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WO2009131470A1 - Compositions et procédés pour le maintien de la santé des os ou pour la réduction de la perte osseuse - Google Patents

Compositions et procédés pour le maintien de la santé des os ou pour la réduction de la perte osseuse Download PDF

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Publication number
WO2009131470A1
WO2009131470A1 PCT/NZ2009/000059 NZ2009000059W WO2009131470A1 WO 2009131470 A1 WO2009131470 A1 WO 2009131470A1 NZ 2009000059 W NZ2009000059 W NZ 2009000059W WO 2009131470 A1 WO2009131470 A1 WO 2009131470A1
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WO
WIPO (PCT)
Prior art keywords
milk
bone
composition
fractions
colostrum
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/NZ2009/000059
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English (en)
Inventor
Linda May Schollum
Marlena Cathorina Kruger
Wei-hang CHANG
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.)
Fonterra Cooperative Group Ltd
Original Assignee
Fonterra Cooperative Group Ltd
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Filing date
Publication date
Application filed by Fonterra Cooperative Group Ltd filed Critical Fonterra Cooperative Group Ltd
Priority to HK11110142.3A priority Critical patent/HK1155675B/xx
Priority to CN2009801221047A priority patent/CN102065877B/zh
Publication of WO2009131470A1 publication Critical patent/WO2009131470A1/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
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/738—Rosa (rose)
    • 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
    • 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 invention relates to uses of a water soluble extract of rosehip for the maintenance or improvement of bone health and to treat or prevent bone disorders characterised by weakened or fragile bones.
  • the invention also relates to compositions comprising a water soluble extract of rosehip useful for the maintenance or improvement of bone health and to treat or prevent bone disorders characterised by weakened or fragile bones.
  • Bone comprises an extracellular protein matrix (osteoid) interspersed with bone cells
  • osteoblasts with a mineral component laid within the extracellular matrix consisting of calcium salts and other minerals. Bone undergoes remodelling which is the process of resorption where bone is broken down by osteoclasts and then replaced by osteoblasts (reformation). Remodelling occurs to regulate calcium homeostasis, repair bone that has been damaged during everyday stress and to shape bone during growth or changes in mechanical stress patterns.
  • Osteoclasts degrade bone at a particular area and then undergo apoptosis. Osteoblasts rebuild new bone and mediate its remineralisation. During remineralisation, some osteoblasts are encased within the calcified material and become osteocytes.
  • Osteopenia is a condition where bone mineral density is lower than normal and has been considered by some to be a precursor to osteoporosis. However, not every person diagnosed with osteopenia WJLU develop osteoporosis. Osteopenia is defined as a bone mineral density T score 1-2.5 standard deviations below peak bone mass (20-year-old healthy female average) as measured by DXA.
  • Osteoporosis is characterised by a gradual thinning and weakening of the bones which without treatment can lead to weakness of the skeleton and an increased risk of fracture. Osteoporosis is defined as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old healthy female average) as measured by DXA.
  • the pathology of osteopenia and osteoporosis is an imbalance between the process of breaking down the bone (resorption) and building up the bone (reformation) by osteoclasts and osteoblasts.
  • this process of bone resorption and bone reformation is almost perfectly balanced. If this balance is disrupted due to various reasons Le. menopause, drugs etc, the break down of bone eventually overtakes the build up of bone and osteopenia or the more severe osteoporosis may develop.
  • Osteopenia is not often diagnosed, and if diagnosed, is generally not medically treated due to the cost and length of treatment. Because sufferers of osteopenia are generally younger than people diagnosed with osteoporosis they require therapy for many years. The cost/benefit ratio of such a long term treatment is unknown and therefore osteopenia is generally not treated medically.
  • Bisphosphonates are often prescribed in cases where the patient is confirmed to be suffering from osteoporosis.
  • oral bisphosphonates are poorly absorbed and must be taken on an empty stomach. Additionally, they can be poorly tolerated in some people and are associated with esophagitis.
  • Other drugs prescribed for osteoporosis such as teriparatide and strontium ranelate are also not well tolerated by some people.
  • Teriparatide must be given by injection and is not suitable for patients who are young, have had previous radiation therapy, or suffer from Paget's disease.
  • Strontium ranelate has fewer side effects than bisphosphonates but has been associated with increasing the risk of a venous thromboembolism. Additionally, strontium ranelate is taken up into the bone matrix in place of calcium which results in a disproportionate increase in bone mineral density measured on DXA scanning.
  • the present invention relates to use of a water soluble extract of rosehip in the manufacture of a composition for treating or preventing a bone condition characterised by weakened or fragile bones.
  • the present invention relates to a composition
  • a composition comprising a water- soluble extract of rosehip for treating or preventing a bone condition characterised by weakened or fragile bones.
  • composition further comprises one or more agents selected from calcium, magnesium, zinc, vitamin D, vitamin K, folic acid or folate, vitamin B6 and vitamin B12.
  • the present invention relates to a method for treating or preventing a bone condition characterised by weakened or fragile bones comprising administering a composition comprising an effective amount of a water soluble extract of rosehip to a subject in need thereof.
  • the present invention relates to a method for treating or preventing osteoporosis comprising administering a composition comprising an effective amount of a water soluble extract of rosehip to a subject in need thereof.
