TWI454273B - Compositions and methods for maintaining bone health or reducing bone loss - Google Patents

Description

Composition and method for maintaining bone health or reducing bone loss

The present invention relates to the use of a water-soluble extract of rose hip for maintaining or improving bone health and treating or preventing a bone disorder characterized by weakened or fragile bone. The invention also relates to compositions comprising a water-soluble extract of rosehip suitable for maintaining or improving bone health and treating or preventing a bone disorder characterized by weakened or fragile bone.

As the world's population ages, bone disorders become more common. These conditions, such as osteopenia and osteoporosis, are costly in terms of funding and the damage that the disease causes to the quality of life of the patient.

The bone contains an extracellular protein matrix (osteoid) interspersed with bone cells (osteocytes), and a mineral component composed of calcium salts and other minerals is deposited in the extracellular matrix. The bone undergoes reshaping, which is a resorption process (recombination) in which the bone is broken down by osteoclasts and subsequently replaced by osteoblasts. Reshaping is performed to adjust calcium stability, repair bone that has been damaged during normal stress, and shape the bone during changes in growth or mechanical stress distribution.

Osteoclasts degrade bone at specific regions and are subsequently subjected to apoptosis. Osteoblasts rebuild new bone and mediate their remineralization. During remineralization, some osteoblasts coat within the calcified material and become bone cells.

Once the peak bone mass has been reached in early adulthood, the resorption process is almost completely coupled with recombination. However, as people age, the effectiveness of the reshaping system is reduced. As women begin menopause, the two processes can become desynchronized and reabsorption predominates. In addition, with aging, there may be loss of bone mineral density, disruption of the bone micro-architecture, and other changes that lead to an increased risk of fracture. Usually, the process of bone loss is gradual and there are no obvious symptoms until the disease is completely advanced.

Therefore, it is important to maintain bone quality and density over time so that bones do not become weak and fragile with aging.

Osteopenia is a condition in which bone mineral density is lower than normal bone mineral density and has been considered by some to be a precursor to osteoporosis. However, not every person diagnosed with osteopenia will develop osteoporosis. Osteopenia was defined as a bone mineral density T score of 1-2.5 standard deviations, as measured by DXA, below the peak bone mass (average of 20 healthy women).

Osteoporosis is characterized by the gradual thinning and weakening of the bone, which can lead to fragile skeleton and increased risk of fracture without treatment. Osteoporosis is defined as the bone mineral density of 2.5 standard deviations, as measured by DXA, below the peak bone mass (average of 20 healthy women).

The pathology of osteopenia and osteoporosis is the imbalance between the broken bones (resorption) of osteoclasts and the process of establishing bones (recombination) of osteoblasts. In healthy individuals, this process of bone resorption and bone reorganization is almost completely balanced. If this balance is broken due to various reasons (ie, menopause, drugs, etc.), the decomposition of the bone eventually exceeds the establishment of the bone and can manifest osteoporosis or more severe osteoporosis.

Women are attributable to a greater risk of osteopenia and osteoporosis due to a decrease in estrogen produced after menopause. However, older men and people with specific hormonal disorders, or long-term users of certain drugs, are also susceptible to osteopenia and osteoporosis.

Treatment of skeletal disorders such as osteoporosis is generally unsatisfactory, which causes the patient to suffer from the side effects of therapies prescribed to treat skeletal disorders.

Osteopenia is usually not diagnosed and, if diagnosed, is usually not medically treated due to the cost and duration of treatment. Because patients with osteopenia are usually younger than those diagnosed with osteoporosis, they need to be treated for many years. The cost/benefit ratio for this long-term treatment is unknown and therefore bone loss is usually not medically treated.

Various drugs are currently prescribed for the treatment of osteoporosis. In cases where it is confirmed that the patient is suffering from osteoporosis, the bisphosphonate is usually prescribed. However, oral bisphosphonates are poorly absorbed and must be taken on an empty stomach. In addition, some people may be poorly tolerated and associated with esophagitis.

Other drugs prescribed for osteoporosis, such as teriparatide and strontium ranelate, are not well tolerated by some. Teriparatide must be administered by injection and is not suitable for young patients who have previously been exposed to radiation therapy or who are plagued by Paget's disease. Barium ranelate has fewer side effects than bisphosphonates but has been associated with an increased risk of venous thromboembolism. In addition, barium ranelate is absorbed into the bone matrix in place of calcium, which results in a disproportionate increase in bone mineral density as measured by DXA scanning.

Accordingly, there is a need to provide a therapy for maintaining or ameliorating bone health that overcomes or ameliorates at least one of the problems associated with known treatments, or at least provides the public with a suitable choice.

Thus, in a first aspect, the invention relates to the use of a water-soluble extract of rosehip in the manufacture of a composition for treating or preventing a skeletal condition characterized by weakened or fragile bone.

In another aspect, the invention relates to a composition comprising a water-soluble extract of rosehip for treating or preventing a skeletal condition characterized by weakened or fragile bone.

In one embodiment, the composition further comprises one or more agents selected from the group consisting of calcium, magnesium, zinc, vitamin D, vitamin K, folic acid or folate, vitamin B6 and vitamin B12.

In another aspect, the invention relates to a method of treating or preventing a skeletal condition characterized by weakened or fragile bones comprising administering to a subject in need thereof a water soluble extract comprising an effective amount of rose hips Composition of matter.

In another aspect, the invention relates to a method of treating or preventing osteoporosis comprising administering to a subject in need thereof a composition comprising a water-soluble extract of an effective amount of rosehip.

In another aspect, the invention relates to a method of treating or preventing osteopenia comprising administering to a subject in need thereof a composition comprising a water-soluble extract of an effective amount of rosehip.

In one embodiment, the subject is required to maintain or increase bone formation, maintain or increase bone mineral density, maintain or increase bone quality (including peak bone mass), bone regeneration during fracture healing, reduce bone resorption, and reduce bone loss. , or maintain or increase bone strength.

The following embodiments may be related to any of the above aspects.

In one embodiment, the composition does not include any of the following: blueberry, blackberry, elderberry, cranberry, rosemary, clove, white chrysanthemum, ramie root, artichoke, ganoderma lucidum, olive extract , green tea extract, grape seed extract, resveratrol, glucosin, Aframomum melegueta, frankincense extract, boswellia forte, ipriflavone, tocotrienol, Evening primrose oil, INM-176, borage seed oil, krill oil, at least one type of lutein (eg reduced astaxanthin), green coffee extract or ferulic acid.

In one embodiment, the condition to be treated is osteoporosis or osteopenia.

In one embodiment, 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, reduces bone loss, or maintains or increases bone strength.

In one embodiment, the composition is a food, dessert, milk, dairy product, milk powder, reconstituted milk, fermented milk, drinking yogurt, coagulated yogurt, beverage, food additive, beverage additive, dietary supplement, nutritional product, Medical food, health food or medicine.

