WO2022185122A1 - Complément nutritionnel destiné à être utilisé pour réduire et/ou prévenir les complications d'une surcharge en fer - Google Patents

Complément nutritionnel destiné à être utilisé pour réduire et/ou prévenir les complications d'une surcharge en fer Download PDF

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WO2022185122A1
WO2022185122A1 PCT/IB2022/000115 IB2022000115W WO2022185122A1 WO 2022185122 A1 WO2022185122 A1 WO 2022185122A1 IB 2022000115 W IB2022000115 W IB 2022000115W WO 2022185122 A1 WO2022185122 A1 WO 2022185122A1
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range
meg
curcumin
vitamin
composition according
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PCT/IB2022/000115
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Dimitrios DEMOS
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Demo Sa Pharmaceutical Industry
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • 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
    • 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
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/04—Chelating agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a composition for oral administration suitable for use in reducing and/or preventing the complications of iron overload in a subject. It also provides combinations of said composition with one or more iron-chelating agents.
  • Iron overload results from excess absorption of iron, repeated blood transfusions, or excess oral intake, typically in patients with disorders of erythropoiesis.
  • the most common cause of iron overload is chronic transfusion therapy for inherited anemias and acquired refractory anemias.
  • hemoglobinopathies eg, sickle cell disease, b-thalassemia, sideroblastic anemias
  • congenital hemolytic anemias eg, hemoglobinopathies, hereditary spherocytosis
  • myelodysplasia undergo regular transfusions.
  • Repeated blood transfusions result in excessive free iron concentration in the blood, causing increased oxidative stress and generation of free radicals.
  • the latter have been implicated in the development of the serious complications of transfusion-related iron overload such as cell damage and subsequent tissue damage.
  • Transfusional iron overload can lead to hepatic fibrosis, arrhythmias and congestive heart failure and a number of endocrinopathies.
  • Iron overload can also result in arthropathy, neurodegenerative disorders, hyperpigmentation, pulmonary hypertension and carcinogenesis.
  • the product disclosed herein contains in a single dose (one tablet per day for adults), the most effective natural active ingredients studied as chelating agents and antioxidants for use in the reduction and/or prevention of the complications of iron overload in a subject, in particular of the complications caused by repeated blood transfusions in patients suffering from thalassemia major, sickle cell disease, aplastic anemia or myelodysplasia.
  • the invention described herein addresses a need to provide a composition comprising natural ingredients for the reduction and/or prevention of the complications of iron overload in a subject.
  • compositions for oral administration comprising curcumin within the range from 20 to 600 mg, N-acetyl-L-cysteine within the range from 150 to 250 mg, and one or more vitamins selected from the group consisting of vitamin D, folic acid and vitamin E.
  • Said compositions may optionally comprise Coenzyme Q10 within the range from 50 to 150 mg, one or more minerals selected from the group consisting of zinc, magnesium and selenium, silicon dioxide within the range from 0.5 wt% to 5.0 wt%, one or more disintegrants, fillers and/or lubricants.
  • compositions of the present invention combined with one or more iron-chelating agents such as deferoxamine, deferiprone, deferasirox, dexrazoxane and ciclopirox.
  • iron-chelating agents such as deferoxamine, deferiprone, deferasirox, dexrazoxane and ciclopirox.
  • compositions according to the present invention for use in reducing and/or preventing the complications of iron overload in a subject.
  • Said compositions are particularly useful in the reduction and/or prevention of transfusion- related iron overload in patients suffering from inherited anemias and acquired refractory anemias such as thalassemia major, sickle cell disease, aplastic anemia or myelodysplasia.
  • compositions for administration to humans comprising curcumin, N- acetyl-L-cysteine and one or more vitamins selected from the group consisting of vitamin D, folic acid and vitamin E.
  • the compositions comprise curcumin within the range from 20 to 600 mg, N-acetyl-L-cysteine within the range from 150 to 250 mg, and one or more vitamins selected from the group consisting of vitamin D, folic acid and vitamin E.
  • the compositions comprise curcumin within the range from 20 to 600 mg, N-acetyl-L-cysteine within the range from 150 to 250 mg, and an effective amount of vitamin D, folic acid and vitamin E.