  • the present invention relates to a method for treating or preventing osteopenia comprising administering a composition comprising an effective amount of a water soluble extract of rosehip to a subject in need thereof.
  • the subject is need of maintained of increased bone formation, maintained or increased bone mineral density, maintained or increased bone mass (including peak bone mass), bone regeneration during fracture healing, reduced bone resorption, decreased bone loss, or maintained or increased bone strength.
  • the composition does not include any of blueberry, blackberry, elderberry, cranberry, rosemary, clove, feverfew, nettle root, artichoke, reishi mushroom, olive extract, green tea extract, grape seed extract, resveratrol, viniferin, Aframomum melegueta, boswellia serrata extract, boswellia forte, iprifiavone, tocotrienols, evening primrose oil, INM-176, borage oil, krill oil, at least one type of xanthophyll (e.g., astaxanthin), green coffee extract or ferulic acid.
  • blueberry blueberry
  • blackberry elderberry
  • cranberry rosemary
  • artichoke reishi mushroom
  • olive extract green tea extract
  • grape seed extract resveratrol
  • viniferin Aframomum melegueta
  • boswellia serrata extract boswellia
  • condition to be treated is osteoporosis or osteopenia.
  • the composition maintains or increases bone formation, maintains or increases bone density, maintains or increases bone mass, stimulates bone regeneration during fracture healing, reduces bone resorption, decreases bone loss, or maintains or increases bone strength.
  • the composition is a food, confectionary, milk, milk product, milk powder, reconstituted milk, cultured milk, drinking yoghurt, set yoghurt, drink, food additive, drink additive, dietary supplement, nutritional product, medical food, nutraceutical or a pharmaceutical.
  • a composition useful in the invention further comprises one or more daky ingredients.
  • the daily ingredient may be selected from the group comprising recombined, powdered or fresh skim milk, reconstituted whole or skim milk powder, skim milk concentrate, skim milk retentate, concentrated milk, ultrafiltered milk retentate, milk protein concentrate, milk protein isolate, calcium depleted milk protein concentrate, low fat milk, low fat milk protein concentrate, casein, caseinate, milk fat, high CLA milk fat, cream, butter, anhydrous milk fat, butter milk, butter serum, hard milk fat fractions, soft milk fat fractions, sphingolipid fractions, milk fat globular membrane fractions, phospholipid fractions, complex lipid fractions, colostrum, a colostrum fraction, colostrum protein concentrate, colostrum whey, an immunoglobulin fraction from colostrum, whey, lactoferrin, one or more lactoferrin fragments, whey protein isolate, whey protein concentrate, sweet
  • soaps or emulsifiers hydrolysates of any of these ingredients, fractions of the hydrolysates, and any combination of any two or more of these ingredients, including combinations of hydrolysed fractions, combinations of non-hydrolysed fractions, and combinations of hydrolysed and non- hydrolysed fractions.
  • the amount of the water soluble extract of rosehip administered is about 1 mg to about 2000 mg per kg body weight, about 100 to about 1000 mg per kg body weight, about 50 to about 500 mg per kg body weight, or about 0.05 mg to about 300 mg per kg body weight per day.
  • calcium is calcium or a calcium salt.
  • magnesium is magnesium or a magnesium salt.
  • zinc is zinc or a zinc salt.
  • vitamin D is vitamin D or a vitamin D derivative (including but not limited to vitamin Dl [lamisterol], vitamin D2 [ergocalciferol], vitamin D3 [cholecalciferol, 1,25- dihydroxycholecalciferol], vitamin D4 [dihydrotachysterol], vitamin D5 [7-dehydrositosterol]), or a vitamin D analog.
  • folic acid is folic acid or a folic acid salt i.e. folate or a derivative thereof.
  • vitamin B12 is vitamin B12 or a derivative thereof.
  • Salts useful herein include but are not limited to ammonium (NH 4 + ), boron, calcium, copper, iron (ferrous, Fe 2+ and ferric, Fe 3+ ), magnesium, manganese, phosphorus, potassium, pyridinium (C 5 H 5 NH + ), quaternary ammonium (NR 4 + ), silicon, sodium, strontium, and zinc salts, or a combination thereof.
  • NH 4 + ammonium
  • boron calcium, copper, iron (ferrous, Fe 2+ and ferric, Fe 3+ ), magnesium, manganese, phosphorus, potassium, pyridinium (C 5 H 5 NH + ), quaternary ammonium (NR 4 + ), silicon, sodium, strontium, and zinc salts, or a combination thereof.
  • a composition useful herein further comprises a pharmaceutically acceptable carrier.
  • the composition is, or is formulated as, a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food, nutraceutical, medicament, pharmaceutical, enteral or parenteral feeding product or meal replacement.
  • the composition is in the form of a tablet, a caplet, a pill, a hard or soft capsule or a lozenge.
  • the composition is in the form of a cachet, a dispensable powder, granules, a suspension, an elixir, a liquid, or any other form that can be added to food or drink, including for example water, milk or fruit juice.
  • the composition further comprises one or more constituents (such as antioxidants) which prevent or reduce degradation of the composition during storage or after administration.
  • these compositions may include any edible consumer product which is able to carry a water soluble extract of rosehip.
