%, even more preferably from 0.4 to 2% by weight, relative to the weight of the liquid composition.
  • Water, sucrose esters orisers, lecithin and guar gum form a clear solution/suspension at a temperature comprised from 15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C.
  • Said iron salt (having the characteristics as disclosed above) is in an amount comprised from 1 to 10%, preferably from 2 to 8%, even more preferably from 4 to 6% by weight, relative to the weight of the liquid composition.
  • an opalescent solution or a homogeneous suspension is obtained.
  • the working temperature is comprised from 15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C.
  • the processing time is comprised from 1 to 60 minutes, preferably from 20 to 50 minutes, even more preferably from 30 to 40 minutes.
  • the liquid composition is subjected to a thermal treatment, for example pasteurization.
  • a thermal treatment for example pasteurization.
  • the liquid composition being at a temperature comprised from 20 to 25°C is heated at a temperature of about 1 10°C and then cooled down at a temperature of about 25-30°C.
  • the thermal treatment step is carried out over a period comprised from 1 to 3 minutes.
  • said liquid compositions (semi-finished or raw material) of the present invention are obtained, which comprise or, alternatively, consist of water, mineral salts, sucrose esters orisers, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and a guar gum, in the amounts by weight specified above.
  • liquid compositions of the present invention comprise or, alternatively, consist of water, magnesium (II) or calcium (II) or iron (II I) or zinc (II) or iodine mineral salts, sucrose esters or Atsters E473, a sunflower lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and a guar gum, in the amounts by weight specified above.
  • the solid compositions (semi-finished or raw material) obtained by said first and second methods as disclosed above can be added of water together with guar gum for obtaining the liquid composition (semi-finished or raw material) of the present invention.
  • liquid compositions obtained by the above-cited methods, are then formulated with pharmacologically acceptable additives and excipients to form the liquid formulations (final products) of the present invention such as suspension or syrup, said liquid formulations being used in conditions of complete or partial deficiency of minerals such as magnesium (II) or calcium (II) or iron (I II) or zinc (II) or iodine, in particular they are for use in the treatment of disorders or diseases related to or derived from a deficiency of one or more of said minerals.
  • minerals such as magnesium (II) or calcium (II) or iron (I II) or zinc (II) or iodine
  • liquid formulations (final products) containing said liquid compositions (semi-finished or raw material) prepared by the methods described above are such that the mineral salt and, thus, the mineral (magnesium (II) or calcium (II) or iron (I II) or zinc (I I) or iodine) is readily absorbable and bioavailable in an effective manner. Furthermore, said liquid formulations shown to be well-tolerated by the body.
  • liquid formulations of the present invention can be administered, even under fasting conditions, to all the subject categories and have a good payability, a high long-term stability from the chemical-physical point of view and optimum organoleptic properties namely, when subjected to stability tests, the mineral salts did not bring about to color, smell, flavor and/or taste changes.
  • the solid compositions for oral use of the present invention obtained from said first and second methods, are raw materials at solid state (granules or agglomerates or powders) which are subsequently mixed with pharmaceutically acceptable additives and excipients to yield pharmaceutical forms for oral use such as orally disintegrating tablets, pastilles, capsules, packets, or powders.
  • the liquid composition for oral use of the present invention is mixed with pharmaceutically acceptable flavors, excipients and additives for obtaining a syrup or liquid suspension for oral use.
  • the supplement product or medical device or pharmaceutical composition for oral use comprising the solid or liquid composition for oral use according to any of the above-cited embodiments, is successfully used in the treatment of disorders or diseases related to an iron deficiency in pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly since they prevent anemia and are useful for increasing the hemoglobin and ferritin values.
  • Said supplement product or medical device or said pharmaceutical composition, in solid form or liquid form, according to any of the above-cited embodiments is suitable for administration over a period comprised from 1 to 5 months, preferably from 2 to 4 months.
  • said supplement product or medical device or said pharmaceutical composition in solid form or orally disintegrating form or liquid form, for use in pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly, is recommended at a dose comprised from 10 to 60 mg of mineral/day, preferably from 15 to 45 mg/day, even more preferably from 20 to 30 mg/day.
  • the solid composition was mixed with the other ingredients of the supplement product through known equipment and methods.
  • the ingredients of the supplement product are as follows:
  • Sweetener xylitol; maltodextrins,
  • vitamin PP nicotinamide
  • vitamin B6 pyridoxine hydrochloride
  • vitamin B2 riboflavin
  • vitamin B1 thiamine mononitrate
  • vitamin B12 cyanocobalamin
  • the content of a supplement product in a 1 .6 g packet is: iron (III) pyrophosphate (solid composition) 12 mg; vitamin C 48 mg; vitamin PP 16 mg; pantothenic acid 6 mg; vitamin B6 1 .4 mg; vitamin B2 1.4 mg; vitamin B1 1 .1 mg; folate 200 meg; biotin 50 meg; vitamin B12 2.5 meg.
  • the iron (I II) contained in said supplement product is able to pass intact through the gastric environment and be absorbed at intestinal level thereby avoiding possible discomforts caused at gastric level .
  • the recommended dose is one packet per day, to be orally taken. The packet content is directly dissolved in the mouth.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Mycology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

The present invention relates to solid compositions, preferably in powder or granule form, based on minerals (semi¬ finished or raw material) and a process for preparing said solid compositions. Furthermore, the present invention relates to solid formulations (final products) and orally disintegrating formulations (final products) containing said solid compositions. Moreover, the present invention relates to a process for preparing said solid formulations and said orally disintegrating formulations. Finally, the present invention relates to the use of said solid compositions or said solid or orally disintegrating formulations in the treatment of disorders or diseases related to or derived from a deficiency of minerals such as magnesium (II), calcium (II), iron (III), zinc (II) and/or iodine. All the compositions or formulations of the present invention are suitable for pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly.

