Field of the invention

This invention relates to dietary supplement products, to a method of diet supplementation and to a product for use in such method. Background to the invention

The field of dietary supplement products is a very crowded field. Numerous patents have been granted in respect of such supplements and a myriad of products are available on the market. Such product as have been disclosed and marketed are of varying compositions and represent different schools of thought as to the desirable content of the various products. Also, such products are formulated for general use, or for the dietary requirements of specific population groups such as babies, children under 12 years of age, adolescents, women, lactating women, pre-menopausal women, post-menopausal women, men, aged persons and the like.

The vast majority of such dietary supplement products are formulated to contain all the selected dietary supplement components in a single dosage form formulation which is usually presented and intended to be taken once a day. In some instances the daily dose is presented in two or three dosage forms, such as capsules or tablets which are intended to be taken together, usually with meals.

In an exception to this general rule there are disclosures in some patents of dosage regimes wherein the dietary supplement product is made up of two or more dosage forms of different compositions. Thus in US patent 5,514,382 (Sultenfuss) the claims are inter alia directed at a daily vitamin and mineral supplement of a certain composition and wherein the daily vitamin and mineral supplement is formed into three oral dosage forms for ingestion on a daily basis for example, one in the morning, one in the afternoon, and one in the evening. It also states that for women over 40 years of age, the preferred embodiment of that invention is formed into four pills with one of these pills containing only iron. It explains that this allows women over 40 years of age the flexibility of ingesting or not ingesting the iron, "since it is not clear at this time whether ingestion of iron by women over 40 years of age has positive or deleterious effects. The fourth pill is the one containing only iron." (see Column 8 lines 25 - 35) Very little attention has been given to the known fact that certain dietary supplement components may affect each other either beneficially or detrimentally. Interactions can occur by means of two fundamental mechanisms. Thus one micronutrient may directly affect the absorption of another micronutrient by either single interference (one micronutrient has a negative effect on the other micronutrient) or double interference (two or more micronutrients have negative effects on one another). Also, deficiency or excess of one nutrient within the organism may affect the in vivo metabolism of another micronutrient.

One patent which would appear to deviate in this regard is US patent 6,471 ,969 (Schlachter). It discloses a product comprising two differently formulated preparations in which the components in the respective preparations are selected with respect to their synergistic and antagonistic effects. However, it fails to provide details in respect of such a selection process other than to mention a few examples. Thus it mentions at column 2 line 56 that it is known that bioflavonoids have antioxidant properties and therefore synergistically complement the effect of vitamins C, E and beta carotene. It also mentions at column 3 line 47 that it is known that the simultaneous intake of minerals and trace elements in a single form of administration can adversely affect the resorption of the individual components and states that amongst others, magnesium and calcium as well as iron, zinc and selenium adversely affect each other.

Another patent which recognises the benefits of avoiding the combination in the same dosage form of dietary supplement components is patent application WO 01/43571 A1 (Hohulin). The present inventor however is not in agreement with all of the alleged beneficial and detrimental combinations which Schlachter and Hohulin teach in the aforesaid patents, Instead, the present inventor has specific combinations which according to present invention are to be avoided or combined in the same dosage forms.

The present inventor also proposes the inclusion of specific amino acids in the said combinations and dosage forms in order to maintain the structural and functional intergrity of the mucosa lining: These specified amino acids show beneficial properties with micronutrient combinations i.e. enhanced absorption from the alimentary tract per se and/or enhanced physiologic function at tissue levels following absorption from the gut. Object of the invention

It is an object of the present invention to provide multi-phase dietary supplement products in which specific detrimental dietary supplement component combinations are absent and, in the preferred form of which, specific beneficial dietary supplement component combinations are present.