  • suitable edible consumer products include aqueous products, baked goods, confectionary products including chocolate, gels, ice creams, reconstituted fruit products, snack bars, food bars, muesli bars, spreads, sauces, dips, dairy products including yoghurts and cheeses, drinks including dairy and non-dairy based drinks, milk, milk powders, sports supplements including dairy and non-dairy based sports supplements, fruit juice, food additives such as protein sprinkles and dietary supplement products including daily supplement tablets.
  • Suitable nutraceutical compositions useful herein may be provided in similar forms.
  • the composition comprises or the method comprises administration of agents such as rosehip, calcium, magnesium, zinc, vitamin D, vitamin K, folic acid or folate, vitamin B6, vitamin B12, a dairy ingredient or a pharmaceutical agent.
  • a composition useful herein comprises, consists essentially of, or consists of at least about 0.01, 0.02, 0.05, 0.07, 0.1, 0.2, 0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, 99.5, 99.8 or 99.9% by weight of one or more of these agents and useful ranges may be selected between any of these foregoing values (for example, from about 0.1 to about 50%, from about 0.2 to about 50%, from about 0.5 to about 50%, from about 1 to about 50%, from about 5 to about 50%, from about 10 to about 50%, from about 15 to about 50%, from about 20 to about 50%, from about 25 to about 50%, from about 30 to about 50%, from about 35 to about
  • a composition useful herein is useful for treating or preventing a bone condition characterised by weakened or fragile bones.
  • the condition to be treated is a condition that requires the maintenance of or an increase in bone mass or bone strength or both bone mass and bone strength.
  • the condition is a condition that requires a decrease in bone loss.
  • the condition is a condition that requires bone cell proliferation, bone cell differentiation, bone cell mediated mineralization or a combination of any two or more of bone cell proliferation, bone cell differentiation and bone cell mediated mineralization.
  • the condition is a condition that requires the inhibition of bone resorption, an increase in bone formation, a decrease in bone loss or a combination of any two or more of the inhibition of bone resorption, an increase in bone formation and a decrease in bone loss.
  • the condition is a condition requiring an improvement in or maintenance of bone density, bone mass, bone strength or bone health or a combination of any two or more of an improvement in or maintenance of bone density, bone mass, bone strength and bone health.
  • the condition is osteoporosis. In one embodiment the condition is osteopenia.
  • treating or preventing a bone condition characterised by weakened or fragile bones includes one or more of maintaining or increasing bone formation, maintaining or increasing bone mineral density, maintaining or increasing bone mass (including peak bone mass), treating or preventing osteoporosis, treating or preventing osteopenia, stimulating bone regeneration during fracture healing, reducing bone resorption or increasing bone quality (for example, as measured by break stress or bone strength).
  • a composition useful herein is useful for administering to a subject in need thereof for the treatment of a bone condition.
  • the subject is in need of an increase in bone mass.
  • the subject is in need of treatment for a condition that requires a decrease in bone loss.
  • the subject is in need of treatment for a condition that requires bone cell proliferation, bone cell differentiation or bone cell mediated mineralization or a combination of any two or more of bone cell proliferation, bone cell differentiation and bone cell mediated mineralization.
  • the subject is in need of a treatment of a condition that requires the inhibition of bone resorption, an increase in bone formation or a decrease in bone loss or a combination of the inhibition of bone resorption, an increase in bone formation and a decrease in bone loss.
  • the subject is in need of treatment for a condition requiring improvement or maintenance of bone density, improvement or maintenance of bone mass, improvement or maintenance of bone strength or improvement or maintenance of bone health or a combination of any two or more of these effects.
  • the subject is in need of decreased bone resorption or decreased osteoclastogenesis or both. Accordingly, in one embodiment the invention relates to amelioration, treatment or prevention of a condition associated with net bone resorption or increased osteoclastogenesis.
  • the subject is in need of increased bone formation or increased osteoblast proliferation, increased osteoblast differentiation increased mineralization or a combination thereof.
  • the invention relates to the amelioration, treatment or prevention of a condition associated with poor bone formation or decreased osteoblast proliferation, decreased differentiation and decreased mineralization or a combination thereof.
  • treating or preventing a bone condition characterised by weakened or fragile bones includes decreasing bone loss, in particular bone loss associated with age in a subject.
  • the composition comprises, consists essentially of, or consists of about 0.1, 0.5, 1, 5, 10, 15, 20, 25, 3O 5 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, 99.5, 99.8 or 99.9 % by weight of one or more dairy ingredients selected from fresh, recombined or powdered whole milk or a milk derivative and useful ranges may be selected between any of these foregoing values (for example, from about 0.1 to about 50%, from about 0.2 to about 50%, from about 0.5 to about 50%, from about 1 to about 50%, from about 5 to about 50%, from about 10 to about 50%, from about 15 to about 50%, from about 20 to about 50% J from about 25 to about 50%, from about 30 to about 50%, from about 35 to about 50%, from about 40 to about 50%, and from about 45 to about 50%).