Description

Description of the invention entitled: Solid compositions based on minerals and orally disintegrating formulations containing the same.
The present invention relates to solid compositions, preferably in powder or granule form, based on minerals (semifinished or raw material) and a process for preparing said solid compositions. Furthermore, the present invention relates to solid formulations (final products) and orally disintegrating formulations (final products) containing said solid compositions. Moreover, the present invention relates to a process for preparing said solid formulations and said orally disintegrating formulations. Finally, the present invention relates to the use of said solid compositions or said solid or orally disintegrating formulations in the treatment of disorders or diseases related to or derived from a deficiency of minerals such as magnesium (II), calcium (II), iron (III), zinc (II) and/or iodine. All the compositions or formulations of the present invention are suitable for pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly.
Solid compositions based on minerals such as for example magnesium, calcium and iron (semi-finished or raw material) are known to be commercially available, which are used for preparing solid formulations (final products) for human use.
However, the solid compositions and formulations containing said solid composition based on minerals, suitable for oral route (per os) have limits and contraindications which, at times, restrict the use thereof.
A first limit is that solid, orally disintegrating formulations based on minerals such as for example magnesium, calcium, iron, zinc, iodine and mixtures thereof are commercially unavailable.
A second limit is that oral solid formulations presently marketed often contain the mineral, for example iron or magnesium or zinc, in a chemical form resulting hardly or poorly absorbable by the body and, thus, not bioavailable for the body. In some cases, in order to avoid a further reduction of the absorption in the organism, compositions based on minerals have to be administered between meals. I n this event the oral administration between meals of said minerals could lead to further drawbacks.
A third drawback is that the solid compositions or formulations containing said solid compositions are poor processable from an industrial point of view, since they suffer from external conditions and, at times, tend to pack and not flow causing problems of mineral titer reproducibility and can lead to granulometric changes, the manufacturing of the formulations as final products is thereby jeopardized.
The above-cited limits/drawbacks represent only some of those most commonly and recurrently found in solid compositions based on minerals and formulations containing said compositions commercially available.
The above-mentioned limits and drawbacks are considered to depend on how the solid compositions based on minerals are prepared, the addition order of the individual components being used in the manufacturing process and the adopted operating conditions.
From the above, it is understood that the selection of the operating conditions of the process being used for preparing the solid compositions or formulations plays a pivotal role.
It would be optimal to have formulations based on minerals in which the mineral, as mineral salt, is highly bioavailable and at the same time formulations are devoid of any limits or drawbacks from the organoleptic point of view (taste, smell, color, long-term stability). Furthermore, it would be desirable to have solid or orally disintegrating formulations (final products) devoid of limits and drawbacks related to, for example, their hygroscopicity, particle agglomeration, color changing and their solubility.
Therefore, there is yet a need for having solid compositions based on minerals (semi-finished or raw material) such as for example magnesium (I I), calcium (II), iron (III), zinc (II), iodine and mixtures thereof devoid of the limits and contraindications still existing in the presently marketed compositions. Moreover, there is yet a need for having solid and orally disintegrating formulations (final products) containing said solid compositions. In addition, there is yet a need for having a process for preparing said solid formulations (final products) and said orally disintegrating formulations (final products). There is also a need to have a process for preparing a solid composition based on minerals such as for example magnesium, calcium, iron, zinc and/or iodine wherein said minerals, existing as mineral salts, are made efficiently absorbable and bioavailable; said process being able to prepare a solid composition based on minerals which, upon formulation as final product is well-tolerable so that it can be administered, even under fasting conditions, to all the subject categories including pregnant women, has a good palatability and is stable over the time from the chemical-physical and organoleptic point of views, namely it is devoid of color, smell, flavor and taste changes.
The aim of the present invention is to provide solid compositions (semi-finished or raw material) based on minerals such as for example magnesium, calcium, iron, zinc, iodine and mixtures thereof in which said minerals, in the form of mineral salts, are made efficiently absorbable and bioavailable and are well-tolerated by the body in order to be administered, upon formulation in solid form and orally disintegrating form as final products, to pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly, even under fasting conditions. Said solid and orally disintegrating formulations, containing said solid compositions based on minerals, have a good palatability and are stable over the time from the chemical-physical and organoleptic point of views since they do not give rise to color, smell, flavor, taste and solubility changes.
It is an object of the present invention solid compositions (semi-finished or raw materials) based on minerals such as magnesium (II), calcium (II), iron (I II), zinc (I I), iodine and mixtures thereof, having the characteristics as disclosed in the appended claims.
It is an object of the present invention a process for preparing said solid compositions, having the characteristics as disclosed in the appended claims.
It is an object of the present invention solid formulations (final products) as powder, granules or agglomerates containing said solid compositions, having the characteristics as disclosed in the appended claims.
It is an object of the present invention solid, orally disintegrating formulations (final products) containing said solid compositions, having the characteristics as disclosed in the appended claims. It is an object of the present invention a process for preparing said solid formulations (final products) as powder, granules and agglomerates, having the characteristics as disclosed in the appended claims.
It is an object of the present invention a process for preparing said solid, orally disintegrating formulations (final products) having the characteristics as disclosed in the appended claims.
It is an object of the present invention the use of said solid and solid, orally disintegrating formulations in the treatment of disorders or diseases related to or derived from a deficiency of minerals such as for example magnesium, calcium, iron, zinc and/or iodine. All the formulations of the present invention are suitable for pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly.
Preferred embodiments of the present invention are disclosed in the following detailed description.
The solid composition (semi-finished or raw material) based on minerals of the present invention is a composition which could exist in the form of granules or powder or aggregates having varying sizes and granulometry depending on the pharmaceutical form of the intended final formulation.
Said compositions of the present invention, at solid state in the form of granules or powders or aggregates, have a bulk density (measured by equipment and methods known to the skilled in the field) comprised from 0.2 to 0.9 g/ml, preferably from 0.4 to 0.8 g/ml.
The solid compositions based on minerals of the present invention comprise minerals selected from the group comprising or, alternatively, consisting of magnesium, calcium, iron, zinc and iodine or mixtures thereof. Minerals (or metal cations) are in the form of mineral salts.
In an embodiment, the mineral or cation magnesium (II) is in said compositions as mineral salt magnesium oxide or, alternatively, as mineral salt magnesium hydroxide; the mineral or cation calcium Ca (II) is in said compositions as mineral salt tricalcium phosphate E341 ; the mineral or cation iron (II I) is in said compositions as mineral salt iron pyrophosphate; the mineral or cation zinc (II) is in said compositions as mineral salt zinc oxide; the mineral iodine is in said compositions as mineral salt sodium iodate; or alternatively said compositions may contain a mixture (two or three or four or five minerals) of said minerals.
In an embodiment, the solid compositions (semi-finished or raw material) based on minerals of the present invention further comprise, besides one o more of the above-cited minerals in the form of mineral salt, a sucrester and a lecithin and also, preferably, a pregelatinized starch to obtain solid compositions as granules or powders or agglomerates (semi-finished or raw material).
In another embodiment, the compositions of the present invention can be in liquid form. The liquid compositions (semi-finished or raw material) based on minerals such as magnesium, calcium, iron, zinc, iodine or mixtures thereof of the present invention further comprise, besides one or more of the above-cited minerals in the form of mineral salt, a sucrester and a lecithin and also, preferably, a guar gum and water to form liquid compositions (semi-finished or raw material).
The solid compositions (semi-finished or raw material) as granules or powder or agglomerates are then formulated with pharmacologically acceptable additives and excipients to obtain solid formulations (final products) such as for example a supplement product, a medical device or a pharmaceutical composition in the form of granules or powder or agglomerates, having a pharmaceutical form such as, for example packet, tablet, pastille or capsule.
Advantageously, the compositions as granules or powder or agglomerates (semi-finished or raw material) are formulated with pharmacologically acceptable additives and excipients to obtain orally disintegrating formulations (final products) such as for example a supplement product, a medical device or a pharmaceutical composition in the form of an orally disintegrating powder, said formulations having a pharmaceutical form of packet or stick.
Therefore, the solid compositions (semi-finished or raw material) as granules or powder or agglomerates are then formulated with sorbitol in an amount comprised from 40 to 90% by weight, preferably from 50 to 80% by weight, with maltodextrins in an amount comprised from 5 to 25% by weight, preferably from 9 to 20% by weight and citric acid in an amount comprised from 0.1 to 1 % by weight and other pharmacologically acceptable additives and excipients for obtaining a final product (a supplement product, a medical device or a pharmaceutical composition) in the form of orally disintegrating granules or powder or agglomerates, preferably as orally disintegrating granules, having a pharmaceutical form such as, for example a packet or stick.