In one embodiment, the compositions suitable for use in the present invention further comprise one or more dairy ingredients. The dairy component can be selected from the group consisting of recombinant, powder 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, decalcified milk protein concentrate, low fat milk, low fat milk protein concentrate, casein, casein salt, milk fat, high CLA milk fat, emulsifiable concentrate, butter, Dehydrated milk fat, white emulsified milk, white whey clear, hard milk fat fraction, soft milk fat fraction, sphingolipid fraction, milk fat globular membrane fraction, phospholipid fraction, complex lipid fraction, colostrum, early Milk fraction, colostrum protein concentrate, colostrum whey, immunoglobulin fraction from colostrum, whey, lactoferrin, one or more lactoferrin fragments, whey protein isolate, whey Protein concentrate, sweet whey, lactic acid whey, inorganic acid whey, reconstituted whey powder, milk minerals, compositions derived from any milk or colostrum processing stream, super processed by any milk or colostrum Filter or microfiltration Or a composition derived from a permeate, a composition derived by or by adsorption of a fraction obtained by chromatography of any milk or colostrum processing stream, including but not limited to ion and gel permeation chromatography, Extract of any of these ingredients, including extraction by multistage fractionation, differential crystallization, solvent fractionation, supercritical fractionation, near supercritical fractionation, distillation, centrifugation fractionation or fractionation with a modifier such as soap or emulsifier Any combination of any one or more of the hydrolysate of any of the components, the hydrolysate, and any combination of the two, including a combination of hydrolyzed fractions, a combination of non-hydrolyzed fractions, and hydrolyzed and non-hydrolyzed A combination of hydrolyzed fractions.

In one embodiment, the amount of water-soluble extract of the administered rose hip is from about 1 mg to about 2000 mg per kg of body weight per day, from about 100 to about 1000 mg per kg of body weight, from about 50 to about 500 mg per kg of body weight, or per kg. The body weight is from about 0.05 mg to about 300 mg.

In one embodiment, the calcium is a calcium or calcium salt. In one embodiment, the magnesium is a magnesium or magnesium salt. In one embodiment, the zinc is a zinc or zinc salt. In one embodiment, the vitamin D is a vitamin D or vitamin D derivative (including but not limited to, vitamin D1 [lamisterol], vitamin D2 [ergocalciferol], vitamin D3 [biliary calcification) Cholecalciferol, 1,25-dihydroxycholecalciferol, vitamin D4 [dihydrotachysterol], vitamin D5 [7-dehydrositosterol] or vitamin D analog. In one embodiment, the folic acid is a folic acid salt (i.e., folate) or a derivative thereof. In one embodiment, the vitamin B12 is vitamin B12 or a derivative thereof.

Salts suitable for use herein include, but are not limited to, ammonium (NH ₄ ⁺ ), boron, calcium, copper, iron (ferrous, Fe ²⁺ and ortho, Fe ³⁺ ), magnesium, manganese, phosphorus, potassium, pyr Ingot (C ₅ H ₅ NH ⁺ ), tetraammonium (NR ₄ ⁺ ), cesium, sodium, rubidium and zinc salts, or a combination thereof.

In one embodiment, a composition suitable for use herein further comprises a pharmaceutically acceptable carrier. In another embodiment, the composition is or formulated as a food, beverage, food additive, beverage additive, dietary supplement, nutritional product, medical food, health food, pharmaceutical, pharmaceutical, enteral or parenteral product or meal substitute. In one embodiment, the composition is in the form of a troche, caplet, pill, hard or soft capsule or buccal. In one embodiment, the composition is in the form of a cachet, dispensable powder, granules, suspension, elixir, liquid or any other form that can be added to the food or beverage, including, for example, water, milk or juice. In one embodiment, the composition further comprises one or more ingredients (such as antioxidants) that prevent or reduce degradation of the composition during or after administration. Such compositions may include any edible consumer product capable of carrying a water soluble extract of rosehip. Examples of suitable edible products include aqueous products, baked products, dessert products (including chocolate, gel, ice cream), reconstituted fruit products, snack bars, food bars, muesli bars, spreads, condiments , pouring juice, dairy products (including yogurt and cheese), beverages (including dairy based and non-dairy based beverages), milk, milk powder, sports supplements (including dairy based and non-dairy based sports supplements), juice , food additives (such as protein food tops) and dietary supplement products (including daily supplement tablets). Suitable health food compositions suitable for use herein can be provided in a similar form.

In one embodiment, the composition comprises or comprises administering a medicament 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. In one embodiment, a composition suitable for use herein comprises 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. And consisting essentially of, consisting of, or consisting of one or more of 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, 99.5, 99.8 or 99.9% by weight of such agents, And the scope of application may be selected between any of the foregoing values (eg, 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 50%, from about 40 to about 50%, From about 45 to about 50%, from about 0.1 to about 60%, from about 0.2 to about 60%, from about 0.5 to about 60%, from about 1 to about 60%, from about 5 to about 60%, from about 10 to about 60%, about 15 to about 60%, about 20 to about 60%, about 25 to about 60%, about 30 to about 60%, about 35 to about 60%, about 40 to about 60%, about 45 to about 60%, about 0.1. Up to about 70%, from about 0.2 to about 70%, from about 0.5 to about 70%, from about 1 to about 70%, from about 5 to about 70%, from about 10 to about 70%, from about 15 to about 70%, from about 20 to About 70%, about 25 to about 70%, about 30 to about 70%, about 35 About 70%, about 40 to about 70%, about 45 to about 70%, about 0.1 to about 80%, about 0.2 to about 80%, about 0.5 to about 80%, about 1 to about 80%, about 5 to about 80%, from about 10 to about 80%, from about 15 to about 80%, from about 20 to about 80%, from about 25 to about 80%, from about 30 to about 80%, from about 35 to about 80%, from about 40 to about 80 %, from about 45 to about 80%, from about 0.1 to about 90%, from about 0.2 to about 90%, from about 0.5 to about 90%, from about 1 to about 90%, from about 5 to about 90%, from about 10 to about 90% From about 15 to about 90%, from about 20 to about 90%, from about 25 to about 90%, from about 30 to about 90%, from about 35 to about 90%, from about 40 to about 90%, from about 45 to about 90%, From about 0.1 to about 99%, from about 0.2 to about 99%, from about 0.5 to about 99%, from about 1 to about 99%, from about 5 to about 99%, from about 10 to about 99%, from about 15 to about 99%, about 20 to about 99%, about 25 to about 99%, about 30 to about 99%, about 35 to about 99%, about 40 to about 99%, and about 45 to about 99%).

The compositions useful herein are useful for treating or preventing skeletal conditions characterized by weakened or fragile bones. In one embodiment, the condition to be treated is a condition in which maintenance or increase in bone mass or bone strength or bone quality and bone strength is desired. In one embodiment, the condition is a condition in which bone loss is required to be reduced. In one embodiment, the condition is any two or more of skeletal cell proliferation, skeletal cell differentiation, skeletal cell-mediated mineralization or skeletal cell proliferation, skeletal cell differentiation, and skeletal cell-mediated mineralization. The condition of the combination. In one embodiment, the condition is a condition in which any two or a combination of two or more of which is required to inhibit bone resorption, increase bone formation, reduce bone loss or inhibit bone resorption, increase bone formation, and reduce bone loss. In one embodiment, the condition is a combination of any two or more of the need to improve or maintain bone density, bone quality, bone strength or bone health or to improve or maintain bone density, bone quality, bone strength, and bone health. The condition. In one embodiment, the condition is osteoporosis. In one embodiment, the condition is osteopenia.