Description of the invention

According to the present invention there is provided a multiple-phase dietary supplement product comprising at least two dosage form preparations which collectively contain a selected combination of dietary supplementation components and wherein none of the dosage forms contain any one of the following combinations of dietary supplementation components, which combinations are herein referred to as detrimental combinations of dietary supplement components, namely:

Fluoride and Calcium; Selenium and Vitamin A;

Iron and Magnesium;

Iron and Zinc;

Copper and Zinc;

Vitamin B12 and Biotin; Iron and Calcium;

Selenium and Zinc;

Copper and Molybdenum;

Iron and Vitamin A; and

Zinc and Vitamin B9. The dietary supplement product described above preferably comprises a combination of dietary supplement components which are formulated in the at least two dosage forms to collectively contain two or more of the group of dietary supplement components consisting of β - carotene; Vitamin E; Vitamin K; Vitamin B1 ; Vitamin B2;

Vitamin B3 (as Nicotinamide)

Vitamin B5 (also called Pantothenic acid);

Vitamin C;

Biotin;

Iron;

Copper;

Choline ;

Selenium;

L-Arginine;

L-Glutamine;

L-Leucine;

Fluoride;

Vitamin D3;

Vitamin B6;

Vitamin B9; Vitamin B12; Magnesium; Chromium; Manganese; Molybdenum; Zinc;

Potassium; Calcium; and Vitamin A.

In the preferred form of the invention at least one of the at least two dosage forms contain at least one of the combinations of dietary supplement components, which combinations are herein referred to as beneficial combinations of dietary components, selected from the group of dietary supplement component combinations consisting of B-carotene and Iron;

B-carotene and Vitamin E;

Vitamin E and Selenium;

Vitamin E and Iron;

Vitamin E and Vitamin C; Vitamin B1 and Iron;

Vitamin B2 and Iron;

Vitamin B5 and Copper;

Iron and Copper; Vitamin C and Iron; Vitamin C and Selenium; Vitamin K and Vitamin C; Zinc and Vitamin A; Magnesium and Calcium; Vitamin D3 and Calcium; Vitamin B6 and Magnesium; Potassium and Calcium; Vitamin D and Magnesium; and Zinc and Vitamin C,

In a further preferred form of the invention the multiple-phase dietary supplement product is a two-phase dietary supplement product and comprises two dosage form preparations of which the first dosage form preparation comprises a combination of at least two of the dietary supplement components selected from the group consisting of β - carotene; Vitamin E; Vitamin B1 ; Vitamin B2; Vitamin B3 (as Nicotinamide);

Vitamin B5 (also called Pantothenic acid);

Vitamin C;

Biotin;

Iron; Copper;

Choline;

Selenium; Fluoride; and Vitamin B9; and of which the second dosage form preparation comprises a combination of at least two of the dietary supplement components selected from the group consisting of

Vitamin D3;

Vitamin K; Vitamin C;

Vitamin B6;

Vitamin B12;

Magnesium;

Chromium; Manganese;

Molybdenum;

Zinc;

Potassium; Calcium; and Vitamin A; and wherein either or both of the dosage form preparations further contain at least one of the group of amino acids consisting of

Arginine; Glutamine and Leucine.

In a further preferred form of the two-phase dietary supplement product of the invention the first dosage form comprises a combination of all of the dietary supplements of the group consisting of β - carotene; Vitamin E; Vitamin B1 ; Vitamin B2;

Vitamin B3 (as Nicotinamide);

Vitamin B5 (also called Pantothenic acid);

Vitamin C;

Biotin;

Iron;

Copper;

Choline;

Selenium; and

Vitamin B9; and the second dosage form comprises a combination of all of the dietary supplements of the group consisting of

Vitamin C; Vitamin K; Vitamin D3; Vitamin B6; Vitamin B9; Vitamin B12; Magnesium; Chromium; Manganese; Molybdenum; Zinc; Potassium; Calcium; Vitamin A; and Vitamin E and wherein either or both of the dosage form preparations further contain at least one of the group of amino acids consisting of

Arginine; Glutamine and Leucine.

In a preferred form of the invention as set out above both dosage form preparations contain Vitamin C and Vitamin K.

The various mineral components of the product, when present in the product, may be present in any suitable form for human or animal digestion. According to the invention there are however certain preferred forms for these components according to a further aspect of the invention, as set out below.

The iron in the product, if present, is preferably present in the form of ferrous lactate.

The copper in the product, if present, is preferably present in the form of copper gluconate. The selenium in the product, if present, is preferably present in the form of selenium nicotinic acid.

The magnesium in the product, if present, is preferably present in the form of magnesium oxide or magnesium chloride.

The chromium in the product, if present, is preferably present in the form of chromium nicotinic acid.

The zinc in the product, if present, is preferably present in the form of zinc gluconate.

