WO2021019185A1 - Compositions comprising a mixture of vitamins and minerals in the form of a combination of a gastro-soluble oral form and a gastro-resistant oral form, and use thereof - Google Patents

Compositions comprising a mixture of vitamins and minerals in the form of a combination of a gastro-soluble oral form and a gastro-resistant oral form, and use thereof Download PDF

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Publication number
WO2021019185A1
WO2021019185A1 PCT/FR2020/051394 FR2020051394W WO2021019185A1 WO 2021019185 A1 WO2021019185 A1 WO 2021019185A1 FR 2020051394 W FR2020051394 W FR 2020051394W WO 2021019185 A1 WO2021019185 A1 WO 2021019185A1
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gastro
composition according
vitamin
solid oral
vitamins
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PCT/FR2020/051394
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French (fr)
Inventor
Elisabeth RAMOND
Alexandre RAMOND
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Laboratoires Grimberg
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Publication of WO2021019185A1 publication Critical patent/WO2021019185A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • 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
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • 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, pantothenic acid
    • 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
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • 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
    • A61K31/33—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
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • 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
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
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    • 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
    • A61K33/26—Iron; 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
    • A61K33/30—Zinc; 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
    • A61K33/34—Copper; 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
    • A61K36/06—Fungi, e.g. yeasts
    • 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
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    • 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

