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WO2015001329A1 - Comprimé à mâcher - Google Patents

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Publication number
WO2015001329A1
WO2015001329A1 PCT/GB2014/051991 GB2014051991W WO2015001329A1 WO 2015001329 A1 WO2015001329 A1 WO 2015001329A1 GB 2014051991 W GB2014051991 W GB 2014051991W WO 2015001329 A1 WO2015001329 A1 WO 2015001329A1
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WO
WIPO (PCT)
Prior art keywords
calcium
magnesium
tablet
chewable
vitamin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB2014/051991
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English (en)
Inventor
Thomas BØHMER
Grete Mæhlum WANG
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Individual
Original Assignee
Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to GB1600342.8A priority Critical patent/GB2530226A/en
Publication of WO2015001329A1 publication Critical patent/WO2015001329A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • 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
    • A61K33/08—Oxides; Hydroxides
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • A—HUMAN NECESSITIES
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • This invention relates to a pharmaceutical or nutraceutical product for oral use containing calcium and magnesium.
  • the product is provided in the form of a tablet which is chewable.
  • the invention further relates to the use of such a product in the treatment or prophylaxis of disorders related to the bone system, especially osteoporosis.
  • Osteoporosis is a bone disease where the bone mineral density is reduced and often leads to an increased risk of bone fracture. Osteoporosis most frequently occurs in females after menopause; this is known as 'postmenopausal
  • osteoporosis' can also be present in men. Hormonal disorders, pharmaceuticals and other chronic disorders can also give rise to the development of osteoporosis. The disease can be prevented with medication, often combined with lifestyle changes including exercise. Medication for prophylaxis or treatment of osteoporosis includes pharmaceutical and nutraceutical products comprising bisphosphonates, calcium and vitamin D. Bisphosphonates are a group of drugs that specifically inhibit osteoclast mediated bone-resorption. Clinically useful bisphosphonates are chemically related to inorganic pyrophosphate which is the endogenous regulator of bone turnover. Products which contain
  • bisphosphonates include alendronate (Fosamax®), clodronate (Bonefos®), pamidonate (Aredia®), ibandronate (Bondronat®), risedronate (Optinate®) and zolendronate (Zometa®).
  • Calcium may be administered orally as standard tablets, chewable tablets or effervescent tablets.
  • Such products include Weifa-Kalsium®, which are chewable tablets comprising 500 mg calcium as calcium carbonate, from Weifa, Oslo, Norway; Calcium-Sandoz®, which are effervescent tablets comprising 500 mg calcium as calcium lactose acetate, from Novartis Norge AS, Oslo, Norway;
  • Phos-E® which are tablets comprising 250 mg calcium as calcium acetate, from Vitaline Corp., Oregon, USA; Calcigran Forte®, which are chewable tablets comprising 500 mg calcium as calcium carbonate and 10 ⁇ g vitamin D 3 , from Nycomed Pharma, Asker, Norway; Nycoplus Calcigran® which are chewable tablets comprising 500 mg calcium as calcium carbonate and 5 ⁇ g vitamin D 3 , from Nycomed Pharma, Asker, Norway; loeos®, which are chewable tablets comprising 500 mg calcium as calcium carbonate and 10 ⁇ g vitamin D 3 , from Laboratoire Innotech, Arcueil, France; and Weifa-kalsium med D-vitamin®, which are chewable tablets comprising 500 mg calcium as calcium carbonate and 10 ⁇ g vitamin D 3 , from Weifa AS, Oslo, Norway.
  • Typical products comprising magnesium include Nycoplus Magnesium®, which are chewable tablets comprising 120 mg magnesium as magnesium lactate and magnesium citrate, from Nycomed, Asker, Norway. These tablets are generally used when the body's magnesium level is low. Magnesium is also present in various anti-ulcer products in the form of magnesium hydroxide and magnesium carbonate. In addition, magnesium can be found in various nutritional products and pharmaceuticals.
