Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
  • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/16—Inorganic salts, minerals or trace elements
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
  • A61K33/10—Carbonates; Bicarbonates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P19/00—Drugs for skeletal disorders
  • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
  • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis

Definitions

• the present invention relates to mineralo-vitamin therapeutic combinations comprising as active principles associated with calcium in elementary form and at least one vitamin D.
• WO-A-96/09036 (Innothéra Laboratory) describes such an association in unit dosage form of tablets, in particular chewable tablets, respecting the absolute and relative doses of calcium and vitamin D indicated by the abovementioned literature.
• the chewable tablet described is dosed so as to allow the desired daily intake of calcium and vitamin D by taking two tablets per day.
• liquid forms have also been proposed, for example packaged in the form of ampoules containing an oral solution of a soluble calcium salt (such as gluconate or lactate).
• a soluble calcium salt such as gluconate or lactate.
• a such a solution due to the solubilization of the calcium salt, however has a certain acidity, which can affect the absorption of the active ingredients and, moreover, not be very well tolerated by the patient.
• Vitamin-calcium food supplements have also been proposed comprising, inter alia, calcium and a vitamin D, for example by WO-A-96/31130 (Abbott Laboratories), which describes a concentrate in solid form to be diluted with water or fruit juices. But, here again, the calcium salt is always in soluble or solubilized form, with the consequence of a low pH leading to the drawbacks mentioned above.
• One of the aims of the invention is to provide a mineral-vitamin combination combining calcium and vitamin D, which is presented in the form of a unitary drinkable liquid preparation devoid of high acidity so as to provide good tolerance and good absorption. - the active ingredients.
• unitary drinkable liquid preparation is meant a ready-to-drink liquid preparation, for example in the form of a drinkable liquid preparation in sachet, in bottle or in ampoule without the patient having to carry out any manipulation, like this. would for example be the case with effervescent granules or soluble powders.
• Another object of the invention is to provide such a preparation in which the unit dose corresponds to a daily dose lying within the values indicated above (i.e. approximately 1000 to 1200 mg of calcium element and 800 IU of vitamin D per day ), which further facilitates adherence to treatment since a single daily intake becomes sufficient.
• Another object of the invention is to provide such a calcium / vitamin D association in the form of an oral liquid having a dosage optimal relationship between calcium and vitamin D, especially for the prevention and treatment of osteoporosis, as explained at the beginning of the description.
• the invention provides a mineralo-vitamin therapeutic association in the form of a unitary drinkable liquid preparation, in particular for the prevention and treatment of osteoporosis in the elderly, this association comprising as active principles associated with calcium- element and at least one vitamin D, characterized in that it comprises: a calcium salt dispersed in an aqueous liquid medium, this salt being essentially insoluble in the aqueous liquid medium; at least one vitamin D; a vitamin D solubilizer in the aqueous medium; and a gelling agent capable of increasing the viscosity of the aqueous medium and thus maintaining the non-soluble calcium salt in homogeneous suspension in this medium.
• the ratio of calcium in elementary form to vitamin D, expressed in mg of elemental Ca per IU of vitamin D, is between 1 and 1.5, preferably between 1.2 and 1.3;
• the association is conditioned in the form of unit daily doses, each dose comprising 800 to 1200 mg of calcium element for 600 to 1000 IU of vitamin D;
• the non-soluble calcium salt is calcium carbonate;
• Vitamin D is chosen from vitamin D2 or ergocalciferol, vitamin D3 or cholecalciferol or a mixture of these;
• the vitamin D solubilizer is chosen from polyoxyethylene glycols and their esters, propylene glycols, ethyl alcohol, diethylene glycol ethers, glycerol and saturated and unsaturated polyglycolysed glycerides, type saccharides liquid fructose, liquid maltitol, polyhydroxyethylated sorbitan esters, hydrogenated and non-hydrogenated polyoxyethylene castor oil and maltodextrins, preferably from a polyhydroxyethylated sorbitan ester;
• the gelling agent is chosen from gums such as guar gum, xanthan gum, tragacanth and gum arabic, agar-agar, carboxymethyl sodium starch, anhydrous colloidal silica, cellulose derivatives such as hydroxypropyl cellulose, hydroxyethylcelluloseulose and sodium carboxymethylcellulose , polymers of acrylic acid and aluminum and magnesium silicates, preferably xanthan gum;
• the association also comprises a preservative, chosen from parahydroxybenzoic acid, its methyl and propyl esters and the sodium derivatives of these esters, benzoic acid and its salts, sorbic acid and its salts, bisulfites and metabisulfites;
• the association also comprises a sweetener, chosen from aspartame, sucrose, potassium acesulfame, sodium saccharinate, sodium cyclamate and fructose; - the association presents the following percentage formula: calcium carbonate 16.67 g (amount corresponding to calcium element: 6.67 g); cholecalciferol, amount corresponding to 5333.33 IU; polyhydroxyethylated sorbitan ester (Polysorbate 80) 0.05 g; xanthan gum 0.75 g; fructose 8.67 g; curator q.s. ; aroma q.s. ; purified water q.s. 100 ml, the final pH being between 7 and 9.