Definitions

  • compositions comprising a mixture of vitamins and minerals in the form of a combination of an oral gastro-soluble form and an oral form
  • the present invention relates to compositions comprising a mixture of vitamins and minerals as well as their use. More specifically, the present invention relates to compositions comprising a mixture of at least vitamin B12 and minerals as well as their use for supplementing patients with vitamins and minerals who have undergone and / or who are to undergo bariatric surgery, the composition being administered orally, including an oral gastro-soluble form and an oral gastro-resistant form.
  • Bariatric surgery is for patients with severe or massive obesity.
  • the first category consists of restricting the volume of the stomach either by fitting a gastric band or by performing a longitudinal gastrectomy (or "sleeve" in English).
  • the second category combines surgical restriction of the stomach and food malabsorption.
  • gastric bypass or “bypass” in English
  • bypass the most widespread technique is that of gastric bypass (or “bypass” in English) which consists on the one hand in restricting the volume of the stomach and on the other hand in creating a bypass. of the digestive tract to bypass part of the stomach and intestine.
  • it helps to reduce both the amount of food ingested and the amount of nutrients absorbed.
  • patients having to undergo or having undergone bariatric surgery may also have iron deficiencies (up to 50% of patients), vitamin B9 (25% of patients), in vitamin B1 (15% of patients) and vitamin D (30-90% of patients).
  • iron deficiencies up to 50% of patients
  • vitamin B9 (25% of patients)
  • vitamin B1 (15% of patients
  • vitamin D (30-90% of patients).
  • vitamins A, C, E, B2, B3, B6, B8 iron, zinc, selenium, calcium, magnesium and copper in patients operated for less than a year, their importance varying according to the type of surgery undergone. For 80% of operated patients, these numerous deficiencies persist for life.
  • compositions comprising a mixture of vitamins and minerals. Mention may be made, by way of example, of the compositions marketed under the brand names LIFINOV®, SURGILINE®, WLS FORTE BYPASS®, WLS OPTIMUM SLEEVE®, BARINUTRICS® and VECTIPASS®. These compositions are in the form of a tablet or capsule for immediate release in the stomach, and have a particularly high dosage of the nutrients they contain, in order to compensate for the reduction in the digestive absorption surface and the malabsorption of nutrients. This is because changes made to the stomach in the form of partial ablation or the placement of a gastric band have the effect of greatly reducing the surface area of absorption of vitamins and minerals by the stomach. The same applies when a bypass or "bypass" is in place: the intestinal absorption surface is also reduced. Therefore, there is uncertainty about the amount of vitamin and mineral actually absorbed from the digestive tract. In addition, these compositions comprising very high doses between 100-20,000 times
  • SUBSTITUTE SHEETS (RULE 26) the nutritional reference value, are in practice ineffective. Indeed, too much minerals and vitamins have the effect of disrupting their absorption. Furthermore, these compositions include elements such as manganese, iodine and chromium for which there is no data in the literature showing that there is a risk of deficiency. Malabsorption is defined as the inability of the digestive tract to absorb much of the food substances necessary to maintain good health. Indeed, due to the anatomical changes caused by the surgery, food arrives faster in the digestive tract and therefore does not have time to be impregnated by digestive enzymes and to be absorbed by the wall of the digestive tract. In addition, food reaches the jejunum, the second part of the small intestine: the absorption surface is therefore reduced.
  • compositions comprising a mixture of vitamins, in particular vitamin B12, amino acids and minerals for
  • SUBSTITUTE SHEETS (RULE 26) supplement deficient patients, and in particular patients who have undergone bariatric surgery.
  • the present invention relates to a composition
  • a composition comprising a mixture of at least vitamin B12 and at least one mineral in the form of two solid oral forms: a first gastro-soluble solid oral form and a second solid oral form gastro-resistant.
  • the gastro-soluble solid oral form and the gastro-resistant solid oral form forming the composition according to the invention are administered concomitantly.
  • the two solid oral forms are a capsule.
  • composition according to the invention further comprises at least one vitamin chosen from vitamin A, D, E, B1, B2, B3, B5, B6, B8, B9 and C and their combinations.
  • At least one mineral is chosen from iron, zinc, selenium, calcium and their combinations.
  • composition according to the invention does not comprise at least one of the minerals chosen from magnesium, manganese, chromium, molybdenum, iodine and their combinations.
  • the composition according to the invention does not include magnesium.
  • the composition according to the invention comprises at least one vitamin and at least one mineral in amounts of between 10% and 100%, preferably between 15% and 50% of the nutritional reference values.
  • composition according to the invention can further comprise copper in an amount of between 50% and 500%, preferably between 100%
  • SUBSTITUTE SHEETS (RULE 26) and 300%, more preferably at about 200% of the nutritional reference values.
  • vitamin B12 is in an amount between 5000% to 20,000%, preferably between 12,000% to 18,000%, more preferably around 16,000% of the nutritional reference values.
  • the composition comprises calcium and vitamin D.
  • composition according to the invention further comprises an additional nutrient chosen from choline and / or inositol.
  • composition according to the invention further comprises at least one excipient.
  • the present invention further relates to the composition according to the invention further comprising L-tryptophan and a yeast.
  • the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same quantitative and qualitative composition.
  • the present invention further relates to the composition according to the invention for its use in patients who have undergone at least one bariatric surgery operation.
  • the present invention further relates to the composition according to the invention for its use in patients to undergo at least one bariatric surgery operation.
  • At least one bariatric surgery operation can be chosen from among longitudinal gastrectomy, adjustable gastric band, gastric bypass and biliopancreatic bypass.
  • composition according to the invention does not include magnesium.
  • the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same qualitative and quantitative composition.
  • the present invention relates to a composition
  • a composition comprising a mixture of at least vitamin B12 and at least one mineral in the form of two solid oral forms: a first solid oral gastro-soluble form and a second solid oral form gastro-resistant.
  • the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same vitamin and mineral composition.
  • the present invention therefore provides a composition which is in the form of a combination of two solid oral forms.
  • the first solid oral form is gastro-soluble, that is, immediate release, and releases its contents in the stomach.
  • gastro-soluble solid oral form stays in the stomach for a period of between 10 and 30 minutes, preferably 15 minutes.
  • the term "gastro-soluble” means a galenic or pharmaceutical form allowing the release of the active principle (s) (or of the constituent (s)) in the stomach.
  • gastric conditions are most often simulated by the use of 0.1 M hydrochloric acid HCl solution, pH 1, 2.
  • the stirring rate is 100 rpm for a paddle apparatus or 10 rpm for the reciprocating cylinder apparatus.
  • the dissolution medium is maintained at 37 ° C to mimic the physiological conditions. Under these conditions, it is observed that the gastro-soluble solid oral form according to the invention releases at least 50%, preferably at least 60%, more preferably at least 70%, even more preferably at least 80%. , more preferably 100% of the vitamins and minerals it contains.
  • the second gastro-resistant solid oral form is designed to release the vitamins and minerals it contains in the intestine.
  • gastro-resistant is meant a dosage form that does not dissolve in the stomach. Such dosage forms are delayed release, that is, they have a coating or coating composition resistant to the acidic pH of the stomach (pH ⁇ 2) to dissolve in the intestine.
  • the gastrosoluble or gastro-resistant character is determined by following the test established by the European Pharmacopoeia.
  • SUBSTITUTE SHEETS (RULE 26) The gastrosoluble nature of a capsule is measured in distilled water at 37 ° C as a disintegration medium. If the disintegration time of a capsule is less than or equal to 30 min, the capsule is considered to be gastrosoluble. Preferably, the gastrosoluble capsule according to the present invention disintegrates within 15 minutes.
  • the gastro-resistant character of a capsule is measured in 0.1 M hydrochloric acid at 37 ° C as a disintegration medium in a disintegration apparatus.
  • This medium mimics the physicochemical conditions of the stomach.
  • the capsules are incubated in this medium for 1 h.
  • the capsule must not show signs of disintegration or cracks which could lead to loss of content.
  • the capsule is then incubated for 1 h in a phosphate buffer solution of pH 6.8 at 37 ° C., this solution mimicking the conditions of the intestinal environment in accordance with the recommendations of the European Pharmacopoeia.
  • the capsule should be completely disintegrated within an hour.
  • the release of the composition according to the invention is delayed between 40 minutes and 1 hour.
  • the vitamins and minerals are therefore also absorbed from the intestine, which increases the amount of vitamins and minerals actually absorbed by the patient, unlike the compositions of the prior art which are only for gastric release.
  • the combination of the two solid oral forms with different release i.e. one in the stomach and the other in the intestine allows the patient to benefit and absorb with greater certainty the vitamins and minerals it needs.
  • the patient is human.
  • the composition according to the invention is not a veterinary composition.
  • the mechanism for releasing the vitamins and minerals contained in the composition is of the same nature at the gastric and intestinal level.
  • the combination of the two solid oral forms, one gastro-soluble and the other gastro-resistant allows the release of minerals and vitamins at different times and anatomical locations.
  • the combination of these two solid oral forms also makes it possible to obtain an optimized vitamin and mineral composition, without excessive overdose for better absorption of the product, the vitamins and minerals absorbed at one time the excess is directly eliminated or stored. in the liver for vitamins A, D, E and K.
  • composition according to the invention includes the gastro-soluble solid oral form and the gastro-resistant solid oral form: a daily dose is therefore sufficient to provide deficient patients with the vitamins and minerals necessary for the proper functioning of their body on the physical level and psychic. Achieving physical and psychological improvement from a single dose makes it easier for the patient to comply with treatment.
  • Vitamin B12 is absorbed by two mechanisms: (i) active absorption via intrinsic factor (Fl) produced by the gastric wall and allowing the transport of vitamin B12 through the intestinal wall; and (ii) passive absorption corresponding to the passive diffusion of vitamin B12 through the digestive mucous membranes.
  • Fl intrinsic factor
  • passive absorption corresponding to the passive diffusion of vitamin B12 through the digestive mucous membranes.
  • this latter mechanism of absorption only absorbs 1% of the vitamin B12 ingested.
  • vitamin B12 is linked to the R protein found in saliva. Binding vitamin B12 to R protein helps protect the vitamin from being broken down in the stomach due to the acidic pH. In parallel, the gastric wall synthesizes and secretes the intrinsic factor (Fl).
  • Fl intrinsic factor
  • Vitamin B12 then binds to intrinsic factor.
  • the whole vitamin B12-FI passes into the ileum.
  • Intrinsic factor binds to transporters located in the ileum membrane and allows vitamin B12 to pass through the intestinal mucosa.
  • Vitamin B12 is then found in the blood where it binds to its specific transporter, transcobalamin, to be transported to target tissues and the liver.
  • the composition according to the invention comprising vitamin B12 further comprises calcium because calcium participates in the good absorption of vitamin B12.
  • vitamin B12 is administered in an amount of between 5,000% and 20,000%, preferably between 10,000% and 18,000%, more preferably about 16,000% of the nutritional reference values in order to optimize passive diffusion as well as binding to the quantity of intrinsic factor actually produced and available.
  • the formulation of the composition according to the invention in two solid oral forms with different release, one in the stomach and the other in the intestine, makes it possible to maximize the possibility of passive diffusion and of binding to the intrinsic factor. This is particularly important for patients with gastric bypass or biliopancreatic bypass in whom gastric restriction is associated with malabsorption.
  • the composition according to the invention can comprise between 12.5 mg and 50 mg, preferably between 25 mg and 45 mg, more preferably around 40 mg.
  • composition according to the invention makes it possible to provide all or part of the minerals and vitamins essential to the human body, in one dose.
  • composition according to the invention makes it possible to maintain or restore the moral well-being of patients.
  • composition according to the invention may further comprise at least one vitamin from among vitamin A, D, E, B1, B2, B3, B5, B6, B8, B9 and C and their combinations.
  • Vitamins are an organic substance necessary in small quantities for the metabolism of a living organism and which cannot be produced by the human body. Vitamins therefore need to be supplied through food (see Lieberman, S, Bruning, N (1990). The Real Vitamin & Minerai Book. NY: Avery Group, 3). Vitamins are powerful antioxidants. Vitamin A is necessary for vision. Vitamin E helps maintain good cardiovascular health. The eight water-soluble vitamins of the B group contribute to numerous metabolic reactions and in particular to psychological well-being. For example, vitamin B1 helps conduction of nerve impulses, and vitamin B6 is used in the synthesis of neurotransmitters. Vitamins B2, B3, B5 and B8 participate in the metabolism of fatty acids. Vitamin C is an enzymatic cofactor involved in physiological hydroxylation reactions such as the synthesis of collagen and red blood cells, and contributes to the immune system.
  • the composition according to the invention further comprises vitamins A, D, E, B1, B2, B3, B5, B6, B8, B9 and C, which makes it possible to obtain a most complete composition. possible and overcoming as many deficiencies as possible.
  • composition according to the invention can comprise vitamins other than vitamin B12 in an amount of between 10% and 100%, preferably between 15% and 50% of the nutritional reference values (NRV), more preferably at around 15% of NRVs.
  • NAV nutritional reference values
  • composition according to the invention can in fact comprise at least one element from iron, copper, zinc, selenium and calcium and their combinations.
  • the composition according to the invention comprises iron, copper, zinc, selenium and calcium.
  • composition according to the invention also includes
  • SUBSTITUTE SHEETS (RULE 26) iron to avoid parallel supplementation. It is also particularly advantageous to combine vitamin C and iron in the same composition. Indeed, vitamin C is essential for the proper absorption of iron. Combining these two elements in the same composition makes it possible to combine the benefit of vitamin C on the skin, healing, weight loss and the reduction of mood disorders with the good absorption of iron.
  • the composition according to the invention comprises calcium. It is also particularly advantageous to combine vitamin D and calcium in the same composition. Indeed, the vast majority of people in France and northern Europe are deficient in vitamin D, regardless of weight. Vitamin D production is indeed induced by the subject's exposure to the sun. It is therefore interesting to supplement patients with vitamin D. In addition, vitamin D is essential for fixing calcium to the bones.
  • the composition according to the invention comprises vitamin B12, calcium and vitamin D. In fact, the presence of calcium makes it possible to facilitate the absorption of vitamin B12 and, as mentioned, vitamin D helps to fix calcium.
  • the combination of vitamin B12, vitamin D and calcium in the same composition has a synergistic effect allowing the patient on the one hand to benefit from the presence of these three essential nutrients to fight against these deficiencies, and on the other hand to '' increase the assimilation of each of these nutrients.
  • patients who have undergone bariatric surgery very frequently develop osteoporosis.
  • the combination of calcium and vitamin D helps reduce the risk of developing osteoporosis, or possibly reduce osteoporosis in patients who have had surgery.
  • the composition according to the invention can comprise the minerals in an amount of between 10% and 100%, preferably between 15% and 50% of the nutritional reference values (NRV), more preferably at 15% of the NRV.
  • the composition comprises copper
  • the copper is in an amount of between 50% and 500%, preferably between 100% and 300%, more preferably at about 200% of the nutritional reference values.
  • SUBSTITUTE SHEETS (RULE 26) in other words, when the composition comprises copper, the copper is in an amount between 0.5 mg and 5 mg, preferably between 1 mg and 3 mg, more preferably about 2 mg.
  • the composition according to the invention therefore makes it possible to administer the vitamins and minerals in an amount large enough to counterbalance the effects of bariatric surgery on gastric and / or intestinal absorption while avoiding, or at the very least, in reducing the phenomenon of malabsorption linked to competition between minerals and vitamins for digestive tract transporters.
  • the composition according to the invention is based on the principle of administering smaller doses distributed between the stomach and the intestine to maximize their absorption.
  • the administration of the composition according to the invention at a low but repeated dose allows the accumulation of vitamins and minerals in the body, and thus to reduce the deficiencies.
  • the European food safety agency EFSA defines the nutritional reference value (NRV) as a set of numerical food values which cover: the average nutritional needs, the nutritional reference for the population, the satisfactory intake and the interval reference macronutrient. These values guide professionals as to the amounts of nutrients needed to maintain the balance of an otherwise healthy person or group of people.
  • the NRVs also cover the upper safe limit which is the maximum amount of a nutrient that can be safely consumed over a long period of time.
  • the recommended daily intakes are benchmarks used as a reference for the labeling of food products, and provide an indication of the daily intakes of micronutrients (vitamins and minerals) necessary for an average adult-type . They were introduced by EU Directive 1990/496. Regulation 1169/2011 replaced the AJR by the VNR.
  • composition according to the invention may not comprise at least one of the elements chosen from magnesium, manganese, chromium, molybdenum, iodine and their combinations.
  • the composition according to the invention does not include magnesium. Indeed, there is no element
  • the composition according to the invention can also comprise an additional nutrient chosen from choline, inositol and their combination.
  • Inositol and choline are also precursors of neurotransmitters, including serotonin, which contributes to the psychological well-being of the patient and to the reduction of his depressive state.
  • Choline is also a drainer of the liver.
  • the inositol is in the form of mesoinositol.
  • a subject of the present invention is also the combination of L-tryptophan and at least one yeast, preferably S. cerevisiae.
  • L-Tryptophan is a precursor of neurotransmitters, including serotonin.
  • serotonin a neurotransmitters that include serotonin.
  • obese patients, candidates for bariatric surgery or who have undergone bariatric surgery are often depressed.
  • L-tryptophan supplementation increases serotonin levels and improves depression in these patients.
  • the yeast makes it possible to provide essential amino acids, vitamins of group B in particular and minerals allowing to restore the psychological well-being of the patients.
  • the presence of yeast also makes it possible to fight hair loss linked to the many deficiencies observed in patients who have undergone bariatric surgery or who are candidates for bariatric surgery.
  • Yeast can be introduced as an extract, that is, a yeast in which the cell content has been removed.
  • the yeast extract is therefore a mixture of peptides, free amino acids, purine and pyrimidine bases as well as water-soluble vitamins of group B.
  • the composition according to the invention as described above. above comprises the combination of L-tryptophan and at least one yeast according to the invention.
  • SUBSTITUTE SHEETS (RULE 26) the invention comprising the combination of L-tryptophan and at least one yeast according to the invention also participates in the maintenance and restoration of the cognitive functions and of the mental well-being of the patient.
  • composition according to the invention is administered orally in solid oral form.
  • solid oral forms include coated or uncoated tablets, hard capsules, sachets, granules and soft capsules.
  • the solid oral form is a capsule.
  • capsule is meant a solid dosage form consisting of a hard shell used for the administration of at least one active principle or ingredient.
  • the capsules according to the invention are preferably of plant origin, for example cellulose derivatives, preferably hydroxypropylmethylcellulose (HPMC). More preferably, they do not contain an element selected from lactose, gluten, titanium dioxide PO2, phthalates and their combinations.
  • composition according to the invention can also comprise at least one excipient such as a bulking agent, a lubricant, a flavoring, a colorant, an emulsifier, a compression agent, a diluent, a preservative, a gelling agent. , a plasticizer, a surfactant or combinations thereof.
  • excipient such as a bulking agent, a lubricant, a flavoring, a colorant, an emulsifier, a compression agent, a diluent, a preservative, a gelling agent. , a plasticizer, a surfactant or combinations thereof.
  • the gastro-soluble capsule and the gastro-resistant capsule are size 1 capsules.
  • a size 1 capsule has a size of 19 mm and an indicative filling volume of the closed capsule of 0.5 ml.
  • This capsule size is particularly suitable for lifelong supplementation and therefore improves patient comfort.
  • one skilled in the art will be able to adjust the size of the capsule depending on the use.
  • the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same quantitative and qualitative composition.
  • a subject of the present invention is also the composition according to the invention as it has been described for its use in any patient with deficiencies in minerals and vitamins, and in particular in vitamin B12.
  • the composition according to the invention is used in patients with deficiencies in minerals and vitamins, and in particular in vitamin B12.
  • SUBSTITUTE SHEETS (RULE 26) had at least one weight loss surgery operation. Indeed, patients who have undergone bariatric surgery are particularly prone to mineral and vitamin deficiencies due to various factors including in particular the significant reduction in the absorption surface following the operation. In addition, these patients present with psychological disorders such as bulimia, depression, anxiety and risk of suicide. Patients who have undergone bariatric surgery are therefore particularly concerned by the need to supplement their diet with the composition according to the invention.
  • composition according to the invention can also be used in patients to undergo at least one bariatric surgery operation. It may indeed be advantageous to supplement patients before proceeding to bariatric surgery. In particular, the reduction of vitamin and mineral deficiencies allows better postoperative recovery.
  • At least one bariatric surgery operation can be chosen from longitudinal gastrectomy, adjustable gastric band, gastric bypass and biliopancreatic bypass.
  • longitudinal gastrectomy means a method of gastrectomy comprising longitudinal and partial removal of the stomach and consisting in removing the left two-thirds of the stomach. This technique is also called “partial gastrectomy by plication” or “sleeve” in English because the stomach thus reduced takes the form of a sleeve. This surgical method is irreversible.
  • adjustable gastric band is meant a surgical operation to place a ring around the stomach, in its upper part, which has the effect of restricting its volume to a small gastric pocket. The patients thus reach the feeling of satiety more quickly.
  • stomach bypass is understood to mean a surgical operation consisting in reducing the volume of the stomach and modifying the food circuit. More
  • the gastric bypass method consists in making a vertical transection of the stomach creating a proximal pouch of restricted capacity in which the food arrives, connected directly to the jejunum (by a Y loop).
  • This technique is also called “bypass” in English as well as “Roux en Y derivation” from the name of its creator César Roux. This method can be reversible if necessary.
  • bilio-pancreatic derivation is understood to mean a surgical operation comprising a resection of the stomach by 50-30% making it possible to reduce the acidity of the stomach as well as a derivation of the bile and the pancreas in order to cause food malabsorption.
  • the composition according to the invention finds its use in patients having to undergo and / or having undergone a bariatric surgery in that it allows in a single dose, to efficiently deliver the amounts of vitamins and minerals. necessary to overcome their deficiencies. This results in greater energy and a reduction in the depressive state of patients, which improves their compliance and therefore induces a virtuous circle.
  • composition according to the invention is administered once a day in the form of a dose of two solid oral forms including a gastro-soluble solid oral form and a gastro-resistant solid oral form.
  • Patients who have undergone or are due to undergo bariatric surgery may indeed have different medications to take during the day.
  • Limiting the daily intake to two solid oral forms, preferably capsules, that is to say a daily dose allows the patient to avoid having to multiply the oral forms to take.
  • the richness of solid oral forms in vitamins and minerals makes it possible to reduce the number of food supplements to be taken by the patient. This also contributes to good patient compliance.
  • the gastro-soluble solid oral form and the gastro-resistant solid oral form forming the composition according to the invention are administered concomitantly.
  • soluble and gastro-resistant solid oral form form form a single dose which should be taken at the same time, i.e. the gastro-soluble solid oral form and gastro-resistant solid oral form are taken together once per day, during the same meal for example.
  • the patient takes the solid oral forms according to the invention within a time interval of less than an hour, preferably less than 30 minutes, more preferably less than 15 minutes, more preferably less than 10 minutes, even more preferably less than 5 minutes and even more preferably less than one minute.
  • time difference of less than one hour is meant, for example, the fact that the patient takes a solid oral form and then the other 60 minutes after or less than 60 minutes after.
  • the joint intake of the gastro-soluble solid oral form and the gastro-resistant solid oral form contributes to the complementary action of the solid oral forms at the gastric and intestinal levels.
  • composition according to the invention at spun dose, that is to say at low and repeated dose, which allows a phenomenon of accumulation in the body and thus allows to treat and prevent mineral and vitamin deficiencies.
  • composition is prepared according to the invention according to Tables 2 and 3 below:
  • Vitamin B12 represents 0.00125% by weight of the premix. Since this proportion is negligible, vitamin B12 is provided in crystallized form in the composition according to the invention, ie 400 pg of vitamin B12 for one dose.
  • the premix is a mixture of several vitamins at a concentration well determined by the supplier.
  • the crystallized form corresponds to one of the possible presentations of vitamin B12.
  • the raw materials that is to say the vitamins and minerals entering into the composition according to the invention, are weighed and introduced through a calibrator into a stainless steel tank with a volume of 150 L or 2000 L, depending on the amount to be prepared.
  • Magnesium stearate is added to the mixture as an excipient.
  • the raw materials are then mixed for 45 min at the speed of 5 revolutions / min.
  • the mixture thus prepared is placed in a size 1 capsule with a vegetable envelope in HPMC.
  • the capsules thus prepared are then packaged in a blister pack of 6 doses, each dose corresponding to a gastro-soluble capsule and a gastro-resistant capsule.
  • the gastro-soluble and gastro-resistant capsules both have the same composition in minerals and vitamins.
  • the gastrosoluble capsule releases its contents in the stomach at most after 30 minutes, its contents are directly absorbed in the stomach or transported in the intestine as measured according to the conditions of the European pharmacopoeia, which allows a release time of the vitamins and minerals it contains long enough for their absorption.
  • a composition is prepared comprising a mixture of vitamins and minerals according to the invention in accordance with Table 2 and according to the same procedure as in Example 1.
  • composition according to the invention has a concentration of each of its respective elements sufficient for the implementation of the invention and also have good bioavailability.
  • concentration of each of its respective elements sufficient for the implementation of the invention and also have good bioavailability.
  • inositol is integrated in the form of meso-inositol
  • composition according to the invention is compared with the formulation of a composition according to the prior art exhibiting a high dosage of vitamins and minerals marketed by the company BARINUTRICS.
  • this composition of the prior art is compared with the formulation of a composition according to the prior art exhibiting a high dosage of vitamins and minerals marketed by the company BARINUTRICS.
  • this composition of the prior art is compared with the formulation of a composition according to the prior art exhibiting a high dosage of vitamins and minerals marketed by the company BARINUTRICS.
  • chromium is integrated in the form of picolinate
  • molybdenum is integrated in the form of sodium molybdenum
  • iodine is integrated as potassium iodide
  • inositol is integrated as inositol
  • choline is integrated in the form of choline bitartrate.
  • the composition according to the invention is a composition comprising all the vitamins and minerals necessary to overcome the deficiencies encountered in subjects with severe or moderate obesity. Thus, it is not useful to multiply the number of drugs or food supplements to take during the day, which is appreciable when it is a life-long treatment and improves treatment compliance.
  • the composition according to the invention comprises only the vitamins and minerals for which a deficiency has been observed in subjects to undergo or who have undergone bariatric surgery. It also contains a combination of yeast and L-tryptophan, which provides essential amino acids for patients and contributes to good recovery after the operation and to improving signs of psychological disorders.
  • composition according to the invention does not include superfluous minerals for which no deficiency
  • SUBSTITUTE SHEETS (RULE 26) in this group of patients was observed such as molybdenum, chromium, iodine, magnesium and manganese. This avoids the phenomena of malabsorption due in particular to competition for transporters between the various vitamins and minerals included in the composition.
  • the composition according to the invention is therefore more effective.
  • the vitamins are all introduced at a minimum dose of 15% of the NRVs or RDAs, with the exception of vitamin B12 and vitamin D for which strong deficiencies are observed.
  • the composition according to the invention contains calcium which makes it possible in particular to strengthen bone health and facilitate the absorption of vitamin B12.
  • composition according to the invention comprising a combination of calcium and vitamin D makes it possible to prevent and reduce the risks of osteoporosis.
  • composition according to the invention therefore makes it possible to restore the good physical and / or psychological health of the patient having to undergo and / or having undergone a bariatric surgery operation by providing him with all the vitamins and minerals for which it is deficient, in a single dose.
  • the combination of a gastro-soluble capsule and a gastro-resistant capsule, forming a single dose makes it possible to optimize the digestive surface of absorption remaining after the operation, to considerably increase the quantity of nutrients absorbed and of reduce the phenomena of malabsorption.