The tablets being obtained can have various shapes among those known in the pharmaceutical form field, such as for example a cylindrical or spheroidal shape. Tablets may have a weight comprised from 200 to 2000 mg. For example, a gel capsule may have a weight of 500 mg, a hard tablet may have a weight comprised from 800 to 1000 mg, whereas a chewable tablet may have a weight comprised from 1000 to 2000 mg. Capsules may consist of hard gelatin or soft gelatin or soft gel. Tablets can be coated or filmed with one or more coating layers or films capable to pass through the gastric barrier. The coating is prepared by using a beeswax solution or a sugar-based solution. The solid compositions (semi-finished or raw material) of the present invention comprise at least a mineral selected from the group comprising or, alternatively, consisting of magnesium, calcium, iron, zinc and iodine or mixtures thereof in an amount comprised from 30 to 70%, preferably from 40 to 60%, even more preferably from 50 to 55% by weight.
In an embodiment, the iron pyrophosphate being used {[Fe^CvJSxhbO], CAS 10058-44-3, dry molecular weight 745.22} is preferably in micronized form and has an iron content comprised from 18 to 24%, preferably from 20 to 22% by weight.
The solid compositions (semi-finished or raw material) of the present invention further comprise, combined with at least a mineral, a lecithin.
Lecithin is a food additive -E322 (Directive 95/2/EC of 20.2.95 published on O.J. L61 of 18.3.95). Lecithin, due to its chemical-physical properties, primarily plays an emulsifying function and, being also rich in natural antioxidant substances, has a secondary antioxidant function as well. Directive 2008/84/EC of 27 August 2008 (published on European Community O.J. No. L253 establishes the purity criteria that lecithin has to meet in order to be considered of food grade quality (E322): Acetone-insoluble (essentially the lecithin active part): 60% min.; Humidity: 2% max.; Acid number: 35 max.; Peroxide value: 10 max.; Toluene-insoluble (essentially impurities): 0.3% max. From the chemical point of view, lecithin is a mixture of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides and phospholipids. Phospholipids represent the main components thereof; they are derived from the triglyceride structure, wherein a fatty acid is replaced by a phosphate group, which confers a negative charge, and thus, polarity to the molecule; said molecule has the generic name of phosphatide. A more complex organic molecule, usually serine, choline, ethanolamine, inositol or a single hydrogen atom is bound through an ester bond to the phosphate group, giving rise to a phospholipid named phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol or phosphatidic acid, respectively. In a more strict sense of lecithin, phosphatidylcholine is often designated. Phospholipids are characterized by a polar, water-soluble head, well- dissolving in water, whereas the two saturated fatty acids represent the two non polar, not water-soluble but lipophilic tails. Such a kind of molecules is called amphipathic and in the presence of water and fat they arrange themselves between the fatty and water molecules emulsifying them. Lecithin is a natural emulsifier.
All the solid compositions of the present invention are for oral use and do not contain neither a hydrolyzed lecithin nor an enzymatically hydrolyzed lecithin.
The lecithin being used is a powdery non-hydrolyzed lecithin and can be selected from sunflower or maize or soya lecithin. The lecithin being used is a powdery lecithin having a water content comprised from 1.5 to 4.5%, preferably from 2 to 4%, even more preferably from 2.5 to 3.5%. Advantageously, the lecithin being used is a powdery sunflower lecithin.
In an embodiment, the sunflower lecithin has a glucose amount comprised from 20 to 60%, preferably from 30 to 50%, for example about 45% by weight, such as in the product Lecico Sun CG 450 from Lecico GmbH Company- Germany.
A sunflower lecithin usable in the context of the present invention may have the following composition by weight (chemical-physical analysis): sunflower lecithin from 40 to 50%, carbohydrates from 40 to 50% (for example about 42%), proteins from 6 to 10%, ashes from 3 to 8%, humidity from 2 to 5% and a glidant others from 0.5 to 1 .5%. In the solid composition of the present invention, lecithin is in an amount comprised from 0.1 to 1 .5%, preferably from 0.4 to 1 .0%, even more preferably from 0.50 to 0.8% by weight.
The solid composition of the present invention comprises or, alternatively, consists of a magnesium (I I) salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight. Advantageously, the mineral or cation magnesium (II) is magnesium oxide or, alternatively, magnesium hydroxide and lecithin is from sunflower and/or maize.
The solid composition of the present invention comprises or, alternatively, consists of a calcium (II) salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight. Advantageously, the mineral or cation calcium (II) is tricalcium phosphate E341 and lecithin is from sunflower and/or maize.
The solid composition of the present invention comprises or, alternatively, consists of an iron (III) salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight. Advantageously, the mineral or cation iron (II I) is iron pyrophosphate and lecithin is from sunflower and/or maize. The solid composition of the present invention comprises or, alternatively, consists of a zinc (II) salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight. Advantageously, the mineral or cation zinc (II) is zinc oxide and lecithin is from sunflower and/or maize.
The solid composition of the present invention comprises or, alternatively, consists of an iodine salt and a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) in the above-cited amounts by weight. Advantageously, the mineral iodine is sodium iodate and lecithin is from sunflower and/or maize.
The solid compositions of the present invention further comprise, combined with a lecithin disclosed above, a sucrose ester or sucrester.
Sucresters are obtained by fatty acid esterification or transesterification of fatty acid methyl esters with carbohydrates, generally sucrose and other polysaccharides, for this reason they are also referred to as fatty acid sucrose esters. The chemical-physical properties of these compounds depend on the number and kind of esterified fatty acids. The abbreviation E473 means that sucresters are food additives permitted by the European Union legislation and regulated by ministerial decree (M. D. 1996). They are essentially emulsifiers and added in order to obtain a better stabilization between an aqueous phase and a fatty phase.
Sucrose esters are sucresters (E473) and used in the composition of the present invention at a HLB value of about 14-18, advantageously a HLB value of about 15 or 16, and used as emulsifiers.
In an embodiment sucrester E473 contains 70% of monoesters, being obtained by sucrose esterification with vegetable fatty acids (stearic and palmitic).
A sucrester usable in the context of the present invention may have the following composition by weight: total ester content at least 90%; free fatty acids (such as oleic acid) content not greater than 3%; free sucrose content not greater than 2%; humidity not greater than 4%; acid value not greater than 5. For example, sucrose esters SP70 from Chimab S.p.A Company -Italy.
Sucrose esters or sucresters are in the solid composition in an amount comprised from 10 to 20%, preferably from
12.5 to 18.5%, even more preferably from 16 to 18.0% by weight.
The solid compositions of the present invention do not contain a diglycerol fatty acid ester.
The solid compositions of the present invention comprise or, alternatively, consist of at least a mineral, a lecithin
E322 (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters E473 in an amount by weight as specified above.
The solid composition of the present invention comprises or, alternatively, consists of a magnesium (II) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters in the above-cited amounts by weight. Advantageously, the mineral or cation magnesium (II) is magnesium oxide or, alternatively, magnesium hydroxide, lecithin is from sunflower and/or maize and the sucrester is E473.
The solid composition of the present invention comprises or, alternatively, consists of a calcium (II) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters in the above-cited amounts by weight. Advantageously, the mineral or cation calcium (II) is tricalcium phosphate E341 , lecithin is from sunflower and/or maize and the sucrester is E473.
The solid composition of the present invention comprises or, alternatively, consists of an iron (III) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters E473 in the above-cited amounts by weight. Advantageously, the mineral or cation iron (II I) is iron pyrophosphate, lecithin is from sunflower and/or maize and the sucrester is E473.
The solid composition of the present invention comprises or, alternatively, consists of a zinc (I I) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters E473 in the above-cited amounts by weight. Advantageously, the mineral or cation zinc (II) is zinc oxide, lecithin is from sunflower and/or maize and the sucrester is E473.
The solid composition of the present invention comprises or, alternatively, consists of an iodine salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters E473 in the above-cited amounts by weight. Advantageously, the mineral iodine is sodium iodate, lecithin is from sunflower and/or maize and sucrester is E473.
In an embodiment, the solid compositions of the present invention can further comprise, combined with a lecithin and a sucrose ester or sucrester, a vegetable starch.
The vegetable starch is selected from rice (Oryza sativa) starches or maize starches. Advantageously, the starch is rice starch. Advantageously, the rice starch is a gelatinized or pregelatinized native rice starch. A pregelatinized rice starch usable in the context of the present invention may have the following chemical-physical characteristics: humidity not greater than 7%; protein content not greater than 1 %; ash content not greater than 1 %; pH (10% solution) comprised from 5.5 to 7.5, density 0.40-0.48 g/cm3; minimum starch content 97% and fats not greater than 0.1 %. An example of starch is given by the pregelatinized rice starch AX-FG-P from Reire Sri Company -Italy. The gelatinized or pregelatinized vegetable starch is in the solid compositions in an amount comprised from 15 to 40%, preferably from 20 to 35, even more preferably from 25 to 30 by weight.