  • the composition of the invention When administered to a human on a regular basis, for example, on a daily basis, the composition of the invention facilitates adequate intake of curcumin, N-acetyl-L-cysteine and vitamins to promote good health.
  • curcuminoids possess several pharmacological properties including antioxidant, iron-chelating, and anti-inflammatory activities.
  • Hatairaktham S. et al. (Ann Hematol. 2021 Jan 3. doi: 10.1007/s00277-020-04379 ⁇ 7) a 24-week curcuminoids supplementation significantly lowered the levels of oxidative stress, hypercoagulability, and inflammatory markers in non- transfused b-thalassemia/Hb E patients.
  • Curcumin is a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa.
  • the extract of Curcuma longa contains curcuminoids in an amount of 95 wt%.
  • Curcuminoids consist of 65-80 wt% curcumin, 15-20 wt% dimethoxycurcumin and 2-5 wt% bis-demethoxycurcumin.
  • the compositions comprise curcumin in the form of the extract. Curcumin itself is not soluble in water and has low bioavailability.
  • the compositions comprise curcumin in a highly bioavailable form.
  • Any highly-bioavailable form of curcumin may be used, such as, for instance, curcumin complexed with gamma-cyclodextrin (commercially available by Wacker under the trade name Cavacurmin ® ), curcumin enclosed in a lipophilic matrix (such as phytosomes, or mixtures of Curcumi Soy Lecithi Microcrystalline Cellulose in a ratio of 1:2:2 CSL), or curcumin enclosed in liposomes, to name a few.
  • Cavacurmin ® is an inclusion complex of natural curcumin with CAVAMAX ® W8 gamma-cyclodextrin.
  • the amount of curcumin included in the compositions of the invention may be substantially reduced.
  • the compositions comprise curcumin in the composition in a complexed, highly bioavailable form, the concentration of curcumin in the composition being within the range from 20 mg to 50 mg.
  • the compositions comprise curcumin complexed with gamma-cyclodextrin, the concentration of curcumin in the composition being within the range from 20 mg to 50 mg.
  • NAC N-acetyl L-cysteine
  • Vitamin D deficiency is common in thalassemia major patients and strongly associated with cardiac iron uptake and ventricular dysfunction. It has been hypothesized that the increased oxidative damage observed in thalassaemia major may be due to the depletion of lipid soluble antioxidants such as vitamin D and vitamin E. Folate - the naturally occurring form of folic acid - is a vitamin essential for the maturation of erythrocytes, therefore it is essential for the uptake of iron in red blood cells.
  • an "effective amount" of a vitamin typically quantifies an amount at least about 10% of the Nutrient Reference Values ("NRV") according to Regulation (EU) No 1169/2011 for that particular vitamin. It is contemplated, however, that amounts of certain vitamins exceeding the NRV may be beneficial for certain subjects. For example, the amount of a given vitamin may exceed the applicable NRV by 100%, 200%, 300% or more.
  • the form of the vitamin may include salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of a vitamin, and metabolites of a vitamin.
  • Vitamin D may be in the form of ergocalciferol (D2), cholecalciferol (D3), calcidiol (25 hydroxyvitamin D), or calcitriol (1, 25 dihydroxyvitamin D).
  • vitamin D is in the form of cholecalciferol.
  • Vitamin E may be in the form of any suitable salt, such as in the form of d-alpha tocopheryl acetate or d-alpha tocopheryl succinate. Vitamin E may also be in the form of any vitamin E isomer, such as alpha (a-), beta (b-), gamma (y-), or delta (d-) tocopherol or alpha (a-), beta (b-), gamma (y-), or delta (d-) tocotrienol, preferably in the form of alpha tocopherol.
  • compositions of the invention may further comprise Coenzyme Q10.
  • the levels of coenzyme Q10 are very low in thalassemia patients. Clinical trials have shown that the administration of Coenzyme Q10 led to significant improvement of biochemical parameters of antioxidant enzymes in beta-thalassemia/Hb E patients (Kalpravidh R.W. et a I., Biofactors. 2005;25(l-4):225-34).