Abstract

The invention relates to a composition comprising a mixture of at least vitamin B12 and minerals in the form of a combination of a gastro-soluble solid oral form and a gastro-resistant solid oral form, and to the use thereof.

Description

Description Description
Titre de l'invention : Compositions comprenant un mélange de vitamines et minéraux sous forme d’une association d’une forme orale gastro-soluble et d’une forme orale Title of the invention: Compositions comprising a mixture of vitamins and minerals in the form of a combination of an oral gastro-soluble form and an oral form
gastro-résistante et utilisation gastro-resistant and use
[0001] DOMAINE DE L’INVENTION [0001] FIELD OF THE INVENTION
[0002] La présente invention porte sur des compositions comprenant un mélange de vitamines et de minéraux ainsi que leur utilisation. Plus précisément, la présente invention porte sur des compositions comprenant un mélange d’au moins la vitamine B12 et de minéraux ainsi que leur utilisation pour supplémenter des patients en vitamines et minéraux ayant subi et/ou devant subir une chirurgie bariatrique, la composition étant administrée par voie orale dont une forme orale gastro-soluble et une forme orale gastro-résistante. [0002] The present invention relates to compositions comprising a mixture of vitamins and minerals as well as their use. More specifically, the present invention relates to compositions comprising a mixture of at least vitamin B12 and minerals as well as their use for supplementing patients with vitamins and minerals who have undergone and / or who are to undergo bariatric surgery, the composition being administered orally, including an oral gastro-soluble form and an oral gastro-resistant form.
[0003] ARRIERE-PLAN TECHNIQUE [0003] TECHNICAL BACKGROUND
[0004] La chirurgie bariatrique s’adresse aux patients ayant une obésité sévère ou massive. Il existe deux principales catégories de chirurgie bariatrique. La première catégorie consiste à restreindre le volume de l’estomac soit en posant un anneau gastrique, soit en procédant à une gastrectomie longitudinale (ou « sleeve » en anglais). Ainsi, les patients atteignent plus vite la sensation de satiété et réduisent de manière importante la quantité d’aliments consommée. La seconde catégorie combine la restriction chirurgicale de l’estomac et la malabsorption des aliments. Parmi cette dernière catégorie, la technique la plus répandue est celle du court- circuit gastrique (ou « by-pass » en anglais) qui consiste d’une part à restreindre le volume de l’estomac et d’autre part à créer une dérivation du tube digestif pour court-circuiter une partie de l’estomac et de l’intestin. Ainsi, cela permet de réduire à la fois la quantité d’aliments ingérée et la quantité de nutriments absorbés. [0004] Bariatric surgery is for patients with severe or massive obesity. There are two main categories of weight loss surgery. The first category consists of restricting the volume of the stomach either by fitting a gastric band or by performing a longitudinal gastrectomy (or "sleeve" in English). Thus, patients reach a feeling of fullness more quickly and significantly reduce the amount of food consumed. The second category combines surgical restriction of the stomach and food malabsorption. Among this last category, the most widespread technique is that of gastric bypass (or “bypass” in English) which consists on the one hand in restricting the volume of the stomach and on the other hand in creating a bypass. of the digestive tract to bypass part of the stomach and intestine. Thus, it helps to reduce both the amount of food ingested and the amount of nutrients absorbed.
[0005] Outre une perte de poids rapide, la chirurgie bariatrique permet d’une part d’améliorer la tension artérielle et les douleurs articulaires, et d’autre part de réduire la résistance à l’insuline, l’apparition du diabète de type 2 et les risques de maladie cardiovasculaire. [0005] In addition to rapid weight loss, bariatric surgery makes it possible on the one hand to improve blood pressure and joint pain, and on the other hand to reduce insulin resistance, the appearance of type diabetes. 2 and the risks of cardiovascular disease.
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FEUILLES DE REMPLACEMENT (RÈGLE 26) [0006] Toutefois, la chirurgie bariatrique n’est pas exempte d’effets secondaires. En effet, la plupart des patients en obésité sévère ou massive présentent déjà d’importantes carences avant leur opération dont notamment d’importantes carences en vitamine B12. La vitamine B12 ou cobalamine ne peut être synthétisée par le corps humain et doit donc être apportée par l’alimentation. Or, la vitamine B12 joue un rôle dans de nombreux processus physiologiques tels que l’assimilation de la vitamine B9, la protection des cellules nerveuses et la production de globules rouges. SUBSTITUTE SHEETS (RULE 26) [0006] However, bariatric surgery is not free from side effects. Indeed, most patients with severe or massive obesity already have significant deficiencies before their operation, including significant deficiencies in vitamin B12. Vitamin B12 or cobalamin cannot be synthesized by the human body and must therefore be provided through food. However, vitamin B12 plays a role in many physiological processes such as the assimilation of vitamin B9, the protection of nerve cells and the production of red blood cells.
[0007] Outre cette carence en vitamine B12, les patients devant subir ou ayant subi une opération de chirurgie bariatrique peuvent également présenter des carences en Fer (jusqu’à 50% des patients), en vitamine B9 (25% des patients), en vitamine B1 (15% des patients) et en vitamine D (30-90% des patients). En plus de ces déficits préexistants, on observe également des carences en vitamines A, C, E, B2, B3, B6, B8, fer, zinc, sélénium, calcium, magnésium et cuivre chez les patients opérés depuis moins d’un an, leur importance variant en fonction du type de chirurgie subie. Pour 80% de patients opérés, ces nombreuses carences perdurent à vie. [0007] In addition to this vitamin B12 deficiency, patients having to undergo or having undergone bariatric surgery may also have iron deficiencies (up to 50% of patients), vitamin B9 (25% of patients), in vitamin B1 (15% of patients) and vitamin D (30-90% of patients). In addition to these pre-existing deficits, there are also deficiencies in vitamins A, C, E, B2, B3, B6, B8, iron, zinc, selenium, calcium, magnesium and copper in patients operated for less than a year, their importance varying according to the type of surgery undergone. For 80% of operated patients, these numerous deficiencies persist for life.
[0008] Pour lutter contre ces carences, les patients opérés sont supplémentés par des compositions comprenant un mélange de vitamines et minéraux. On peut citer à titre d’exemple, les compositions commercialisées sous les noms de marque LIFINOV®, SURGILINE®, WLS FORTE BYPASS®, WLS OPTIMUM SLEEVE®, BARINUTRICS® et VECTIPASS®. Ces compositions se présentent sous forme de comprimé ou de gélule à libération immédiate dans l’estomac, et présentent un dosage particulièrement élevé en nutriments qu’elles contiennent, afin de compenser la réduction de la surface d’absorption digestive et la malabsorption des nutriments. En effet, les modifications apportées à l’estomac sous forme d’ablation partielle ou la pose d’un anneau gastrique ont pour effet de réduire fortement la surface d’absorption de vitamines et minéraux par l’estomac. Il en va de même lorsqu’une dérivation ou un « by-pass » est mis en place : la surface d’absorption intestinale est également réduite. Par conséquent, il existe une incertitude sur la quantité de vitamines en minéraux effectivement absorbés par le tube digestif. De plus, ces compositions comprenant des doses très élevées entre 100-20 000 fois To combat these deficiencies, operated patients are supplemented with compositions comprising a mixture of vitamins and minerals. Mention may be made, by way of example, of the compositions marketed under the brand names LIFINOV®, SURGILINE®, WLS FORTE BYPASS®, WLS OPTIMUM SLEEVE®, BARINUTRICS® and VECTIPASS®. These compositions are in the form of a tablet or capsule for immediate release in the stomach, and have a particularly high dosage of the nutrients they contain, in order to compensate for the reduction in the digestive absorption surface and the malabsorption of nutrients. This is because changes made to the stomach in the form of partial ablation or the placement of a gastric band have the effect of greatly reducing the surface area of absorption of vitamins and minerals by the stomach. The same applies when a bypass or "bypass" is in place: the intestinal absorption surface is also reduced. Therefore, there is uncertainty about the amount of vitamin and mineral actually absorbed from the digestive tract. In addition, these compositions comprising very high doses between 100-20,000 times
2 2
FEUILLES DE REMPLACEMENT (RÈGLE 26) la valeur nutritionnelle de référence, sont en pratique peu efficaces. En effet, la trop grande quantité de minéraux et de vitamines a pour effet de perturber leur absorption. Par ailleurs, ces compositions comprennent des éléments tels que le manganèse, l'iode et le chrome pour lesquels il n’existe pas de donnée dans la littérature montrant qu’il existe un risque de carence. La malabsorption est définie par l’incapacité du tube digestif à absorber une grande partie des substances alimentaires, nécessaires au maintien d’une santé correcte. En effet, en raison des modifications anatomiques engendrées par la chirurgie, les aliments arrivent plus vite dans le tube digestif et n’ont donc pas le temps d’être imprégnés par les enzymes digestives et d’être absorbés par la paroi du tube digestif. De plus, les aliments parviennent au niveau du jéjunum, la deuxième partie de l’intestin grêle : la surface d’absorption est donc réduite. SUBSTITUTE SHEETS (RULE 26) the nutritional reference value, are in practice ineffective. Indeed, too much minerals and vitamins have the effect of disrupting their absorption. Furthermore, these compositions include elements such as manganese, iodine and chromium for which there is no data in the literature showing that there is a risk of deficiency. Malabsorption is defined as the inability of the digestive tract to absorb much of the food substances necessary to maintain good health. Indeed, due to the anatomical changes caused by the surgery, food arrives faster in the digestive tract and therefore does not have time to be impregnated by digestive enzymes and to be absorbed by the wall of the digestive tract. In addition, food reaches the jejunum, the second part of the small intestine: the absorption surface is therefore reduced.
[0009] Un autre élément à prendre en compte est que la chirurgie bariatrique, si elle permet une forte perte de poids et une amélioration considérable du diabète de type 2 et des maladies cardiovasculaires notamment, nécessite une modification drastique des habitudes alimentaires, un suivi médical et très souvent une supplémentation en vitamines et minéraux à vie. Or, l’observance du traitement diminue avec le temps, ce qui peut entraîner l’échec du traitement et des pathologies liées aux carences observées chez le patient. [0009] Another element to take into account is that bariatric surgery, if it allows a strong weight loss and a considerable improvement in type 2 diabetes and cardiovascular diseases in particular, requires a drastic change in eating habits, medical monitoring and very often lifelong vitamin and mineral supplementation. However, treatment adherence decreases over time, which can lead to treatment failure and pathologies related to the deficiencies observed in the patient.
[0010] On connaît le document US 2005/0214388 A1 qui porte sur une composition de magnésium comprenant une forme orale à libération immédiate et une forme orale à libération retardée. Cependant, ce document n’aborde pas le problème des patients opérés par chirurgie bariatrique ayant des problèmes particuliers d’absorption. [0010] Document US 2005/0214388 A1 is known which relates to a magnesium composition comprising an oral form with immediate release and an oral form with delayed release. However, this document does not address the problem of patients undergoing bariatric surgery with particular absorption problems.
[001 1 ] Enfin, les problèmes de santé mentale tels que la dépression et la boulimie sont fréquents chez les patients devant subir une opération de chirurgie bariatrique. Si l’opération permet chez certains patients de soulager ces problèmes, de nombreux patients continuent de montrer des signes de dépression et d’anxiété malgré la chirurgie. [0011] Finally, mental health problems such as depression and bulimia are frequent in patients having to undergo bariatric surgery. While the operation helps some patients alleviate these problems, many patients continue to show signs of depression and anxiety despite the surgery.
[0012] Il existe donc un besoin de proposer des compositions comprenant un mélange de vitamines, en particulier la vitamine B12, d’acides aminés et de minéraux pour [0012] There is therefore a need to provide compositions comprising a mixture of vitamins, in particular vitamin B12, amino acids and minerals for
3 3
FEUILLES DE REMPLACEMENT (RÈGLE 26) supplémenter les patients carencés, et notamment les patients ayant subi une opération de chirurgie bariatrique. SUBSTITUTE SHEETS (RULE 26) supplement deficient patients, and in particular patients who have undergone bariatric surgery.
[0013] RESUME DE L’INVENTION [0013] SUMMARY OF THE INVENTION
[0014] Ces objectifs sont atteints grâce aux compositions selon l’invention et leur utilisation. [0014] These objectives are achieved by virtue of the compositions according to the invention and their use.
[0015] La présente invention concerne une composition comprenant un mélange d’au moins la vitamine B12 et d’au moins un minéral se présentant sous forme de deux formes orales solides : une première forme orale solide gastro-soluble et une seconde forme orale solide gastro-résistante. The present invention relates to a composition comprising a mixture of at least vitamin B12 and at least one mineral in the form of two solid oral forms: a first gastro-soluble solid oral form and a second solid oral form gastro-resistant.
[0016] Dans un mode de réalisation préféré, la forme orale solide gastro-soluble et la forme orale solide gastro-résistante formant la composition selon l’invention sont administrées concomitamment. [0016] In a preferred embodiment, the gastro-soluble solid oral form and the gastro-resistant solid oral form forming the composition according to the invention are administered concomitantly.
[0017] Dans un mode de réalisation préféré, les deux formes orales solides sont une gélule. [0017] In a preferred embodiment, the two solid oral forms are a capsule.
[0018] Avantageusement, la composition selon l’invention comprend en outre au moins une vitamine choisie parmi la vitamine A, D, E, B1 , B2, B3, B5, B6, B8, B9 et C et leurs combinaisons. [0018] Advantageously, the composition according to the invention further comprises at least one vitamin chosen from vitamin A, D, E, B1, B2, B3, B5, B6, B8, B9 and C and their combinations.
[0019] Avantageusement, l’au moins un minéral est choisi parmi le fer, le zinc, le sélénium, le calcium et leurs combinaisons. [0019] Advantageously, at least one mineral is chosen from iron, zinc, selenium, calcium and their combinations.
[0020] Avantageusement, la composition selon l’invention ne comprend pas au moins un des minéraux choisi parmi le magnésium, le manganèse, le chrome, le molybdène, l’iode et leurs combinaisons. [0020] Advantageously, the composition according to the invention does not comprise at least one of the minerals chosen from magnesium, manganese, chromium, molybdenum, iodine and their combinations.
[0021 ] De préférence, la composition selon l’invention ne comprend pas de magnésium. [0021] Preferably, the composition according to the invention does not include magnesium.
[0022] Avantageusement, la composition selon l’invention comprend l’au moins une vitamine et l’au moins un minéral en quantités comprises entre 10% et 100%, de préférence entre 15% et 50% des valeurs nutritionnelles de référence. [0022] Advantageously, the composition according to the invention comprises at least one vitamin and at least one mineral in amounts of between 10% and 100%, preferably between 15% and 50% of the nutritional reference values.
[0023] Avantageusement, la composition selon l’invention peut en outre comprendre du cuivre en une quantité comprise entre 50% et 500%, de préférence entre 100% Advantageously, the composition according to the invention can further comprise copper in an amount of between 50% and 500%, preferably between 100%
4 4
FEUILLES DE REMPLACEMENT (RÈGLE 26) et 300%, de manière davantage préférée à environ 200% des valeurs nutritionnelles de référence. SUBSTITUTE SHEETS (RULE 26) and 300%, more preferably at about 200% of the nutritional reference values.
[0024] Avantageusement, la vitamine B12 est comprise en une quantité comprise entre 5 000% à 20 000%, de préférence entre 12 000% à 18 000 %, de manière davantage préférée à environ 16 000% des valeurs nutritionnelles de référence. Advantageously, vitamin B12 is in an amount between 5000% to 20,000%, preferably between 12,000% to 18,000%, more preferably around 16,000% of the nutritional reference values.
[0025] Avantageusement, la composition comprend du calcium et de la vitamine D. [0025] Advantageously, the composition comprises calcium and vitamin D.
[0026] Avantageusement, la composition selon l’invention comprend en outre un nutriment supplémentaire choisi parmi la choline et/ou l’inositol. [0026] Advantageously, the composition according to the invention further comprises an additional nutrient chosen from choline and / or inositol.