  • Combination products comprising calcium and magnesium are known and, in some cases, have been suggested for use in the treatment or prophylaxis of osteoporosis.
  • US 5,514,382 suggests a daily vitamin and mineral supplement for women comprising very many different vitamins and minerals, including calcium and magnesium.
  • a typical daily supplement comprises 1 ,000 to 1 ,500 mg calcium and 400 to 600 mg magnesium together with 26 other minerals and vitamins. No specific compositions of tablets are described and chewable tablets are not mentioned.
  • US 2006/0029641 suggests a calcium and magnesium nutritional supplement which is especially beneficial for use in subjects for the treatment or prevention of osteoporosis, arthritis, demineralisation of teeth and bones, body pain and lack of energy.
  • Magnesium deficiency has been identified as a possible risk factor for osteoporosis (Rude, J. Bone Miner. Res. 1998; 13(4):749-758). A moderate degree of magnesium reduction will increase s-PTH, but a pronounced deficiency will inhibit the PTH secretion and its peripheral effect. Magnesium deficiency can induce hypocalcemia due to a reduced concentration of PTH.
  • Ca and Mg for intestinal transport (Hardwick et al., J. Nutrition 1991 ; 121 :13-23.) It is likely therefore that intake of 1 ,000 mg /day Ca, which is often advised in osteoporosis treatment, will reduce the Mg uptake from the gut.
  • Mg deficiency is related to osteoporosis, both from epidemiological studies as well as the presence of Mg deficiency in osteoporotic patients.
  • the induced bone loss caused by Mg deficiency seems to be exerted through a variety of mechanisms: (1) increased release of substance P with increased TNF-a and I L-1 ⁇ production; (2) increased oxidative stress; (3) decreased osteoblast function due to decreased PTH secretion; and (4) formation of larger and more perfect crystals which contribute to skeletal fragility (see Rude et al., J. Nutritional Biochemistry 2004; 15:710-716).
  • a calcium intake of 1 ,000-1 ,200 mg /day and magnesium intake of 320-420 mg/day has been recommended where the median intake for American women was 735 mg/day and 243 mg/day, respectively. This leaves 500 mg calcium and 250-350 mg magnesium per day as supplementation to achieve optimal health (Price et al., Open Orthop. J. 2012; 6: 143-149). They also suggested an intake of vitamin D of 400-1000 lU/day based on the low median intake of 150-300 IU.
  • This treatment regime can be achieved by daily administration of one or more tablets having the desired ratio of Ca:Mg.
  • the invention thus provides a chewable nutraceutical or pharmaceutical tablet for oral administration comprising calcium and magnesium at a weight ratio in the range from 3:1 to 5: 1 , more preferably 3.5:1 to 4.5: 1 , e.g. about 4: 1.
  • the tablet comprises at least 200 mg calcium, preferably at least 250 mg calcium. Tablets comprising up to about 500 mg calcium form a preferred aspect of the present invention.
  • the invention provides a chewable nutraceutical or pharmaceutical tablet for oral administration comprising at least 200 mg calcium and at least 40 mg magnesium.
  • the tablet comprises at least 250 mg calcium and at least 50 mg magnesium, more preferably at least 500 mg calcium and at least 100 mg magnesium.
  • a preferred aspect of the invention is a pharmaceutical tablet, i.e. one which is suitable for use as a pharmaceutical.
  • chewable it is meant that the tablets are readily deformable rather than rigid, i.e. the tablets may be readily broken or fragmented upon chewing so that these need not be swallowed whole.
  • the product according to the invention may be a pharmaceutical or nutraceutical product, but preferably it will be a pharmaceutical product.
  • pharmaceutical means a product that in the European Union (including Norway) requires a marketing approval from a national medicines agency, such as the Norwegian Medicine Agency (Legemiddelverket) in Norway.
  • Norwegian Medicine Agency Legemiddelverket
  • nutraceutical it is meant that the product is not regarded from a regulatory perspective as a pharmaceutical composition.
