GB2507473A

GB2507473A - A composition for enhancing the strength of bones

Info

Publication number: GB2507473A
Application number: GB1216397.8A
Authority: GB
Inventors: Ajit Ramanial Patel
Original assignee: Individual
Current assignee: Individual
Priority date: 2012-09-13
Filing date: 2012-09-13
Publication date: 2014-05-07
Also published as: GB201216397D0

Abstract

A composition for oral ingestion comprises powdered Lithothamnion calcareum, manganese, zinc, vitamin C, vitamin K and vitamin D. The composition is suitable for enhancing bone health, while reducing the number of high-level ingredients that are not targeted at improving or maintaining bone health. Also disclosed are capsules and medical devices comprising the aforementioned composition.

Description

A COMPOSITION FOR ENHANCING THE STRENGTH OF BONES

This invention relates to compositions for enhancing or maintaining bone health, and for preventing or treating bone weakness caused by conditions such as osteoporosis.

Background of the invention

Maintenance of adequate bone density is essential to resist bone fractures as there is a statistical association between poor bone density and higher probability of fracture.

Fractured bones are immobilising and can take a long time to heal, requiring specialist medical treatment and, in some cases, hospitalisation. Thus fractures are a significant public health issue due to the expense of health care provision in addition to the pain, discomfort, and reduction in productivity imposed on a subject with a broken bone.

There are a number of risk factors associated with reduced bone density. Those at higher risk of low bone density include, for example, the elderly, women and in particular those with low levels of oestrogen, sufferers of anorexia nervosa, subjects with a poor diet and in particular those with diets lacking in the micronutrients calcium and vitamin D, tobacco smokers, excessive alcohol drinkers, and those with osteoporosis.

Calcium is a divalent cation involved in many essential processes in the body, such as muscle contraction. neurotransmission and hormone secretion. As a result it is tightly regulated and is stored in the body primarily in bones and teeth.

Accordingly, if a diet is low in calcium, the body mobilises calcium from bones and teeth to compensate, which can lead to bone weakness.

Vitamin D is a secosteroid that can take various structurally related forms. Vitamin D2 (ergocalciferol) is produced by UV irradiation of ergosterol in some organisms of phytoplankton, invertebrates, yeasts, and higher fungi such as mushrooms.

Vitamin D3 (cholecalciferol) is produced by UV irradiation of dehydrocholesterol, which is for example present in the skin of vertebrates, including humans. Vitamin D helps the body absorb calcium in the gastrointestinal tract.

In subjects who are at risk of developing low bone density due to a deficiency in a particular micronutrient, restoring normal levels of that micronutrient may prevent low bone density. For example, subjects identified as being at risk of developing a lowered bone mass may be advised to adjust their diet to increase the amount of foods rich in calcium and/or vitamin D. Foods high in calcium include dairy products, green leafy vegetables, fish dishes in which the bones are eaten, and soya bean curd. Foods high in vitamin D include oily fish, such as salmon and sardines, and eggs. However, it may be impossible to precisely adjust, or undesirable to change, a subject's diet in this manner, for example due to lactose intolerance precluding dairy intake or a fish allergy.

Alternatively, endogenous vitamin D3 synthesis in the body may be enhanced by increased exposure to sunlight. However, increasing exposure to sunlight may be undesirable for cosmetic or medical reasons.

Medical treatments aim to reduce osteoclast-mediated resorption of bones.

Pharmacological agents that inhibit bone resorption include bisphosphonates such as alendronate, oestrogen analogues and calcitonin. Each of these drugs may be associated with undesirable side effects and therefore must be taken under medical supervision, precluding them from being used as home-use, over-the-counter prophylactics for enhancing bone mass.