  • the compositions of the present invention may additionally comprise one or more minerals selected from the group consisting of zinc, magnesium and selenium.
  • compositions further comprise zinc, magnesium and selenium.
  • the compositions may include one or more forms of an effective amount of any of the minerals described herein or otherwise known in the art.
  • An "effective amount" of a mineral typically quantifies an amount at least about 10% of the Nutrient Reference Values ("NRV") according to Regulation (EU) No 1169/2011 for that particular mineral for a subject. It is contemplated, however, that amounts of certain minerals exceeding the NRV may be beneficial for certain subjects. For example, the amount of a given mineral may exceed the applicable NRV by 50%, 100% or more.
  • the minerals may be supplied in any suitable form, either organic or inorganic. Suitable forms of minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof.
  • Zinc is characterized as an anti-oxidant due to its ability to protect the cell from the effects of oxidative damage, possibly through its interaction with cellular thiols, preventing their oxidative inactivation, and by competing with metal ions that produce reactive oxygen species.
  • Zinc deficiency may occur during treatment with iron chelators and particularly with deferiprone, thus requiring supplementation.
  • Magnesium is an essential mineral element. Magnesium deficiency is rather common, occurring approximately in 2.5-15% of the general population. It is believed that magnesium deficiency affects iron metabolism, possibly by evoking inefficient iron utilization and iron deposition in tissues that is reinforced by oral iron overload.
  • Selenium functions as cofactor for reduction of antioxidant enzymes, such as glutathione peroxidases.
  • Selenium deficiency increases iron levels in serum and various tissues because of iron liberated by promoted hemolysis.
  • Selenium has been shown to synergize with vitamin E to provide an antioxidant defense in iron-overloaded tissues and especially in the myocardium.
  • Any suitable form of selenium, either organic or inorganic may be used.
  • a preferred form of selenium suitable for the present invention is selenium combined with a rice protein hydrolyzate (obtained through a controlled enzymatic hydrolysis of rice proteins), supplied by Pileje Laboratoires under the trade name Hypro-ri ® Se.
  • compositions disclosed herein are intended for oral administration.
  • the compositions of the invention are formulated in liquid form, such as in the form of aqueous solutions, syrups and the like.
  • compositions of the invention are formulated in solid form.
  • the solid compositions may, in some embodiments, contain liquid or semi-solid components.
  • Suitable solid dosage forms of the present invention include, but are not limited to, tablets, caplets, capsules including soft gel capsules, chewable dosage forms of and sachets and the like.
  • the compositions disclosed herein are in the form of a tablet.
  • the compositions of the present invention are in the form of a capsule, such as a soft gelatin capsule or a hard capsule.
  • the compositions of the invention are formulated in solid form.
  • compositions may further comprise excipients and processing aides such as: absorbents, diluents, flavorants, colorants, stabilizers, fillers, binders, disintegrants, lubricants, wetting agents, glidants, antiadherents, sugar or film coating agents, preservatives, pH buffering agents, artificial sweeteners, natural sweeteners, dispersants, carriers, phospholipids, thickening agents, solvents, salts for varying the osmotic pressure, thickeners, solubilizing agents and the like or some combination thereof.
  • excipients and processing aides such as: absorbents, diluents, flavorants, colorants, stabilizers, fillers, binders, disintegrants, lubricants, wetting agents, glidants, antiadherents, sugar or film coating agents, preservatives, pH buffering agents, artificial sweeteners, natural sweeteners, dispersants, carriers, phospholipids, thickening agents,
  • the solid compositions of the invention apart from the active substances, also comprise one or more disintegrants, one or more fillers and/or one or more lubricants.
  • the excipient may be a disintegrant.
  • Suitable disintegrants are, for example, sodium starch glycolate, cross-linked povidone, cross-linked sodium carboxymethyl cellulose.
  • the disintegrant is cross-linked sodium carboxymethyl cellulose.
  • the excipient may be a filler.
  • suitable fillers include carbohydrates, inorganic compounds, and polyvinylpirrolydone.