  • the tablet size can vary depending upon the amount of calcium and magnesium present in each tablet and the choice and quality of calcium and magnesium salts and any excipients used in the formulation. Typical tablet diameters may be 13 mm or above, for example 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm and 22 mm.
  • the tablets herein described do not comprise any active agent other than calcium and magnesium (which are provided in the form of one or more calcium-containing compounds and one or more magnesium-containing compounds), i.e. these are substantially free from other active agents.
  • active agent is meant any substance having a desirable therapeutic or prophylactic effect on an animal (e.g. human) body other than as a nutrient, i.e. substances of the type for which regulatory approval as a drug is required in, for example, the US or the European Union. Vitamins may be considered an active agent for regulatory purposes. Tablets which consist essentially of calcium and magnesium-containing compounds form a preferred aspect of the invention.
  • the calcium present in the tablets may be provided in any physiologically acceptable form.
  • the preferred calcium compounds are, for example, calcium chloride, calcium sulphate, calcium oxide, calcium carbonate, calcium citrate malate, calcium gluconate, calcium hydrogen phosphate, calcium phosphate and tricalcium phosphate. Mixtures of calcium compounds may also be used.
  • the most preferred calcium compound for use according to the present invention is calcium carbonate.
  • Various qualities of calcium carbonate for use in tablet formulations are commercially available. Such qualities have different particle size, bulk density and specific surface area.
  • the calcium carbonate can be any quality of calcium carbonate for use in a pharmaceutical and/or food. Typical products include various Scoralite® qualities available from SCO RA S .A .
  • the magnesium present in the tablets may be provided in any combination
  • magnesium compounds such as for example, magnesium salts and magnesium oxides, and organic magnesium compounds.
  • preferred magnesium compounds are, for example, magnesium chloride, magnesium sulphate, magnesium carbonate, magnesium citrate, magnesium lactate and magnesium oxide. Mixtures of magnesium compounds may also be used.
  • Preferred for use according to the present invention is a combination of magnesium citrate and magnesium lactate.
  • other active agents may be present in the tablets.
  • these may further comprise one or more additional active agents selected from the group consisting of vitamin D and other vitamins and/or minerals.
  • additional active agents selected from the group consisting of vitamin D and other vitamins and/or minerals.
  • these will not be vitamins or minerals, with the exception of vitamin D (e.g. vitamin D 3 ).
  • a preferred aspect of the present invention relates to tablets containing only calcium, magnesium and vitamin D (e.g. vitamin D 3 ) as active ingredients.
  • vitamin D e.g. vitamin D 3
  • vitamin D is intended to encompass any vitamin D compound, including but not limited to vitamin D 2 and vitamin D 3 .
  • Preferred for use in the invention is vitamin D 3 .
  • the content of vitamin D in a tablet according to the invention may be in the range of from 5 to 50 ⁇ g, preferably about 10 ⁇ g.
  • excipients may be present in the tablets, such as diluents, binders, disintegrants, lubricants, glidants, colorants, flavourings, etc. The amount of these may be readily determined by those skilled in the art.
  • sugar alcohols may be present in the tablets, for example as a binding material.
  • suitable sugar alcohols include sorbitol, xylitol, mannitol, isomalt, maltitol, inositol, lactol, and mixtures of two or more of these sugar alcohols.
  • the content of any sugar alcohol, or mixture of sugar alcohols, in the tablet according to the invention may be in the range from 10 to 600 mg, preferably 30 to 400 mg.
  • the chewable tablets of the invention may be produced by compression or compaction of a formulation containing calcium and magnesium compounds and optionally vitamin D and certain excipients, typically selected to aid in the processing and to improve the properties of the chewable tablet.
  • the chewable tablets of the invention may be coated or uncoated and can be made from various amorphous and/or crystalline materials.
  • Chewable tablets may be plain, film or sugar coated, bisected, embossed, layered, or adapted for sustained release. Any film coating may be used, although those which comprise a physiologically acceptable water-soluble organic polymer are preferred.
