EP2247199A1 - Procédés et compositions pour le traitement d'affections osseuses - Google Patents

Procédés et compositions pour le traitement d'affections osseuses

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Publication number
EP2247199A1
EP2247199A1 EP09706153A EP09706153A EP2247199A1 EP 2247199 A1 EP2247199 A1 EP 2247199A1 EP 09706153 A EP09706153 A EP 09706153A EP 09706153 A EP09706153 A EP 09706153A EP 2247199 A1 EP2247199 A1 EP 2247199A1
Authority
EP
European Patent Office
Prior art keywords
nutritional composition
composition according
vitamin
milk
bone
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.)
Withdrawn
Application number
EP09706153A
Other languages
German (de)
English (en)
Inventor
Anne Schaafsma
Cornelis Glas
Elisabeth Gertruda Hendrika Maria Van Den Heuvel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
FrieslandCampina Nederland BV
Original Assignee
Friesland Brands BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Friesland Brands BV filed Critical Friesland Brands BV
Publication of EP2247199A1 publication Critical patent/EP2247199A1/fr
Withdrawn legal-status Critical Current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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • 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
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • 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
    • A23L33/15—Vitamins
    • 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
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/19—Dairy proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20—Milk; Whey; Colostrum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs

Definitions

  • the present invention relates to methods and compositions for treatment of bone conditions, especially bone loss such as osteoporosis.
  • the present invention especially relates to milk based nutritional compositions supplemented with prebiotics and a separate vitamin K 2 source, and methods using such nutritional compositions for treatment or prophylaxis of bone conditions, especially bone loss such as osteoporosis.
  • Bone conditions especially bone loss such as osteoporosis, are important diseases affecting elderly people worldwide.
  • Nutrition besides other factors, plays an important role in the prophylaxis and/or treatment of such bone conditions.
  • the nutritional intake of vitamin K appears, at least partially, to be an important nutritional component influencing the role of nutrition in the prophylaxis and/or treatment of bone conditions, such as osteoporosis
  • vitamin K is an essential co-factor in transforming specific glutamate residues (GIu) into gamma-carboxyglutamic acid (GIa) .
  • GIa residues increase the affinity of proteins for calcium.
  • Matrix GIa protein, protein S, nephrocalcin and osteocalcin are vitamin Independent proteins involved in bone metabolism.
  • Matrix GIa protein, synthesized in osteoblasts, chondrocytes and most soft tissues, is stimulated by calcitrol and does not react with hydroxyapatite . This protein appears earlier than osteocalcin and possibly prevents or inhibits calcification of arteries and cartilage through the surface coupled Rank ligand (RANKL) .
  • RNKL surface coupled Rank ligand
  • RANKL on osteoblast/stromal cells binds to RANK, a transmembrane receptor on osteoclast precursor cells. This interaction initiates a signaling and gene expression cascade that results in differentiation and maturation of osteoclast precursor cells.
  • OPG protein osteoprotegerin
  • OPG is produced by osteoblasts and other cell tissue types including the aorta and other large arteries. Because of this synthesis in the latter tissue, it is presently presumed that a normal function of OPG may be to prevent calcification of the large arteries.
  • Hormones and cytokines like calcitrol, PTH, PGE 2 and IL-Il appear to act through inhibition of OPG production and stimulation of RANKL synthesis.
  • the final ratio between RANKL and OPG appears to control the degree of osteoclast differentiation, activation and apoptosis.
  • Estrogen on the other hand appears to inhibit production of RANKL, but stimulates OPG synthesis.
  • Vitamin K denotes a class of related compounds having in common a methylated naphthoquinone ring structure. The variation within this group of compounds occurs in the aliphatic side chain attached at the three position of the ring structure.
  • vitamin Ki is commonly designated as vitamin Ki or phylloquinone.
  • This compound comprises an aliphatic side chain of four isoprenoid residues, of which one is saturated.
  • the other members of the vitamin K group are commonly designated as vitamins K 2 or menaquinones .
  • the aliphatic side chain of these compounds is comprised of a variable number of unsaturated isoprenoid residues.
  • vitamin K 2 compounds are also denoted as MK-n, wherein n indicates the number of unsaturated isoprenoid residues.
  • MK-4 to MK-13 are known.