  • dairy ingredients selected from fresh, recombined or powdered whole milk or a milk derivative and useful ranges may be selected between any of these foregoing values (for example
  • the milk derivative is preferably selected from recombined, powdered or fresh skim milk, reconstituted whole or skim milk powder, skim milk concentrate, skim milk retentate, concentrated milk, ultrafiltered milk retentate, milk protein concentrate (MPC), milk protein isolate (MPI), calcium depleted milk protein concentrate (MPC), low fat milk, low fat milk protein concentrate (MPC), casein, caseinate, milk fat, high CLA milk fat, cream, butter, anhydrous milk fat (AMF), butter milk, butter serum, hard milk fat fractions, soft milk fat fractions, sphingolipid fractions, milk fat globular membrane fractions, phospholipid fractions, complex lipid fractions, colostrum, a colostrum fraction, colostrum protein concentrate (CPC), colostrum whey, an immunoglobulin fraction from colostrum, whey, lactoferrin, one or more lactoferrin fragments, whey protein isolate (WPI), whey protein concentrate (WPC), sweet
  • soaps or emulsifiers hydrolysates of any of these derivatives, fractions of the hydrolysates, and any combination of any two or more of these derivatives, including combinations of hydrolysed fractions, combinations of non-hydrolysed fractions, and combinations of hydrolysed and non- hydrolysed fractions.
  • the invention may also be said broadly to consist in the parts, elements and features referred to or indicated in the specification of the application, individually or collectively, in any or all combinations of two or more of said parts, elements or features, and where specific integers are mentioned herein which have known equivalents in the art to which the invention relates, such known equivalents are deemed to be incorporated herein as if individually set forth.
  • Figure 2 is a graph showing the effect of rosehip extract on osteoclastogenesis. Rosehip dose-dependently suppressed formation of osteoclasts. Results are compared with control at p ⁇ 0.05.
  • Figure 3 is a graph showing break stress results of a three-point bending test for the right femur.
  • One group of rats was sham operated (Sham; n ⁇ l ⁇ ) and fed a control diet for 28 weeks.
  • Results are shown as mean ⁇ SEM.
  • Figure 4 is a graph showing maximum load for the right femur. Maximum load is defined as the maximum force that the femur can withstand during a three point bending test.
  • Figure 6 is a graph showing die energy expended to break the right femur in rats.
  • the present invention is based on the discovery that a water extract of rosehip has a positive effect on the maintenance of bone health and the treatment of bone disease such as osteoporosis or osteopenia.
  • water soluble extract of rosehip means an extract produced by a method where any food grade polar solvent such as water, acetic acid, and alcohols (such as methanol, ethanol, propanol or butanol, for example) are used to extract water soluble components from rosehips.
  • the solvent is water.
  • the term "maintenance of bone health” means maintaining an individual's bone at a healthy density for example, as defined by WHO standards for DEXA, within ⁇ 1 SD of bone density for a 20 year old person.
  • weakened ot fragile bones means an individual has a bone density below the healthy density for example, as defined by WHO standards for DEXA, within ⁇ 1 SD of bone density for a 20 year old person.
  • an "effective amount” is the amount required to confer a therapeutic effect.
  • the interrelationship of dosages for animals and humans (based on milligrams per meter squared of body surface) is described by Freireich, et al. (1966).
  • Body surface area can be approximately determined from height and weight of the subject. See, e.g., Scientific Tables, Geigy Pharmaceuticals, Ardley, New York, 1970, 537.
  • Effective doses also vary, as recognized by those skilled in the art, dependent on route of administration, carrier usage, species and individual genetic variation, and the like.
  • oral administration includes oral, buccal, enteral and intra-gastric administration.
  • pharmaceutically acceptable carrier is intended to refer to a carrier including but not limited to an excipient, diluent, auxiliary or combination thereof that can be administered to a subject as a component of a composition of the invention that does not reduce the activity of the composition and is not toxic when administered in doses sufficient to deliver an effective amount of a rosehip extract.
  • the formulations can be administered orally, nasally and topically.
  • a "subject" in accordance with the invention is an animal, preferably a mammal, more preferably a mammalian companion animal or human.
  • Preferred companion animals include cats, dogs and horses.
  • treat broadly includes amelioration or prevention or amelioration and prevention of the onset of the symptoms or severity of a particular condition; for example preventing or ameliorating a reduction in bone density, preventing or otherwise reducing the risk of developing osteoporosis, preventing or otherwise reducing the risk of developing osteopenia, or preventing or ameliorating other disease symptoms.
  • the term “treat” also broadly includes the maintenance of good bone health and building bone quality for disease or disorder prevention.
  • Rosehip sometimes called rosehaw, is a fruit found on the rose plant (Rosa spp.) which contains several vitamins including high levels of vitamin C. Other vitamins found in rosehip are vitamin A, D and E. Rose hip also contains high levels of iron and some essential fatty acids and antioxidants.
  • Rosacea species can be used to make the water soluble extract of rosehip useful in the present invention. These species include but are not limited to Rosa canina, Rosa dumalis subsp. boissieri, Rosa dmnalis subsp. antayl en ⁇ s, Rosa villosa, Rosa pulverulenta, Rosa mqyesii Rosa gallica, Rosa condita, Rosa rugosa and Rosa pisiformis.
  • a possible extraction process of rosehip is as follows. Fresh rose hips are macerated or dried rose hips are powdered. The macerated or powdered rosehips are mixed with distilled water or other aqueous solutions (e.g. buffers) in a ratio of 1:5 (w/w), to allow extraction of the water soluble components from the rosehips.