Accordingly, dietary supplements have been developed to provide micronutrients that promote normal bone health, typically as salts that can be absorbed by the gastrointestinal system. For example, broad-spectrum multivitamin and mineral supplements are widely available. However, these supplements are expensive due the inclusion of a wide variety of ingredients and they may not have the required quantity of the specific agents that are particularly useful for enhancing bone density. Moreover, when taking such supplements, one cannot adjust the dose of the bone-related micronutrients without also increasing the amount of the other nutrients. Therefore, simply increasing the intake amount of a broad-spectrum multivitamin and mineral supplement may be dangerous, since consumption of large quantities of vitamins or minerals that are not required may result in side effects and undesired interactions. These side effects and interactions will not be apparent to subjects who are not medically trained.

There is therefore a need for a dietary supplement that promotes bone health, which can be conveniently tailored to a subject's requirements.

WO 2010008976 relates to a composition useful for enhancing bone health consisting of calcium, magnesium and vitamin 0.

WO 2010292194 relates to a composition useful for promoting bone health and alleviating osteoporosis comprising calcium, magnesium, zinc and vitamin 0.

DE 202004005428 relates to a dietary supplement for bone health comprising vitamin D3, vitamin K1 and calcium.

HU 9901057 relates to a bone strengthening composition containing vitamin K1, L-lysine, calcium, boron, and optionally, magnesium, zinc, selenium, manganese, iron, glycine and vitamins B6, C and D3.

EP 0702954 relates to a dietic preparation for preventing bone loss consisting of calcium carbonate, vitamin D3, zinc, copper, magnesium, manganese, and borate.

GB 2458467 relates to a dietary supplement for maintenance of bone health having two components: one composition consisting of calcium, magnesium, zinc, vitamin 03. manganese, selenium, copper, and boron; and a second composition consists of vitamin C, vitamin D3, soya isoflavone, and omega-3 fatty acids.

Thus, at present, numerous substances and combinations of substances have been used for promoting bone strength. However, there is a need for an alternative or improved nutritional supplement that provides micronutrients that enhance bone health, while reducing the number of high-level ingredients that are not targeted at improving or maintaining bone health, thus simplifying dosage management and reducing the undesirable side effects associated with overconsumption of other dietary supplements.

Summary of the invention

The present invention provides an alternative or improved composition for enhancing bone health. The compositions provide a means of increasing bone strength in a synergistic manner, while enhancing management of vitamin and mineral dosage in the absence of medical supervision.

Accordingly, in a first aspect, the invention provides a composition for oral ingestion comprising calcium, magnesium, manganese, zinc, vitamin C, vitamin Ki and vitamin D. Thus, the invention provides a composition that advantageously includes components that work in tandem to enhance bone mass.

Magnesium is a divalent cation involved in many essential processes in the body, such as muscle contraction, neurotransmission, hormone secretion and immune function. As a result it is tightly regulated and is stored in the body mostly in bones, but also in other tissues and organs. The amount of magnesium in the invention is selected to be beneficial for bone health and is considered to be useful in preventing or treating post-menopausal osteoporosis.

Manganese is a divalent cation involved in many essential processes in the body, mainly as an enzyme cofactor. It is found in the body mostly in bones, the liver and kidneys. The amount of manganese in the invention is selected to be beneficial for bone health and is considered to be useful in preventing or treating bone malformation.

Zinc is a divalent cation involved in many essential processes in the body, mainly as an enzyme cofactor. A daily dietary intake of zinc is required because the body has no bulk, long-term zinc storage system. The amount of zinc in the invention is selected to be beneficial for bone formation.

Vitamin C (ascorbate) cannot be produced in humans and so a daily dietary intake of vitamin C is required. A deficiency in vitamin C can cause scurvy, which causes a number of symptoms due to the role of vitamin C in collagen formation. A loss in collagen formation may lead to bone weakness, and in extreme cases rickets. The amount of vitamin C in the invention is selected to be beneficial for bone strength.