  • Examples of natural food matrices of vitamin K are leafy green vegetables such as spinach and lettuce; Brassica vegetables such as kale, cabbage, cauliflower, broccoli and Brussels sprouts; wheat bran; organ meats; cereals; fruits such as avocado, kiwifruit and bananas; meats; cow milk and other dairy products; eggs; and soy products.
  • Examples of artificial food matrices of vitamin K are, for example, described in WO 02/052954, PCT/NL95/00396, and JP-2006-213627.
  • WO 02/052954 discloses a nutritional composition comprising sources of protein, carbohydrate, fat, calcium, magnesium, zinc, vitamin D and vitamin K (type of vitamin K not defined) . A beneficial effect on bone conditions is claimed.
  • PCT/NL95/00396 discloses a composition comprising a calcium source, ground eggshell in particular, in combination with macronutrients and a mineral and vitamin premix containing among others vitamin K (type of vitamin K not defined) . It is of interest to know that eggshell powder as a calcium source has shown to reduce serum PTH for a longer period as compared to standard calcium sources like calcium carbonate.
  • JP-2006-213627 discloses a composition comprising a calcium source, such as powdered fish bones, a vitamin K 2 source and citric acid. A beneficial effect on bone conditions is claimed.
  • this object is met by providing a nutritional composition as defined in appended claim 1.
  • the nutritional compositions according to the present invention comprise: a) one or more milk derived fractions and/or components; b) optionally, but preferably one or more prebiotics; c) optionally, but preferably, one or more calcium and/or magnesium salts; and d) vitamin K 2 (menaquinone) comprising 7 to 13
  • the one or more milk derived fractions and/or components are fractions or components naturally present in milk such as cow milk.
  • milk sources such as goat or horse milk, can also be considered.
  • milk fractions preferably derived from cow milk
  • skimmed milk full cream milk
  • partially skimmed milk buttermilk, cheese and yoghurt.
  • These milk fractions can be obtained using generally known milk processing techniques and, therefore, will not be further discussed in detail.
  • these milk fractions are preferable used in dry powder form.
  • milk components are whey protein derivatives, alpha-lactalbumine, beta-lactoglobuline, casein, casein-glycomacropeptide, hydrolysates of milk proteins such as casein hydrolysate and whey-protein hydrolysate, milk-calcium preparations, and lactose.
  • milk components can be obtained using generally known milk processing techniques and, therefore, will not be further discussed in detail.
  • these milk components are preferable used in a dry powder form.
  • the nutritional composition comprises one or more prebiotics.
  • prebiotics are non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria residing in the colon or reaching the colon as probiotic germs, thus improving host health.
  • preferred vitamin K2 producing bacteria are species of lactic acid producing bacteria (e.g. Lactobacilli, Leuconostoc, Lactococci, Bifidobacteria) and/or propionic acid producing bacteria.
  • the vitamin K2 producing bacteria are Lactococcus lactis ssp cremoris TsH473, as a producer of predominantly MK-9, and/or Propioni bacterium FF7645, as a producer of predominantly MK-IO.
  • Prebiotics according to the present invention are preferably oligosaccharides with a defined prebiotic activity.
  • Preferred examples are inulin, fructo- polysaccharides (FPS), fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS) , fuco-oligosaccharides, sialic acid comprising carbohydrates such as sialyl lactose and/or carob bean gum.
  • Suitable prebiotic ranges in the present compositions are between 3 and 40% (w/w) , such as 3, 4, 5, 6 ,7 ,8 , 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25% or up to 40% (w/w), preferably 10 to 25% (w/w) .
  • the one or more calcium and/or magnesium salts can be any calcium and/or magnesium salt suitable for (human) consumption. Suitable, and preferred examples, of the present one or more calcium and/or magnesium salts are carbonate, chloride, hydroxide, sulphate, phosphate, citrate, lactate, short- chain fatty acid, fumarate, ascorbate, gluconate and glycerophosphate salts of calcium and/or magnesium. According to a preferred embodiment, the ratio Ca 2 VMg 2+ is maximal 10:1.
  • the present nutritional composition comprises, as a separate component, vitamin K 2 (menaquinone) comprising 7 to 13 (MK-7 to MK 13) isopropenoid residues, such as MK-7, MK-8, MK-9, MK-10, MK- 11, MK-12 and/or MK-13, preferably 8 to 13, more preferably such as 9 to 13, most preferably 10 to 13 or 9-10
  • vitamin K 2 menaquinone
  • MK-7 to MK 13 isopropenoid residues
  • a suitable and preferred MK-7 source is a K2-oil such as a MenaQ7 oil formulation sold by NattoPharma ASA, Norway.