  • the aqueous solvent may be replaced one or more times, preferably 3 times, and each amount of solvent is allowed to remain in contact with the plant material for several hours, preferably 12, 24 or 48 hours, preferably with continuous stirring. After filtration or centrifugation of the total extracts, the water solutions can then be freeze or spray dried to form a powder that can be used as the water extract for use herein.
  • This extract can be further fractionated by standard methods of ion exchange chromatography or membrane separation or other such separation techniques that are known in the art. See for example Ion Exchange Chromatography & Chromatofocusing, Principles and Methods, Amersham Biosciences Limited 2004, Code 11-0004-21, Edition AA, http://www.amersham.com.
  • compositions and uses of the compositions described herein are useful for treating or preventing a bone condition characterised by weakened or fragile bones, such as osteoporosis or osteopenia.
  • the condition to be treated is a condition that requires an increase in bone mass.
  • the condition is a condition that requires a decrease in bone loss.
  • the condition is a condition that requires bone cell proliferation, bone cell differentiation, or bone cell mediated mineralisation, or a combination of two or more thereof.
  • the condition is a condition that requires the inhibition of bone resorption, an increase in bone formation, or a decrease in bone loss, or a combination of two or more thereof.
  • the condition is a condition requiring an improvement or maintenance of bone strength, bone density, or bone mass, or a combination of two or more thereof.
  • the condition is osteoporosis.
  • the condition is osteopenia.
  • composition comprising, consisting essentially of or consisting of a water soluble extract of rosehip and one or more ingredients selected from calcium, magnesium, zinc, vitamin D, vitamin K, folic acid or folate, vitamin B6 and vitamin B12.
  • composition consisting essentially of a water soluble extract of rosehip and one or more ingredients selected from calcium, magnesium, zinc, vitamin D, folic acid, folate, and vitamin B 12, wherein the composition is formulated for simultaneous, separate or sequential administration of the water soluble extract of rosehip and the one or more ingredients.
  • compositions comprising a water soluble extract of rosehip and one or more dairy ingredients.
  • a composition useful herein includes any composition that can carry a water soluble extract of rosehip, including any consumer product and any pharmaceutical product that is able to carry a water soluble extract of rosehip.
  • the composition may be formulated as a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
  • a composition of the invention is formulated as a powder, liquid, food bar, spread, sauce, ointment, tablet or capsule. Suitable foods and drinks include dairy and non-dairy foods and drinks.
  • the composition is a milk powder, milk drink, yoghurt, yoghurt powder, yoghurt drink, soy, acidified beverages, UHT, pasteurised, butter or cheese.
  • Appropriate formulations may be prepared by an art skilled worker with regard to that skill and the teaching of this specification.
  • a nutraceutical composition for use according to the invention can be a dietary supplement (e.g., a capsule, a mini-bag, or a tablet) or a food product (e.g., milk, juice, a soft drink, a herbal tea-bag, or confectionary).
  • the composition can also include other nutrients, such as protein, carbohydrate, lipids, vitamins, minerals, ot amino acids.
  • the composition can be in a form suitable for oral use, such as a tablet, a hard or soft capsule, an aqueous or oil suspension, or a syrup; or in a form suitable for parenteral use, such as an aqueous propylene glycol solution, or a buffered aqueous solution.
  • the amount of the active ingredient in the nutraceutical composition depends to a large extent on a subject's specific need. The amount also varies, as recognized by those skilled in the art, dependent on administration route, species, genetic/ physiological predisposition and possible co- usage of other bone-enhancing agents
  • Foods, food additives ot food supplements comprising a rosehip extract for use according to the invention include any edible consumer product which is able to carry a water soluble plant extract.
  • suitable edible consumer products include confectionary products, reconstituted fruit products, snack bars, muesli bars, bakery products, spreads, dips, dairy products including yoghurts and cheeses, drinks including dairy and non-dairy based drinks, milk powders, sports supplements including dairy and non-dairy based sports supplements, food additives such as protein sprinkles and dietary supplement products including daily supplement tablets.
  • suitable nutraceutical compositions useful herein may be provided in similar forms.
  • compositions useful herein may be formulated to allow for administration to a subject by any chosen route, including but not limited to oral or nasal administration.
  • the composition useful herein is administered orally.
  • the dose of the composition administered, the period of administration, and the general administration regime may differ between subjects depending on such variables as the severity of symptoms of a subject, the type of disorder to be treated, the mode of administration chosen, and the age, sex and general health of a subject.
  • the inventors contemplate administration of from about 1 mg to about 2000 mg per kg body weight of rosehip per day, preferably about 100 to 1000 mg per kg body weight of rosehip per day or about 50 to about 500 mg per kg body weight of rosehip per day. In one embodiment, the inventors contemplate administration of from about 0.05 mg to about 300 mg per kg body weight of rosehip.
  • the composition useful herein is administered at least once a day.
  • the composition useful herein is administered 2-3 times a day.
  • the composition useful herein may be administered once a week.
  • the composition useful herein is administered as a prophylactic before the onset of menopause.
  • the composition useful herein is administered after the onset of menopause for maintaining or increasing bone health or for treating or preventing a bone condition.