[0027] Avantageusement, la composition selon l’invention comprend en outre au moins un excipient. [0027] Advantageously, the composition according to the invention further comprises at least one excipient.
[0028] La présente invention porte en outre sur la composition selon l’invention comprenant en outre du L-tryptophane et une levure. [0028] The present invention further relates to the composition according to the invention further comprising L-tryptophan and a yeast.
[0029] De préférence, la forme orale solide gastro-soluble et la forme orale solide gastro-résistante ont la même composition quantitative et qualitative. [0029] Preferably, the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same quantitative and qualitative composition.
[0030] La présente invention porte en outre sur la composition selon l’invention pour son utilisation chez des patients ayant subi au moins une opération de chirurgie bariatrique. [0030] The present invention further relates to the composition according to the invention for its use in patients who have undergone at least one bariatric surgery operation.
[0031 ] La présente invention porte en outre sur la composition selon l’invention pour son utilisation chez des patients devant subir au moins une opération de chirurgie bariatrique. [0031] The present invention further relates to the composition according to the invention for its use in patients to undergo at least one bariatric surgery operation.
[0032] Avantageusement, l’au moins une opération de chirurgie bariatrique peut être choisie parmi la gastrectomie longitudinale, l’anneau gastrique ajustable, le court- circuit gastrique et la dérivation biliopancréatique. [0032] Advantageously, at least one bariatric surgery operation can be chosen from among longitudinal gastrectomy, adjustable gastric band, gastric bypass and biliopancreatic bypass.
[0033] Avantageusement, la composition selon l’invention ne comprend pas de magnésium. [0033] Advantageously, the composition according to the invention does not include magnesium.
[0034] De préférence, la forme orale solide gastro-soluble et la forme orale solide gastro-résistante ont la même composition qualitative et quantitative. [0034] Preferably, the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same qualitative and quantitative composition.
5 5
FEUILLES DE REMPLACEMENT (RÈGLE 26) [0035] DESCRIPTION DETAILLEE DE L’INVENTION SUBSTITUTE SHEETS (RULE 26) [0035] DETAILED DESCRIPTION OF THE INVENTION
[0036] La présente invention concerne une composition comprenant un mélange d’au moins la vitamine B12 et d’au moins un minéral se présentant sous forme de deux formes orales solides : une première forme orale solide gastro-soluble et une seconde forme orale solide gastro-résistante. Dans un mode de réalisation préféré, la forme orale solide gastro-soluble et la forme orale solide gastro-résistante ont la même composition en vitamines et minéraux. The present invention relates to a composition comprising a mixture of at least vitamin B12 and at least one mineral in the form of two solid oral forms: a first solid oral gastro-soluble form and a second solid oral form gastro-resistant. In a preferred embodiment, the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same vitamin and mineral composition.
[0037] La présente invention propose donc une composition se présentant sous la forme d’une association de deux formes orales solides. La première forme orale solide est gastro-soluble, c’est-à-dire à libération immédiate, et libère son contenu dans l’estomac. Une telle forme orale solide gastro-soluble séjourne dans l’estomac pendant une période comprise entre 10 et 30 min, de préférence 15 min. On entend par « gastro-soluble » une forme galénique ou pharmaceutique permettant la libération du/des principe(s) actif (s) (ou du / des constituant (s)) dans l’estomac. [0037] The present invention therefore provides a composition which is in the form of a combination of two solid oral forms. The first solid oral form is gastro-soluble, that is, immediate release, and releases its contents in the stomach. Such a gastro-soluble solid oral form stays in the stomach for a period of between 10 and 30 minutes, preferably 15 minutes. The term "gastro-soluble" means a galenic or pharmaceutical form allowing the release of the active principle (s) (or of the constituent (s)) in the stomach.
[0038] Selon la pharmacopée européenne, les conditions gastriques sont le plus souvent simulées par l’utilisation de solution d’acide chlorhydrique HCl à 0.1 M, pH 1 ,2. Le taux d’agitation est de 100 rpm pour un appareil à pâles ou de 10 rpm pour l’appareil à cylindres alternatifs. Le milieu de dissolution est maintenu à 37°C pour mimer les conditions physiologiques. Dans ces conditions, il est observé que la forme orale solide gastro-soluble selon l’invention libère au moins 50%, de préférence au moins 60%, de manière davantage préférée au moins 70%, de manière encore plus préférée au moins 80%, de manière plus préférée 100% des vitamines et minéraux qu’elle contient. [0038] According to the European Pharmacopoeia, gastric conditions are most often simulated by the use of 0.1 M hydrochloric acid HCl solution, pH 1, 2. The stirring rate is 100 rpm for a paddle apparatus or 10 rpm for the reciprocating cylinder apparatus. The dissolution medium is maintained at 37 ° C to mimic the physiological conditions. Under these conditions, it is observed that the gastro-soluble solid oral form according to the invention releases at least 50%, preferably at least 60%, more preferably at least 70%, even more preferably at least 80%. , more preferably 100% of the vitamins and minerals it contains.
[0039] La seconde forme orale solide gastro-résistante est conçue pour libérer les vitamines et minéraux qu’elle contient dans l’intestin. On entend par « gastro résistante » une forme galénique qui ne se dissout pas dans l’estomac. De telles formes galéniques sont à libération différée c’est-à-dire qu’elles présentent un enrobage ou une composition d’enrobage résistant au pH acide de l’estomac (pH<2) pour se dissoudre dans l’intestin. Le caractère gastrosoluble ou gastrorésistant est déterminé en suivant le test établi par la Pharmacopée européenne. [0039] The second gastro-resistant solid oral form is designed to release the vitamins and minerals it contains in the intestine. By "gastro-resistant" is meant a dosage form that does not dissolve in the stomach. Such dosage forms are delayed release, that is, they have a coating or coating composition resistant to the acidic pH of the stomach (pH <2) to dissolve in the intestine. The gastrosoluble or gastro-resistant character is determined by following the test established by the European Pharmacopoeia.
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FEUILLES DE REMPLACEMENT (RÈGLE 26) [0040] Le caractère gastrosoluble d’une gélule est mesuré dans de l’eau distillée à 37°C comme milieu de désagrégation. Si le temps de désagrégation d’une gélule est inférieur ou égal à 30 min, la gélule est considérée comme gastrosoluble. De préférence, la gélule gastrosoluble selon la présente invention se désagrège en 15 minutes. SUBSTITUTE SHEETS (RULE 26) The gastrosoluble nature of a capsule is measured in distilled water at 37 ° C as a disintegration medium. If the disintegration time of a capsule is less than or equal to 30 min, the capsule is considered to be gastrosoluble. Preferably, the gastrosoluble capsule according to the present invention disintegrates within 15 minutes.
[0041 ] Le caractère gastrorésistant d’une gélule est mesuré dans de l’acide chlorhydrique 0, 1 M à 37°C comme milieu de désagrégation dans un appareil à désagrégation. Ce milieu mime les conditions physicochimiques de l’estomac. Les gélules sont incubées dans ce milieu pendant 1 h. La gélule ne doit présenter ni signe de désagrégation, ni fissure pouvant entraîner une perte de contenu. La gélule est ensuite incubée pendant 1 h dans une solution de tampon phosphate de pH 6,8 à 37°C, cette solution mimant les conditions du milieu intestinal conformément aux recommandations de la pharmacopée européenne. La gélule doit être totalement désagrégée en moins d’une heure. De préférence, la libération de la composition selon l’invention est retardée entre 40 minutes et 1 heure. [0041] The gastro-resistant character of a capsule is measured in 0.1 M hydrochloric acid at 37 ° C as a disintegration medium in a disintegration apparatus. This medium mimics the physicochemical conditions of the stomach. The capsules are incubated in this medium for 1 h. The capsule must not show signs of disintegration or cracks which could lead to loss of content. The capsule is then incubated for 1 h in a phosphate buffer solution of pH 6.8 at 37 ° C., this solution mimicking the conditions of the intestinal environment in accordance with the recommendations of the European Pharmacopoeia. The capsule should be completely disintegrated within an hour. Preferably, the release of the composition according to the invention is delayed between 40 minutes and 1 hour.
[0042] Les vitamines et minéraux sont donc également absorbés au niveau de l’intestin ce qui augmente la quantité de vitamines et minéraux effectivement absorbée par le patient, contrairement aux compositions de l’art antérieur qui ne sont qu’à libération gastrique. Ainsi, la combinaison des deux formes orales solides à libération différente, c’est-à-dire l’une dans l’estomac et l’autre dans l’intestin, permet au patient de bénéficier et d’absorber avec une plus grande certitude les vitamines et minéraux dont il a besoin. Au sens de l’invention, le patient est humain. La composition selon l’invention n’est pas une composition vétérinaire. [0042] The vitamins and minerals are therefore also absorbed from the intestine, which increases the amount of vitamins and minerals actually absorbed by the patient, unlike the compositions of the prior art which are only for gastric release. Thus, the combination of the two solid oral forms with different release i.e. one in the stomach and the other in the intestine allows the patient to benefit and absorb with greater certainty the vitamins and minerals it needs. For the purposes of the invention, the patient is human. The composition according to the invention is not a veterinary composition.
[0043] Le mécanisme de libération des vitamines et minéraux contenus dans la composition est de même nature au niveau gastrique et intestinal. Cependant, l’association des deux formes orales solides, l’une gastro-soluble et l’autre gastro résistante, permet une libération des minéraux et vitamines à des temps et des localisations anatomiques différents. L’association de ces deux formes orales solides permet également d’obtenir une composition en vitamines et minéraux optimisée, sans surdosage excessif pour une meilleure absorption du produit, les vitamines et les minéraux absorbés en une seule fois l’excès est directement éliminé ou stocké dans le foie pour les vitamines A, D, E et K. The mechanism for releasing the vitamins and minerals contained in the composition is of the same nature at the gastric and intestinal level. However, the combination of the two solid oral forms, one gastro-soluble and the other gastro-resistant, allows the release of minerals and vitamins at different times and anatomical locations. The combination of these two solid oral forms also makes it possible to obtain an optimized vitamin and mineral composition, without excessive overdose for better absorption of the product, the vitamins and minerals absorbed at one time the excess is directly eliminated or stored. in the liver for vitamins A, D, E and K.
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FEUILLES DE REMPLACEMENT (RÈGLE 26) [0044] La chirurgie bariatrique modifie profondément le fonctionnement du tube digestif et réduit de manière importante la surface d’absorption de l’estomac, et parfois de l’intestin également. Contrairement aux compositions de l’art antérieur exclusivement gastro-solubles, la composition selon l’invention permet d’utiliser au maximum la surface d’absorption modifiée par la chirurgie. De par son action complémentaire au niveau gastrique et au niveau intestinal, la composition selon l’invention permet donc d’obtenir une libération à différentes localisations anatomiques. SUBSTITUTE SHEETS (RULE 26) [0044] Bariatric surgery profoundly modifies the functioning of the digestive tract and significantly reduces the absorption surface of the stomach, and sometimes of the intestine as well. Unlike the compositions of the prior art which are exclusively gastro-soluble, the composition according to the invention allows maximum use of the absorption surface modified by surgery. By virtue of its complementary action at the gastric level and at the intestinal level, the composition according to the invention therefore makes it possible to obtain a release at different anatomical locations.
[0045] Grâce au rééquilibrage des niveaux minéraux et de vitamine B12, le patient est également en meilleur santé physique. Par ailleurs, la supplémentation en vitamine B12 et en minéraux permet également de rétablir l’équilibre neurochimique et par conséquent d’améliorer l’état de santé psychologique du patient. Le patient ressent une sensation de bien-être grâce à la composition selon l’invention. Une dose de composition comprend la forme orale solide gastro-soluble et la forme orale solide gastro-résistante : il suffit donc d’une dose quotidienne pour apporter aux patients carencés les vitamines et minéraux nécessaires au bon fonctionnement de leur corps sur le plan physique et psychique. L’obtention d’une amélioration sur le plan physique et psychologique grâce à une seule dose facilite l’observance du traitement par le patient. [0045] Thanks to the rebalancing of the mineral and vitamin B12 levels, the patient is also in better physical health. In addition, vitamin B12 and mineral supplementation also helps to restore neurochemical balance and therefore improve the patient's psychological health. The patient feels a sensation of well-being thanks to the composition according to the invention. One dose of composition includes the gastro-soluble solid oral form and the gastro-resistant solid oral form: a daily dose is therefore sufficient to provide deficient patients with the vitamins and minerals necessary for the proper functioning of their body on the physical level and psychic. Achieving physical and psychological improvement from a single dose makes it easier for the patient to comply with treatment.
[0046] La vitamine B12 est absorbée selon deux mécanismes : (i) l’absorption active via le facteur intrinsèque (Fl) produit par la paroi gastrique et permettant le transport de la vitamine B12 à travers la paroi intestinale ; et (ii) l’absorption passive correspondant à la diffusion passive de la vitamine B12 à travers les muqueuses digestives. Cependant, ce dernier mécanisme d’absorption ne permet d’absorber qu’1 % de la vitamine B12 ingérée. [0046] Vitamin B12 is absorbed by two mechanisms: (i) active absorption via intrinsic factor (Fl) produced by the gastric wall and allowing the transport of vitamin B12 through the intestinal wall; and (ii) passive absorption corresponding to the passive diffusion of vitamin B12 through the digestive mucous membranes. However, this latter mechanism of absorption only absorbs 1% of the vitamin B12 ingested.
[0047] Plus exactement, le trajet de la vitamine B12 est le suivant. Dans la bouche, la vitamine B12 est liée à la protéine R contenue dans la salive. La liaison de la vitamine B12 à la protéine R permet de protéger la vitamine de la dégradation dans l’estomac en raison du pH acide. En parallèle, la paroi gastrique synthétise et sécrète le facteur intrinsèque (Fl). Lorsque l’ensemble vitamine B12-protéine R se retrouve dans le duodénum, l’ensemble vitamine B12-protéine R se retrouve en contact avec une enzyme sécrétée par le pancréas, permettant de cliver l’ensemble More exactly, the path of vitamin B12 is as follows. In the mouth, vitamin B12 is linked to the R protein found in saliva. Binding vitamin B12 to R protein helps protect the vitamin from being broken down in the stomach due to the acidic pH. In parallel, the gastric wall synthesizes and secretes the intrinsic factor (Fl). When the vitamin B12-protein R set is found in the duodenum, the vitamin B12-protein R set comes into contact with an enzyme secreted by the pancreas, making it possible to cleave the whole
8 8
FEUILLES DE REMPLACEMENT (RÈGLE 26) et de libérer la vitamine B12 de la protéine R. La vitamine B12 se lie alors au facteur intrinsèque. L’ensemble vitamine B12-FI passe dans l’iléon. Le facteur intrinsèque se lie aux transporteurs situés dans la membrane de l’iléon et permet de faire passer la vitamine B12 à travers la muqueuse intestinale. La vitamine B12 se retrouve alors dans le sang où elle se lie à son transporteur spécifique, la transcobalamine, pour être transportée vers les tissus cibles et le foie. De préférence, la composition selon l’invention comprenant de la vitamine B12 comprend en outre du calcium car le calcium participe à la bonne absorption de la vitamine B12. SUBSTITUTE SHEETS (RULE 26) and to release vitamin B12 from protein R. Vitamin B12 then binds to intrinsic factor. The whole vitamin B12-FI passes into the ileum. Intrinsic factor binds to transporters located in the ileum membrane and allows vitamin B12 to pass through the intestinal mucosa. Vitamin B12 is then found in the blood where it binds to its specific transporter, transcobalamin, to be transported to target tissues and the liver. Preferably, the composition according to the invention comprising vitamin B12 further comprises calcium because calcium participates in the good absorption of vitamin B12.