  • the filler may be calcium sulfate, both di- and tri-basic, starch, calcium carbonate, magnesium carbonate, microcrystalline cellulose, dibasic calcium phosphate, magnesium carbonate, magnesium oxide, calcium silicate, talc, modified starches, lactose, sucrose, mannitol, and sorbitol, or a combination of the above.
  • the filler is microcrystalline cellulose and/or calcium phosphate.
  • the excipient may be a lubricant.
  • Suitable non-limiting examples of lubricants include a magnesium salt of fatty acid such as magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate or a combination thereof.
  • the lubricant is magnesium stearate.
  • Tablets according to the invention may be uncoated or may be coated by known techniques.
  • Capsules containing the intended ingredients can be produced, for example, by mixing the intended ingredients with an inert carrier such as cellulose, microcrystalline cellulose, hydroxypropylmethyl cellulose, lactose or sorbitol and encapsulating them in gelatin capsules.
  • an inert carrier such as cellulose, microcrystalline cellulose, hydroxypropylmethyl cellulose, lactose or sorbitol
  • Tableting compositions containing N-acetyl L-cysteine and (where included in the composition) Coenzyme Q10 present challenges.
  • the presence of these ingredients made the mixture sticky which causes problems during the tableting process.
  • These properties which include, but are not limited to picking and sticking of materials to tooling, materials sticking to the pistons of the tableting machine during compression and poor tablet weight control. Due to the increase in heat in the tabletop machine during production, these ingredients melted, resulting in the mixture becoming sticky.
  • Turmeric extract (like many extracts) is in itself difficult to handle, especially in combination with other active ingredients that present such difficulties.
  • the inventors conducted extensive laboratory tests to identify additional excipients that may be added to the composition to facilitate the tableting step.
  • the efforts also focused on finding a solution that would obviate the need to split the daily dose into 2 tablets (or capsules) per day by increasing the amount of excipients or reducing the amount of problematic active ingredients.
  • the inventors have unexpectedly found that the addition of colloidal silica (silicon dioxide) within the range from 0.5 wt% to 5.0 wt% greatly facilitated the tableting process.
  • the solid compositions of the invention further comprise silicon dioxide within the range from 0.5 wt% to 5.0 wt%.
  • the compositions comprise silicon dioxide within the range from 0.5 wt% to 2.0 wt%.
  • the compositions comprise silicon dioxide at a concentration of 1 wt%.
  • a preferred tablet or capsule composition of the present invention comprises curcumin within the range from 300 mg to 600 mg, wherein curcumin is in the form of an extract;
  • N-acetyl-L-cysteine within the range from 150 mg to 250 mg;
  • Coenzyme Q.10 within the range from 50 mg to 150 mg;
  • vitamin E within the range from 8 mg to 16 mg
  • vitamin D within the range from 3 meg to 7 meg
  • folic acid within the range from 300 meg to 700 meg
  • magnesium within the range from 30 mg to 80 mg, dosed in the form of a pharmaceutically acceptable magnesium compound
  • the tablet or capsule compositions comprise: curcumin within the range from 20 to 50 mg, wherein curcumin is in a form complexed with gamma-cyclodextrin;
  • N-acetyl-L-cysteine within the range from 150 mg to 250 mg;
  • the tablet or capsule compositions comprise: curcumin within the range from 20 to 50 mg, wherein curcumin is in a form complexed with gamma-cyclodextrin;
  • N-acetyl-L-cysteine within the range from 180 mg to 220 mg;
  • Coenzyme Q10 within the range from 80 mg to 120 mg; vitamin E within the range from 10 mg to 14 mg; vitamin D within the range from 4 meg to 6 meg; folic acid within the range from 400 meg to 600 meg; magnesium within the range from 40 mg to 70 mg, dosed in the form of a pharmaceutically acceptable magnesium compound; zinc within the range from 8 mg to 12 mg, dosed in the form of a pharmaceutically acceptable zinc compound; selenium within the range from 0.03 mg to 0.13 mg, dosed in the form of a pharmaceutically acceptable selenium compound; silicon dioxide within the range from 0.5 wt% to 2.0 wt% microcrystalline cellulose within the range from 20 wt% to 30 wt%; cross-linked sodium carboxymethyl cellulose within the range from 0.5 wt% to 5 wt%; calcium phosphate within the range from 8 wt% to 18 wt%; and magnesium stearate within the range from 0.5 wt% to 2.5 wt%.