  • composition useful according to this invention can be evaluated both in vitro and in vivo. See, e.g., the examples below. Briefly, the composition can be tested for its ability to promote osteoblast development and activity or inhibit osteoclastogenesis, limit osteoclast activity, or reduce osteoclast numbers in vitro. For in vivo studies, the composition can be administered to an animal (e.g., a rat) and its effects on bone tissues are then accessed. Based on the results, an appropriate dosage range and administration route can be determined.
  • compositions useful herein may be used alone or in combination with one or more other therapeutic agents.
  • the therapeutic agent may be a food, drink, food additive, drink additive, food component, drink component, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
  • the therapeutic agent is preferably effective to promote osteoblast development and activity, inhibit osteoclastogenesis reduce osteoclast numbers or limit osteoclast activity.
  • the administration of a composition useful herein and the other therapeutic agent may be simultaneous or sequential.
  • simultaneous administration includes the administration of a single dosage form that comprises all components or the administration of separate dosage forms at substantially the same time.
  • Sequential administration includes administration according to different schedules, preferably so that there is an overlap in the periods during which the composition useful herein and other therapeutic agent are provided.
  • a composition useful herein includes or is administered simultaneously or sequentially with milk components such as whey protein, whey protein fractions (including acidic or basic whey protein fractions or a combination thereof), glycomacropeptide, lactoferrin or a functional lactoferrin variant, or a lactoferrin fragment, a vitamin D, vitamin D derivative, vitamin D analog, or calcium and its salts or combinations thereof.
  • milk component-containing compositions include compositions such as a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food or nutraceutical. Milk fractions enriched for these components may also be employed.
  • Compositions useful herein may further include another bone-health agent, such as calcium, fluoride, magnesium, zinc, calcium salts, fluoride salts, magnesium salts, zinc salts, vitamin A, folate, or folic acid, or vitamin B12, vitamin B6, vitamin C, vitamin D, vitamin D derivatives (including but not limited to vitamin D (including vitamin Dl [lamisterol], vitamin D2 [ergocalciferol], vitamin D3 [cholecalciferol, l ⁇ S-dihydroxycholecalciferol], vitamin D4 [drhydrotachysterol] and vitamin D5 [7-dehydrositosterol], and vitamin D analogs), vitamin E, vitamin E derivatives, vitamin E analogs, vitamin K, vitamin K derivatives, vitamin K analogs, vitamin K2, whey protein, whey protein fractions (including acidic or basic whey protein fractions or a combination thereof), glycomacropeptide, lactoferrin, a functional lactoferrin variant, a functional
  • a pharmaceutical composition that contains rosehip or components thereof.
  • the pharmaceutical composition can be used to prevent and treat bone-related disorders described above.
  • the pharmaceutical composition can further include an effective amount of another bone-enhancing agent.
  • the pharmaceutically acceptable carrier includes a solvent, a dispersion medium, a coating, an antibacterial and antifungal agent, and an isotonic and absorption delaying agent
  • a pharmaceutical composition useful in the invention may be formulated with an appropriate pharmaceutically acceptable carrier (including excipients and diluents) selected with regard to the intended route of administration and standard pharmaceutical practice.
  • a composition of the invention can be administered orally as a powder, liquid, tablet, effervescent tablet or capsule.
  • Suitable formulations may contain additional agents as required, including emulsifying agents, antioxidants, flavouring or colouring agents, and may be adapted for immediate-, delayed-, modified-, sustained-, pulsed- or controlled-release.
  • composition for use according to the invention is formulated for ingestion.
  • Capsules can contain any standard pharmaceutically acceptable materials such as gelatin or cellulose. Tablets can be formulated in accordance with conventional procedures by compressing mixtures of the active ingredients with a solid carrier and a lubricant. Examples of solid carriers include but are not limited to starch and sugar bentonite. Active ingredients can also be administered in a form of a hard shell tablet or a capsule containing a binder, e.g., lactose or mannitol, a conventional filler, and a tabletting agent.
  • a binder e.g., lactose or mannitol
  • Effervescent tablets can be formulated using any conventional procedures and may include any suitable pharmaceutically acceptable effervescent material.
  • effervescent materials include but are not limited to, citric acid, malic acid, sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate.
  • compositions of the invention can be formulated into dosage forms for different administration routes utilizing conventional methods.
  • it can be formulated in a capsule, a gel seal, or a tablet for oral administration.
  • a suitable pharmaceutical composition may be formulated with appropriate pharmaceutically acceptable excipients, diluents or carriers selected with regard to the intended dosage form and standard pharmaceutical formulation practice.
  • a dosage form useful herein can be administered orally as a powder, liquid, tablet or capsule. Suitable dosage forms may contain additional agents as required, including emulsifying, antioxidant, flavouring or colouring agents. Dosage forms useful herein may be adapted for immediate, delayed, modified, sustained, pulsed or controlled release of the active components.
  • a composition comprising rosehip may be used to treat or prevent skeletal disorders.