In a preferred embodiment, the solid compositions of the present invention comprise or, alternatively, consist of at least a mineral, as mineral salt, a lecithin E322 (neither non-hydrolyzed nor enzymatically hydrolyzed), sucrose esters or sucresters E473 and a vegetable starch, in the above-cited amounts by weight. Preferably, said vegetable starch is a rice (Oryza sativa) starch or a pregelatinized rice (Oryza sativa) starch.
The solid composition of the present invention comprises or, alternatively, consists of a magnesium (II) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed), sucrose esters or sucresters in the above-cited amounts by weight. Advantageously, the mineral or cation magnesium (II) is magnesium oxide or, alternatively, magnesium hydroxide, lecithin is from sunflower and/or maize, the sucrester is E473 and the starch is a pregelatinized vegetable starch.
The solid composition of the present invention comprises or, alternatively, consists of a calcium (II) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters in the above-cited amounts by weight. Advantageously, the mineral or cation calcium (II) is tricalcium phosphate E341 , lecithin is from sunflower and/or maize, the sucrester is E473 and the starch is a pregelatinized vegetable starch.
The solid composition of the present invention comprises or, alternatively, consists of an iron (III) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters E473 in the above-cited amounts by weight. Advantageously, the mineral or cation iron (II I) is iron pyrophosphate, lecithin is from sunflower and/or maize, the sucrester is E473 and the starch is a pregelatinized vegetable starch.
The solid composition of the present invention comprises or, alternatively, consists of a zinc (I I) salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters E473 in the above-cited amounts by weight. Advantageously, the mineral or cation zinc (II) is zinc oxide, lecithin is from sunflower and/or maize, the sucrester is E473 and the starch is a pregelatinized vegetable starch.
The solid composition of the present invention comprises or, alternatively, consists of an iodine salt, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and sucrose esters or sucresters E473 in the above-cited amounts by weight. Advantageously, the mineral iodine is sodium iodate, lecithin is from sunflower and/or maize and the sucrester is E473 and the starch is a pregelatinized vegetable starch.
It is an object of the present invention a first method for preparing the solid compositions (semi-finished or raw material) of the present invention.
Said first method of the present invention is for preparing a solid composition comprising or, alternatively, consisting of a mineral, in the form of mineral salt, a lecithin, a sucrose ester or sucrester and, preferably, a vegetable starch, according to the above-cited embodiments.
Said first method does not contemplate the addition of solvents or water since it is a method in which all the individual components existing in the solid composition are mixed at solid state as powders or granules and in no case in aqueous solution or in the presence of solvents.
Said first method of the present invention comprises or, alternatively, consists of a series of processing steps through which the mineral salt selected from the group comprising magnesium (I I) salts, preferably magnesium oxide or magnesium hydroxide; or calcium (II) salts, preferably tricalcium phosphate; or iron (III) salts, preferably iron pyrophosphate; or zinc salt, preferably zinc oxide; or iodine salts, preferably sodium iodate; or mixtures thereof is coated or enveloped or encapsulated with said lecithin and/or said sucrose ester or sucrester, depending on the adopted addition order, and with said vegetable starch, if any. The mineral salt at solid state is firstly contacted with said lecithin and then, secondly, with said sucrose ester or sucrester and/or said vegetable starch.
The mineral salt at solid state as powder or granules has a water content of less than 5%, preferably of less than 3% by weight.
The mineral salt containing the mineral magnesium (I I) or calcium (II) or iron (III) or zinc (II) or iodine is used in an amount comprised from 50 to 90%, preferably from 60 to 80%, even more preferably from 70 to 75% by weight. The lecithin being used has the characteristics as described above. The contact time between mineral salt and lecithin is comprised from 1 to 60 minutes, preferably from 10 to 50, even more preferably from 20 to 40 minutes. The lecithin being used can be selected from a sunflower or maize or soya lecithin. The lecithin being used is a powdery lecithin having a water content comprised from 1 .5 to 4.5%, preferably from 2 to 4%, even more preferably from 2.5 to 3.5%. Advantageously, the lecithin used in said first method is a powdery, sunflower lecithin E322.
In said first method for preparing the solid compositions of the present invention neither a hydrolyzed lecithin nor an enzymatically hydrolyzed lecithin is used.
Lecithin is in the solid compositions of the present invention in an amount comprised from 0.1 to 1 %, preferably from 0.4 to 0.8%, even more preferably from 0.50 to 0.6% by weight.
Lecithin, when contacted with said mineral salt, arranges itself uniformly over said salt and, thus, over the mineral magnesium (I I) or calcium (II) or iron (II I) or zinc (II) or iodine as well.
The gelatinized or pregelatinized vegetable starch is selected from a rice starch or maize starch. Advantageously, the starch is rice starch. Advantageously, the rice starch is a gelatinized or pregelatinized native rice starch. The vegetable starch has the characteristics as described above.
The starch is in the solid compositions of the present invention in an amount comprised from 15 to 40%, preferably from 20 to 35%, even more preferably from 25 to 30% by weight.
The starch in the form of gelatinized or pregelatinized starch is advantageously more fluid and flowable and can be carefully dosed without causing errors or weight variations. Furthermore, it arranges itself in a more even and homogeneous manner. Finally, the pregelatinized starch enhances the bioavailability of the mineral salt and thus, of the mineral (cation contained within said mineral salt) as the obtained compound is better dissolved at temperatures comprised from 15 to 30°C (pressure 1 atmosphere), preferably from 20 to 25°C, even more preferably from 18 to 23°C.
Following to said first preparing method, the solid compositions (semi-finished or raw material) as powder or granules or agglomerates of the present invention are obtained, which comprise or, alternatively, consist of mineral salts, a sucrose ester or sucrester, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and, preferably, a pregelatinized vegetable starch, in the above-cited amounts by weight.
Particularly, by said first preparing method the solid compositions of the present invention are obtained, which comprise or, alternatively, consist of a mineral salt, a sunflower lecithin E322 (neither non-hydrolyzed nor enzymatically hydrolyzed), a sucrose ester or sucrester E473 and a pregelatinized rice starch, in the above-cited amounts by weight.
The Applicant found that in order to further enhance the bioavailability of the mineral salt and thus, of the mineral (cation contained within said mineral salt), the amount by weight of lecithin to be used in the process for preparing the solid compositions of the present invention has to be reduced as much as possible.
Advantageously, the non-hydrolyzed lecithin is in an amount of less than 1 % by weight, relative to the weight of the solid composition; in an embodiment the non-hydrolyzed lecithin is in an amount of less than 0.8% by weight, preferably of less than 0.6% by weight.
Moreover, the Applicant found that in order to further enhance the bioavailability of the mineral salt and, thus, of the mineral (cation contained within said mineral salt), it is important to use a specific amount by weight of sucrose esters or sucresters in association with a reduced amount by weight of lecithin.
Advantageously, the sucrose ester or sucrester to lecithin ratio is comprised from 30: 1 to 25: 1. In an embodiment said ratio is comprised from 20: 1 to 15: 1 .
It is an object of the present invention a second method for preparing the solid compositions of the present invention. Said second method of the present invention is for preparing the solid compositions comprising or, alternatively, consisting of a mineral salt, sucrose esters or sucresters, a lecithin and a gelatinized or pregelatinized starch.
Said second method does not contemplate the addition of solvents or water since it is a method in which all the individual components existing in the solid composition are mixed at solid state as powders or granules and in no case in aqueous solution or in the presence of solvents.
Said second method of the present invention comprises or, alternatively, consists of a technology developed in order to create a coating or encapsulation around the mineral salt so that to improve the stability and bioavailability of the mineral salt and, thus, of the mineral (cation) therein contained as well.
Basically, said second method contemplates the formation of agglomerates or granules comprising the mineral salt, sucrose esters or sucresters, lecithin and a gelatinized or pregelatinized starch. All of these components have the characteristics as specified above.
The sucrose esters or sucresters and lecithin act by enhancing the absorption of the mineral salt and, accordingly, of the mineral (cation contained within said mineral salt). The admixture with lecithin and starch gives rise to the formation of "chimeric" agglomerates capable to protect and shield the cation contained within said mineral salt from the gastric acid.
The mineral salt containing the mineral (cation) is used in an amount comprised from 30 to 70%, preferably from 40 to 60%, even more preferably from 50 to 55% by weight.
The mineral salt being used has the characteristics as described above.
The processing time is comprised from 1 to 60 minutes, preferably from 10 to 50, even more preferably from 20 to 40 minutes.
The sucrose esters or sucresters are in an amount comprised from 10 to 30%, preferably from 15 to 25%, even more preferably from 16 to 20% by weight.
The lecithin being used is a maize or sunflower or soya lecithin. The lecithin being used is a powdery lecithin having a water content comprised from 1 .5 to 4.5%, preferably from 2 to 4%, even more preferably from 2.5 to 3.5%. Advantageously, the lecithin being used is a powdery sunflower lecithin. The lecithin being used has the characteristics as specified above. The lecithin being used is neither a hydrolyzed lecithin nor an enzymatically hydrolyzed lecithin.
Lecithin is in an amount comprised from 0.1 to 1 %, preferably from 0.4 to 0.8% even more preferably from 0.5 to 0.6% by weight.
Lecithin arranges itself over the outer surface of granules or powders of the mineral salts when directly added to said mineral salts, or arranges itself over the outer surface of granules or powders comprising the mineral salt and sucrester, when added subsequently to sucrester.
Thereafter, a gelatinized or pregelatinized vegetable starch selected from a rice starch or maize starch is used. Advantageously, the starch is a rice starch. Advantageously, the rice starch is a gelatinized or pregelatinized native rice starch. The starch (Oryza sativa) being used has the characteristics as specified above.