In one embodiment, treating or preventing a skeletal condition characterized by weakened or fragile bones includes maintaining or increasing bone formation, maintaining or increasing bone mineral density, maintaining or increasing bone quality (including peak bone mass), treatment or prevention Osteoporosis, treating or preventing osteopenia, stimulating bone regeneration during fracture healing, reducing bone resorption or increasing bone quality (eg, as measured by resistance to stress or bone strength).

The compositions useful herein are suitable for administration to a subject in need thereof for the treatment of a skeletal condition. In one embodiment, the subject needs to increase bone quality. In one embodiment, the subject is in need of treatment for a condition that requires a reduction in bone loss. In one embodiment, the subject is in need of treatment for any two or both of skeletal cell proliferation, skeletal cell differentiation, skeletal cell-mediated mineralization or skeletal cell proliferation, skeletal cell differentiation, and bone cell-mediated mineralization. The condition of the combination of the above. In one embodiment, the subject is in need of treatment for a condition that requires inhibition of bone resorption, increased bone formation or reduced bone loss or inhibition of bone resorption, increased bone formation, and reduced bone loss. In one embodiment, the subject is in need of treatment for a combination of two or more of the need to improve or maintain bone density, improve or maintain bone quality, improve or maintain bone strength, or improve or maintain bone health or such effects. The condition.

In one embodiment, the subject needs to reduce bone resorption or reduce osteoclastogenesis or both. Thus, in one embodiment, the invention is directed to ameliorating, treating or preventing a condition associated with increased bone resorption or increased osteoclastogenesis.

In another embodiment, the subject is in need of increased bone formation or increased osteoblast proliferation, increased osteoblast differentiation, increased mineralization, or a combination thereof. Thus, in this embodiment, the present invention relates to the improvement, treatment or prevention of conditions associated with poor bone formation or decreased osteoblast proliferation, reduced differentiation and reduced mineralization, or a combination thereof.

In one embodiment, treating or preventing a skeletal condition characterized by weakened or fragile bones includes reducing bone loss in the subject, particularly bone loss associated with aging.

In one embodiment, the composition comprises about 0.1, 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, consisting essentially of, consisting of, or consisting of one or more dairy ingredients of fresh, recombinant or powdered whole milk or milk derivatives, and the scope of application is Choose between any of the foregoing values (eg, 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%, about 15 to about 50%, about 20 to about 50%, about 25 to about 50%, about 30 to about 50%, about 35 to about 50%, about 40 to about 50%, and about 45 to about 50%). The milk derivative is preferably selected from the group consisting of recombinant, powder or fresh skim milk, reconstituted whole fat or skim milk powder, skim milk concentrate, skim milk retentate, concentrated milk, ultrafiltration milk retentate, milk protein concentrate (MPC), Milk protein isolate (MPI), decalcified milk protein concentrate (MPC), low fat milk, low fat milk protein concentrate (MPC), casein, casein salt, milk fat, high CLA milk fat, emulsifiable concentrate, White oil, dehydrated milk fat (AMF), white milk, white whey, hard milk fat fraction, soft milk fat fraction, sphingolipid fraction, milk fat globular membrane fraction, phospholipid fraction, complex lipid Separate, colostrum, colostrum fraction, colostrum protein concentrate (CPC), colostrum whey, immunoglobulin fraction from colostrum, whey, lactoferrin, one or more lactoferrin Fragments, whey protein isolate (WPI), whey protein concentrate (WPC), sweet whey, lactic acid whey, inorganic acid whey, reconstituted whey powder, milk minerals, derived from any milk or colostrum processing stream The composition is obtained by ultrafiltration or microfiltration of any milk or colostrum processing stream Retention or permeate-derived composition, a combination derived from separation by adsorption or separation of any milk or colostrum processing stream (including but not limited to ion and gel permeation chromatography) Extracts of any of these milk derivatives, including by multistage fractionation, differential crystallization, solvent fractionation, supercritical fractionation, near supercritical fractionation, distillation, centrifugation fractionation or with modifiers such as soaps or emulsifiers Extracts prepared by fractionation, hydrolysates of any such derivatives, fractions of hydrolysate, and any combination of any two or more of these derivatives, including combinations of hydrolyzed fractions, non-hydrolyzed fractions Combination, and a combination of hydrolyzed and non-hydrolyzed fractions.

It is intended that the recitation of ranges of numbers (e.g., 1 to 10) disclosed herein also include all rational numbers within the scope (e.g., 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and Any reference to 10) and any range of rational numbers within the scope (e.g., 2 to 8, 1.5 to 5.5, and 3.1 to 4.7) and thus all sub-ranges of all ranges explicitly disclosed herein are expressly disclosed. All such possible combinations of numerical values between the minimum and maximum values recited are to be construed as being

In the present specification, where reference is made to a patent specification, other external document or other information source, this is generally for the purpose of providing a background for the discussion of the features of the invention. References to such external documents are not to be construed as an admission that such documents or such sources are prior art or form part of common general knowledge in the art, unless specifically stated otherwise.

It is also to be understood that the present invention resides in a part of the elements, features and features In any and all combinations of the above, and where specific integers having known equivalents in the technology to which the invention pertains are referred to herein, such known equivalents are considered to be included herein. As clarified in general.

The present invention is based on the discovery that the extract of rosehip water has a positive effect on maintaining bone health and treating bone diseases such as osteoporosis or osteopenia.

Definition

The term "comprising" as used in the specification and claims is intended to mean "consist at least in part." When interpreting statements in this specification and the scope of the claims, including the terminology, the features in the beginning of the term must be present in each statement, but other features may be present. Terms such as "include" and "included" should be interpreted in the same way.

The term "water-soluble extract of rosehip" means an extract produced by a method in which any food-grade polar solvent such as water, acetic acid and an alcohol such as methanol, ethanol, propanol or butanol is used. Used to extract water-soluble components from rose hips. Preferably, the solvent is water.

The term "maintaining bone health" means maintaining the bone quality of an individual at a healthy density, for example within ±1 SD of the bone density of a 20-year-old as defined by the WHO DEXA standard.

The term "weakened or fragile bone" means that the individual has a bone density below the healthy density, which is, for example, within ±1 SD of the bone density of a 20-year-old as defined by the WHO DEXA standard.

The "effective amount" is the amount required to impart a therapeutic effect. The correlation between doses for animals and humans (in milligrams per square meter) is described by Freireich et al. (1966). The body surface area can be approximated from the height and weight of the subject. See, for example, Scientific Tables, Geigy Pharmaceuticals, Ardley, New York, 1970, 537. As recognized by those skilled in the art, the effective dose will also vary depending on the route of administration, the use of the carrier, the species and individual genetic variation, and the like.

The term "oral administration" includes oral, buccal, enteral, and intragastric administration.