[0048] Or, la réduction de la surface gastrique par chirurgie bariatrique implique la réduction de la synthèse de facteur intrinsèque. La quantité de vitamine B12 se trouve d’autant réduite. Pour surmonter cet obstacle, la vitamine B12 est administrée en une quantité comprise entre 5 000% et 20 000%, de préférence entre 10 000% et 18 000%, de manière davantage préférée d’environ 16 000 % des valeurs nutritionnelles de référence afin d’optimiser la diffusion passive ainsi que la liaison à la quantité de facteur intrinsèque effectivement produite et disponible. La formulation de la composition selon l’invention en deux formes orales solides à libération différente, une dans l’estomac et l’autre dans l’intestin, permet de maximiser la possibilité de diffusion passive et de liaison au facteur intrinsèque. Ceci est particulièrement important pour les patients ayant subi un court-circuit gastrique ou une dérivation bilio-pancréatique chez lesquels la restriction gastrique est associée à la malabsorption. However, the reduction of the gastric surface by bariatric surgery involves the reduction of the synthesis of intrinsic factor. The amount of vitamin B12 is further reduced. To overcome this obstacle, vitamin B12 is administered in an amount of between 5,000% and 20,000%, preferably between 10,000% and 18,000%, more preferably about 16,000% of the nutritional reference values in order to optimize passive diffusion as well as binding to the quantity of intrinsic factor actually produced and available. The formulation of the composition according to the invention in two solid oral forms with different release, one in the stomach and the other in the intestine, makes it possible to maximize the possibility of passive diffusion and of binding to the intrinsic factor. This is particularly important for patients with gastric bypass or biliopancreatic bypass in whom gastric restriction is associated with malabsorption.
[0049] Le Règlement européen n° 1169/2011 définit la valeur nutritionnelle de référence pour la vitamine B12 à 2,5 pg. Ainsi, la composition selon l’invention peut comprendre entre 12.5 mg et 50 mg, de préférence entre 25 mg et 45 mg, de manière davantage préférée environ 40 mg. European Regulation No. 1169/2011 defines the reference nutritional value for vitamin B12 at 2.5 pg. Thus, the composition according to the invention can comprise between 12.5 mg and 50 mg, preferably between 25 mg and 45 mg, more preferably around 40 mg.
[0050] Vitamines autres que la vitamine B12, minéraux et acides aminés [0050] Vitamins other than vitamin B12, minerals and amino acids
[0051 ] Compte tenu de la réduction de la surface d’absorption combinée ou non à la malabsorption induites par la chirurgie bariatrique, la quantité de vitamines et minéraux effectivement absorbée par le système digestif modifié est considérablement réduite. La composition selon l’invention permet d’apporter en tout ou partie les minéraux et vitamines essentiels au corps humain, en une dose. [0051] Taking into account the reduction in the absorption surface combined or not with the malabsorption induced by bariatric surgery, the amount of vitamins and minerals actually absorbed by the modified digestive system is considerably reduced. The composition according to the invention makes it possible to provide all or part of the minerals and vitamins essential to the human body, in one dose.
9 9
FEUILLES DE REMPLACEMENT (RÈGLE 26) De plus, la composition selon l’invention permet de maintenir ou rétablir le bien- être moral des patients. SUBSTITUTE SHEETS (RULE 26) Furthermore, the composition according to the invention makes it possible to maintain or restore the moral well-being of patients.
[0052] Notamment, la composition selon l’invention peut en outre comprendre au moins une vitamine parmi la vitamine A, D, E, B1 , B2, B3, B5, B6, B8, B9 et C et leurs combinaisons. [0052] In particular, the composition according to the invention may further comprise at least one vitamin from among vitamin A, D, E, B1, B2, B3, B5, B6, B8, B9 and C and their combinations.
[0053] Une vitamine est une substance organique nécessaire en faible quantité au métabolisme d'un organisme vivant et qui ne peut être produite par le corps humain. Les vitamines nécessitent donc d’être amenées par l’alimentation (voir Lieberman, S, Bruning, N (1990). The Real Vitamin & Minerai Book. NY: Avery Group, 3). Les vitamines sont de puissants antioxydants. La vitamine A est nécessaire pour la vision. La vitamine E permet de maintenir une bonne santé cardiovasculaire. Les huit vitamines hydrosolubles du groupe B contribuent à de nombreuses réactions métaboliques et notamment à un bien-être psychologique. Par exemple, la vitamine B1 contribue à la conduction de l’influx nerveux et la vitamine B6 entre dans la synthèse des neurotransmetteurs. Les vitamines B2, B3, B5 et B8 participent au métabolisme des acides gras. La vitamine C est un cofacteur enzymatique impliqué dans les réactions d’hydroxylation physiologiques telles que la synthèse du collagène et des globules rouges, et contribue au système immunitaire. A vitamin is an organic substance necessary in small quantities for the metabolism of a living organism and which cannot be produced by the human body. Vitamins therefore need to be supplied through food (see Lieberman, S, Bruning, N (1990). The Real Vitamin & Minerai Book. NY: Avery Group, 3). Vitamins are powerful antioxidants. Vitamin A is necessary for vision. Vitamin E helps maintain good cardiovascular health. The eight water-soluble vitamins of the B group contribute to numerous metabolic reactions and in particular to psychological well-being. For example, vitamin B1 helps conduction of nerve impulses, and vitamin B6 is used in the synthesis of neurotransmitters. Vitamins B2, B3, B5 and B8 participate in the metabolism of fatty acids. Vitamin C is an enzymatic cofactor involved in physiological hydroxylation reactions such as the synthesis of collagen and red blood cells, and contributes to the immune system.
[0054] De préférence, la composition selon l’invention comprend en outre les vitamines A, D, E, B1 , B2, B3, B5, B6, B8, B9 et C, ce qui permet d’obtenir une composition la plus complète possible et palliant le maximum de carences possibles. Preferably, the composition according to the invention further comprises vitamins A, D, E, B1, B2, B3, B5, B6, B8, B9 and C, which makes it possible to obtain a most complete composition. possible and overcoming as many deficiencies as possible.
[0055] La composition selon l’invention peut comprendre les vitamines autres que la vitamine B12 en quantité comprises entre 10% et 100%, de préférence entre 15% et 50% des valeurs nutritionnelles de référence (VNR), de manière davantage préférée à environ 15% des VNR. En effet, l’Annexe XIII du Règlement UE N°1 169/201 1 concernant l’information des consommateurs sur les denrées alimentaires impose de doser les vitamines et minéraux à une quantité minimale de 15% des VNR comme reproduit ci-dessous : The composition according to the invention can comprise vitamins other than vitamin B12 in an amount of between 10% and 100%, preferably between 15% and 50% of the nutritional reference values (NRV), more preferably at around 15% of NRVs. Indeed, Annex XIII of EU Regulation No. 1 169/201 1 concerning consumer information on foodstuffs requires that vitamins and minerals be dosed at a minimum quantity of 15% of the NRVs as reproduced below:
[0056] [Tableau 1 ]
Figure imgf000011_0001
[0056] [Table 1]
Figure imgf000011_0001
10 10
FEUILLES DE REMPLACEMENT (RÈGLE 26)
Figure imgf000012_0001
SUBSTITUTE SHEETS (RULE 26)
Figure imgf000012_0001
[0057] Il est également intéressant d’administrer des minéraux dans la composition selon l’invention. Les minéraux, également désignés par le terme « oligoélément », sont des ions métalliques présents dans l’organisme en très faible quantité. Cela permet de proposer au patient une composition la plus complète possible et de diminuer le nombre de médicaments ou compléments à prendre par jour. La composition selon l’invention peut en effet comprendre au moins un élément parmi le fer, le cuivre, le zinc, le sélénium et le calcium et leurs combinaisons. De préférence, la composition selon l’invention comprend du fer, du cuivre, du zinc, de sélénium et du calcium. [0057] It is also of interest to administer minerals in the composition according to the invention. Minerals, also referred to by the term "trace element", are metal ions present in the body in very small quantities. This makes it possible to offer the patient a composition as complete as possible and to reduce the number of drugs or supplements to be taken per day. The composition according to the invention can in fact comprise at least one element from iron, copper, zinc, selenium and calcium and their combinations. Preferably, the composition according to the invention comprises iron, copper, zinc, selenium and calcium.
[0058] Le fer est un élément essentiel au transport de l’oxygène par l’hémoglobine. Il est donc intéressant que la composition selon l’invention comprenne également du il [0058] Iron is essential for the transport of oxygen by hemoglobin. It is therefore interesting that the composition according to the invention also includes
FEUILLES DE REMPLACEMENT (RÈGLE 26) fer afin d’éviter une supplémentation parallèle. Il est en outre particulièrement avantageux d’associer vitamine C et fer dans la même composition. En effet, la vitamine C est essentielle à la bonne absorption du fer. Combiner ces deux éléments dans la même composition permet d’associer le bénéfice de la vitamine C sur la peau, la cicatrisation, la perte de poids et la diminution des troubles de l’humeur à la bonne absorption du fer. SUBSTITUTE SHEETS (RULE 26) iron to avoid parallel supplementation. It is also particularly advantageous to combine vitamin C and iron in the same composition. Indeed, vitamin C is essential for the proper absorption of iron. Combining these two elements in the same composition makes it possible to combine the benefit of vitamin C on the skin, healing, weight loss and the reduction of mood disorders with the good absorption of iron.
[0059] Le calcium est également important pour une bonne densité osseuse, la formation des tissus, le confort digestif et un bon équilibre du système nerveux. Par conséquent, il est avantageux que la composition selon l’invention comprenne du calcium. Il est en outre particulièrement avantageux d’associer vitamine D et calcium dans la même composition. En effet, la grande majorité des personnes en France et en Europe du nord est en déficit de vitamine D, indépendamment du poids. La production de vitamine D est en effet induite par l’exposition du sujet au soleil. Il est donc intéressant de supplémenter les patients en vitamine D. En outre, la vitamine D est essentielle à la fixation du calcium sur les os. Dans un mode de réalisation particulièrement préféré, la composition selon l’invention comprend la vitamine B12, le calcium et la vitamine D. En effet, la présence de calcium permet de faciliter l’absorption de la vitamine B12 et, comme mentionné, la vitamine D aide à fixer le calcium. Ainsi, l’association de vitamine B12, vitamine D et calcium dans la même composition présente un effet synergique permettant d’une part au patient de bénéficier de la présence de ces trois nutriments essentiels pour lutter contre ces carences, et d’autre part d’augmenter l’assimilation de chacun de ces nutriments. Par ailleurs, les patients ayant subi une chirurgie bariatrique développent très fréquemment une ostéoporose. L’association de calcium et vitamine D permet de réduire le risque de développer une ostéoporose, ou le cas échéant de réduire l’ostéoporose chez les patients opérés. Calcium is also important for good bone density, tissue formation, digestive comfort and a good balance of the nervous system. Therefore, it is advantageous that the composition according to the invention comprises calcium. It is also particularly advantageous to combine vitamin D and calcium in the same composition. Indeed, the vast majority of people in France and northern Europe are deficient in vitamin D, regardless of weight. Vitamin D production is indeed induced by the subject's exposure to the sun. It is therefore interesting to supplement patients with vitamin D. In addition, vitamin D is essential for fixing calcium to the bones. In a particularly preferred embodiment, the composition according to the invention comprises vitamin B12, calcium and vitamin D. In fact, the presence of calcium makes it possible to facilitate the absorption of vitamin B12 and, as mentioned, vitamin D helps to fix calcium. Thus, the combination of vitamin B12, vitamin D and calcium in the same composition has a synergistic effect allowing the patient on the one hand to benefit from the presence of these three essential nutrients to fight against these deficiencies, and on the other hand to '' increase the assimilation of each of these nutrients. Moreover, patients who have undergone bariatric surgery very frequently develop osteoporosis. The combination of calcium and vitamin D helps reduce the risk of developing osteoporosis, or possibly reduce osteoporosis in patients who have had surgery.
[0060] La composition selon l’invention peut comprendre les minéraux en quantité comprises entre 10% et 100%, de préférence entre 15% et 50% des valeurs nutritionnelles de référence (VNR), de manière davantage préférée à 15% des VNR. Lorsque la composition comprend du cuivre, le cuivre est compris en une quantité comprise entre 50% et 500%, de préférence entre 100% et 300%, de manière davantage préférée à environ 200% des valeurs nutritionnelles de référence. En [0060] The composition according to the invention can comprise the minerals in an amount of between 10% and 100%, preferably between 15% and 50% of the nutritional reference values (NRV), more preferably at 15% of the NRV. When the composition comprises copper, the copper is in an amount of between 50% and 500%, preferably between 100% and 300%, more preferably at about 200% of the nutritional reference values. In
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FEUILLES DE REMPLACEMENT (RÈGLE 26) d’autres termes, lorsque la composition comprend du cuivre, le cuivre est compris en une quantité comprise entre 0.5 mg et 5 mg, de préférence entre 1 mg et 3 mg, de manière davantage préférée à environ 2 mg. SUBSTITUTE SHEETS (RULE 26) in other words, when the composition comprises copper, the copper is in an amount between 0.5 mg and 5 mg, preferably between 1 mg and 3 mg, more preferably about 2 mg.
[0061 ] La composition selon l’invention permet donc d’administrer les vitamines et minéraux en quantité suffisamment importante pour contrebalancer les effets de la chirurgie bariatrique sur l’absorption gastrique et/ou intestinale tout en évitant, ou à tout le moins, en réduisant le phénomène de malabsorption lié à une compétition entre minéraux et vitamines pour les transporteurs du tube digestif. En effet, plutôt que d’administrer de fortes doses de vitamines et minéraux dans l’estomac, la composition selon l’invention a pour principe d’administrer de plus faibles doses réparties entre l’estomac et l’intestin pour maximiser leur absorption. De plus, l’administration de la composition selon l’invention à dose faible mais répétée permet l’accumulation des vitamines et minéraux dans l’organisme, et de réduire ainsi les carences. The composition according to the invention therefore makes it possible to administer the vitamins and minerals in an amount large enough to counterbalance the effects of bariatric surgery on gastric and / or intestinal absorption while avoiding, or at the very least, in reducing the phenomenon of malabsorption linked to competition between minerals and vitamins for digestive tract transporters. Indeed, rather than administering large doses of vitamins and minerals into the stomach, the composition according to the invention is based on the principle of administering smaller doses distributed between the stomach and the intestine to maximize their absorption. In addition, the administration of the composition according to the invention at a low but repeated dose allows the accumulation of vitamins and minerals in the body, and thus to reduce the deficiencies.
[0062] L’agence européenne de sécurité alimentaire EFSA définit la valeur nutritionnelle de référence (VNR) comme un ensemble de valeurs alimentaires numériques qui couvrent : les besoins nutritionnels moyens, la référence nutritionnelle pour la population, l’apport satisfaisant et l’intervalle de référence des macronutriments. Ces valeurs guident les professionnels quant aux quantités de nutriments nécessaires pour maintenir l’équilibre d’une personne ou d’un groupe de personnes par ailleurs en bonne santé. Les VNR couvrent également la limite supérieure de sécurité qui correspond à la quantité maximale d'un nutriment susceptible d’être consommé en toute sécurité sur une longue période de temps. The European food safety agency EFSA defines the nutritional reference value (NRV) as a set of numerical food values which cover: the average nutritional needs, the nutritional reference for the population, the satisfactory intake and the interval reference macronutrient. These values guide professionals as to the amounts of nutrients needed to maintain the balance of an otherwise healthy person or group of people. The NRVs also cover the upper safe limit which is the maximum amount of a nutrient that can be safely consumed over a long period of time.