  • the concentration of vitamin K 2 is such that preferably a daily intake is provided of between 40 micrograms to 8 milligrams vitamin K 2 (menaquinone) comprising ' 7 to 13 (MK-7 to MK 13) isopropenoid residues such as 40, 50, 60 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 300, 400, 500 microgram, 1, 2, 3, 4 , 5 , 6, 7 , 8 mg. More preferably, a daily intake is provided of between 50 to 150 microgram/day, such as 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, and 150 micrograms.
  • a daily intake is provided of between 40 micrograms to 8 milligrams vitamin K 2 (menaquinone) comprising ' 7 to 13 (MK-7 to MK 13) isopropenoid residues such as 40, 50, 60 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 1
  • the indicated daily dosages of vitamin K 2 comprising 7 to 13 (MK-7 to MK 13) isopropenoid residues are preferably provided as a single daily dosage in the form for a once daily intake of the present nutritional compositions.
  • the nutritional composition according to the present invention can be in dry powder form, a concentrate or a ready-to-use form.
  • the nutritional composition according to the present invention is dissolved, or suspended, using an aqueous solution, preferably water.
  • Preferred is to dissolve, or suspend, 5 to 35 g of the dry powder per 100 ml solution, more preferably 12 to 26 g per 100 ml, such as 12.5 or 25 g/100 ml.
  • a concentrate is suitably diluted with an aqueous solution, such as water, to provide an amount similar to the above ranges cited with respect to the dry matter (DM) .
  • vitamin K 2 menaquinone
  • MK-7 to MK 13 isopropenoid residues
  • the peak plasma levels i.e., bioavailability
  • the peak plasma levels were more than two times to more than 5 times higher, wherein a positive correlation was observed between the peak plasma levels and the number of isopropenoid residues of the vitamin K 2 source.
  • the precise mechanism (s) of action of the present nutritional compositions due to complex in vivo factors such as intestinal absorption, transport, tissue distribution is/are not known, the increased beneficial effects of the present nutritional composition, such as bioavailability, are, for example, indicated by the observation that a once daily intake, during a sufficient time-period, of the present nutritional composition provides a sufficient vitamin K source to control or to prevent negative bone conditions.
  • Examples of sufficient time-periods are from 1 month to several years.
  • the effects will further improve when the vitamin K2 is combined with a calcium source having an extended lowering effect on serum PTH, such as ground eggshell powder and low-pH milk-calcium preparations.
  • the composition is supplemented with one ore more other known calcium absorption, bone synthesis and/or recovery compounds.
  • Preferred examples are biphosphonate, casein phosphopeptides, isoflators of soy and/or vitamin D.
  • the present nutritional composition is further supplemented with a lipid-fraction.
  • a lipid fraction according to the present invention is preferably provided in the form of a mixture of animal, plant, microbial fats, and/or phospholipids.
  • the long chain polyunsaturated fatty acid (LCP) ratio of n3 to n ⁇ fatty acids is >1.
  • Preferred sources of phospholipids are soy lecithin or milk phospholipid fractions.
  • the lipid fraction of the present nutritional composition only comprises as a separate constituent phospholipids, for example obtained from the above-identified sources. It has been found within the context of the present nutritional composition that the presence of lipid fractions further increases, amongst others, the bioavailability of vitamin K.
  • Suitable concentration ranges of the present lipid fraction are between 1 to 25 % (w/w) , such as 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25% (w/w) .
  • the present nutritional composition is further supplemented with nutritionally acceptable microbial organisms, preferably lactic acid bacteria and or propionic bacteria, although other microbial organisms providing additional sources of vitamin K through de novo synthesis are contemplated within the scope of the present invention.
  • nutritionally acceptable microbial organisms preferably lactic acid bacteria and or propionic bacteria
  • preferred bacteria are the Propioni bacterium FF7645 and Lactococcus bacterium FF0429 or Lactococcus lactis ssp cremoris TsH473 as they produce relatively high levels of vitamin K2 during fermentation of skimmed milk.
  • the present invention also relates to methods for the prophylaxis or treatment of an individual, preferably a human individual, at risk of or suffering from bone conditions, such as bone loss and especially osteoporosis, comprising administering the present nutritional composition during a sufficient time-period such as from 1 month to several years.