Vitamin K refers to a group of fat-soluble vitamins, which are 2-methyl-i 4-naphthoquinone (3-) derivatives. Vitamin K contains a functional naphthoquinone ring and an aliphatic side-chain. The two known natural K vitamins are vitamins Ki and K2. Vitamin Ki is also known as phylloquinone, which is characterised by a phytyl side-chain. Vitamin K2 is a family of homologues known as menaquinones, which are characterised by a side-chain comprising a varying number of isoprenoid residues. The amount of vitamin K in the invention is selected to be beneficial to bone health.

The composition may contain from 45 to 95 % by weight of calcium, from 0.8 to 17 % by weight of magnesium, from 0.2 to 7 % by weight of manganese, from 0.2 to 7 % by weight of zinc, from 3 to 40 % by weight of vitamin C, from 0.002 to 0.06 % by weight of vitamin K, from 0.0002 to 0.008 % by weight of vitamin D. More particularly, the composition may contain from 65 to 85 % by weight of calcium, from 3 to 12 % by weight of magnesium, from ito 4 % by weight of manganese, from ito 4 % by weight of zinc, from 7 to 30 % by weight of vitamin C, from 0.01 to 0.03 % by weight of vitamin K, from 0.001 to 0.004 % by weight of vitamin D. The composition may contain from 200 to 500 parts by weight of calcium, from 4 to parts by weight of magnesium, from ito 40 parts by weight of manganese, from ito 40 parts by weight of zinc, from 20 to 200 parts by weight of vitamin C, from 0.01 to 0.3 parts by weight of vitamin K, from 0.001 to 0.04 parts by weight of vitamin 0.

More particularly, the composition may contain from 200 mg to 1 g of the calcium, from 10 mg to 50 g of the magnesium, from 2.5mg to 20 mg of the manganese, from 2.5 mg to 20 nig of the zinc, from 40mg to 150 mg of the vitamin C, from 30 pg to 150 pg of the vitamin K, and from 2.5 pg to 20 pg of the vitamin D. For example, the composition may contain from 300 mg to 600 mg of the calcium, from 20 mg to 50mg of the magnesium, from 5 mg to 15mg of the manganese, from 5 mg to 15 mg of the zinc, from 60 mg to 100 mg of the vitamin C, from 60 pg to 100 pg of the vitamin K, and from 5 pg to 15 pg of the vitamin D. In one preferred embodiment, the composition contains approximately 400 mg of the calcium, approximately 30 mg of the magnesium, approximately 10 mg of the manganese, approximately 10 mg of the zinc, approximately 80 mg of the vitamin C, approximately 75 pg of the vitamin K, and approximately 10 pg of the vitamin 0.

In an embodiment, the composition consists or consists essentially of calcium, magnesium, manganese, zinc, vitamin C, vitamin K, and vitamin D, optionally with pharmaceutically acceptable excipients.

By consists essentially' it is meant that the compositions contain the recited components with less than 5 pg, preferably 1 pg of other components.

The components (and the concentrations thereof) of the compositions of the invention are preferably selected such that there is a synergistic enhancement of digestion.

Thus, the formulation is targeted specifically at enhancing bone health and does not contain any additional nutritional components (e.g. additional vitamins or dietary minerals), the dosing of which would change when the dosing of the bone health-enhancing components are changed. Since any additional nutritional components may e.g. become toxic at high doses, inclusion of such components could render dosing of the composition inflexible or difficult without medical supervision. Accordingly, the present compositions advantageously simplify dosing.

The compositions ot the invention may be presented in any pharmaceutically acceptable form, such as capsules, tablets, powders or liquids, preferably capsules. Capsules of the invention may be filled with powder, pellets, gel or liquid.

Tablets of the invention may take the form of chewable tablets, dispersible tablets or tablets designed to be swallow whole. Powders of the inventions may be designed for dissolution or suspension in water and may optionally comprise an agent or agents that produce effervescence on addition to water. Powders of the invention may be packaged in the form of sachets. Liquids of the invention may take the form of a solution, suspension or emulsion.