[0063] Les apports journaliers recommandés (AJR) sont des valeurs-repères utilisées en tant que référence pour l'étiquetage des produits alimentaires, et fournissent une indication sur les apports journaliers en micronutriments (vitamines et minéraux) nécessaires à un adulte-type moyen. Ils ont été introduits par la Directive UE 1990/496. Le Règlement 1169/2011 a remplacé les AJR par les VNR. The recommended daily intakes (RDI) are benchmarks used as a reference for the labeling of food products, and provide an indication of the daily intakes of micronutrients (vitamins and minerals) necessary for an average adult-type . They were introduced by EU Directive 1990/496. Regulation 1169/2011 replaced the AJR by the VNR.
[0064] Toutefois, la composition selon l’invention peut ne pas comprendre au moins un des éléments choisi parmi le magnésium, le manganèse, le chrome, le molybdène, l’iode et leurs combinaisons. De préférence, la composition selon l’invention ne comprend pas de magnésium. En effet, il n’existe aucun élément [0064] However, the composition according to the invention may not comprise at least one of the elements chosen from magnesium, manganese, chromium, molybdenum, iodine and their combinations. Preferably, the composition according to the invention does not include magnesium. Indeed, there is no element
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FEUILLES DE REMPLACEMENT (RÈGLE 26) dans la littérature scientifique indiquant que les patients obèses présentent, avant ou après leur opération de chirurgie bariatrique, une carence dans l’un de ces éléments. Par ailleurs, le chrome est mal éliminé et tend à s’accumuler dans l’organisme. Ainsi, ne pas inclure ces éléments permet d’éviter de saturer inutilement des transporteurs et éviter les problèmes de malabsorption rencontrés avec les compositions de l’art antérieur. SUBSTITUTE SHEETS (RULE 26) in the scientific literature indicating that obese patients present, before or after their bariatric surgery, a deficiency in one of these elements. In addition, chromium is poorly eliminated and tends to accumulate in the body. Thus, not including these elements makes it possible to avoid unnecessarily saturating transporters and to avoid the problems of malabsorption encountered with the compositions of the prior art.
[0065] Dans un mode de réalisation préféré selon n’importe quel objet de la présente invention, la composition selon l’invention peut également comprendre un nutriment supplémentaire choisi parmi la choline, l’inositol et leur combinaison. L’inositol et la choline sont également des précurseurs de neurotransmetteurs et notamment de sérotonine, ce qui contribue au bien-être psychologique du patient et à la réduction de son état dépressif. La choline est en outre un draineur du foie. De préférence, l’inositol est sous forme de méso-inositol. [0065] In a preferred embodiment according to any object of the present invention, the composition according to the invention can also comprise an additional nutrient chosen from choline, inositol and their combination. Inositol and choline are also precursors of neurotransmitters, including serotonin, which contributes to the psychological well-being of the patient and to the reduction of his depressive state. Choline is also a drainer of the liver. Preferably, the inositol is in the form of mesoinositol.
[0066] Combinaison de L-tryptophane et d’au moins une levure [0066] Combination of L-tryptophan and at least one yeast
[0067] La présente invention a également pour objet la combinaison de L-tryptophane et d’au moins une levure, de préférence S. cerevisiae. Le L-Tryptophane est un précurseur de neurotransmetteurs, et notamment de la sérotonine. Or, il a été observé que les patients obèses, candidats à la chirurgie bariatrique ou ayant subi une chirurgie bariatrique, sont souvent déprimés. Une supplémentation en L- tryptophane permet d’augmenter le niveau de sérotonine et d’améliorer l’état dépressif de ces patients. [0067] A subject of the present invention is also the combination of L-tryptophan and at least one yeast, preferably S. cerevisiae. L-Tryptophan is a precursor of neurotransmitters, including serotonin. However, it has been observed that obese patients, candidates for bariatric surgery or who have undergone bariatric surgery, are often depressed. L-tryptophan supplementation increases serotonin levels and improves depression in these patients.
[0068] La levure permet d’apporter des acides aminés essentiels, des vitamines du groupe B notamment et des minéraux permettant de rétablir le bien-être psychologique des patients. La présence de levure permet également de combattre la chute des cheveux liée aux nombreuses carences observées chez les patients ayant subi une chirurgie bariatrique ou candidat à la chirurgie bariatrique. La levure peut être introduite sous forme d’extrait, c’est-à-dire une levure dans laquelle le contenu cellulaire a été retiré. L’extrait de levure est donc un mélange de peptides, d'acides aminés libres, de bases puriques et pyrimidiques ainsi que de vitamines hydrosolubles du groupe B. Dans un mode de réalisation préféré, la composition selon l’invention telle que décrite ci-dessus comprend la combinaison de L- tryptophane et d’au moins une levure selon l’invention. Ainsi, la composition selon [0068] The yeast makes it possible to provide essential amino acids, vitamins of group B in particular and minerals allowing to restore the psychological well-being of the patients. The presence of yeast also makes it possible to fight hair loss linked to the many deficiencies observed in patients who have undergone bariatric surgery or who are candidates for bariatric surgery. Yeast can be introduced as an extract, that is, a yeast in which the cell content has been removed. The yeast extract is therefore a mixture of peptides, free amino acids, purine and pyrimidine bases as well as water-soluble vitamins of group B. In a preferred embodiment, the composition according to the invention as described above. above comprises the combination of L-tryptophan and at least one yeast according to the invention. Thus, the composition according to
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FEUILLES DE REMPLACEMENT (RÈGLE 26) l’invention comprenant la combinaison de L-tryptophane et d’au moins une levure selon l’invention participe également au maintien et à la restauration des fonctions cognitives et du bien-être psychique du patient. SUBSTITUTE SHEETS (RULE 26) the invention comprising the combination of L-tryptophan and at least one yeast according to the invention also participates in the maintenance and restoration of the cognitive functions and of the mental well-being of the patient.
[0069] Mode d’administration et forme galénique [0069] Method of administration and dosage form
[0070] La composition selon l’invention est administrée par voie orale sous forme orale solide. De telles formes orales solides comprennent les comprimés enrobés ou non, les gélules, les sachets, les granulés et les capsules molles. [0070] The composition according to the invention is administered orally in solid oral form. Such solid oral forms include coated or uncoated tablets, hard capsules, sachets, granules and soft capsules.
[0071 ] De préférence, la forme orale solide est une gélule. On entend par « gélule » une forme galénique solide constituée d’une enveloppe dure utilisée pour l’administration d’au moins un principe actif ou ingrédient. Les gélules selon l’invention sont de préférence d’origine végétale, par exemple des dérivés cellulosiques, de préférence en hydroxypropylmethylcellulose (HPMC). De manière davantage préférée, elles ne contiennent pas d’élément choisi parmi le lactose, le gluten, le dioxyde de titane PO2, les phtalates et leurs combinaisons. Preferably, the solid oral form is a capsule. By "capsule" is meant a solid dosage form consisting of a hard shell used for the administration of at least one active principle or ingredient. The capsules according to the invention are preferably of plant origin, for example cellulose derivatives, preferably hydroxypropylmethylcellulose (HPMC). More preferably, they do not contain an element selected from lactose, gluten, titanium dioxide PO2, phthalates and their combinations.
[0072] La composition selon l’invention peut en outre comprendre au moins un excipient tel qu’un agent de charge, un lubrifiant, un arôme, un colorant, un émulsifiant, un agent de compression, un diluant, un conservateur, un gélifiant, un plastifiant, un tensioactif ou leurs combinaisons. The composition according to the invention can also comprise at least one excipient such as a bulking agent, a lubricant, a flavoring, a colorant, an emulsifier, a compression agent, a diluent, a preservative, a gelling agent. , a plasticizer, a surfactant or combinations thereof.
[0073] De préférence, la gélule gastro-soluble et la gélule gastro-résistante sont des gélules de taille 1 . Dans la pharmacopée française, une gélule de taille 1 présente une taille de 19 mm et volume de remplissage indicatif de la gélule fermée de 0,5 ml. Cette taille de gélule est particulièrement adaptée à la supplémentation à vie et permet donc d’améliorer le confort du patient. Cependant, l’homme du métier pourra adapter la taille de la gélule en fonction de l’utilisation. Preferably, the gastro-soluble capsule and the gastro-resistant capsule are size 1 capsules. In the French pharmacopoeia, a size 1 capsule has a size of 19 mm and an indicative filling volume of the closed capsule of 0.5 ml. This capsule size is particularly suitable for lifelong supplementation and therefore improves patient comfort. However, one skilled in the art will be able to adjust the size of the capsule depending on the use.
[0074] De préférence, la forme orale solide gastro-soluble et la forme orale solide gastro-résistante ont la même composition quantitative et qualitative. [0074] Preferably, the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same quantitative and qualitative composition.
[0075] Utilisation [0075] Use
[0076] La présente invention a également pour objet la composition selon l’invention telle qu’elle a été décrite pour son utilisation chez tout patient présentant des carences en minéraux et vitamines, et notamment en vitamine B12. Dans un mode de réalisation, la composition selon l’invention est utilisée chez des patients ayant [0076] A subject of the present invention is also the composition according to the invention as it has been described for its use in any patient with deficiencies in minerals and vitamins, and in particular in vitamin B12. In one embodiment, the composition according to the invention is used in patients with
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FEUILLES DE REMPLACEMENT (RÈGLE 26) subi au moins une opération de chirurgie bariatrique. En effet, les patients ayant subi une opération de chirurgie bariatrique sont particulièrement sujets aux carences en minéraux et en vitamines en raison de différents facteurs dont notamment l’importante réduction de la surface d’absorption suite à l’opération. De plus, ces patients présentent des troubles psychologiques tels que boulimie, dépression, anxiété et risque suicidaire. Les patients ayant subi une opération de chirurgie bariatrique sont donc particulièrement concernés par la nécessité de supplémenter leur alimentation par la composition selon l’invention. SUBSTITUTE SHEETS (RULE 26) had at least one weight loss surgery operation. Indeed, patients who have undergone bariatric surgery are particularly prone to mineral and vitamin deficiencies due to various factors including in particular the significant reduction in the absorption surface following the operation. In addition, these patients present with psychological disorders such as bulimia, depression, anxiety and risk of suicide. Patients who have undergone bariatric surgery are therefore particularly concerned by the need to supplement their diet with the composition according to the invention.
[0077] La composition selon l’invention peut également être utilisée chez des patients devant subir au moins une opération de chirurgie bariatrique. Il peut en effet être avantageux de supplémenter les patients avant de procéder à une opération de chirurgie bariatrique. Notamment, la réduction des carences en vitamines et en minéraux permet une meilleure récupération post-opératoire. [0077] The composition according to the invention can also be used in patients to undergo at least one bariatric surgery operation. It may indeed be advantageous to supplement patients before proceeding to bariatric surgery. In particular, the reduction of vitamin and mineral deficiencies allows better postoperative recovery.
[0078] Avantageusement, l’au moins une opération de chirurgie bariatrique peut être choisie parmi la gastrectomie longitudinale, l’anneau gastrique ajustable, le court- circuit gastrique et la dérivation biliopancréatique. Advantageously, at least one bariatric surgery operation can be chosen from longitudinal gastrectomy, adjustable gastric band, gastric bypass and biliopancreatic bypass.
[0079] On entend par « gastrectomie longitudinale » une méthode de gastrectomie comprenant une ablation longitudinale et partielle de l’estomac et consistant à retirer les deux tiers gauches de l’estomac. Cette technique est également appelée « gastrectomie partielle par plicature » ou « sleeve » en anglais car l’estomac ainsi réduit prend la forme d’un manchon. Cette méthode chirurgicale est irréversible. The term "longitudinal gastrectomy" means a method of gastrectomy comprising longitudinal and partial removal of the stomach and consisting in removing the left two-thirds of the stomach. This technique is also called "partial gastrectomy by plication" or "sleeve" in English because the stomach thus reduced takes the form of a sleeve. This surgical method is irreversible.
[0080] On entend par « anneau gastrique ajustable » une opération chirurgicale visant à placer un anneau autour de l’estomac, dans sa partie supérieure, ce qui a pour effet de restreindre son volume à une petite poche gastrique. Les patients atteignent ainsi plus rapidement le sentiment de satiété. By "adjustable gastric band" is meant a surgical operation to place a ring around the stomach, in its upper part, which has the effect of restricting its volume to a small gastric pocket. The patients thus reach the feeling of satiety more quickly.
[0081 ] Les méthodes reposant sur la réduction du volume gastrique, telles l’anneau gastrique ajustable et la gastrectomie longitudinale, impliquent très souvent une carence en minéraux et vitamines du fait de la réduction de la prise alimentaire et nécessitent une supplémentation à vie. [0081] Methods based on reducing gastric volume, such as adjustable gastric band and longitudinal gastrectomy, very often involve a deficiency in minerals and vitamins due to reduced food intake and require lifelong supplementation.
[0082] On entend par « court-circuit gastrique » une opération chirurgicale consistant à réduire le volume de l’estomac et à modifier le circuit alimentaire. Plus The term "gastric bypass" is understood to mean a surgical operation consisting in reducing the volume of the stomach and modifying the food circuit. More
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FEUILLES DE REMPLACEMENT (RÈGLE 26) exactement, la méthode de court-circuit gastrique consiste à faire une transsection verticale de l'estomac créant une poche proximale de capacité restreinte dans laquelle arrivent les aliments, reliée directement au jéjunum (par une anse en Y). Cette technique est également appelée « bypass » en anglais ainsi que « dérivation Roux en Y » du nom de son créateur César Roux. Cette méthode peut être réversible en cas de nécessité. SUBSTITUTE SHEETS (RULE 26) exactly, the gastric bypass method consists in making a vertical transection of the stomach creating a proximal pouch of restricted capacity in which the food arrives, connected directly to the jejunum (by a Y loop). This technique is also called "bypass" in English as well as "Roux en Y derivation" from the name of its creator César Roux. This method can be reversible if necessary.
[0083] On entend par « dérivation bilio-pancréatique » une opération chirurgicale comprenant une résection de l’estomac de 50-30% permettant de réduire l’acidité de l’estomac ainsi qu’une dérivation de la bile et du pancréas afin de causer une malabsorption des aliments. Les méthodes associant restriction du volume de l’estomac et malabsorption des aliments, tels la dérivation biliopancréatique et le court-circuit gastrique, causent inévitablement des carences en fer et en minéraux nécessitant une supplémentation à vie. The term "bilio-pancreatic derivation" is understood to mean a surgical operation comprising a resection of the stomach by 50-30% making it possible to reduce the acidity of the stomach as well as a derivation of the bile and the pancreas in order to cause food malabsorption. Methods that combine restriction of stomach volume with malabsorption of food, such as biliopancreatic bypass and gastric bypass, inevitably cause iron and mineral deficiencies requiring lifelong supplementation.
[0084] Par conséquent, la composition selon l’invention trouve son utilisation chez les patients devant subir et/ou ayant subi une opération de chirurgie bariatrique en ce qu’elle permet en une seule dose, de délivrer efficacement les quantités de vitamines et minéraux nécessaires pour palier leurs carences. Il en résulte une plus grande énergie et une réduction de l’état dépressif des patients, ce qui améliore leur observance et induit donc un cercle vertueux. Consequently, the composition according to the invention finds its use in patients having to undergo and / or having undergone a bariatric surgery in that it allows in a single dose, to efficiently deliver the amounts of vitamins and minerals. necessary to overcome their deficiencies. This results in greater energy and a reduction in the depressive state of patients, which improves their compliance and therefore induces a virtuous circle.