The starch is in the solid compositions of the present invention in an amount comprised from 15 to 40%, preferably from 20 to 35%, even more preferably from 25 to 30% by weight.
The gelatinized or pregelatinized starch is prepared according to the equipment and techniques known to the person skilled in the field. The gelatinization process of rice flour aims to modify its technological properties bringing about a molecular rearrangement of the starchy component: said changes allow to providing a greater plasticity and viscosity to the mixtures and improving several characteristics of the products in which they are used. The properties obtained by gelatinization and subsequent structural change of native starches contained in rice, allow the process to confer a faster hydration and a higher viscosity to flours. Moreover, the gelatinized starch strongly binds the water to the starchy matrix itself, thereby becoming less available. Accordingly, a longer storage time and a lower effect of chemical and enzymatic degradation phenomena are obtained. Pregelatinization is a physical technique (thus it does not contemplate the addition of other components) that modifies the starch properties and is based on cooking and subsequently drying an aqueous native starch suspension (namely "rough" flour). The pregelatinized starches display the pivotal functional property of adsorbing a high water amount, thus they are used as thickeners and gelling agents in several food formulations, especially when (and this is the case of rice or maize flours) the gluten protein fraction is absent. The cooking-extrusion (namely a short treatment at high temperatures and pressures) and drying carried out on cylinders represent the most common method for obtaining pregelatinization. Pregelatinized starch-based products show, among others, good storage characteristics. This is because the water being present is strongly structured and captured within the pregelatinized starch matrix, whereby becoming not more available for degradation reactions, while at the same time the thermal treatment abolished some enzymatic (lipase and lipoxygenase) activities which often promote oxidative rancidity phenomena in "rough" flours and products derived therefrom.
In an embodiment, lecithin is used in an amount comprised from 0.48 to 0.62% by weight, while sucrose esters or sucresters are used in an amount comprised from 16.5 to 18.5% by weight, relative to the weight of the final solid composition of the present invention. These combinations allow to enhancing the bioavailability of the cation contained within said mineral salt of interest.
Following to said second preparing method, the solid compositions (semi-finished or raw material) of the present invention are obtained, which comprise or, alternatively, consist of at least a mineral, in the form of mineral salt, sucrose esters or sucresters, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and a pregelatinized vegetable starch, in the amounts by weight disclosed above.
Particularly, by said second preparing method, the solid compositions (semi-finished or raw material) of the present invention are obtained, which comprise or, alternatively, consist of magnesium (II), preferably magnesium oxide or magnesium hydroxide; or calcium (II), preferably tricalcium phosphate; or iron (III), preferably iron pyrophosphate; or zinc (I I), preferably zinc oxide; or iodine, preferably sodium iodate mineral salts; or mixtures thereof, sucrose esters or sucresters E473, a sunflower lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and a pregelatinized rice starch, in the amounts by weight disclosed above.
The solid compositions (semi-finished or raw material) of the present invention have a granulometry (that is understood as average granulometry measured by available equipment and techniques) comprised from 5 to 20 microns, preferably from 8 to 15 microns, even more preferably from 1 1 to 13 microns.
The solid compositions (semi-finished or raw material) of the present invention obtained through said first and second methods have a content of:
- magnesium (II), if present as magnesium oxide salt, comprised from 250 to 450 mg/g, preferably from 300 to 400 mg/g of composition,
- magnesium (II), if present as magnesium hydroxide salt, comprised from 150 to 300 mg/g, preferably from 200 to 250 mg/g of composition,
- calcium (II), if present as tricalcium phosphate salt, comprised from 250 to 450 mg/g, preferably from 300 to 400 mg/g of composition,
- iron (III), if present as iron pyrophosphate salt, comprised from 60 mg/g to 140 mg/g, preferably from 80 mg/g to 120 mg/g, even more preferably from 90 to 1 10 mg/g,
- zinc (II), if present as zinc oxide salt, comprised from 350 to 600 mg/g, preferably from 400 to 550 mg/g of composition,
- iodine, if present as sodium iodate salt, comprised from 5 to 20 mg/g, preferably from 8 to 15 mg/g of composition. The solid compositions as granules or powder or agglomerates (semi-finished or raw materials), obtained by said first and second methods, are formulated with pharmacologically acceptable additives and excipients to obtain the formulations (final products) of the present invention in solid form such as powder or granules or agglomerates or solid, orally disintegrating powders.
It is an object of the present invention the orally disintegrating formulations (final products) as disclosed hereinafter. The solid compositions (semi-finished or raw material) obtained as granules or powder or agglomerates are then formulated, by mixing, with sorbitol in an amount comprised from 40 to 90% by weight, preferably from 50 to 80% by weight, with maltodextrins in an amount comprised from 5 to 25% by weight, preferably from 9 to 20% by weight and citric acid in an amount comprised from 0.1 to 1 % by weight and with other pharmacologically acceptable additives and excipients to obtain a final product (a supplement product, a medical device or a pharmaceutical composition) in the form of orally disintegrating granules or powder or agglomerates, preferably orally disintegrating granules, having a pharmaceutical form such as, for example a packet or stick.
All the solid formulations (final products) are used in conditions of complete or partial deficiency of minerals such as magnesium (II) or calcium (II) or iron (I II) or zinc (II) or iodine, in particular they are for use in the treatment of disorders or diseases related to or derived from a deficiency of one or more of said minerals. Furthermore, all the formulations (final products) object of the present invention are successfully used in the treatment of (i) a proper cognitive development, for example in adolescents; (ii) an adequate red blood cell and hemoglobin production; (iii) a reduction of tiredness and physical fatigue in an individual.
Advantageously, the solid formulations (final products) containing said solid compositions (semi-finished or raw material) prepared by the method disclosed above (said first and second methods) are such that the mineral salt and, thus, the mineral (magnesium (II) or calcium (II) or iron (III) or zinc (II) or iodine or mixtures thereof) is readily absorbable and bioavailable in an affective manner. The mineral is able to pass the gastric environment and, accordingly, can be directly absorbed at intestinal level thereby avoiding possible discomforts caused at gastric level. Therefore, said formulations shown to be well-tolerated by the body.
Advantageously, the solid formulations of the present invention can be administered, even under fasting conditions, to all the subject categories and have a good payability, a high long-term stability from the chemical-physical point of view and optimum organoleptic properties namely, when subjected to stability tests, the mineral salts did not bring about color, smell, flavor and/or taste changes.
It is an object of the present invention a liquid composition (semi-finished or raw material).
The liquid compositions (semi-finished or raw material) based on minerals of the present invention further comprise, besides one or more of the above-cited minerals in the form of mineral salt, a sucrester and a lecithin and, preferably, also a guar gum and water for obtaining liquid compositions (semi-finished or raw material).
The liquid compositions can be formulated with pharmacologically acceptable additives and excipients to obtain liquid formulations for oral use as suspension or syrup form.
The liquid formulations (final products) of the present invention are for oral use and suitable as supplement product, medical device or pharmaceutical composition (briefly the liquid compositions of the present invention, for the sake of brevity).
The liquid formulations (final products) of the present invention are suitable in conditions of complete or partial deficiency of minerals such as magnesium (II) or calcium (II) or iron (I II) or zinc (II) or iodine, in particular they are for use in the treatment of disorders or diseases related to or derived from a deficiency of one or more of said minerals. The liquid compositions (semi-finished or raw material) of the present invention comprise or, alternatively, consist of water, mineral salts, a lecithin as disclosed above, sucrose esters or sucresters as disclosed above and a guar gum. All of these components have the characteristics and chemical-physical properties, as specified above.
The liquid compositions (semi-finished or raw material) of the present invention do not contain neither a hydrolyzed lecithin nor an enzymatically hydrolyzed lecithin.
The liquid compositions (semi-finished or raw material) of the present invention do not contain a diglycerol fatty acid ester.
The liquid compositions (semi-finished or raw material) of the present invention have a viscosity (measured under standard conditions and by known equipment and techniques) comprised from 1 .01 to 1 .15 g/ml, preferably from 1.02 to 1.12 g/ml, even more preferably from 1.03 to 1.10 g/ml. The liquid compositions of the present invention comprise the minerals, as mineral salts, magnesium (I I) or calcium (II) or iron (II I) or zinc (II) or iodine; the mineral magnesium (II) can be magnesium oxide or magnesium hydroxide; the mineral calcium can be tricalcium phosphate E473; the mineral iron (III) can be iron pyrophosphate; the mineral zinc (II) can be zinc oxide and iodine can be sodium iodate.
The liquid compositions (semi-finished or raw material) of the present invention contain at least a mineral salt in an amount comprised from 1 to 10%, preferably from 2 to 8%, even more preferably from 4 to 6% by weight, relative to the weight of the liquid composition.
The liquid compositions (semi-finished or raw material) of the present invention further comprise sucrose esters or sucresters, having the characteristics as disclosed above.
Sucrose esters or sucresters E473 are in said liquid composition of the present invention in an amount comprised from 0.10 to 5%, preferably from 0.5 to 4%, even more preferably from 1 to 3% by weight, relative to the weight of the liquid composition.