  • the tablets may be provided in a variety of sizes, shapes and colours.
  • excipients which may be used are classified according to the function they perform. For example, a glidant may be used to improve the flow of powder blend in the hopper and into the tablet die.
  • Preferred excipients include sugar alcohols, preferably sorbitol, xylitol, mannitol, isomalt, maltitol, inositol, lactol or mixtures of two or more of these sugar alcohols.
  • Lubricants are typically added to prevent the tableting materials from sticking to punches, to minimise friction during tablet compression, and to allow for removal of the compressed tablet from the die. Such lubricants are commonly included in the final tablet mix in amounts of less than 1 % by weight. The most commonly used lubricants are magnesium stearate, stearic acid, hydrogenated oil, and sodium stearyl fumarate.
  • Tablets often contain diluents, such as lactose, which are added to increase the bulk weight of the blend resulting in a practical size for compression.
  • Typical diluents include for example dicalcium phosphate, calcium sulphate, lactose, cellulose, kaolin, mannitol, sodium chloride, dry starch and other sugars.
  • the cellulose can preferably be microcrystalline cellulose (Avicel).
  • Binders are agents which impart cohesive qualities to the powdered material. Commonly used binders include starch, gelatin, sugars such as sucrose, glucose, dextrose, and lactose, natural and synthetic gums,
  • carboxymethylcellulose methylcellulose, polyvinylpyrrolidone, ethylcellulose and waxes.
  • Disintegrants may be included to ensure that the tablet has an acceptable rate of disintegration.
  • Typical disintegrants include starch derivatives,
  • crospovidone croscaramelose and salts of carboxymethylcellulose.
  • Some binders such as starch and cellulose, are also excellent disintegrants.
  • excipients include high compressibility to allow strong tablets to be made at low compression forces, good flow properties that can improve the flow of other excipients in the composition and cohesiveness (to prevent the tablet from crumbling during processing, shipping and handling).
  • any known method for tablet formation may be used in producing the tablets herein described.
  • the three main processes for making compressed tablets are wet granulation, direct compression, and dry granulation (slugging or roller compaction). Whilst all three methods can be used to form the tablets of the invention, it is preferred if direct compression is employed.
  • Dry granulation consists of blending, slugging the ingredients, dry screening, lubrication, and compression.
  • the wet granulation method is used to convert a powder mixture into granules having suitable flow and cohesive properties for tableting.
  • the procedure consists of mixing the powders in a suitable blender followed by adding the granulating solution under shear to the mixed powders to obtain a granulation.
  • the damp mass is then screened through a suitable screen and dried by tray drying or fluidized bed drying. Alternatively, the wet mass may be dried and passed through a mill.
  • the overall process includes: weighing, dry powder blending, wet granulating, drying, milling, blending lubrication and compression.
  • Direct compression is a relatively quick process where the powdered materials are compressed directly without changing the physical and chemical properties of the drug.
  • the active components, direct compression excipients and any other auxiliary substances, such as a glidant and lubricant are blended, e.g. in a twin shell blender or similar low shear apparatus, before being compressed into tablets.
  • the advantages of direct compression include uniformity of blend, few manufacturing steps involved (i.e. the overall process involves weighing of powders, blending and compression, hence less cost), elimination of heat and moisture, prime particle dissociation, and physical stability.
  • the size of the tablets according to the present invention can vary.
  • the tablet diameter can vary from 6 mm to 22 mm.
  • the tablet weight can vary from 500 mg to 4 grams.
  • the most preferred tablets have tablet weights between 1 ,000 mg and 3 grams, e.g. with a diameter of from 13 to 20 mm.
  • the tablets herein described find use in the treatment and/or prevention of a range of bone-related disorders, including osteoporosis, osteopenia, increased bone resorption, bone fracture and loss of bone mineral density. They find particular use in the treatment or prevention of osteoporosis, particularly in females, more particularly in females aged 70 years and over.