The term "pharmaceutically acceptable carrier" means a carrier including, but not limited to, excipients, diluents, auxiliaries or combinations thereof, which can be administered as a component of the compositions of the present invention. Those which are administered at a dose sufficient to deliver an effective amount of rosehip extract do not degrade the activity of the composition and are non-toxic. Formulations can be administered orally, nasally, and topically.

A "subject" according to the invention is an animal, preferably a mammal, a better mammal companion animal or a human. Preferred companion animals include cats, dogs and horses.

The term "treatment" and its derivatives should be interpreted in its broadest possible context. This term should not be understood to imply that the subject is treated until complete recovery. Therefore, "treatment" broadly includes improving or preventing or ameliorating and preventing the onset of symptoms or the severity of a particular condition; for example, preventing or ameliorating the reduction of bone density, preventing or otherwise reducing the risk of developing osteoporosis, prevention or Other ways to reduce the risk of osteopenia, or to prevent or improve other disease symptoms. The term "treatment" also broadly includes maintaining good bone health and establishing bone quality in order to prevent a disease or condition.

2. Rose hip

Rosehip is sometimes called rosehaw, a fruit found on rose plants ( Rosa spp. ) that contains several vitamins, including high levels of vitamin C. Other vitamins found in rose hips are vitamins A, D and E. Rose hips also contain high levels of iron and some essential fatty acids and antioxidants.

The fruit of several rose species can be used to make a water soluble extract of rose hip suitable for use in the present invention. Such species include (but are not limited to) Dog rose (Rosa canina), dog rose gray blue Busia species (Rosa dumalis subsp. Boissieri), gray-blue Antalya dog rose species (Rosa dumalis subsp. Antalyensis), Rosa villosa , Rosa pulverulenta , Rosa moyesii , Rosa gallica , Rosa condita , Rosa rugosa and Rosa pisiformis ).

The possible extraction methods of rose hips are as follows. Fresh rose hips are macerated or dried rose hips are powdered. The macerated or powdered rose hips are mixed with distilled water or other aqueous solution (e.g., buffer) at a ratio of 1:5 (w/w) to allow extraction of the water soluble component from rose hips. The aqueous solvent may be replaced one or more times, preferably three times, and each amount of solvent is maintained in contact with the plant material for several hours, preferably 12, 24 or 48 hours, preferably with continuous agitation. After filtering or centrifuging the entire extract, the aqueous solution can then be frozen or spray dried to form a powder that can be used as an aqueous extract for use herein.

The extract can be further fractionated by standard methods of ion exchange chromatography or membrane separation or other such separation techniques known in the art. See, for example, Ion Exchange Chromatography & Chromatofocusing, Principles and Methods, Amersham Biosciences Limited 2004, Code 11-0004-21, AA Edition, http://www.amersham.com.

3. Treatment or prevention methods

The use of the compositions and compositions described herein is useful for treating or preventing a skeletal condition characterized by weakened or fragile bone, such as osteoporosis or osteopenia.

In one embodiment, the condition to be treated is a condition in which bone quality is required to be increased. In one embodiment, the condition is a condition in which bone loss is required to be reduced. In one embodiment, the condition is a condition requiring skeletal cell proliferation, skeletal cell differentiation, or skeletal cell-mediated mineralization, or a combination of two or more thereof. In one embodiment, the condition is a condition in which inhibition of bone resorption, increased bone formation, or reduction of bone loss, or a combination of two or more thereof. In one embodiment, the condition is a condition in which improvement or maintenance of bone strength, bone density or bone quality, or a combination of two or more thereof is desired. In one embodiment, the condition is osteoporosis. In one embodiment, the condition is osteopenia.

4. Applicable compositions of the invention

Illustrated herein, consisting essentially of or consisting of a water-soluble extract of rosehip and one or more components selected from the group consisting of calcium, magnesium, zinc, vitamin D, vitamin K, folic acid or folate, vitamin B6 and vitamin B12 A composition of its composition.

Also described is a composition consisting essentially of a water-soluble extract of rosehip and one or more components selected from the group consisting of calcium, magnesium, zinc, vitamin D, folic acid, folate, and vitamin B12, wherein the composition is formulated to simultaneously, The water-soluble extract of rose hips and the ingredients or ingredients are administered separately or sequentially.

Compositions comprising a water soluble extract of rosehip and one or more dairy ingredients are also described herein.

Suitable compositions herein include any composition that can carry a water-soluble extract of rosehip, including any consumer product and any pharmaceutical product that can carry a water-soluble extract of rosehip. The composition can be formulated as a food, beverage, food additive, beverage additive, dietary supplement, nutritional product, medical food, health food, medicine or medicine. Preferably, the compositions of the present invention are formulated as powders, liquids, food bars, spreads, dressings, ointments, lozenges or capsules. Suitable for food and beverages including dairy and non-dairy foods and beverages. In one embodiment, the composition is a milk powder, a milk beverage, a yogurt, a yogurt powder, a yogurt drink, a soy sauce, an acidified beverage, UHT, pasteurization, butter oil or cheese. Suitable formulations can be prepared by those skilled in the art in view of the teachings of the art and the teachings herein.

The health food composition for use in accordance with the present invention may be a dietary supplement (e.g., a capsule, mini bag or lozenge) or a food product (e.g., milk, juice, soft drink, herbal tea bag, or dessert). The composition may also include other nutrients such as proteins, carbohydrates, lipids, vitamins, minerals or amino acids. The composition may be in a form suitable for oral use such as a troche, a hard or soft capsule, an aqueous or oily suspension, or a syrup; or in a form suitable for parenteral use, such as an aqueous solution of propylene glycol, or a buffered aqueous solution. The amount of active ingredient in the health food composition will depend to a large extent on the particular needs of the subject. As will be recognized by those skilled in the art, this amount will also vary depending on the route of administration, the species, the genetic/physiological qualities, and other bone enhancing agents that may be used in combination.

Food, food additives or food supplements comprising rose hip extract for use in accordance with the present invention include any edible consumer product capable of carrying a water soluble plant extract. Examples of suitable consumer products include dessert products, reconstituted fruit products, snack bars, muesli bars, baked products, spreads, sauces, dairy products (including yogurt and cheese), beverages (including dairy based and non-based) Dairy beverages), milk powder, sports supplements (including dairy based and non-dairy based sports supplements), food additives (such as protein food tops) and dietary supplement products (including daily supplement tablets). Suitable health food compositions suitable for use herein can be provided in a similar form.

Suitable compositions herein can be formulated to allow administration to a subject by any selected route including, but not limited to, oral or nasal administration.

Preferably, the suitable compositions herein are administered orally.

As will be appreciated, the dosage of the administered composition, the time of administration, and the general dosage regimen can be such as the severity of the symptoms of the subject, the type of condition being treated, the mode of administration selected, and the age of the subject, The gender and general health status vary from subject to subject. However, as a general example, the inventors expect to administer from about 1 mg to about 2000 mg of rose hip per kg body weight per day, preferably from about 100 to about 1000 mg of rose hip per kg of body weight per day or from about 50 to about 500 mg per kg of body weight per day. Rose hips. In one embodiment, the inventors expect to administer from about 0.05 mg to about 300 mg of rose hip per kg body weight.