The liquid compositions (semi-finished or raw material) of the present invention further comprise a lecithin, having the characteristics as disclosed above.
The lecithin E322 being used can be selected from a sunflower or maize or soya lecithin. Advantageously, the lecithin being used is a sunflower lecithin.
In an embodiment, the sunflower lecithin contains a glucose amount comprised from 20 to 60%, preferably from 30 to 50%, for example 45% by weight such as in the product Lecico Sun CG 450 from Lecico GmbH Company-Germany. A sunflower lecithin usable in the context of the present invention can have the following composition by weight (chemical-physical analysis): sunflower lecithin from 40 to 50%, carbohydrates from 40 to 50% (for example, carbohydrates 42%), proteins from 6 to 10%, ashes from 3 to 8%, humidity from 2 to 5% and a glidant others from 0.5 to 1 .5%.
Lecithin is in said liquid compositions in an amount comprised from 0.1 to 4%, preferably from 0.5 to 3.5%, even more preferably from 1.5 to 2.5% by weight, relative to the weight of the liquid composition.
The liquid compositions (semi-finished or raw material) of the present invention further comprise a guar gum.
The guar gum is in said liquid compositions in an amount comprised from 0.1 to 5%, preferably from 0.2 to 4%, even more preferably from 0.4 to 2% by weight, relative to the weight of the liquid composition.
In an embodiment, the guar gum is selected from those commercially available and has a viscosity (cPs, 2 hours) comprised from 3000-4500, preferably from 3500 to 4000; starch-free; with a content of acid-insoluble substances comprised from 5 to 9, preferably from 6 to 8, for example 7; with a R.U.A comprised from 2.5 to 4%, preferably from 3 to 3.5% and a granulometry comprised from 100 to 300, preferably from 150 to 250, for example 200.
It is an object of the present invention a process for preparing said liquid composition, which comprises or, alternatively, consists of a technology capable to yield a time-stable composition or emulsion or suspension depending on the operating conditions being used. The process provides the liquid compositions devoid of deposit (precipitates or agglomerates in suspension) and having an even and sustained concentration over the time. In an embodiment, water is in an amount of 90%, or 92%, or 94% by weight. Water is kept under stirring at a temperature comprised from 15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C.
Next, sucrose esters or sucresters, lecithin, guar gum and iron (III) salts (having the characteristics as disclosed above) are added in the amounts specified below. Sucrose esters or sucresters are in an amount comprised from 0.10 to 5%, preferably from 0.5 to 4%, even more preferably from 1 to 3% by weight, relative to the weight of the liquid composition.
Water and sucrose esters or sucresters form a clear solution/suspension at a temperature comprised from 15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C.
The processing time is comprised from 1 to 60 minutes, preferably from 10 to 50 minutes, even more preferably from 20 to 40 minutes.
Lecithin (having the characteristics as disclosed above) is used in an amount comprised from 0.1 to 4%, preferably from 0.5 to 3.5%, even more preferably from 1 .5 to 2.5% by weight, relative to the weight of the liquid composition.
Water, sucrose esters or sucresters and lecithin form a clear solution/suspension at a temperature comprised from
15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C.
The guar gum (having the characteristics as disclosed above) is used in an amount comprised from 0.1 to 5%, preferably from 0.2 to 4%, even more preferably from 0.4 to 2% by weight, relative to the weight of the liquid composition.
Water, sucrose esters or sucresters, lecithin and guar gum form a clear solution/suspension at a temperature comprised from 15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C.
Said iron salt (having the characteristics as disclosed above) is in an amount comprised from 1 to 10%, preferably from 2 to 8%, even more preferably from 4 to 6% by weight, relative to the weight of the liquid composition.
At the end of the processing step, an opalescent solution or a homogeneous suspension is obtained. The working temperature is comprised from 15 to 45°C (pressure 1 atmosphere), preferably from 20 to 35°C, even more preferably from 25 to 30°C. The processing time is comprised from 1 to 60 minutes, preferably from 20 to 50 minutes, even more preferably from 30 to 40 minutes.
Next, the liquid composition is subjected to a thermal treatment, for example pasteurization. Basically, the liquid composition being at a temperature comprised from 20 to 25°C is heated at a temperature of about 1 10°C and then cooled down at a temperature of about 25-30°C. The thermal treatment step is carried out over a period comprised from 1 to 3 minutes.
Following to said process for preparing said liquid compositions, said liquid compositions (semi-finished or raw material) of the present invention are obtained, which comprise or, alternatively, consist of water, mineral salts, sucrose esters or sucresters, a lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and a guar gum, in the amounts by weight specified above. In particular, from said preparing process the liquid compositions of the present invention are obtained, which comprise or, alternatively, consist of water, magnesium (II) or calcium (II) or iron (II I) or zinc (II) or iodine mineral salts, sucrose esters or sucresters E473, a sunflower lecithin (neither non-hydrolyzed nor enzymatically hydrolyzed) and a guar gum, in the amounts by weight specified above.
In an embodiment of the present invention, the solid compositions (semi-finished or raw material) obtained by said first and second methods as disclosed above, can be added of water together with guar gum for obtaining the liquid composition (semi-finished or raw material) of the present invention.
The liquid compositions, obtained by the above-cited methods, are then formulated with pharmacologically acceptable additives and excipients to form the liquid formulations (final products) of the present invention such as suspension or syrup, said liquid formulations being used in conditions of complete or partial deficiency of minerals such as magnesium (II) or calcium (II) or iron (I II) or zinc (II) or iodine, in particular they are for use in the treatment of disorders or diseases related to or derived from a deficiency of one or more of said minerals.
Advantageously, the liquid formulations (final products) containing said liquid compositions (semi-finished or raw material) prepared by the methods described above are such that the mineral salt and, thus, the mineral (magnesium (II) or calcium (II) or iron (I II) or zinc (I I) or iodine) is readily absorbable and bioavailable in an effective manner. Furthermore, said liquid formulations shown to be well-tolerated by the body.
Advantageously, the liquid formulations of the present invention can be administered, even under fasting conditions, to all the subject categories and have a good payability, a high long-term stability from the chemical-physical point of view and optimum organoleptic properties namely, when subjected to stability tests, the mineral salts did not bring about to color, smell, flavor and/or taste changes.
The solid compositions for oral use of the present invention, obtained from said first and second methods, are raw materials at solid state (granules or agglomerates or powders) which are subsequently mixed with pharmaceutically acceptable additives and excipients to yield pharmaceutical forms for oral use such as orally disintegrating tablets, pastilles, capsules, packets, or powders.
The liquid composition for oral use of the present invention is mixed with pharmaceutically acceptable flavors, excipients and additives for obtaining a syrup or liquid suspension for oral use. Advantageously, the supplement product or medical device or pharmaceutical composition for oral use comprising the solid or liquid composition for oral use according to any of the above-cited embodiments, is successfully used in the treatment of disorders or diseases related to an iron deficiency in pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly since they prevent anemia and are useful for increasing the hemoglobin and ferritin values. Said supplement product or medical device or said pharmaceutical composition, in solid form or liquid form, according to any of the above-cited embodiments is suitable for administration over a period comprised from 1 to 5 months, preferably from 2 to 4 months. Advantageously, said supplement product or medical device or said pharmaceutical composition, in solid form or orally disintegrating form or liquid form, for use in pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly, is recommended at a dose comprised from 10 to 60 mg of mineral/day, preferably from 15 to 45 mg/day, even more preferably from 20 to 30 mg/day.
EXAMPLES
Example 1 :
Preparing a food supplement product comprising iron (III) pyrophosphate in packet form.
Firstly, a solid composition (semi-finished or raw material) containing iron (II I) pyrophosphate 53.71 % by weight, pregelatinized rice starch 28.57% by weight, sucresters E473 17.14% by weight and sunflower lecithin 0.58% by weight was prepared. Iron (III) pyrophosphate, sunflower lecithin and sucresters E473, in the above-cited amounts by weight, were mixed together over 30 minutes at a rate of 12.5 Hz to obtain a first mixture; next, the pregelatinized rice starch was added to the mixture obtained above and the whole was further mixed over 30 minutes at a rate of 12.5 Hz for obtaining a mixture which was subjected to a sieving step by a 0.7 mm sieve. Finally, the sieved mixture was further mixed for additional 30 minutes at a rate of 12.5 Hz.
Then, a food supplement product (final product) as 1.6 gram packet form comprising said solid composition was prepared.
Basically, the solid composition was mixed with the other ingredients of the supplement product through known equipment and methods. The ingredients of the supplement product are as follows:
Sweetener: xylitol; maltodextrins,
solid composition containing iron (III) pyrophosphate, pregelatinized rice starch, sucresters E473 and sunflower lecithin (prepared above),
L-ascorbic acid (vitamin C),
nicotinamide (vitamin PP),
flavors, acidity regulator: citric acid;
calcium D-pantothenate (pantothenic acid),
pyridoxine hydrochloride (vitamin B6),
riboflavin (vitamin B2),
thiamine mononitrate (vitamin B1 ),
cyanocobalamin (vitamin B12).
The content of a supplement product in a 1 .6 g packet is: iron (III) pyrophosphate (solid composition) 12 mg; vitamin C 48 mg; vitamin PP 16 mg; pantothenic acid 6 mg; vitamin B6 1 .4 mg; vitamin B2 1.4 mg; vitamin B1 1 .1 mg; folate 200 meg; biotin 50 meg; vitamin B12 2.5 meg.
The iron (I II) contained in said supplement product is able to pass intact through the gastric environment and be absorbed at intestinal level thereby avoiding possible discomforts caused at gastric level . The recommended dose is one packet per day, to be orally taken. The packet content is directly dissolved in the mouth.