[0085] La composition selon l’invention est administrée une fois par jour sous la forme d’une dose de deux formes orales solides dont une forme orale solide gastro soluble et une forme orale solide gastro-résistante. Les patients ayant subi ou devant subir une opération de chirurgie bariatrique peuvent en effet avoir différents médicaments à prendre dans la journée. Limiter la prise quotidienne à deux formes orales solides, de préférence des gélules, c’est-à-dire une dose quotidienne, permet d’éviter au patient de multiplier les formes orales à prendre. Par ailleurs, la richesse des formes orales solides en vitamines et minéraux permet de réduire le nombre de compléments alimentaires à prendre par le patient. Ceci contribue également à une bonne observance du patient. [0085] The composition according to the invention is administered once a day in the form of a dose of two solid oral forms including a gastro-soluble solid oral form and a gastro-resistant solid oral form. Patients who have undergone or are due to undergo bariatric surgery may indeed have different medications to take during the day. Limiting the daily intake to two solid oral forms, preferably capsules, that is to say a daily dose, allows the patient to avoid having to multiply the oral forms to take. Moreover, the richness of solid oral forms in vitamins and minerals makes it possible to reduce the number of food supplements to be taken by the patient. This also contributes to good patient compliance.
[0086] Dans un mode de réalisation particulièrement préféré, la forme orale solide gastro-soluble et la forme orale solide gastro-résistante formant la composition selon l’invention sont administrées concomitamment. La forme orale solide gastro- In a particularly preferred embodiment, the gastro-soluble solid oral form and the gastro-resistant solid oral form forming the composition according to the invention are administered concomitantly. The solid oral gastro-
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FEUILLES DE REMPLACEMENT (RÈGLE 26) soluble et la forme orale solide gastro-résistante forment une seule dose qu’il convient de prendre en même temps, c’est-à-dire que la forme orale solide gastro soluble et la forme orale solide gastro-résistante sont prises conjointement une fois par jour, au cours du même repas par exemple. En d’autres termes, le patient prend les formes orales solides selon l’invention dans un écart de temps de moins d’une heure, de préférence de moins de 30 minutes, de manière davantage préférée de moins de 15 minutes, de manière plus préférée de moins de 10 minutes, de manière encore plus préférée de moins de 5 minutes et de manière encore davantage préférée de moins d’une minute. On entend par « écart de temps de moins d’une heure », par exemple, le fait que le patient prenne une forme orale solide puis l’autre 60 minutes après ou moins de 60 minutes après. La prise conjointe de la forme orale solide gastro-soluble et de la forme orale solide gastro résistante concourt à l’action complémentaire des formes orales solides aux niveaux gastrique et intestinal. SUBSTITUTE SHEETS (RULE 26) soluble and gastro-resistant solid oral form form a single dose which should be taken at the same time, i.e. the gastro-soluble solid oral form and gastro-resistant solid oral form are taken together once per day, during the same meal for example. In other words, the patient takes the solid oral forms according to the invention within a time interval of less than an hour, preferably less than 30 minutes, more preferably less than 15 minutes, more preferably less than 10 minutes, even more preferably less than 5 minutes and even more preferably less than one minute. By "time difference of less than one hour" is meant, for example, the fact that the patient takes a solid oral form and then the other 60 minutes after or less than 60 minutes after. The joint intake of the gastro-soluble solid oral form and the gastro-resistant solid oral form contributes to the complementary action of the solid oral forms at the gastric and intestinal levels.
[0087] L’administration des vitamines et minéraux compris dans la composition selon l’invention à dose filée, c’est-à-dire à dose faible et répétée, ce qui permet un phénomène d’accumulation dans l’organisme et permet ainsi de traiter et prévenir les carences en minéraux et vitamines. The administration of vitamins and minerals included in the composition according to the invention at spun dose, that is to say at low and repeated dose, which allows a phenomenon of accumulation in the body and thus allows to treat and prevent mineral and vitamin deficiencies.
[0088] EXEMPLES [0088] EXAMPLES
[0089] Dans la suite de la présente description, les exemples sont fournis à titre illustratif de la présente invention et ne visent en aucun cas à en limiter la portée. In the remainder of the present description, the examples are provided by way of illustration of the present invention and are in no way intended to limit its scope.
[0090] Exemple 1 [0090] Example 1
[0091 ] On prépare une composition selon l’invention selon les tableaux 2 et 3 ci- dessous : A composition is prepared according to the invention according to Tables 2 and 3 below:
[0092] [Tableau 2] [0092] [Table 2]
Figure imgf000019_0001
Figure imgf000019_0001
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FEUILLES DE REMPLACEMENT (RÈGLE 26)
Figure imgf000020_0001
SUBSTITUTE SHEETS (RULE 26)
Figure imgf000020_0001
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FEUILLES DE REMPLACEMENT (RÈGLE 26) [Tableau 3] SUBSTITUTE SHEETS (RULE 26) [Table 3]
Figure imgf000021_0001
Figure imgf000021_0001
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FEUILLES DE REMPLACEMENT (RÈGLE 26)
Figure imgf000022_0001
SUBSTITUTE SHEETS (RULE 26)
Figure imgf000022_0001
[0093] La vitamine B12 représente 0.00125 % en poids du premix. Cette proportion étant négligeable, la vitamine B12 est apportée sous forme cristallisée dans la composition selon l’invention, soit 400 pg de vitamine B12 pour une dose. Le prémix est un mélange de plusieurs vitamines à une concentration bien déterminée par le fournisseur. La forme cristallisée correspond à une des présentations possibles de la vitamine B12. Vitamin B12 represents 0.00125% by weight of the premix. Since this proportion is negligible, vitamin B12 is provided in crystallized form in the composition according to the invention, ie 400 pg of vitamin B12 for one dose. The premix is a mixture of several vitamins at a concentration well determined by the supplier. The crystallized form corresponds to one of the possible presentations of vitamin B12.
[0094] Brièvement, les matières premières, c’est-à-dire les vitamines et les minéraux entrant dans la composition selon l’invention, sont pesées et introduites à travers un calibreur dans une cuve en inox d’un volume de 150 L ou de 2000 L, en fonction de la quantité à préparer. On ajoute au mélange du stéarate de magnésium à titre d’excipient. Les matières premières sont ensuite mélangées pendant 45 min à la vitesse de 5 tours/min. Le mélange ainsi préparé est mis en gélule à enveloppe végétale en HPMC de taille 1. Les gélules ainsi préparées sont ensuite conditionnées sous blister de 6 doses, chaque dose correspondant à une gélule gastro-soluble et une gélule gastro-résistante. Briefly, the raw materials, that is to say the vitamins and minerals entering into the composition according to the invention, are weighed and introduced through a calibrator into a stainless steel tank with a volume of 150 L or 2000 L, depending on the amount to be prepared. Magnesium stearate is added to the mixture as an excipient. The raw materials are then mixed for 45 min at the speed of 5 revolutions / min. The mixture thus prepared is placed in a size 1 capsule with a vegetable envelope in HPMC. The capsules thus prepared are then packaged in a blister pack of 6 doses, each dose corresponding to a gastro-soluble capsule and a gastro-resistant capsule.
[0095] Les gélules gastro-soluble et gastro-résistante ont toutes deux la même composition en minéraux et vitamines. The gastro-soluble and gastro-resistant capsules both have the same composition in minerals and vitamins.
[0096] La gélule gastrosoluble libère son contenu dans l’estomac au maximum au bout de 30 minutes, son contenu est directement absorbé dans l’estomac ou véhiculé dans l’intestin comme mesuré selon les conditions de la pharmacopée européenne, ce qui permet un temps de libération des vitamines et minéraux qu’elle contient suffisamment long pour leur absorption. The gastrosoluble capsule releases its contents in the stomach at most after 30 minutes, its contents are directly absorbed in the stomach or transported in the intestine as measured according to the conditions of the European pharmacopoeia, which allows a release time of the vitamins and minerals it contains long enough for their absorption.
21 21
FEUILLES DE REMPLACEMENT (RÈGLE 26) [0097] Exemple 2 SUBSTITUTE SHEETS (RULE 26) [0097] Example 2
[0098] On prépare une composition comprenant un mélange de vitamines et de minéraux selon l’invention conformément au tableau 2 et selon le même mode opératoire qu’à l’exemple 1 . A composition is prepared comprising a mixture of vitamins and minerals according to the invention in accordance with Table 2 and according to the same procedure as in Example 1.
[0099] Les matières premières utilisées pour la préparation de la composition selon l’invention présentent une concentration en chacun de ses éléments respectifs suffisante pour la mise en œuvre de l’invention et présentent en outre une bonne biodisponibilité. Dans cet exemple de composition selon l’invention : The raw materials used for the preparation of the composition according to the invention have a concentration of each of its respective elements sufficient for the implementation of the invention and also have good bioavailability. In this example of composition according to the invention:
• le fer, le cuivre, le zinc et la choline sont intégrés sous forme de citrate ; • iron, copper, zinc and choline are integrated in the form of citrate;
• le calcium est intégré sous forme de carbonate et/ou de phosphate, et/ou de citrate et/ou de malate et/ou de bisglycinate • calcium is integrated in the form of carbonate and / or phosphate, and / or citrate and / or malate and / or bisglycinate
• l’inositol est intégré sous forme de méso-inositol ; et • inositol is integrated in the form of meso-inositol; and
• le sélénium est intégré sous forme de levure séléniée. • selenium is integrated in the form of seleniated yeast.
[0100] La formulation de la composition selon l’invention est comparée à la formulation d’une composition selon l’art antérieur présentant un fort dosage en vitamines et minéraux commercialisée par la société BARINUTRICS. Dans cette composition de l’art antérieur : [0100] The formulation of the composition according to the invention is compared with the formulation of a composition according to the prior art exhibiting a high dosage of vitamins and minerals marketed by the company BARINUTRICS. In this composition of the prior art:
• le fer est intégré sous forme de fumarate ; • iron is integrated in the form of fumarate;
• le cuivre et le manganèse sont intégrés sous forme de citrate ; • copper and manganese are integrated in the form of citrate;
• le zinc est intégré sous forme de bisglycinate ; • zinc is integrated in the form of bisglycinate;
• le sélénium est intégré sous forme de sélémethionine ; • selenium is integrated in the form of selemethionine;
• le chrome est intégré sous forme de picolinate ; • chromium is integrated in the form of picolinate;
• le molybdène est intégré sous forme de molybdène de sodium ; • molybdenum is integrated in the form of sodium molybdenum;
• l’iode est intégré sous forme d’iodure de potassium ; • iodine is integrated as potassium iodide;
• l’inositol est intégré sous forme d’inositol ; et • inositol is integrated as inositol; and
• la choline est intégrée sous forme de bitartrate de choline. • choline is integrated in the form of choline bitartrate.
[0101 ] [Tableau 4] [0101] [Table 4]
22 22
FEUILLES DE REMPLACEMENT (RÈGLE 26)
Figure imgf000024_0001
SUBSTITUTE SHEETS (RULE 26)
Figure imgf000024_0001
23 23
FEUILLES DE REMPLACEMENT (RÈGLE 26)
Figure imgf000025_0001
SUBSTITUTE SHEETS (RULE 26)
Figure imgf000025_0001
[0102] Comme on peut le voir ci-dessus, la composition selon l’invention est une composition comprenant toutes les vitamines et les minéraux nécessaires pour pallier les carences rencontrées chez les sujets en obésité sévère ou modérée. Ainsi, il n’est pas utile de multiplier le nombre de médicaments ou de compléments alimentaires à prendre dans la journée, ce qui est appréciable lorsqu’il s’agit d’un traitement à vie et améliore l’observance du traitement. La composition selon l’invention ne comprend que les vitamines et minéraux pour lesquels il a été observé une carence chez les sujets devant subir ou ayant subi une opération de chirurgie bariatrique. Elle contient en outre une association de levure et de L- tryptophane permettant d’apporter des acides aminés essentiels aux patients et contribuant à la bonne récupération après l’opération et à l’amélioration des signes des troubles psychologiques. [0102] As can be seen above, the composition according to the invention is a composition comprising all the vitamins and minerals necessary to overcome the deficiencies encountered in subjects with severe or moderate obesity. Thus, it is not useful to multiply the number of drugs or food supplements to take during the day, which is appreciable when it is a life-long treatment and improves treatment compliance. The composition according to the invention comprises only the vitamins and minerals for which a deficiency has been observed in subjects to undergo or who have undergone bariatric surgery. It also contains a combination of yeast and L-tryptophan, which provides essential amino acids for patients and contributes to good recovery after the operation and to improving signs of psychological disorders.
[0103] Contrairement aux compositions de l’art antérieur, la composition selon l’invention ne comprend pas de minéraux superflus pour lesquels aucune carence [0103] Unlike the compositions of the prior art, the composition according to the invention does not include superfluous minerals for which no deficiency
24 24
FEUILLES DE REMPLACEMENT (RÈGLE 26) chez ce groupe de patients n’a été observée tels que le molybdène, le chrome, l’iode, le magnésium et le manganèse. Ceci évite les phénomènes de malabsorption dus notamment à la compétition pour les transporteurs entre les différentes vitamines et minéraux compris dans la composition. La composition selon l’invention est donc plus efficace. En outre, comme on peut l’observer, les vitamines sont toutes introduites à la dose minimale de 15% des VNR ou AJR, à l’exception de la vitamine B12 et de la vitamine D pour lesquelles de fortes carences sont observées. Par ailleurs, la composition selon l’invention contient du calcium ce qui permet notamment de renforcer la santé des os et de faciliter l’absorption de la vitamine B12. En effet, les patients ayant subi une chirurgie bariatrique présentent un risque particulièrement élevé de développer une ostéoporose du fait de la malabsorption du calcium. Par conséquent, la composition selon l’invention comprenant une association de calcium et de vitamine D permet de prévenir et réduire les risques d’ostéoporose. SUBSTITUTE SHEETS (RULE 26) in this group of patients was observed such as molybdenum, chromium, iodine, magnesium and manganese. This avoids the phenomena of malabsorption due in particular to competition for transporters between the various vitamins and minerals included in the composition. The composition according to the invention is therefore more effective. In addition, as can be observed, the vitamins are all introduced at a minimum dose of 15% of the NRVs or RDAs, with the exception of vitamin B12 and vitamin D for which strong deficiencies are observed. Furthermore, the composition according to the invention contains calcium which makes it possible in particular to strengthen bone health and facilitate the absorption of vitamin B12. In fact, patients who have undergone bariatric surgery are at particularly high risk of developing osteoporosis due to calcium malabsorption. Consequently, the composition according to the invention comprising a combination of calcium and vitamin D makes it possible to prevent and reduce the risks of osteoporosis.
[0104] La composition selon l’invention permet donc de rétablir la bonne santé physique et/ou psychologique du patient devant subir et/ou ayant subi une opération de chirurgie bariatrique en lui apportant toutes les vitamines et minéraux pour lesquels il est carencé, en une seule dose. L’association d’une gélule gastro soluble et d’une gélule gastro-résistante, formant une seule dose, permet d’optimiser la surface digestive d’absorption restante après l’opération, d’augmenter considérablement la quantité de nutriments absorbés et de réduire les phénomènes de malabsorption. The composition according to the invention therefore makes it possible to restore the good physical and / or psychological health of the patient having to undergo and / or having undergone a bariatric surgery operation by providing him with all the vitamins and minerals for which it is deficient, in a single dose. The combination of a gastro-soluble capsule and a gastro-resistant capsule, forming a single dose, makes it possible to optimize the digestive surface of absorption remaining after the operation, to considerably increase the quantity of nutrients absorbed and of reduce the phenomena of malabsorption.
25 25
FEUILLES DE REMPLACEMENT (RÈGLE 26) SUBSTITUTE SHEETS (RULE 26)