Preferably, the suitable compositions herein are administered at least once a day. Preferably, the suitable compositions herein are administered 2-3 times a day. Alternatively, the suitable compositions herein can be administered once a week.

Preferably, the suitable compositions herein are administered as prophylactic agents prior to the onset of menopause. Alternatively, the compositions herein are administered after the onset of menopause in order to maintain or increase bone health or to treat or prevent skeletal conditions.

It will be appreciated that those skilled in the art will be able to determine an effective dosage regimen (including daily dosage and timing of administration) for a given condition without undue experimentation, in view of the teachings of the present invention.

The efficacy of compositions suitable for use in accordance with the present invention can be assessed in vitro and in vivo. See, for example, the following example. Briefly, the composition can be tested in vitro to promote osteoblast development and activity or to inhibit osteoclastogenesis, limit osteoclast activity, or reduce the number of osteoclasts. For in vivo studies, the composition can be administered to an animal (e.g., a rat) and subsequently obtained for its effect on bone tissue. Based on the results, a suitable dosage range and route of administration can be determined.

Suitable compositions herein may be used alone or in combination with one or more other therapeutic agents. The therapeutic agent can be a food, a beverage, a food additive, a beverage additive, a food component, a beverage component, a dietary supplement, a nutritional product, a medical food, a health food, a medicine, or a medicine. The therapeutic agent is preferably effective for promoting osteoblast development and activity, inhibiting osteoclastogenesis, reducing the number of osteoclasts, or limiting osteoclast activity.

When used in combination with another therapeutic agent, the administration of a suitable composition herein and another therapeutic agent can be simultaneous or sequential. Simultaneous administration includes administration of a single dosage form comprising all of the components or administration of the divided dosage forms substantially simultaneously. Sequential administration includes administration according to different time courses, preferably such that there is an overlap in the period of providing the applicable compositions and other therapeutic agents herein.

In one embodiment, suitable compositions herein include, for example, whey protein, whey protein fraction (including acidic or basic whey protein fractions or combinations thereof), glycomacropeptide, lactoferrin or functionality. A milk component of a lactoferrin variant or a lactoferrin fragment, a vitamin D, a vitamin D derivative, a vitamin D analog or calcium and a salt thereof, or a combination thereof, or a simultaneous or sequential administration thereof. Suitable compositions containing the milk component include compositions such as foods, beverages, food additives, beverage additives, dietary supplements, nutritional products, medical foods or health foods. Milk fractions that are concentrated for use in such components can also be used.

It will be appreciated that the additional therapeutic agents listed above (based on both food and pharmaceutical agents) can also be used in the methods of the invention, in which it is administered separately, simultaneously or sequentially from the applicable compositions herein.

Suitable compositions herein may further comprise another bone health agent such as calcium, fluoride, magnesium, zinc, calcium, fluoride, magnesium, zinc, 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 D1 [photo oxime], vitamin D2 [ergocalciferol], vitamin D3 [cholecalciferol, 1, 25-dihydroxycholecalciferol], vitamin D4 [dihydrotachysterol] and vitamin D5 [7-dehydrophytosterol] and vitamin D analogues), vitamin E, vitamin E derivatives, vitamin E analogues, vitamin K , vitamin K derivatives, vitamin K analogs, vitamin K2, whey protein, whey protein fractions (including acidic or basic whey protein fractions or combinations thereof), glycomacropeptide, lactoferrin, functionality a lactoferrin variant, a functional lactoferrin fragment, an isoflavone, a phytoestrogens, a probiotic or probiotic, or a combination of any two or more of these, which may affect mineral absorption, Polyunsaturated fatty acids, and Co.

The use of a pharmaceutical composition containing rose hips or a component thereof is also within the scope of the invention. Pharmaceutical compositions are useful for the prevention and treatment of bone related disorders as described above. The pharmaceutical composition can further comprise an effective amount of another bone enhancing agent. Pharmaceutically acceptable carriers include solvents, dispersion media, coatings, antibacterial and antifungal agents, and isotonic and absorption delaying agents.

The pharmaceutical compositions suitable for use in the present invention may be formulated in a suitable pharmaceutically acceptable carrier (including excipients and diluents) selected in accordance with the desired route of administration and standard pharmaceutical practice. For example, the compositions of the present invention can be administered orally in the form of a powder, a liquid, a lozenge, an effervescent tablet or a capsule. Suitable formulations may contain additional agents, including emulsifiers, antioxidants, flavoring or coloring agents, as appropriate, and may be suitable for immediate release, delayed release, modified release, sustained release, pulsed release or controlled release.

In a preferred embodiment, the compositions used in accordance with the present invention are formulated for ingestion.

The capsules may contain any standard pharmaceutically acceptable material such as gelatin or cellulose. The lozenge can be formulated according to conventional procedures by compressing the active ingredient with a mixture of the solid carrier and the lubricant. Examples of solid carriers include, but are not limited to, starch and sugar bentonite. The active ingredient may also be administered in the form of a hard shell or capsule containing a binder such as lactose or mannitol, conventional fillers and tableting agents.

Effervescent lozenges can be formulated using any conventional procedure and can include any suitable pharmaceutically acceptable effervescent material. Examples of effervescent materials include, but are not limited to, citric acid, malic acid, sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate.

The compositions of the present invention can be formulated into dosage forms for different routes of administration using conventional methods. For example, it can be formulated as a capsule, gel seal or lozenge for oral administration.

Suitable pharmaceutical compositions can be formulated with suitable pharmaceutically acceptable excipients, diluents or carriers in accordance with the desired dosage form and standard pharmaceutical formulation practice. Dosage forms for use herein can be administered orally in the form of a powder, liquid, lozenge or capsule. Suitable dosage forms may contain additional agents, including emulsifiers, antioxidants, flavoring or coloring agents, as desired. Formulations suitable for use herein may be suitable for immediate, delayed, modified, sustained, pulsed or controlled release of the active ingredient.

Compositions comprising rose hips can be used to treat or prevent skeletal disorders. Examples of such conditions include, but are not limited to, osteoporosis, hepatic bone dystrophy, rickets, rickets, cystic fibrosis, renal bone dystrophy, osteosclerosis, osteopenia, poor bone fibrogenesis, Secondary hyperparathyroidism, hypoparathyroidism, hyperparathyroidism, chronic kidney disease, sarcoidosis, glucocorticoid-induced osteoporosis, idiopathic hypercalcemia, Pei Git's disease and osteogenesis imperfecta.

Rosehip extract can be used alone or in combination with one or more other therapeutic agents, such as health foods, pharmaceuticals or medical foods. When used in combination with another therapeutic agent, the administration of the two agents can be separate, simultaneous or sequential. Simultaneous administration includes administration of a single dosage form comprising two agents and administration of two agents in a divided dosage form substantially simultaneously. Sequential administration involves administering two agents according to different time courses, preferably such that there is an overlap in the period in which the two agents are provided. Suitable agents with which the compositions of the present invention may be administered include other bone growth agents or bone disease treatments, as well as other suitable agents known in the art. Preferably, the agents are parenteral (preferably by intravenous, subcutaneous, intramuscular, intraperitoneal, intramedullary, epidural, intradermal, transdermal (topical), transmucosal, intra-articular, and intrapleural) It is administered orally, by inhalation and rectal administration.