The potassium in the product, if present, is preferably present in the form of potassium sulphate.

The calcium in the product, if present, is preferably present in the form of calcium carbonate or calcium lactogluconate or both. The molybdenum in the product, if present, is preferably present in the form of ammonium molybdate.

The Amino acids in the product if present, is preferably present in the form of free amino acids, or peptides thereof, or metabolic precursors of the free amino acids, or peptides thereof, or metabolites of the free amino acids or peptides thereof, or salts of the free amino acids or peptides thereof, or metabolic intermediary metabolites in combination with such amino acids, or mixtures of any two or more of the foregoing, The amino acids, if present, is preferably L- Arginine, L-Glutamine and L-Leucine.

The product may be made up in any suitable dosage form formulations and may thus comprise tablets, capsules, caplets, syrups, beverages, powders, granulates or the like and in each instance the dosage forms may contain any suitable excipients such as fillers, lubricants, disintegrants, taste masking agents and the like. The at least two dosage form preparations of the multiple-phase dietary supplement product according to the invention are preferably the same but may also be of different forms.

In the preferred form of the invention the at least two dosage forms are capsules.

A product according to the invention may contain quantities of the various components which are about equal to the Recommended Daily Allowance quantities for any specific country for such components. However, the composition may be modified to provide the various selected dietary supplement components in such quantities as may be considered appropriate for specific population groups such as babies, children under 12 years of age, adolescents, women, lactating women, pre-menopausal women, post-menopausal women, men, aged persons and the like.

According to a second aspect of the invention there is provided a multiple-stage dietary supplement product as defined in any one of the above product definitions for use in a method for supplementing diet by administration of the at least two dosage form preparations to a person in need of such dietary supplementation at spaced time intervals. The spaced time intervals may be any interval form 30 minutes to 23 hours.

Preferably the spaced time interval may be the time between two sequential meals.

According to a third aspect of the invention there is provided a method for supplementing the diet of a patient in need of diet supplementation comprising the steps of administering the at least two dosage form formulations of the multi-stage dietary supplement product as defined in any of the above product definitions at spaced time intervals to the person

Again the spaced time intervals may be any interval form 30 minutes to 23 hours.

Preferably the spaced time interval may again be the time between two sequential meals. Thus the second dosage form is preferably taken after the firtst dosage form and more preferably after last sequential meal for the day. EXAMPLES OF THE INVENTION

Without thereby limiting the scope of the invention an example of a multi-phase dietary supplement product in which the aforementioned detrimental combinations of dietary supplement components in the same dosage form formulation are avoided, and in which the aforementioned beneficial combination of dietary components are present, will now be described.

Example 1

A two-phase dietary supplement product according to the present invention is produced in the conventional manner for producing capsule products and according to the procedures and under conditions as required for the preparation of such products in terms of the regulations and guidelines for Good Manufacturing Practices as applied by the relevant regulatory authority. The product is formulated to contain, in a first capsule: β - carotene about 000IU

Vitamin E (having approximately equal quantities of a- tocopherol and γ-tocopherol) about 10 mg;

Vitamin B1 (also called Thiamin) about 0.7 mg;

Vitamin B2 (also called Riboflavin) about 0.8 mg;

Vitamin B3 ( as Nicotinamide) about 8.5 mg;

Vitamin B5 (also called Pantothenic acid) about 3.5 mg;

Vitamin C (also called Ascorbic acid) about 40 mg;

Biotin about 10pg;

Iron (as ferrous lactate) about 10 mg;

Copper (as copper gluconate) about 0.7 pg;

Choline (as choline butyrate) about 30 mg;

Selenium (as selenium nicotinic acid) about 25 pg; L-Arginine ( as L-Arginine-HCI) about 50 mg; L-Glutamine about 100 mg; Fluoride about 1.2 mg; and in a second capsule: Vitamin K about 30 Mg;

Vitamin C (also called Ascorbic acid) about 40 mg; Vitamin D3 about 200 IU;

Vitamin B6 (also called pyridoxine phosphate) about 0.8 mg;

Vitamin B9 (also called folic acid) about 200 pg; Vitamin B12 (also called cyanocobalamine) about 1.1 pg;

Magnesium (as magnesium oxide) about 50 mg;