  • Ostoporosis refers generally to a thinning of the bones with reduction in bone mass due to depletion of calcium and bone protein. This results in an increase in bone fragility and susceptibility to fracture (e.g. cracking or collapse of bone). All types of
  • osteoporosis may benefit from the treatment herein described including, in particular, senile osteoporosis (which typically occurs after the age of 70) and postmenopausal osteoporosis (this generally develops in women after menopause when the amount of estrogen in the body greatly decreases).
  • the invention thus provides a chewable tablet as herein described for use in therapy.
  • the invention provides a chewable tablet as herein described for use in the treatment or prophylaxis of a bone-related disorder, for example osteoporosis.
  • the invention provides a method of treatment or prophylaxis of a disorder related to the bone system, especially osteoporosis, said method comprising the step of orally administering to a patient (e.g. a human) in need thereof, one or more chewable tablets as herein described.
  • a patient e.g. a human
  • the recommended number of tablets to be taken on a daily basis will vary according to several factors, such as the gender of the patient, their age, weight, condition to be treated, etc., as well as the content of calcium and/or magnesium in each tablet.
  • a typical daily dose of calcium and magnesium in an adult patient can vary over a large range. Typical ranges for daily intake of calcium may range from 500 to 2,000 mg and for magnesium the daily intake may range from 100 mg to 600 mg.
  • a typical standard daily dose could be 1 ,000 mg calcium and 200-330 mg magnesium, which would ideally be taken in the form of two tablets according to the present invention.
  • the required daily dosages of calcium and magnesium and the required ratio of these actives as herein disclosed may be achieved by separate administration (e.g. simultaneous or sequential) of calcium and magnesium-containing products (e.g. chewable tablets). Dosage regimes which involve separate administration of such products in order to achieve the desired ratio of calcium to magnesium as set out herein are considered to form a further aspect of the invention.
  • the invention thus provides a method of treatment or prophylaxis of a disorder related to the bone system, especially osteoporosis, said method comprising the step of administering to a patient (e.g. a human) in need thereof, a daily dose of at least 500 mg calcium together with at least 100 mg magnesium, optionally together with vitamin D, more preferably at least 1 ,000 mg calcium and at least 200 mg magnesium.
  • a patient e.g. a human
  • a daily dose of at least 500 mg calcium together with at least 100 mg magnesium, optionally together with vitamin D, more preferably at least 1 ,000 mg calcium and at least 200 mg magnesium.
  • the calcium and magnesium will be administered in a weight range of from 3: 1 to 5: 1.
  • Example 1 Chewable tablets comprising calcium carbonate and magnesium citrate
  • Calcigran tablets 500 mg (Batch no. 10768408 from Nycomed Pharma AS, Asker, Norway) were pulverized using a mortar and pestle. Magnesium citrate tribasic nonahydrate (Lot no. 1402967V from Fluka) was added. The powder was mixed in the mortar and tablets were prepared. A mixture of tablet powder (696 mg) and magnesium citrate tribasic nonahydrate (1277 mg) was pressed to tablets comprising 200 mg calcium and 50 mg magnesium (ratio 4:1). Tablet diameter was 13 mm, tablet height was 12 mm and tablet weight was 1.97 gram.
  • the tablet comprised cholecalciferol (2.5 mg - equivalent to 100 IE vitamin D 3 ), sorbitol , povidone, citric taste substance, magnesium stearate, aspartame, mono- and diglycerides of fatty acids, racemic alpha-tocopherol, saccharose, modified corn starch, triglycerides (medium chain length), sodium ascorbate and colloidal water-free silica.
  • Chewing tablets comprising: (1) 200 mg calcium and 40-66 mg magnesium; (2) 250 mg calcium and 50-83 mg magnesium; and (3) 500 mg calcium and 100-164 mg magnesium can be prepared in a similar way using tabletting tools with larger diameter (typically 14 to 22 mm). Exam le 2 - Study
  • the mean age of the women was 73.6 years. They had an optimal BMI, and a low CRP which showed they had no actual disease or inflammation (see Table 1). Two patients were lost from the (Mg+) group and three from the (Mg-) group. Some were allowed use of medicines which did not influence their calcium/magnesium metabolism and were kept constant during the experimental period.