  • osteoporosis examples include, but are not limited to osteoporosis, hepatic osteodystrophy, osteomalacia, rickets, osteitis fibrosa cystica, renal osteodystrophy, osteosclerosis, osteopenia, fibrogenesis-imperfecta ossium, secondary hyperparathyrodism, hypoparathyroidism, hyperparathyroidism, chronic renal disease, sarcoidosis, glucocorticoid-induced osteoporosis, idiopathic hypercalcemia, Paget' s disease, and osteogenesis imperfecta.
  • the rosehip extract may be used alone or in combination with one or more other therapeutic agents (nutraceuticals, pharmaceuticals or medical foods, for example).
  • administration of the two agents may be separate, simultaneous or sequential.
  • Simultaneous administration includes the administration of a single dosage form that comprises both agents and the administration of the two agents in separate dosage forms at substantially the same time.
  • Sequential administration includes the administration of the two agents according to different schedules, preferably so that there is an overlap in the periods during which the two agents are provided.
  • Suitable agents with which the compositions of the invention can be co-administered include other bone growth agents or bone disease treatments, and other suitable agents known in the art.
  • Such agents are preferably administered parenterally, preferably by intravenous, subcutaneous, intramuscular, intraperitoneal, intramedullar, epidural, intradermal, transdermal (topical), transmucosal, intra-articular, and intrapleural, as well as oral, inhalation, and rectal administration.
  • Suitable agents with which the compositions useful herein can be co-adrninistered include alpha v beta 3 integrin receptor antagonists, antiestrogens or SERMs (Selective Estrogen Receptor Modulators) (including but not limited to tamoxifen, raloxifene, lasofoxifene, toremifene, azorxifene, clomiphene, droloxifene, idoxifene, levormeloxifene, zuclomiphene, enclomiphene, nafoxidene, and salts thereof), antiresorptive agents, bisphosphonates (including but not limited to alendronate, clodronate, etidronate, ibandronate, incadronate, minodronate, neridronate, olpadronate, pamidronate, pii ⁇ dronate, risedronate, tiludronate, zoledronate,
  • composition in accordance with the invention may be formulated with additional active ingredients which may be of benefit to a subject in particular instances.
  • additional active ingredients which may be of benefit to a subject in particular instances.
  • therapeutic agents that target the same or different facets of the disease process may be used.
  • MC3T3-E1 preosteobkst cells were obtained from ATCC, Manassas, VA, USA. Rosehip extract was purchased from Paninkret, Germany.
  • MC3T3-E1 /4 cells were seeded at 0.55 x 10 s cells /ml in 48-well plates with 0.3ml per well. Quadruplicate wells per treatment were used within each experiment and experiments were replicated three times to ensure consistency of results.
  • Culture media was ⁇ -MEM with 10% FCS. Treatments were added 24 hours following initial seeding of plates to allow cells to adhere to wells. Following 3 days of culture, media was changed to ⁇ -MEM with 10% FCS, lOmM ⁇ - glycerophosphate and 50 ⁇ g/ml ascorbic acid with and without treatments. Media was changed every 2-3 days. Following 10 days of culture, media was removed from wells and cells were washed with PBS.
  • Triton-X 100 (0.2% in dd H 2 O), 500 ⁇ L/well, was added to dried plates and plates were incubated at room temperature for 2 hours to solubilise absorbed dye. Duplicate aliquots of lOO ⁇ L were taken from each well and transferred to a 96-well plate. Absorbance was read using a ELx808 Ultra microplate reader (Bio-Tek Instruments, Inc. Vermont, USA) at 550nm using 0.2% Triton-X 100 as a blank.
  • Alkaline phosphatase activity on a per cell basis was determined by dividing the absorbance measurement at 405nm (a measure of p-nitrophenyl production or alkaline phosphatase activity) by the absorbance measurement at 550nm (from the crystal violet assay, a measure of cell number). The resultant index figure was used to represent alkaline phosphatase activity on a per cell basis. The results are shown in Figure 1. Administration of rosehip increased differentiation by 17% compared to control. EXAMPLE 2 - OSTEOCLAST FORMATION
  • Osteoclasts can be generated from the murine macrophage RAW 264.7 cell line.
  • RAW 264.7 cells were seeded into 24 well plates containing coverslips and treated with murine RANK-L.
  • the effect of a compound on osteoclast formation was tested by the addition of the compound to the RANK-L containing cell culture media at different concentrations. These cells were incubated for 5 days with a media change on day 3.
  • the coverslips were then fixed and stained for TRAP and then counterstained with hematoxylin. Large multinucleated osteoclasts were quantified. Osteoclasts appeared as large multinucleated cells staining purple red and may form even larger giant cells.
  • This study is designed to assess whether diets supplemented with rosehip are able to impact bone quality in the OVX rat model.
  • ovariectomised rats were randomly assigned to either a control group (OVX) and fed a casein control diet or a treatment group (Rosehip) and fed a Rosehip extract at 0.5% w/w of the control diet for 28 weeks.
  • OVX control group
  • Rosehip treatment group
  • Rosehip extract 0.5% w/w of the control diet for 28 weeks.
  • the right femurs were scraped clean of adhering flesh and stored in phosphate buffered saline solution at — 20 0 C. Before biomechanical testing, the bones were thawed. The length of the femurs was measured using an electronic calliper. The midpoint was marked with a waterproof pen and the width and thickness of the femurs at midpoint were also recorded. The femurs were then held at 23°C to be at room temperature before and during the test. The femurs were placed i ⁇ a testing jig constructed for a three point bending test. The distance between the supporting rods had a fixed length of 12 mm.