  • administering the present nutritional composition comprises a daily intake of the present composition thereby providing 40 microgram to 8 mg vitamin K 2 (menaquinone) comprising 7 to 13 (MK-7 to MK
  • isopropenoid residues such as 40, 50, 60, 70, 80, 90,
  • the daily intake preferably comprises a single daily 'dosage .
  • the present prophylaxis or treatment is preferably supplemented with physical exercises.
  • Preferred physical exercises are directed to reinforcement of fracture sensitive bone such as preferably the vertebral column and hip, and to reinforce arthrose vulnerable joints such as knee .
  • Figure 1 plasma levels, expressed as Z-scores, of healthy adults, after intake of compositions according to the present invention
  • Figure 2 provides suitable, and illustrative, examples of physical exercises according to the present invention.
  • Figures IA to 1C show suitable knee reinforcing exercises;
  • Figures ID and IE show suitable vertebral column reinforcing exercises;
  • Figures IF to IH show suitable hip reinforcing exercises .
  • a base product was prepared by 1) standardizing full cream cow's milk (12.5% DM, 4% fat) and skimmed milk (8% DM, 1% fat) at 16% milk fat in the DM (excluded inulin) , 2) adding CaCO 3 , MgCC> 3 , vitamin A-acetate, vitamin D3-oil, vitamin K2-oil (MK-7-MK13) , and lecithin, and 3) concentrating this mixture by evaporation followed by drying by known methods on a wheel dryer to form a powder.
  • the base powder obtained was mixed with a vitamin and mineral premix in dry form. This product was further enriched with 7.5g inulin per lOOg by dry blending.
  • the final product comprised per 100 grams: 29% protein, 14.7% fat, 39.1% carbohydrates (lactose), 7.5% inulin, and 1079mg Ca, 152mg Mg, 375 IU D3, and l ⁇ Omcg K2.
  • the final product is dissolved in water (25 g/200 ml) and is in particularly suitable for premenopausal women, provided in one portion daily.
  • a base product was prepared by mixing liquid demineralized whey (28% DM, 3.7% protein, 23.8% lactose, 0.29% fat), a casein hydrolysate (38-40 0 DH, 87% protein), milk fat, Ca-lactate, Ca-caseinate, MgCO 3 , vitamin A-acetate, vitamin D3-oil, vitamin K2-oil (MK-7-MK13) , and lecithin, to provide a whey protein to casein ratio of 1 and a fat content of 16% in the DM (excluded prebiotics) .
  • This mixed product was concentrated by evaporation and dried by known methods on a wheel dryer to form a powder.
  • the base powder obtained was mixed with a vitamin and mineral premix in dry form, in combination with sialyl-lactose.
  • the final product comprised per 100 grams: 29% protein, 14.7% fat, 39.1% carbohydrates (lactose), 7.5% sialyl lactose, and 1079mg Ca, 152mg Mg, 375 IU D3, and 160mcg K2.
  • the final product is dissolved in water 25g/100 ml) .
  • the product is provided in a once-daily portion, and particularly suitable for habitual dairy consuming premenopausal women under stressful conditions, and stimulates as well the intestinal vitamin K2 production.
  • a product was prepared as described in example 2, but instead of sialyl-lactose, a mixture of sialyl-lactose and galactooligosaccharides (GOS) was added.
  • the final product comprised per 100 grams: 29% protein, 14.7% fat, 39.1% carbohydrates (lactose), 2.5% sialyl lactose, 5% GOS, and 1079mg Ca, 152mg Mg, 375 IU D3, and 160mcg K2.
  • the final product is dissolved in water (25g/100 ml) .
  • the product is provided in a once-daily portion, and in particular suitable for premenopausal women under stressful conditions, and stimulates as well the intestinal vitamin K2 production.
  • a product was prepared as described in example 2, but in stead of sialyl-lactose, a mixture of sialyl-lactose and fructooligosaccharides (FOS) was added.
  • the final product comprised per 100 grams: 29% protein, 14.7% fat, 39.1% carbohydrates (lactose), 2.5% sialyl lactose, 5% FOS, and 1079mg Ca, 152mg Mg, 375 IU D3, and l ⁇ Omcg K2.
  • the final product is dissolved in water (25g/100 ml) .