  • compositions of the invention in a tablet or capsule form may be prepared using ay suitable method known in the art.
  • tablets may be prepared by combining the components by blending, mixing, stirring, shaking, tumbling, rolling or by any other methods of combining the formulation components to achieve a homogeneous blend.
  • the composition may be formed into tablets using compression methods, for example.
  • the tablets may be coated using tablet coating materials and methods such as those known to those skilled in the art.
  • the amounts of the active ingredients disclosed herein are for a daily dose and that dose may be delivered in a single delivery unit.
  • the compositions were designed so that the daily dose can be administered in a single delivery unit (one tablet/capsule per day) in order to achieve better patient compliance.
  • the daily dose may administered in multiple delivery units and consumption of these units may occur at the same time or different times during the day.
  • packaging design may be used to facilitate identification of the proper daily dosage to the consumer. For example, a blister pack with labeling to indicate a daily dosage may be used.
  • the compositions of the present invention are administered in combination with one or more additional active substances.
  • the one or more additional active substances are iron-chelating agents.
  • the one or more iron chelating agents include, but are not limited to, deferoxamine, deferiprone, deferasirox, dexrazoxane and ciclopirox.
  • the composition should be taken 2 to 4 hours before the administration of the chelating agent, preferably 2 hours before the administration of the chelating agent.
  • the compositions are suitable for use in the reduction of one or more symptoms and/or complications of iron overload in a subject.
  • symptoms include, but are not limited to, fatigue, irregular heartbeat, joint pain, abdominal pain generalised darkening of skin colour, weight loss, to name a few.
  • Complications of iron overload in a subject include, but are not limited to, liver damage, liver cirrhosis, pancreatic islet cell damage, diabetes, hypothyroidism and hypogonadism.
  • the iron overload is transfusion-related.
  • the compositions are suitable for use in the reduction of one or more symptoms and/or complications of transfusion-related iron overload in a subject suffering from thalassemia major, sickle cell disease, aplastic anemia or myelodysplasia.
  • compositions are suitable for use in the prevention of one or more symptoms and/or complications of iron overload in a subject.
  • symptoms include, but are not limited to, fatigue, irregular heartbeat, joint pain, abdominal pain generalised darkening of skin colour, weight loss, to name a few.
  • Complications of iron overload in a subject include, but are not limited to, liver damage, liver cirrhosis, pancreatic islet cell damage, diabetes, hypothyroidism and hypogonadism.
  • the iron overload is transfusion-related.
  • the compositions are suitable for use in the prevention of one or more symptoms and/or complications of transfusion-related iron overload in a subject suffering from thalassemia major, sickle cell disease, aplastic anemia or myelodysplasia.

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Abstract

La présente invention concerne des compositions pour administration orale comprenant de la curcumine, de la N-acétyl-L-cystéine et une ou plusieurs vitamines choisies dans le groupe constitué de la vitamine D, de l'acide folique et de la vitamine E. Lesdites compositions peuvent éventuellement comprendre du Coenzyme Q10 et un ou plusieurs minéraux choisis dans le groupe constitué du zinc, du magnésium et du sélénium en tant que substances actives. Les compositions se présentent de préférence sous la forme d'un comprimé, d'une capsule ou d'une poudre pour solution orale. Les compositions de la présente invention peuvent être combinées avec un ou plusieurs agents chélateurs du fer tels que la déféroxamine, la défériprone, le déférasirox, le dexrazoxane et le ciclopirox. Les compositions conviennent à une utilisation pour réduire et/ou prévenir les symptômes et les complications liées à la surcharge en fer chez un sujet.
PCT/IB2022/000115 2021-03-02 2022-03-03 Complément nutritionnel destiné à être utilisé pour réduire et/ou prévenir les complications d'une surcharge en fer WO2022185122A1 (fr)

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