Claims

1. A solid composition for use in the treatment of disorders or diseases related to a mineral deficiency comprising or, alternatively, consisting of:
- a mineral salt selected from the group comprising or, alternatively, consisting of magnesium (II), calcium (II), iron (II I), zinc (II), iodine mineral salts and mixtures thereof,
- sucrose esters or sucresters E473, and a lecithin;
wherein said lecithin is a non-hydrolyzed lecithin and is in an amount of less than 1 % by weight, relative to the weight of the composition.
2. The composition for use according to claim 1 , wherein said sucrose esters or sucresters E473 and said lecithin are in a weight ratio comprised from 30: 1 to 25: 1.
3. The composition for use according to claim 1 , wherein said composition further comprises a gelatinized or pregelatinized vegetable starch, preferably Oryza sativa rice starch.
4. The composition for use according to any one of claims 1 -3, wherein said mineral salt is in an amount comprised from 30 to 70%, preferably from 40 to 60% by weight; preferably said magnesium (II) mineral salt is selected from magnesium oxide and magnesium hydroxide, said calcium (II) mineral salt is tricalcium phosphate E341 , said iron (II I) mineral salt is iron pyrophosphate, said zinc mineral salt is zinc (II) oxide, said iodine mineral salt is sodium iodate; or mixtures thereof.
5. The composition for use according to claims 1 -4, wherein said sucrose esters or sucresters E473 are in an amount comprised from 10 to 30%, preferably from 15 to 25% by weight.
6. The composition for use according to any one of claims 1 -5, wherein said lecithin is a lecithin E322 and selected from the group comprising maize, sunflower or soya lecithin; said lecithin is in an amount comprised from 0.1 to 1.5, preferably from 0.4 to 1 % by weight.
7. The composition for use according to any one of claims 1 -6, wherein said sucrose ester or sucrester and said lecithin are in the composition in a weight ratio comprised from 25: 1 to 20: 1 ; preferably in a weight ratio comprised from 20: 1 to 15: 1 .
8. The composition for use according to any one of claims 1 -7, wherein said gelatinized or pregelatinized vegetable starch is selected from the group comprising rice starch or maize starch; said starch is in an amount comprised from 15 to 40%, preferably from 20 to 35% by weight.
9. The composition for use according to any one of claims 1 -8, wherein said solid composition for oral use has a granulometry comprised from 8 to 16 microns, preferably from 10 to 14 microns; a bulk density comprised from 0.3 to 0.8 g/ml, preferably from 0.4 to 0.7 g/ml and a content of mineral magnesium (I I) or calcium (II) or iron (I II) or zinc (II) or iodine comprised from 60 mg/g to 140 mg/g, preferably from 80 mg/g to 120 mg/g, even more preferably from 90 to 1 10 mg/g.
10. A method for preparing a solid composition according to any one of claims 1 -9, wherein said method comprises a step in which the mineral salt is mixed in the presence of non-hydrolyzed lecithin and sucrose esters or sucresters E473 to obtain said composition.
1 1 . The method according to claim 10, wherein said composition can be added of a vegetable starch, preferably pregelatinized rice starch.
12. A solid formulation comprising a composition according to any one of claims 1 -9 for use in the treatment of disorders or diseases related to or derived from a deficiency of minerals such as magnesium (II), calcium (II), iron (II I), zinc (II), iodine or mixtures thereof in pediatric subjects, adolescents, athletes, men, women, pregnant women and elderly.
13. The formulation according to claim 12, for use in a treatment for reducing tiredness and physical fatigue.
14. The solid formulation for use according to claims 12 or 13, wherein said formulation is in orally disintegrating form and, preferably, comprises sorbitol in an amount comprised from 40 to 90% by weight, preferably from 50 to 80% by weight, maltodextrins in an amount comprised from 5 to 25% by weight, preferably from 9 to 20% by weight, and citric acid in an amount comprised from 0.1 to 1 % by weight and other pharmacologically acceptable additives and excipients.
PCT/IB2014/001780 2013-09-09 2014-09-09 Solid compositions based on minerals and orally disintegrating formulations containing the same. WO2015033216A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA2925188A CA2925188C (en) 2013-09-09 2014-09-09 Solid compositions based on minerals and orally disintegrating formulations containing the same
US15/024,709 US11813290B2 (en) 2013-09-09 2014-09-09 Solid compositions based on minerals and orally disintegrating formulations containing the same
EP14792856.8A EP3043872B1 (en) 2013-09-09 2014-09-09 Solid compositions based on minerals and orally disintegrating formulations containing the same.
RS20240841A RS65812B1 (en) 2013-09-09 2014-09-09 Solid compositions based on minerals and orally disintegrating formulations containing the same.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI2013A001483 2013-09-09
IT001483A ITMI20131483A1 (en) 2013-09-09 2013-09-09 COMPOSITIONS IN SOLID FORM BASED ON MINERALS AND ORO-SOLUBLE FORMULATIONS CONTAINING THE SAME.