  • the product is provided in a once-daily portion, and in particular suitable for premenopausal women under stressful conditions, and stimulates as well the intestinal vitamin K2 production.
  • a base product was prepared by mixing demineralized hydrolyzed sweet whey (28% DM, 3.7% peptides, 23.8% lactose, 0.29% vet, 5 0 DH) with a vegetable source of fat in combination with fish oil (12% DHA, 18% EPA), and furthermore with Ca-citrate, MgCO 3 , vitamin A-acetate, vitamin D3-oil, vitamin K2-oil (MK-7-MK13) , and lecithin. This mixture was concentrated and dried by known methods on a wheel dryer to form a powder. The base powder obtained, with 16% fat, was blended with a vitamin and mineral premix in dry form, in combination with inulin. The final product comprised per 100 grams: 29% protein, 14.7% fat, 39.1% carbohydrates (lactose), 7.5% inulin, and 1079mg Ca, 152mg Mg, 375 IU D3, 160mcg K2.
  • the final product is dissolved in water (25 g/200 ml) and in particular suitable for premenopausal women with sleeping problems.
  • the product is adviced to be taken once daily, preferably in the evening.
  • Example 6 of a composi tion according to the present invention A base product in accordance with example 1 was prepared, mixing low-fat skimmed milk (9.18% DM, 3.57% protein, 4.8% lactose, 0.07% fat) and demineralized whey to standardize the protein content at 31.5% in the DM. Furthermore, Ca-acetate and MgCO3 are added. The lipid fraction (containing vitamin D3-oil, vitamin K2-oil [MK-7- MK13] , and phospholipids) was added during the concentration process before spray-drying. The powder obtained was mixed with FOS, vitamin and mineral premix in dry form. The final product comprised per 100 grams: 31.5% protein, 1% lipids, 48% carbohydrates, 10% FOS, and 1079mg Ca, 152mg Mg, 375 IU D3, l ⁇ Omcg K2.
  • the final product is dissolved in water (25 g/200 ml) .
  • the product is provided in a once-daily portion, and in particular suitable for premenopausal women on a fat-low diet.
  • a ready to drink product is prepared by dissolving fat-free milk dry substances (40% protein, 52% lactose, 8% minerals) , milk fat, vanilla, CaCO 3 , MgHPO 4 , vitamin C, vitamin K2-oil (MK7-13) , vitamin D3-oil, Na-citrate, FPS, and stabilizers.
  • the product is homogenized and sterilized by known techniques.
  • the final product comprises per 200 ml: 7 g protein, 9.4g lactose, 3g fat, 2g FPS, 0.006 g vanilla, 40mcg K2, 200 IU D3, 300mg Ca, 55mg Mg, and 60mg vitamin C.
  • the product is especially prepared for teenagers and premenopausal women, and is advised to be used as one portion daily.
  • a vitamin K2 enriched yoghurt is prepared by using a mixture of whole and skimmed milk and a thermophilic yoghurt culture. Additionally, vitamin K2-oil (MK7-13) , vitamin D3-oil, CaP04, MgPO4 and GOS were added. The final product contains per 100 grams: 2g milk fat, 4.4g protein, 8.9g milk solids non fat (40% protein, 52% lactose, 8% minerals), 2 g GOS, 200 mg Ca, 55mg Mg, 2.5mcg D3, and 80mcg K2.
  • the product is especially prepared for those who cannot tolerate or do not like non-fermented sweet milk.
  • the product is advised to be consumed once-daily.
  • a vitamin K2-enriched yoghurt is produced by using whole milk and a selected yoghurt culture of high K2- producing lactic-acid bacteria. Additionally, vitamin K2-oil (MK7-13), vitamin D3-oil, MgPO 4 , and milk solids non-fat (40% protein, 52% lactose, and 8% minerals among which milk- calcium) , and GOS were added. The final product contains per 100 grams: 3g milk fat, 4.6g milk protein, 4.6 g carbohydrates, 2g GOS, 175 mg Ca, 55mg Mg, 2.5mcg D3, and 80 meg K2.
  • This product is characterized by a higher natural content of vitamin K2, MK-8 in particular, and as well is a vehicle to stimulate the intestinal vitamin K2 production.