Chromium (as chromium nicotinic acid) about 20pg;

Manganese (as manganese sulphate) about 1 pg;

Molybdenum (as Ammonium Molybdate) about 35pg; Zinc (as zinc gluconate) about 5 mg;

Potassium (as potassium sulphate) about 2 mg;

Calcium (as calcium carbonate) about 40 mg;

Calcium (as calcium lactogluconate) about 45mg; and

Vitamin A. (about 700IU). Example 2

A two-phase dietary supplement product according to the present invention is similarly produced as described above in the form of two differently colour coded capsules, in this instance white and green/white capsules. The product is formulated to contain in the dietary supplement components as set out in Table 1 below. Table 1 also reflects the percentage of recommended daily allowance (RDA) of such components when the reflected number of capsules are taken by different population groups as indicated.

In this example of the invention the capsules may be packed in a single container with directions that the white capsules and white/green capsules are not to be taken at the same time but in a spaced time routine, e.g. the white capsules at breakfast and the white/green capsules at dinner, and in the quantities as reflected below by the different population groups.

TABLE 1

CHILDREN FEMALES MALES ELDERLY

1-3 4-8 9-13 10-50 PREGLAC- 10-50

years years years years NANT TATING years 50 years*

1 1 1 2 2 2 2 2 capsule capsule capsules capsules capsules capsules capsules capsules

WHITE CAPSULE %RDA %RDA %RDA %RDA %RDA %RDA %RDA %RDA

B-carotene 999 IU ND ND ND ND ND ND ND ND

Vit E 10 mg 116 100 100 145 140 116 140 140

Vit B1 0,7 mg 140 116 116 109 100 93 127 116

Vit B2 0,8 mg 160 133 88 145 114 100 123 123

Vit B3 8,5 mg 141 106 70 121 94 100 106 106

Vit B5 3,5 mg 175 116 87 140 116 100 140 140

Vit C 40 mg 100 88 88 133 114 84 33 133

Biotin 15 ug 187 126 75 100 100 86 100 100

Iron 10 mg 00 100 100 33 66 133 200 133

Copper 0,7 ug 100 70 70 140 140 140 140 140

Choline 30 mg ND ND ND ND ND ND ND ND

Selenium 25 ug 125 125 125 136 88 100 107 107

L-Arginine 50 mg ND ND ND ND ND ND ND ND

100

L-Glutamine mg ND ND ND ND ND ND ND ND

Fluoride 1 ,2 mg 171 120 60 160 120 120 120 120

Vit B9 [Folic

acidl 200 ug 133 100 100 150 100 120 150 150

GREEN/WHITE 1 1 1 3 3 3 3 3 CAPSULE capsule capsule capsules capsules capsules capsules capsules capsules

Vit C 40 mg 100 88 88 133 114 84 133 133

Vit K 30 ug 200 150 150 100 92 92 75 75

Vit D3 200 iu 100 100 100 100 200 200 100 100

Vit B6 0,8 mg 160 133 125 123 84 100 88 100

Vit B12 1, 1 ug 121 91 91 137 126 126 137 137

Magnesium 60 mg 25 15 8 6 6 6 4 4

Chromium 20 ug 100 40 33 100 100 100 100 100

Manganese 1 ug 66 66 50 100 100 100 100 100

Molybdenium 35 ug 120 120 83 90 90 90 90 90

Zinc 5 mg 100 100 100 125 100 78 100 100

Potassium 2 mg ND ND ND ND ND ND ND ND

Calsium 40 mg 28 17 11 43 43 43 43 35

Vit A 666 IU 125 100 71 125 125 83 100 100 Example 3

A further alternative formulation of the product according to the invention, specifically formulated for children is prepared as described above and is formulated to contain the dietary supplement components in the quantities as shown in Table 2. Again the RDA % for different subgroups of that population group is shown.

Table 2 JUNIOR FORMULATION

Example 4

A further alternative formulation of the product according to the invention, specifically formulated for adults and the elderly is prepared as described above and is formulated to contain the dietary supplement components in the quantities as shown in Table 3. Again the RDA % for different subgroups of that population group is shown.

Table 3 SENIOR FORMULATION

It will be appreciated that many variations of the invention may be devised without thereby departing from the general scope and spirit of the invention.