The compositions of the invention may also be presented as medical devices, the term medical device as used herein refeiring to a substance which whilst providing a medical benefit to a subject, is not absorbed significantly from the subject's GI tract and does not exert its actions by pharmacological means.

The composition, capsule or medical device of the invention as defined herein may be used for treating the or promoting bone weakness associated with conditions such as osteoporosis hypoestrogenism, anorexia nervosa or lactose intolerance, and with factors such as old age, pregnancy or deficient diet.

Calcium, magnesium, manganese and zinc are obtainable in a suitable divalent form from a number of commercial chemical suppliers. In the invention calcium, magnesium, manganese and zinc may be presented in any bioavailable form known to the skilled person. For example, calcium, magnesium, manganese and zinc may be presented in the form of a salt. Preferably calcium and/or magnesium are in a carbonate salt. Preferably, manganese and zinc are in a citrate salt. The form in which calcium, magnesium, manganese and zinc is presented may be selected independently for each component.

Alternatively, calcium, magnesium, manganese and zinc may be sourced from one or more natural sources, for example, algal, plant or microbial sources, and may be isolated from the natural source, or taken as powdered natural source.

In an embodiment, the formulation of the invention comprises algae, preferably Lithothamnion calcareurn, which is a source of calcium carbonate and magnesium carbonate in significant amounts, and other minerals in smaller amounts. The smaller amounts of these other minerals advantageously provide a degree of dietary supplementation, while making overdose of these other minerals less likely in the event that the dose of L. ca/careum (and thus calcium and magnesium) is increased.

Preferably, the L. ca/careum is presented in the form of a powder.

The L. calcareurn may be presented in powder form wherein at least 99.5% by weight of the particles forming the powder have a particle size (e.g. diameter) of 600 pM or less. Such particles will pass through a 30 mesh sieve. In one embodiment, at least 99.5% by weight of the particles have a particle size (e.g. diameter) of 400 pM or less. Such particles will pass through a 40 mesh sieve. In another embodiment, at least 99.5% by weight of the particles have a particle size (e.g. diameter) of 300 pM or less. Such particles will pass through a 50 mesh sieve. In a further embodiment, at least 95% by weight of the particles have a particle size (e.g. diameter) of 210 pM or less. Such particles will pass through a mesh sieve. In another embodiment, at least 75% by weight of the particles will pass through a 50 to 60 mesh sieve and have particle sizes in the range from 230 to 280 pM.

Where the source of calcium and magnesium in the formulation of the invention is powdered L. ca/care urn, the composition may contain from 80 to 99 % by weight of powdered L. calcareurn, from 0.05 to 3 % by weight of manganese, from 0.05 to 3 % by weight of zinc, from ito 20 % by weight of vitamin C, from 0.001 to 0.02 % by weight of vitamin K, from 0.0001 to 0.003 % by weight of vitamin D. More particularly, the composition may contain from 90 to 98 % by weight of powdered L. ca/care urn, from 0.3 to 1 % by weight of manganese, from 0.3 to 1 % by weight of zinc, from 2.5 to 10 % by weight of vitamin C, from 0.003 to 0.01 % by weight of vitamin K, from 0.0003 to 0.001 % by weight of vitamin D. The composition may contain from 1300 to 1700 parts by weight of powdered L. calcareurn, from 1 to 45 parts by weight of manganese, from 1 to 45 parts by weight of zinc, from 20 to 300 parts by weight of vitamin C, from 0.01 to 0.07 parts by weight of vitamin K, from 0.001 to 0.005 parts by weight of vitamin D. More particularly, the composition may contain from 700 mg to 4 g of the powdered L. calcareurn, from 2.5 mg to 20 mg of the manganese, from 2.5 mg to 20 mg of the zinc, from 40 mg to 150 mg of the vitamin C, from 30 pg to 150 pg of the vitamin K, and from 2.5 pg to 20 pg of the vitamin D. For example, the composition may contain from 1.1 g to 2.5 g of the powdered L. ca/careurn, from 5 mg to 15 mg of the manganese, from 5 mg to 15 mg of the zinc, from 60 mg to 100 mg of the vitamin C. from 60 pg to 100 pg of the vitamin K, and from 5 pg to 15 pg of the vitamin D. In one preferred embodiment, the composition contains approximately 1.5 g of the powdered L. ca/careurn, approximately 10mg of the manganese, approximately 10 mg of the zinc, approximately 80 mg of the vitamin C, approximately 75 pg of the vitamin K, and approximately 10 pg of the vitamin 0.