  • Example 10 of a composition according to the present invention A product as prepared in example 9, but using sialyl-lactose instead of GOS. Furthermore, the selected yoghurt culture is further enriched with Propionic bacterium (FF7645) . The final product contains per 100 grams: 3g milk fat, 4.6g milk protein, 4.6 g carbohydrates, 2g sialyl- lactose, 175 mg Ca, 55mg Mg, 2.5mcg D3, and 80 meg K2.
  • FF7645 Propionic bacterium
  • This product is characterized by a higher natural content of vitamin K2, MK-8 and MK-10 in particular, and as well is a vehicle to stimulate the intestinal vitamin K2 production.
  • the product is advised to be used as one portion daily.
  • the final product contains per 100 grams: 3g milk fat, 4.6g milk protein, 4.6 g carbohydrates, Ig sialyl-lactose, Ig GOS, 175 mg Ca, 55mg Mg, 2.5mcg D3, and 80 meg K2.
  • This product is characterized by a higher natural content of vitamin K2, MK-8 in particular, and as well is a vehicle to stimulate the intestinal vitamin K2 production.
  • the product is advised to be used as one portion daily.
  • the final product contains per 100 grams: 3g milk fat, 4.6g milk protein, 4.6 g carbohydrates, Ig sialyl-lactose, Ig FOS, 175 mg Ca, 55mg Mg, 2.5mcg D3, and 80 meg K2.
  • This product is characterized by a higher natural content of vitamin K2, MK-8 in particular, and as well is a vehicle to stimulate the intestinal vitamin K2 production.
  • the product is advised to be used as one portion daily.
  • the final product contains per 100 grams: 3g milk fat, 4.6g milk protein, 4.6 g carbohydrates, Ig sialyl-lactose, Ig FPS, 175 mg Ca, 55mg Mg, 2.5mcg D3, and 80 meg K2.
  • This product is characterized by a higher natural content of vitamin K2, MK-8 in particular, and as well is a vehicle to stimulate the intestinal vitamin K2 production.
  • the product is advised to be used as one portion daily.
  • a low-fat fresh cheese product was prepared, which contained 1Og milk proteins, 3.5g carbohydrates, and 8% fat per 100 gram. Under stirring, per lOOg of this product, 3g ground eggshell (as Ca and Mg source) , 2g GOS, 120mg Mg (as MgPO 4 salt), 100 meg vitamin K2-oil (MK7-13) , and 5mcg vitamin D3 oil were aseptically added until a homogeneous product of good taste was obtained. Then portion packages were filled with the thus prepared product. This product is typically for the 5O + age category, with proven effects on bone metabolism. It is advised to consume the product once daily, preferable in the evening.
  • the final product comprised per 100 gram: 29% protein, 14.7% fat 39.1% carbohydrates (lactose), 4.9g inulin, 3g ground eggshell powder, 16mg astaxanthin, 160 mgdocosahexaenoic acid, 40mg eicosapentaenoic acid, and 1070mg Ca, 152mg Mg, 375IU D3, and 160mcg K2.
  • the final product is dissolved in water
  • the product is designed to be consumed once daily, and in particular by those who suffer from arthrose or have an increased risk to develop arthrose.
  • Emmenthaler-like cheese was produced according to the state of the art applying K2-producing propionic bacteria, low-pH milk calcium preparation, MgPO 4 , vitamin D3- oil, and GOS.
  • the final product comprised per 100 gram: 29g protein, 3Og fat, 2g GOS, llOOmg Ca, 115mg Mg, 130mcg K2, 5mcg D3.
  • the product was developed typically for those who have a low consumption of liquid dairy, and is preferable consumed as two slides during breakfast or lunch.
  • Example 11 Appearance and clearance of vitamin Kl and K2 vitamins
  • a vitamin Kl and vitamin K2 (MK-7, 9, and 10) enriched serving of buttermilk was orally consumed by 12 adult volunteers (20-45 years of age) , in the laboratory in combination with a standard breakfast.

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Abstract

L'invention concerne des procédés et compositions pour le traitement d'affections osseuses, en particulier d'une perte osseuse telle que l'ostéoporose. La présente invention concerne en particulier des compositions nutritionnelles à base de lait de préférence complétées avec des prébiotiques et une source de vitamine K2 séparée, et des procédés faisant appel à de telles compositions nutritionnelles pour le traitement ou la prophylaxie d'affections osseuses en particulier d'une perte osseuse telle que l'ostéoporose. La présente composition comprend : une ou plusieurs fractions et/ou un ou plusieurs composants dérivés du lait ; de préférence un ou plusieurs prébiotiques ; de préférence un ou plusieurs sels de calcium et/ou de magnésium ; et de la vitamine K2 (ménaquinone) comprenant 7 à 13 (MK-7 à MK13) résidus isopropénoïde.