Suitable agents with which the compositions of the invention may be co-administered include αvβ3 integrin receptor antagonists, antiestrogens or SERMs (selective estrogen receptor modulators) including but not limited to tamoxifen (tamoxifen), raloxifene, lasofoxifene, toremifene, azorxifene, clomiphene, droloxifene, Idoxifene, levomeloxifene, zuclomiphene, enclomiphene, nafoxidene and its salts, anti-resorptive agents, Bisphosphonates (including but not limited to) alendronate, clodronate, etidronate, ibandronate, incaphosphine Incadronate, minodronate, neridronate, olpadronate, pamidronate, piridronate, Ripedronate, tiludronate, zoledronate and pharmaceutically acceptable salts thereof Calcium receptor antagonists, calcium supplements, cathepsin K inhibitors, dual acting bone forming agents (DABA) (including but not limited to strontium ranelate), estrogens and estrogen derivatives (including (but not limited to) 17β-estradiol, estrone, conjugated estrogen, equine estrogen and 17β-ethynyl estradiol), flavonoids, folic acid, folate, vitamin B12, stimulating bone proliferator, bone protection , progesterone and progesterone derivatives (including but not limited to norethisterone and medroxyprogesterone), vacuolar ATPase inhibitors, VEGF antagonists, thiazolidinedione, calcitonin, protein kinase inhibitors, Parathyroid hormone (PTH), PTH analog, recombinant parathyroid hormone, growth hormone secretagogue, growth hormone releasing hormone, hyperhomocysteinemia insulin-like growth factor inhibitor, bone morphogenetic protein (BMP), Inhibitors of BMP antagonism, prostaglandin derivatives, fibroblast growth factor, statin (including but not limited to lovastatin, simvastatin, pravastatin (pravastatin) ), fluvastatin, atorvastat (atorvastatin), cerivastatin, rosuvastatin and pitavastatin, calcium, fluoride, magnesium, zinc, calcium, fluoride, magnesium, zinc, vitamin A , vitamin A derivatives, vitamin A analogues, vitamin B6, vitamin C, vitamin C derivatives, vitamin C analogs, vitamin D, vitamin D derivatives (including but not limited to vitamin D (including vitamin D1 [photo sterol ], vitamin D2 [ergocalciferol], vitamin D3 [cholecalciferol, 1,25-dihydroxycholecalciferol], vitamin D4 [dihydrotachysterol] and vitamin D5 [7-dehydrophytosterol] and vitamins D analog), vitamin E, vitamin E derivative, vitamin E analog, vitamin K, vitamin K derivative, vitamin K analog, vitamin K2, whey protein, whey protein fraction (including acidic or alkaline milk) Albumin fraction or combination thereof, glycomacropeptide, lactoferrin, functional lactoferrin variant, functional lactoferrin fragment, milk fat, high CLA milk fat, milk fat fraction, isoflavone Phytoestrogens, probiotics Or probiotic biomass is or may be any combination of two or more of these agents, or both of mineral absorption, polyunsaturated fatty acids and combinations thereof, and other suitable agents known in the art.

The application of lactoferrin and lactoferrin fragments and hydrolysates is described in the published International Patent Application No. WO 03/082921 and WO 2007/043900, the disclosure of which is incorporated herein by reference.

The published international patent application WO 2008/147228 describes fatty acids, fatty acid derivatives and milk fat compositions comprising high CLA milk fat and milk fat fractions which are capable of treating or preventing skeletal conditions which will benefit from reduced bone resorption and are cited The way is incorporated in this article.

Additionally, it is contemplated that the compositions according to the present invention may be formulated with additional active ingredients which may be beneficial to the subject in certain circumstances. For example, therapeutic agents that target the same or different aspects of the disease process can be used.

The following examples are now described in a non-limiting manner to illustrate various aspects of the invention.

Instance Cell culture, assay substance

All cell culture materials were purchased from Invitrogen. MC3T3-E1 pre-osteoblasts were obtained from ATCC, Manassas, VA, USA. Rosehip extract was purchased from Paninkret, Germany.

Example 1 - Osteoblast differentiation

MC3T3-E1/4 cells were seeded at 0.55 x 10 ⁵ cells/ml in 0.3 ml 48-well plates per well. Four wells were used for each treatment in each experiment and the experiment was repeated three times to ensure consistency of results. The medium was α-MEM with 10% FCS. A treatment was added 24 hours after the initial inoculation of the plate to adhere the cells to the wells. After 3 days of culture, the medium was changed to α-MEM with 10% FCS, 10 mM β-glycerophosphate and 50 μg/ml ascorbic acid, with or without treatment. The medium was changed every 2-3 days. After 10 days of culture, the medium was removed from the wells and the cells were washed with PBS. The cells were incubated with 200 μl of alkaline phosphatase test reagent (0.05 M p-nitrophenyl phosphate in TBS (pH 9.5)) for 1 hr at 37 °C. Two samples (100 μl) of test reagent from each well were transferred to a 96-well plate and the absorbance was read at 405 nm using an ELx808 Ultra microplate reader (Bio-Tek Instruments Inc., Vermont, USA). The cells were again washed with PBS, fixed with 1% formaldehyde for 15 minutes and the number of cells was determined by crystal violet assay. The cells were incubated with 300 μL of 1% crystal violet (dissolved in PBS) for two hours and then washed under running water for 15 minutes to remove excess dye and air dry. 500 μl/well of Triton-X 100 (0.2% in dd H ₂ O) was added to the dried plate and the plate was incubated at room temperature for 2 hours to dissolve the absorbed dye. Two aliquots of 100 [mu]l were removed from each well and transferred to a 96 well plate. Absorbance was read using a 0.2% Triton-X 100 as a control at 550 nm using an ELx808 Ultra microplate reader (Bio-Tek Instruments, Inc. Vermont, USA). Determined by dividing the absorbance measurement at 405 nm (a measure of p-nitrophenyl production or alkaline phosphatase activity) by the absorbance measurement at 550 nm (from the crystal violet assay, a measure of the number of cells) One cell counts alkaline phosphatase activity. The resulting index is used to represent alkaline phosphatase activity per cell. The results are shown in Figure 1. Compared with the control, the administration of rosehip increased the differentiation by 17%.

Example 2 - Osteoclast Formation

Osteoclasts can be produced from murine macrophage RAW 264.7 cell line. RAW 264.7 cells were seeded in 24-well plates containing coverslips and treated with murine RANK-L. Different concentrations of compounds were added to the cell culture medium containing RANK-L to test the effect of the compound on osteoclast formation. The cells were incubated for 5 days and the medium was changed on day 3. The coverslips were then fixed and stained for TRAP and subsequently stained with hematoxylin. Quantify larger multinucleated osteoclasts. Osteoclasts appear as large multinucleated cells that stain purple and can form even larger giant cells. Micrographing was performed on three random regions on each coverslip and then calculating the number of TRAP(+) cells with more than three cores, and with "TRAP(+) cells with more than three cores per unit area The number is used to quantify the effect of the agent on osteoclast formation. TRAP staining was also dissolved and measured by colorimetry. These results are presented as a chart. In the first step of verification of the in vitro assay, cell density titration is performed.