In a further embodiment of the invention, the composition contains both powdered L. ca/careurn and another source of calcium and magnesium.

In an embodiment of the invention, the composition comprises only powdered Lithothamnion calcareurn, manganese, zinc, vitamin C, vitamin K and vitamin 0.

Vitamins C, D and K may be prepared chemically and/or biotechnologically via fermentation and/or bioconversion processes known to skilled person.

Alternatively, vitamins C, D and K may be sourced from one or more natural sources, for example, algal, plant or microbial sources, and may be isolated from the natural source, or taken as powdered natural source.

In an embodiment of the invention, vitamin K is provided in the form of vitamin K1.

In an embodiment of the invention, vitamin D is provided in the form of vitamin 03.

The compositions of the invention are typically administered with or without meals one or more times per day. For example, the compositions may be administered from one to four times per day.

In an embodiment of the invention, the compositions may be administered so that the daily intakes are as follows: Calcium: 100mg to 1.59 Magnesium: 10mg to 500mg Manganese: 2 mg to 200 mg Zinc: 2 mg to 200 mg Vitamin C: 20mg to 2g Vitamin K: 20 pg to 2 mg Vitamin 0: 2 pg to 200 pg In an alternative embodiment of the invention, the compositions may be administered so that the daily intakes are as follows: Powdered L. calcareum: 300 mg to 5 g Manganese: 2 mg to 200 mg Zinc: 2 mg to 200 mg Vitamin C: 20 mg to 2 g Vitamin K: 20 pg to 2 mg Vitamin 0: 2 pg to 200 pg The amounts of the metals listed above relate to amounts of their divalent ions. In the formulations of the invention, the divalent ions would be provided in suitable compound forms, known to the skilled person, that are readily absorbed in the gastrointestinal tract. For example, in the case that the calcium and magnesium is provided in the form of powdered L. ca/care urn, the predominant form of calcium and magnesium will be theft carbonate salts.

The compositions ot the invention enhance the dietary intake of minerals that are thought to enhance bone mass and/or maintain noimal one mass.

The invention will now be illustrated, but not limited, by reference to the following

specific examples.

EXAMPLE 1

Capsule formulation 1 Two part capsule shells formed from hydroxypropyl methylcellulose are filled with a mixture of powdered L. calcareum, manganese citrate, zinc citrate, vitamin C, vitamin Ki and Vitamin D3 in the following amounts per three capsules: Powdered L. calcareum: 1490 mg Manganese citrate: 10 mg Zinc citrate: 10 mg Vitamin C: 80 mg Vitamin Ki: 75 pg Vitamin D3: 10 pg Three to four capsules per day are taken as a food supplement.

EXAMPLE 2

Cacisule formulation 2 Two part capsule shells foimed from hydroxypropyl methylcellulose are filled with a mixture of calcium carbonate, magnesium carbonate, manganese citrate, zinc citrate, vitamin C, vitamin Ki and Vitamin D3 in the following amounts per three capsules: Calcium carbonate: 1000 mg Magnesium carbonate: 115 mg Manganese citrate: 10 mg Zinc citrate: 10 mg Vitamin C: 80 mg Vitamin Ki: 75 pg Vitamin D3: 10 pg Three to four capsules per day are taken as a food supplement.

It will readily be apparent that numerous modifications and alterations may be made to the specific embodiments of the invention described above without departing from the principles underlying the invention. All such modifications and alterations are intended to be embraced by this application.