• a sweetener chosen from aspartame, sucrose, potassium acesulfame, sodium saccharinate, sodium cyclamate and fructose
• a sweetener chosen from aspartame, sucrose, potassium acesulfame, sodium saccharinate, sodium cyclamate and
• Vitamin D This vitamin is cholecalciferol (vitamin D3 Roche), either in the form of an oily solution (vegetable oil) titrated to 1 million IU / g, or in granulated form, for example of the 100 CWS® type. Rock titrated to 100,000 IU / g. In both cases, the presence of dl- ⁇ -tocopherol gives them great stability and prevents their oxidation.
• this salt must be a salt that is essentially insoluble (nor soluble) in this formulation, so as to always be present in the liquid medium in the dispersed state, and without there is a shift in the balance of the salt: so the salt does not change in nature (hence good absorption) and the solution does not acidify.
• the final pH is between 7 and 9.
• Solubilizer This involves making a lipophilic vitamin (vitamin D3) compatible with a hydrophilic aqueous environment, that is to say, in other words, finding a solvent or a co-solvent vitamin D3 which is compatible with the latter (that is to say that the vitamin must remain soluble and stable in the solvent) and which is compatible with water.
• the solubilizer must also have an acceptable taste and must not destabilize the chosen gelling agent (see below), nor attack the components of the packaging of the liquid preparation.
• PEG polyoxyethylene glycols
• - propylene glycols and ethers of diethylene glycol such as diethylene glycol monoethyl ether (Transcuto ⁇ ), - ethyl alcohol, - glycerol and saturated polyglycolysed glycerides (type PEG-8 glyceryl caprylate / caprate (Labrasol ® )) and unsaturated (type PEG-6 glyceryl monooleate (Labrafil ® M 1944 CS),
• polysorbate 80 can be used with a content of 0.03% to 0.5% by weight of the final preparation, preferably approximately 0, 05%, - hydrogenated polyoxyethylenated castor oil (type Croduret ® 50 special), Crumophor ® RH 40) and non-hydrogenated (type Etocas ® 35 HV),
• Gelling agent The role of this gelling agent is to maintain the calcium salt in homogeneous suspension in the aqueous medium without dissolving it or displacing the salt. To do this, the aqueous medium is viscosed by the addition of a polymer, this polymer having to have a good texture in order to disperse the calcium carbonate and keep it in dispersion and, also, to present in the mouth a pleasant taste and texture.
• a polymer this polymer having to have a good texture in order to disperse the calcium carbonate and keep it in dispersion and, also, to present in the mouth a pleasant taste and texture.
• suitable gelling agents there may be mentioned:
• guar type gums xanthan type, tragacanth type and arabic type - the currently preferred choice of gelling agent being xanthan gum in a proportion of 0.1 to 1% by weight, preferably approximately 0.75%, - agar- agar,
• Sweetener Various types of sweeteners can be chosen, this choice not being critical for the implementation of the invention. These include: aspartame, sucrose, acesulfame potassium (Sunet), sodium saccharinate, sodium cyclamate or fructose (Fructofin C type Al 21). Advantageously, one chooses fructose, which is a natural sweetener having the advantage of not providing sucrose and of not being contraindicated in non-insulin-dependent diabetic subjects.
• Preservative Various preservatives can be chosen, which here again are not critical for the implementation of the invention, such as parahydroxybenzoic acid, its methyl and propyl esters and the sodium derivatives of these esters, benzoic acid and its salts, sorbic acid and its salts (especially potassium sorbate), bisulfites and metabisulfites.
• Aroma It is chosen from conventional additives according to the taste (lemon, orange, etc.) that one wishes to give to the preparation.
• the operating protocol is as follows:
• the 0.05 g of polysorbate 80 can be replaced by: PEG 400 (1 g), propylene glycol (1 g), Transcutol ® (0.5 g), ethyl alcohol (10 g), glycerol (3 g ), liquid maltitol (1 g) or hydrogenated polyoxyethylene castor oil (1 g).
• xanthan gum can be replaced by: guar gum (1 g), hydroxypropylcellulose (1 g), hydroxyethylcellulose (1 g), Veegum ® HV (5 g), sodium carboxymethylcellulose (1 g ), Carbopol ® 974 P (0.3 g) or agar-agar (0.5 g).

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Epidemiology (AREA)
• Inorganic Chemistry (AREA)
• Physical Education & Sports Medicine (AREA)
• Rheumatology (AREA)
• Orthopedic Medicine & Surgery (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
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• Food Science & Technology (AREA)
• Polymers & Plastics (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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• 1997
  • 1997-03-14 FR FR9703061A patent/FR2760639B1/fr not_active Expired - Fee Related
• 1998
  • 1998-03-04 WO PCT/FR1998/000425 patent/WO1998041217A1/fr not_active Application Discontinuation
  • 1998-03-04 CN CN98803347A patent/CN1250374A/zh active Pending
  • 1998-03-04 JP JP54018498A patent/JP2001521495A/ja active Pending
  • 1998-03-04 CA CA002283691A patent/CA2283691A1/fr not_active Abandoned
  • 1998-03-04 EP EP98913826A patent/EP0971719A1/de not_active Withdrawn
  • 1998-03-04 EA EA199900830A patent/EA199900830A1/ru unknown

Non-Patent Citations (1)

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