To determine the optimal cell density of the seeded cells, cells were seeded at 2 x 10 ³ -6 x 10 ⁴ cells/ml with 35 ng/ml RANK-L. A density of 1.5 x 10 ⁴ cells/ml was thus selected for use in other assay plates. RANK-L titration (1 ng/ml - 35 ng/ml) was then performed using the selected cell density. From these two results, a cell seeding density of 1.5 × 10 ⁴ cells/ml and a RANK-L concentration of 15 ng/ml were selected as the optimal conditions for observing osteoclastogenesis in all future in vitro assays. The results are shown in Figure 2. Compared to the control, the administration of rose hips resulted in a 29% reduction in the number of osteoclasts. At 10 μg/ml, no osteoclast-like cells were observed compared to the control. Does not affect cell viability.

Example 3 - Bone resorption

This study was designed to assess whether dietary supplementation of rose hips can affect bone quality in the OVX rat model.

animal

A casein-based diet was administered to 44 female rats of 5.5 months old for two weeks (week-2 to week 0). At week -2, the rats were subjected to an in vivo DEXA scan under anesthesia. At week 0, the rats were sham operated (false treatment; n=15) or ovariectomized (n=30). The sham-treated rats were anesthetized by inhalation of isoflurane and caused an incision but the ovaries remained intact. The ovaries of the ovariectomized group animals were removed. Ovariectomized rats were randomly assigned to a control group (OVX) and fed a casein control diet or treatment group (rose hips) and supplied with rose fruit extract at 0.5% w/w of the control diet for 28 weeks.

Confirmation of successful oophorectomy is determined by measuring uterine weight. The OVX (0.14 g; p < 0.0001) and rose hip (0.13 g; p < 0.0001) groups all had significantly lower uterine weight than the sham treatment (0.86 g).

At week 28, the rats were fasted overnight and then euthanized by bleeding (puncture of the heart under anesthesia). After puncture of the heart, the animals were exposed to 100% CO ₂ . The body was dissected and various bones were collected and fixed for further analysis.

meal

Animals are supplied with 15% (w/w) casein (in the form of caseinate), 5% (w/w) cellulose, 5% (w/w) corn oil, 0.5% (w/w) calcium, A balanced semi-synthetic diet consisting of 62% (w/w) starch and added vitamins, minerals and amino acids to meet the requirements of AIN93M (National Research Council, 1995).

Mechanical properties of bones

The adhesion muscles of the right femur were scraped clean and stored in a phosphate buffered physiological saline solution at -20 °C. The bones are thawed prior to biomechanical testing. The length of the femur was measured using an electronic caliper gauge. The midpoint was marked with a waterproof pen and the width and thickness of the femur at the midpoint were also recorded. The femur was then maintained at 23 ° C at room temperature before and during the test. The femur was placed in a test stand constructed for a three point bending test. The distance between the support rods has a fixed length of 12 mm. The load was applied at a constant deformation rate of 50 mm min ^-1 . The maximum load (N), hardness (Nmm ^-2 ), and energy (J) were measured using a Shimadzu Ezi-Test Texture Analyzer (Kyoto, Japan). The results are shown in Figure 3. For the pseudo-treatment, OVX, and rose hips, the amount of energy required to fracture the right femur in the three-point bending test was 118, 96, and 101 N/mm ^{2 , respectively} . False processing and OVX were significantly different (p=0.0105). Rose hips are not significantly different from pseudo-treatment or OVX, but are located in the middle of which makes the bone more elastic for fracture.

Example 4 - Bone resorption and mechanical properties

This study was designed to assess whether dietary supplementation of rose hips can inhibit bone resorption or affect bone biochemical and mechanical properties in an OVX rat model.

animal

Forty-five female Sprague Dawley rats, approximately 5 months old, were individually housed in shoebox cages and Milli-Q water was taken ad libitum. It is adapted to the diet and its environment for three weeks, and is supplied with a nutrient-based diet based on casein, 14% (w/w) casein, 5% (w/w) cellulose, 5%. (w/w) vitamins, 5% (w/w) minerals, 1.3% (w/w) calcium carbonate, 4% (w/w) corn oil, 5.7% (w/w) sucrose, and 60% (w/ w) Wheat corn starch composition.

Vitamin C is not added to any meal and the vitamin mixture does not contain any vitamin C. Adding rose hips to their diet provides about 0.08% (w/w) vitamin C.

Three weeks later, 30 animals were ovariectomized and another 15 were sham operated to simulate oophorectomy without actually removing the ovaries. Since then, 15 randomly selected ovariectomized rats and 15 sham-operated animals have been fed a standard casein-based diet, while another 15 ovariectomized animals receive supplementation with 2% rosehip extract. meal. After 24 weeks, the animals were euthanized as described in Example 3, their right femurs were removed and prepared for use in bone biomechanical testing using the 3-point break test protocol as described in Example 3. The results were compared by a factor of ANOVA.

Biochemical analysis

Biomechanical analysis was performed on the right femur of OVX, pseudo-treated and rosehip animals. The maximum load, breaking load and energy were all calculated using a Shimadzu Ezi-Test Texture Analyzer (Kyoto, Japan). The maximum load is defined as the maximum recording force applied to the femur during the three-point bending test. The breaking load is defined as the force of the fracture during the three-point bending test. This force is measured by a force transducer. This unit breaks the bones and collects and records forces and displacements. This is plotted to produce a force-displacement curve that clearly identifies the maximum and breaking load. The software automatically recognizes these points.

Energy is a measure of the energy consumed to break a bone and is also calculated using the Shimadzu Ezi-Test Texture Analyzer (Kyoto, Japan) using force recording and obtaining known points of fracture and maximum force measurements.

These results show that the fracture from the bone of the animal supplying 2% rosehip extract requires more force/energy than the OVX animal and the same force/energy as the sham treated animal. The maximum load is shown in Figure 4, the breaking load is shown in Figure 5 and the energy is shown in Figure 6.

Industrial application

The present invention has the utility of maintaining bone health or improving bone remodeling imbalance leading to bone loss.

The compositions described can be used as foods, beverages, food additives, beverage additives, dietary supplements, nutritional products, medical foods, health foods, pharmaceuticals or pharmaceuticals.

Those skilled in the art will appreciate that the above description is provided by way of illustration only and the invention is not limited thereto.

references

Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE (1966) Quantitative comparison of toxicity to anticancer agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemother Rep 50: 219-244

Gillies, R. Didier, N., Denton, M. Determination of cell number in monolayer cultures, Analytical Biochemistry, 1986, 159: 109-113)

Green JH, Booth C, Bunning R. Post prandial metabolic responses to milk enriched with milk calcium are different from responses to milk enriched with calcium carbonate. Asia Pacific J Clin Nutr 2003;12:109-19

Murray T. Calcium nutrition and osteoporosis. CMAJ 1996; 155:935-9.