EP09706153A 2008-01-28 2009-01-27 Procédés et compositions pour le traitement d'affections osseuses Withdrawn EP2247199A1 (fr)

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NL1034964A NL1034964C2 (nl) 2008-01-28 2008-01-28 Werkwijze en composities voor de behandeling van botaandoeningen.
PCT/EP2009/000578 WO2009095240A1 (fr) 2008-01-28 2009-01-27 Procédés et compositions pour le traitement d'affections osseuses

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DK2419506T3 (en) 2009-04-15 2018-01-15 Dupont Nutrition Biosci Aps BAKERY STUMS WITH AN EXCELLENT ABILITY TO MAKE MENAQUINON
CN102781258A (zh) * 2009-09-14 2012-11-14 雀巢产品技术援助有限公司 包含外源性维生素k2的用于调节炎症的营养组合物
WO2011150949A1 (fr) 2010-06-04 2011-12-08 N.V. Nutricia Oligosaccharides non digestibles pour l'induction d'une tolérance orale contre des protéines alimentaires
US8765118B2 (en) 2010-08-17 2014-07-01 Chr. Hansen A/S Lactococcus lactis strain with high vitamin K2 production
AU2011290850B2 (en) * 2010-08-17 2015-08-27 Chr. Hansen A/S Lactococcus lactis strain with high vitamin K2 production
NL2008294C2 (en) * 2011-05-20 2013-08-19 Friesland Brands Bv Food composition comprising vitamin k and saturated fat.
WO2012161572A1 (fr) * 2011-05-20 2012-11-29 Friesland Brands B.V. Composition comprenant de la vitamine k2
WO2013144267A2 (fr) * 2012-03-29 2013-10-03 Nestec S.A. Amélioration de la santé musculosquelettique par nutrition et exercice
WO2013144268A1 (fr) * 2012-03-29 2013-10-03 Nestec S.A. Nutrition et exercice physique contre la malnutrition associée à la prise de médicaments chez les enfants
EP3139904B1 (fr) 2014-05-05 2021-03-03 Basf Se Formulation de vitamine liposoluble
ITUA20163791A1 (it) * 2016-05-25 2017-11-25 Alfonso Colacchio Composto nutraceutico per il potenziamento del sistema immunitario ed il benessere delle ossa
CN106615099A (zh) * 2016-10-12 2017-05-10 西宝生物科技（上海）股份有限公司 一种包含mk‑7和活性维生素d3的酸奶及其制备方法
EP3572087B9 (fr) * 2017-01-23 2023-10-04 Cupione Co., Ltd. Composition destinée à la prévention ou au traitement de l'arthrose contenant comme principe actif du sialyllactose ou un sel correspondant
US20200338031A1 (en) * 2019-04-26 2020-10-29 Lanny Leo Johnson Compositions for the treatment of non-articular cartilage-associated bone conditions
EP4285997A1 (fr) * 2021-01-26 2023-12-06 Megmilk Snow Brand Co. Ltd. Composition pour améliorer la fonction d'articulation

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NL9401958A (nl) * 1994-11-23 1996-07-01 Friesland Brands Bv Met eierschalenmeel verrijkt melkprodukt.
NZ507335A (en) * 2000-10-05 2004-10-29 New Zealand Dairy Board Bone health compositions derived from milk comprising an acidic protein fraction but that does not contain CGMP
GB0100273D0 (en) * 2001-01-08 2001-02-14 Nestle Sa Nutritional composition for a bone condition
JP2006213627A (ja) * 2005-02-02 2006-08-17 Isamu Kajima 骨粗鬆症発症予防剤
US20100048704A1 (en) * 2006-07-14 2010-02-25 Nattopharma Asa Pharmaceutical and nutraceutical products comprising vitamin k2

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EA020252B1 (ru) 2014-09-30
WO2009095240A1 (fr) 2009-08-06
MX2010008144A (es) 2010-08-04
EA201070893A1 (ru) 2011-02-28
NL1034964C2 (nl) 2009-07-30

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