Publications (1)

Publication Number Publication Date
WO2015033216A1 true WO2015033216A1 (en) 2015-03-12

Family

ID=49354803

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2014/001780 WO2015033216A1 (en) 2013-09-09 2014-09-09 Solid compositions based on minerals and orally disintegrating formulations containing the same.

Country Status (6)

Country Link
US (1) US11813290B2 (en)
EP (1) EP3043872B1 (en)
CA (1) CA2925188C (en)
IT (1) ITMI20131483A1 (en)
RS (1) RS65812B1 (en)
WO (1) WO2015033216A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT201800006288A1 (en) * 2018-06-13 2019-12-13 Compositions comprising sucrosomal minerals containing mineral salts for use in the conditions of deficiency of such minerals
IT201900012804A1 (en) * 2019-07-24 2021-01-24 S I I T S R L Servizio Int Imballaggi Termosaldanti Composition comprising simethicone and sucrose esters and its use as an antifoam agent
IT202100011084A1 (en) 2021-04-30 2022-10-30 Pharmanutra S P A NUTRACEUTICAL COMPOSITION FOR USE IN THE TREATMENT OF CHRONIC FATIGUE/FATIGUE POST COVID-19

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997048392A1 (en) * 1996-06-21 1997-12-24 Mission Pharmacal Dietary supplements containing calcium citrate and carbonyl iron
WO2005082167A1 (en) * 2004-02-27 2005-09-09 Taiyo Kagaku Co., Ltd. Minera-containing composition and method of use thereof

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0870435B1 (en) * 1996-10-03 2004-01-14 TAIYO KAGAKU Co., LTD. Mineral composition
US6495177B1 (en) * 1999-08-13 2002-12-17 Warner Chilcott Laboratories Ireland Limited Orally dissolvable nutritional supplement
DE10206159A1 (en) * 2002-02-14 2003-08-28 Kosmas Kg Agent containing folic acid, vitamin B6 and vitamin B12, and their use
WO2007052289A2 (en) * 2005-07-22 2007-05-10 Rubicon Research Pvt Ltd. Novel dispersible tablet composition
EP1973552B1 (en) 2005-12-23 2017-04-12 Ajay Gupta Parenteral nutrition composition containing iron
ES2395862T3 (en) 2006-09-28 2013-02-15 Bayer Consumer Care Ag Mixture of iron and copper salts to mask the metallic taste
US20120288531A1 (en) 2011-01-14 2012-11-15 Shmuel Tuvia pharmaceutical compositions for delivery of ferric iron compounds, and methods of use thereof
ITMI20121350A1 (en) * 2012-07-31 2014-02-01 Alesco Srl IRON SOLID COMPOSITION FOR USE IN IRON DEFICIENCY CONDITIONS.
ITMI20121351A1 (en) 2012-07-31 2014-02-01 Alesco Srl IRON-BASED LIQUID COMPOSITION FOR USE IN IRON DEFICIENCY CONDITIONS.

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997048392A1 (en) * 1996-06-21 1997-12-24 Mission Pharmacal Dietary supplements containing calcium citrate and carbonyl iron
WO2005082167A1 (en) * 2004-02-27 2005-09-09 Taiyo Kagaku Co., Ltd. Minera-containing composition and method of use thereof

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT201800006288A1 (en) * 2018-06-13 2019-12-13 Compositions comprising sucrosomal minerals containing mineral salts for use in the conditions of deficiency of such minerals
WO2019239372A1 (en) * 2018-06-13 2019-12-19 Pharmanutra S.P.A. Composition comprising sucrosomial minerals containing mineral salts for use in conditions of deficiency of such minerals
IT201900012804A1 (en) * 2019-07-24 2021-01-24 S I I T S R L Servizio Int Imballaggi Termosaldanti Composition comprising simethicone and sucrose esters and its use as an antifoam agent
WO2021014426A1 (en) * 2019-07-24 2021-01-28 S.I.I.T. s.r.l. - SERVIZIO INTERNAZIONALE IMBALLAGGI TERMOSALDANTI A composition comprising simethicone and sucrose esters and use thereof as an antifoam agent
CN114144189A (en) * 2019-07-24 2022-03-04 国际热封包装服务 Composition comprising dimethicone and sucrose ester and use thereof as defoamer
CN114144189B (en) * 2019-07-24 2024-05-28 国际热封包装服务 Composition comprising simethicone and sucrose esters and use thereof as defoamer
IT202100011084A1 (en) 2021-04-30 2022-10-30 Pharmanutra S P A NUTRACEUTICAL COMPOSITION FOR USE IN THE TREATMENT OF CHRONIC FATIGUE/FATIGUE POST COVID-19

Also Published As

Publication number Publication date
EP3043872A1 (en) 2016-07-20
EP3043872B1 (en) 2024-05-01
EP3043872C0 (en) 2024-05-01
CA2925188C (en) 2023-02-14
RS65812B1 (en) 2024-08-30
CA2925188A1 (en) 2015-03-12
ITMI20131483A1 (en) 2015-03-10
US20160287633A1 (en) 2016-10-06
US11813290B2 (en) 2023-11-14

Similar Documents

Publication Publication Date Title
US10765752B2 (en) Solid composition comprising iron for use in iron deficient conditions
CN102089075B (en) Manufacture process for the preparation of an iron containing phosphate adsorbent
EP3043872B1 (en) Solid compositions based on minerals and orally disintegrating formulations containing the same.
WO2012001977A1 (en) Disintegrating composition and easily disintegrating compression molded article
JP5432563B2 (en) Phosphatidylserine-containing capsule and phosphatidylserine composition for capsule filling
JP2019206518A (en) Oil and fat-containing composition and oral preparation
JP2008237058A (en) Dietary supplement
US20040101555A1 (en) Method for stable and controlled delivery of (—)-hydroxycitric acid
JP2019534046A (en) Gamma-polyglutamic acid and zinc composition
WO2014009805A1 (en) Liquid compositions comprising iron for use in the treatment of disorders or diseases related to an iron deficiency
US20160022594A1 (en) Soft gel encapsulation
CN104041584A (en) Lecithin yogurt
CN103877041B (en) A kind of piroxicam dispersible tablet and preparation method thereof
KR20230136513A (en) Stable sustained-release formulation of vitamin C and method for producing the same
JP2005350419A (en) Antiallergic composition

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14792856

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2925188

Country of ref document: CA

REEP Request for entry into the european phase

Ref document number: 2014792856

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 15024709

Country of ref document: US

Ref document number: 2014792856

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: P-2024/0841

Country of ref document: RS