  • Energy is a measure of the energy expended to break the bone and was also calculated using the Shimadzu Ezi-test texture analyzer (Kyoto, Japan) using the force recordings and the known points at which the break and max force measurements were made.
  • the present invention has utility in maintaining bone health of ameliorating imbalances in bone remodelling leading to bone loss.
  • compositions may be employed as foods, drinks, food additives, drink additives, dietary supplements, nutritional products, medical foods, nutraceuticals, medicaments or pharmaceuticals .

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Abstract

La présente invention a pour objet l’utilisation d’un extrait hydrosoluble de cynorrhodon pour le maintien ou l’amélioration de la santé des os ou de la résistance des os et pour le traitement ou la prévention de troubles osseux caractérisés par des os affaiblis ou fragiles. L’invention concerne également des compositions renfermant un extrait hydrosoluble de cynorrhodon utiles pour le maintien ou l’amélioration de la santé des os ou de la résistance des os et pour le traitement ou la prévention de troubles osseux caractérisés par des os affaiblis ou fragiles.
PCT/NZ2009/000059 2008-04-24 2009-04-23 Compositions et procédés pour le maintien de la santé des os ou pour la réduction de la perte osseuse Ceased WO2009131470A1 (fr)

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HK11110142.3A HK1155675B (en) 2008-04-24 2009-04-23 Compositions and methods for maintaining bone health or reducing bone loss
CN2009801221047A CN102065877B (zh) 2008-04-24 2009-04-23 用于维持骨健康或减少骨质流失的组合物和方法

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Cited By (4)

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RU2562837C1 (ru) * 2014-06-03 2015-09-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования Воронежский государственный университет инженерных технологий (ФГБОУ ВПО ВГУИТ) Способ получения соуса на основе белкового концентрата колострума
CN113396984A (zh) * 2021-06-17 2021-09-17 优贺普食品(上海)有限公司 一种具有日晚两种配方及包装形式的儿童奶粉
US11425915B2 (en) 2018-05-02 2022-08-30 Land O'lakes, Inc. Methods of concentrating phospholipids
US12161131B2 (en) 2018-12-20 2024-12-10 Land O'lakes, Inc. Cheese sauce

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* Cited by examiner, † Cited by third party
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CN116585300B (zh) * 2023-05-30 2024-04-19 苏州大学附属第一医院 洋蓟素在制备预防或治疗激素性股骨头坏死药物中的应用

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WO1999053934A1 (fr) * 1998-04-17 1999-10-28 HANSEN, Otto, Torbjørn Formulations de cynorrhodon utilisees comme medicament anti-inflammatoire naturel permettant d'attenuer/diminuer les symptomes associes a l'inflammation et a l'arthrite
WO2008003314A1 (fr) * 2006-07-03 2008-01-10 Hyben Vital Licens Aps Méthode de préparation d'un glycoside d'un produit à base de mono- ou diacylglycérol provenant d'une matière végétale
WO2008006589A2 (fr) * 2006-07-14 2008-01-17 Dsm Ip Assets B.V. Nouvelles compositions
WO2008006582A1 (fr) * 2006-07-14 2008-01-17 Dsm Ip Assets B.V. Compositions comprenant du magnolol ou de l'honokiol et d'autres agents actifs pour le traitement de maladies inflammatoires

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WO1999053934A1 (fr) * 1998-04-17 1999-10-28 HANSEN, Otto, Torbjørn Formulations de cynorrhodon utilisees comme medicament anti-inflammatoire naturel permettant d'attenuer/diminuer les symptomes associes a l'inflammation et a l'arthrite
WO2008003314A1 (fr) * 2006-07-03 2008-01-10 Hyben Vital Licens Aps Méthode de préparation d'un glycoside d'un produit à base de mono- ou diacylglycérol provenant d'une matière végétale
WO2008006589A2 (fr) * 2006-07-14 2008-01-17 Dsm Ip Assets B.V. Nouvelles compositions
WO2008006582A1 (fr) * 2006-07-14 2008-01-17 Dsm Ip Assets B.V. Compositions comprenant du magnolol ou de l'honokiol et d'autres agents actifs pour le traitement de maladies inflammatoires

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2562837C1 (ru) * 2014-06-03 2015-09-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования Воронежский государственный университет инженерных технологий (ФГБОУ ВПО ВГУИТ) Способ получения соуса на основе белкового концентрата колострума
US11425915B2 (en) 2018-05-02 2022-08-30 Land O'lakes, Inc. Methods of concentrating phospholipids
US12402642B2 (en) 2018-05-02 2025-09-02 Land O'lakes, Inc. System for concentrating phospholipids
US12161131B2 (en) 2018-12-20 2024-12-10 Land O'lakes, Inc. Cheese sauce
CN113396984A (zh) * 2021-06-17 2021-09-17 优贺普食品(上海)有限公司 一种具有日晚两种配方及包装形式的儿童奶粉

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MY177020A (en) 2020-09-01
TW200946125A (en) 2009-11-16
CN102065877B (zh) 2013-06-19

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