National Research Council .1995. Nutrient requirements of laboratory animals. 4th edition National Academic Press. Washington, DC.

Zikan V, Roubal P, Haast T, Stepan JJ. "Acute effects of calcium carbonate and milk on the calcium-parathyroid axis and bone resorption in healthy women." In: Bruckhardt P, Dawson-Hughes B, Heaney RP, Editorial Aspects of Osteoporosis: Proceedings of the 4 ^th International Symposium Lausanne, May 2000. Academic Press, London, 2001. 131-140.

Figure 1 is a graph showing the effect of rose hips expressed by alkaline phosphatase production on osteoblast differentiation compared to control (p = 0.0093).

Figure 2 is a graph showing the effect of rosehip extract on osteoclastogenesis. Rose hips inhibit the formation of osteoclasts as a function of dosage. The results were at p < 0.05 compared to the control.

Figure 3 is a graph showing the results of the stress resistance of the three-point bending test of the right femur. One group of rats underwent sham surgery (fake treatment; n=15) and the control diet was administered for 28 weeks. Another group of ovariectomized and treated diets (OVX; n=15) or a therapeutic diet containing rose hip extract (rose hips; n=15) lasted 28 weeks. Results are expressed as mean ± SEM. The results showed a significant difference between the pseudo-treatment and OVX (p=0.0105) and no significant difference between the pseudo-treatment and rose hip (p=0.8450) or between OVX and rose hip (p=0.5754).

Figure 4 is a graph showing the maximum load of the right femur. The maximum load is defined as the maximum force the femur can withstand during the three-point bending test. A control diet was administered to 45 rats for 3 weeks. After 3 weeks, a group of rats underwent sham surgery (fake treatment; n=15) and continued to supply a control diet. Another 30 rats were ovariectomized. A group of ovariectomized rats were fed a control diet (OVX; n=15) and the other group was supplemented with a rose hip diet (rose hips; n=15). Results are expressed as mean ± SEM. The results showed a significant difference between OVX and rose hip, p=0.035.

Figure 5 is a graph showing the breaking load. The breaking load is the force at which the femur is fractured, usually less than the maximum force. A control diet was administered to 45 rats for 3 weeks. After 3 weeks, a group of rats underwent sham surgery (fake treatment; n=15) and continued to supply a control diet. Another 30 rats were ovariectomized. A group of ovariectomized rats were fed a control diet (OVX; n=15) and the other group was supplemented with a rose hip diet (rose hips; n=15). Results are expressed as mean ± SEM. The results showed a significant difference between OVX and rose hip, p=0.030.

Figure 6 is a graph showing the energy consumed when the right femur of a rat is broken. A control diet was administered to 45 rats for 3 weeks. After 3 weeks, a group of rats underwent sham surgery (fake treatment; n=15) and continued to supply a control diet. Another 30 rats were ovariectomized. A group of ovariectomized rats were fed a control diet (OVX; n=15) and the other group was supplemented with a rose hip diet (rose hips; n=15). Results are expressed as mean ± SEM. The results showed a significant difference between OVX and rose hip, p=0.030.

(no component symbol description)

Claims (15)

A use of a water-soluble extract of rosehip in the manufacture of a composition for treating or preventing a skeletal condition characterized by weakened or fragile bone. The use of claim 1, wherein the use is to maintain or increase bone formation, maintain or increase bone mineral density, maintain or increase bone quality, stimulate bone regeneration during fracture healing, reduce bone resorption, reduce bone loss, or maintain or Increase bone strength. The use of claim 1, wherein the composition provides from about 1 mg to about 2000 mg of rosehip water-soluble extract per kg of body weight per day. The use of claim 1, wherein the composition provides from about 100 mg to about 1000 mg of rosehip water-soluble extract per kg of body weight per day. The use of claim 1, wherein the composition provides from about 50 mg to about 500 mg of rosehip water-soluble extract per kg body weight per day. The use of claim 1, wherein the composition provides from about 0.05 mg to about 300 mg of rosehip water-soluble extract per kg of body weight per day. The use of claim 2, wherein the composition provides from about 1 mg to about 2000 mg of rosehip water-soluble extract per kg of body weight per day. The use of claim 2, wherein the composition provides from about 100 mg to about 1000 mg of rosehip water-soluble extract per kg of body weight per day. The use of claim 2, wherein the composition provides from about 50 mg to about 500 mg of rosehip water-soluble extract per kg of body weight per day. The use of claim 2, wherein the composition provides from about 0.05 mg to about 300 mg of rosehip water-soluble extract per kg of body weight per day. The use of claim 1, wherein the composition further comprises one or more Dairy ingredients. The use of claim 11, wherein the dairy component is selected from the group consisting of recombinant, powder or fresh skim milk, reconstituted whole or skim milk powder, skim milk concentrate, skim milk retentate, concentrated milk, super Milk Retention Retention, Milk Protein Concentrate, Milk Protein Isolate, Calcium-Free Milk Protein Concentrate, Low-fat Milk, Low-fat Milk Protein Concentrate, Casein, Casein Salt, Milk Fat, High CLA Milk Fat, Emulsifiable Oil , butter, dehydrated milk fat, buttermilk, butter whey, hard milk fat fraction, soft milk fat fraction, sphingolipid fraction, milk fat globular membrane fraction, phospholipid fraction, compound Lipid fraction, colostrum, colostrum fraction, colostrum protein concentrate, colostrum whey, immunoglobulin fraction from colostrum, whey, lactoferrin, one or more lactoferrin fragments, Whey protein isolate, whey protein concentrate, sweet whey, lactic acid whey, mineral acid whey, reconstituted whey powder, milk minerals, compositions derived from any milk or colostrum processing stream, from any milk or Colostrum processing logistics a retentate or permeate-derived composition obtained by ultrafiltration or microfiltration, a composition derived by or separated from any milk or colostrum processing stream by chromatographic separation, an extract derived from any of the components, Including extracts prepared by multi-stage fractionation, differential crystallization, solvent fractionation, supercritical fractionation, near supercritical fractionation, distillation, centrifugal fractionation or fractionation with modifiers, hydrolysates of any of these components, such hydrolysates Any combination of any two or more of the fractions and the components, including combinations of hydrolyzed fractions, combinations of non-hydrolyzed fractions, and combinations of hydrolyzed and non-hydrolyzed fractions. The use of claim 1, wherein the composition further comprises one or more agents selected from the group consisting of calcium, magnesium, zinc, vitamin D, vitamin K, folic acid or folate, vitamin B6 and vitamin B12. The use of claim 1, wherein the composition is food, dessert, milk, dairy product, milk powder, reconstituted milk, fermented milk, yogurt, drinking yogurt, coagulated yogurt, beverage, food additive, beverage additive, meal Additives, nutritional products, medical foods, health foods or medicines. The use of any one of claims 1 to 14, wherein the condition is osteoporosis or osteopenia.