Claims

Revendications Claims
[Revendication 1 ] Composition comprenant un mélange d’au moins la vitamine B12 et d’au moins un minéral se présentant sous forme de deux formes orales solides : une première forme orale solide gastro-soluble et une seconde forme orale solide gastro-résistante. [Claim 1] A composition comprising a mixture of at least vitamin B12 and at least one mineral in the form of two solid oral forms: a first gastro-soluble solid oral form and a second gastro-resistant solid oral form.
[Revendication 2] Composition selon la revendication 1 dans laquelle la forme orale solide gastro-soluble et la forme orale solide gastro-résistante sont administrées concomitamment. [Claim 2] A composition according to claim 1 wherein the gastro-soluble solid oral form and the gastro-resistant solid oral form are administered concomitantly.
[Revendication 3] Composition selon l’une des revendications précédentes comprenant en outre le L-tryptophane et une levure. [Claim 3] A composition according to one of the preceding claims further comprising L-tryptophan and a yeast.
[Revendication 4] Composition selon l’une des revendications précédentes comprenant en outre au moins une vitamine choisie parmi la vitamine A, D, E, B1 , B2, B3, B5, B6, B8, B9 et C et leurs combinaisons. [Claim 4] Composition according to one of the preceding claims further comprising at least one vitamin selected from vitamin A, D, E, B1, B2, B3, B5, B6, B8, B9 and C and combinations thereof.
[Revendication 5] Composition selon l’une des revendications précédentes dans laquelle l’au moins au moins un minéral est choisi parmi le fer, le zinc, le sélénium, le calcium et leurs combinaisons. [Claim 5] A composition according to one of the preceding claims wherein at least at least one mineral is selected from iron, zinc, selenium, calcium and combinations thereof.
[Revendication 6] Composition selon l’une des revendications précédentes comprenant en outre du cuivre compris entre 50% et 500%, de préférence environ 200% des valeurs nutritionnelles de référence. [Claim 6] Composition according to one of the preceding claims further comprising copper of between 50% and 500%, preferably about 200% of the nutritional reference values.
[Revendication 7] Composition selon l’une des revendications précédentes dans laquelle la vitamine B12 est comprise en une quantité comprise entre 5 000 à 20 000%, de préférence environ 16 000%, des valeurs nutritionnelles de référence. [Claim 7] Composition according to one of the preceding claims, in which the vitamin B12 is in an amount between 5,000 to 20,000%, preferably about 16,000%, of the nutritional reference values.
[Revendication 8] Composition selon l’une des revendications précédentes comprenant en outre de la choline et/ou de l’inositol. [Claim 8] Composition according to one of the preceding claims further comprising choline and / or inositol.
[Revendication 9] Composition selon l’une des revendications précédentes comprenant du calcium et de la vitamine D. [Claim 9] Composition according to one of the preceding claims comprising calcium and vitamin D.
[Revendication 10] Composition selon l’une des revendications précédentes dans laquelle la forme orale solide gastro-soluble et la forme orale solide gastro résistante sont des gélules. [Claim 10] A composition according to any one of the preceding claims wherein the gastro-soluble solid oral form and the gastro-resistant solid oral form are hard capsules.
26 26
FEUILLES DE REMPLACEMENT (RÈGLE 26) SUBSTITUTE SHEETS (RULE 26)
[Revendication 11 ] Composition selon l’une des revendications précédentes pour son utilisation chez des patients ayant subi et/ou devant subir au moins une opération de chirurgie bariatrique. [Claim 11] Composition according to one of the preceding claims for its use in patients who have undergone and / or are to undergo at least one bariatric surgery operation.
[Revendication 12] Composition selon la revendication 11 dans laquelle l’au moins une opération de chirurgie bariatrique est choisie parmi la gastrectomie longitudinale, l’anneau gastrique ajustable, le court-circuit gastrique et la dérivation biliopancréatique. [Claim 12] The composition of claim 11 wherein the at least one weight loss surgery is selected from longitudinal gastrectomy, adjustable gastric band, gastric bypass and biliopancreatic bypass.
[Revendication 13] Composition selon l’une des revendications précédentes ne comprenant pas de magnésium. [Claim 13] A composition according to one of the preceding claims not comprising magnesium.
[Revendication 14] Composition selon l’une des revendications précédentes dans laquelle la forme orale solide gastro-soluble et la forme orale solide gastro résistante ont la même composition quantitative et qualitative. [Claim 14] Composition according to one of the preceding claims, in which the gastro-soluble solid oral form and the gastro-resistant solid oral form have the same quantitative and qualitative composition.
27 27
FEUILLES DE REMPLACEMENT (RÈGLE 26) SUBSTITUTE SHEETS (RULE 26)
PCT/FR2020/051394 2019-07-29 2020-07-28 Compositions comprising a mixture of vitamins and minerals in the form of a combination of a gastro-soluble oral form and a gastro-resistant oral form, and use thereof WO2021019185A1 (en)

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Citations (4)

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US2703302A (en) * 1952-12-08 1955-03-01 Merck & Co Inc Vitamin b12-active composition and process of preparing same
US20050214388A1 (en) 2004-02-18 2005-09-29 Gorham Thomas R Multivitamin formulations containing controlled-release magnesium
EP1598063A1 (en) * 2003-10-22 2005-11-23 Ravi Shrivastava Synergic compositions comprising vitamins, minerals and trace elements to stimulate removal of intracellular lipids
EP2719291A1 (en) * 2012-10-09 2014-04-16 International Nutrition Research Company Dietetic product for long-term administration to patients after bariatric surgery

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US2703302A (en) * 1952-12-08 1955-03-01 Merck & Co Inc Vitamin b12-active composition and process of preparing same
EP1598063A1 (en) * 2003-10-22 2005-11-23 Ravi Shrivastava Synergic compositions comprising vitamins, minerals and trace elements to stimulate removal of intracellular lipids
US20050214388A1 (en) 2004-02-18 2005-09-29 Gorham Thomas R Multivitamin formulations containing controlled-release magnesium
EP2719291A1 (en) * 2012-10-09 2014-04-16 International Nutrition Research Company Dietetic product for long-term administration to patients after bariatric surgery

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Title
LIEBERMAN, SBRUNING, N: "The Real Vitamin & Minerai Book", vol. 3, 1990, AVERY GROUP

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