  • both groups were given calcium carbonate (500 mg calcium) and cholecalciferol (5 ⁇ g vitamin D 3 ) twice daily.
  • the (Mg+) group was given two chewable tablets of magnesium daily - each tablet contained magnesium lactate (1 10 mg Mg) and magnesium citrate (10 mg Mg) - totalling 240 mg Mg daily.
  • Measurements of blood and urine were done on days 0, 7 and 28: Concentrations of calcium (s-Ca), ionised Ca (s-Ca 2+ ), magnesium (s-Mg), phosphate (s-P), and creatinine were measured simultaneously in serum and urine (except s-Ca- 2+ in urine only), the hormones s-parathyroid, s-calcidiol, s-calcitriol, and bone markers in serum (s-osteocalcin and undercarboxylated osteocalcin s-bALP, s-1-CTP, PINP, pg CTX-1) and in urine (u-DPYD and u-NTx). The concentrations in urine were related to creatinine or magnesium from the same sample.
  • BCE Bone collagen Equivalents Table 3 - Differences in concentrations (Mean ⁇ SD) of s-calcium, s-magnesium, ratios of calcium and magnesium to creatinin in the urine, s-calcidiol, s-calcitriol, s-PTH and bone parameters between 0-7, 7-28 and 0-28 days in the (Mg -) and (Mg+) groups
  • Osteocalcin was significantly increased in the (Mg+) group after 7 and 28 days.
  • U-PYD was reduced after 7 and 28 days and U-NTX was reduced in both groups after 7 days, and in the (Mg+) group after 28 days where there was a significant difference between the groups.
  • the reduced concentration in measures for bone resorption, U-PYD and U-NTX, are of therapeutic value and contribute to an increased calcium absorption and increased intracellular Mg concentrations which are likely to improve muscle function and thereby also reduce hip fractures.

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  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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Abstract

La présente invention concerne un comprimé pharmaceutique à mâcher comprenant du calcium, du magnésium et facultativement de la vitamine D (par ex. de la vitamine D3) utile dans le traitement ou la prophylaxie de troubles osseux. Ce produit, dans lequel le calcium et le magnésium sont présents selon un rapport pondéral dans la plage allant de 3/1 à 5/1, de préférence de 3,5/1 à 4,5/1, par ex. environ 4/1, s'est avéré particulièrement utile dans le traitement et/ou la prévention de l'ostéoporose chez des femmes âgées de 70 ans et plus.
PCT/GB2014/051991 2013-07-01 2014-07-01 Comprimé à mâcher Ceased WO2015001329A1 (fr)

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CN110354091A (zh) * 2019-07-17 2019-10-22 宿迁市现代生物科技股份有限公司 一种保健品用可直接压片的颗粒碳酸钙的配方
CN111493321A (zh) * 2020-05-11 2020-08-07 南通励成生物工程有限公司 一种钙镁咀嚼片及其制备方法

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CN112370429A (zh) * 2019-10-21 2021-02-19 广州富诺营养科技有限公司 一种直压型有机钙维生素d3咀嚼片及其制备方法

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Publication number Priority date Publication date Assignee Title
US4446135A (en) * 1982-06-07 1984-05-01 Sterling Drug Inc. Chewable antacid tablets
US20060024384A1 (en) * 2004-07-29 2006-02-02 Giordano John A Compositions and methods for nutrition supplementation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4446135A (en) * 1982-06-07 1984-05-01 Sterling Drug Inc. Chewable antacid tablets
US20060024384A1 (en) * 2004-07-29 2006-02-02 Giordano John A Compositions and methods for nutrition supplementation

Cited By (2)

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CN111493321A (zh) * 2020-05-11 2020-08-07 南通励成生物工程有限公司 一种钙镁咀嚼片及其制备方法

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