AU2017101419A4 - Compositions for selenium delivery - Google Patents

Abstract

Abstract Provided herein are compositions for the administration of selenium. Compositions in accordance with embodiments of the disclosure comprise high selenium yeast, selenocysteine (typically in the form of L-Se-methylselenocysteine), and optionally Momordica charantia, or Silybum marianum and lecithin. Also provided are uses of compositions of the disclosure for DNA repair, regulation of blood glucose levels, and the treatment or prevention of diabetes and liver disease.

Description

Compositions for selenium delivery

Field of the Disclosure [0001] The present disclosure relates to compositions for administration of selenium to a subject. More specifically, the present disclosure relates to compositions comprising high selenium yeast, selenocysteine (typically in the form of L-Se-methylselenocysteine), and optionally Momordica charantia, or Silybum marianum and lecithin. This disclosure also relates to uses of such compositions generally for DNA repair, regulation of blood glucose levels, and the treatment or prevention of diabetes and liver disease.

Background of the Disclosure [0002] Selenium is an essential micronutrient in humans and animals. In humans, it is a trace element functioning as a cofactor for antioxidant enzymes such as glutathione peroxidases. In addition to antioxidant properties, selenium plays a vital role in a range of metabolic pathways, including in relation to thyroid metabolism and immune function. As our understanding of the properties of selenium increase, additional benefits of selenium to human health are being elucidated.

[0003] Selenium deficiency has been linked to the development of numerous diseases and conditions, including, for example, cardiovascular disease, hyperthyroidism, cognitive decline, and a weakened immune system, thereby making the body more susceptible to a range of conditions and illnesses. The importance of selenium to human health, and reports of declining blood levels of selenium in various populations, have led to the implementation of public health recommendations for the dietary intake of selenium. However the bioavailability of selenium is dependent upon the form in which the selenium is provided, e.g. organic (such as selenocysteine or selenomethionine) or inorganic. The use of an inorganic form of selenium as a dietary source is not recommended due to the risk of toxicity.

[0004] Major dietary sources of selenium include seafood, meats, cereals, grains, eggs and dairy, however, the selenium content of plant-based sources may vary greatly depending on the selenium present in the soil, the soil pH and the form of the selenium. A large number of countries such as Australia and China have significant environmental selenium deficiencies, for example in soil. Animal selenium content varies with the plant source consumed by the animal. Selenium supplements typically include selenium in the form of selenomethionine and high selenium yeast. Approximately 80% of selenium in high selenium yeast is selenomethionine. However the bioavailability of ingested selenomethionine is poor, as it is required to be metabolised via multiple enzyme pathways into usable form.

[0005] There remains a need for the development of novel formulations and compositions containing selenium, typically in a highly bioavailable form, for use as supplements.

Summary of the Disclosure [0006] In a first aspect, the present disclosure provides a composition comprising a combination of a high selenium yeast and selenocysteine, optionally further comprising one or more of Momordica charantia or an extract thereof, Silybum marianum or an extract thereof, and lecithin.

[0007] The selenocysteine may be in the form of, for example, L-selenocysteine or a methylselenocysteine . Typically, the selenocysteine is L-Se-methylselenocysteine.

[0008] The high selenium yeast may comprise, for example, Saccharomyces cerevisiae. The high selenium yeast is typically cultured in a selenium-enriched growth medium. The composition may comprise between about 10 mg and about 60 mg high selenium yeast per unit dosage form (or equivalent to between about 20 μg and about 120 μg selenium per unit dosage form). In exemplary embodiments, the composition comprises between about 25 mg to about 37.5 mg high selenium yeast per unit dosage form (or equivalent to between about 50 μg and about 75 μg selenium per unit dosage form).

[0009] The composition may comprise between about 100 μg and about 200 μg selenocysteine per unit dosage form (or equivalent to between about 43 μg and about 86 μg selenium per unit dosage form). In exemplary embodiments, the composition comprises between about 116 pg to about 174.5 pg selenocysteine per unit dosage form (or equivalent to between about 50 pg and about 75 pg selenium per unit dosage form).

[0010] In one exemplary embodiment, the composition comprises about 37.5 mg of high selenium yeast and about 174.5 pg of selenocysteine per unit dosage form (or equivalent to about 75 pg selenium from high selenium yeast and about 75 pg selenium from selenocysteine per unit dosage form). In another exemplary embodiment, the composition comprises about 25 mg of high selenium yeast, about 116 pg of selenocysteine (or equivalent to about 50 pg selenium from high selenium yeast and about 50 pg selenium from selenocysteine per unit dosage form) and about 300 mg of Momordica charantia per unit dosage form. In yet another exemplary embodiment, the composition comprises about 37.5 mg of high selenium yeast, about 174.5 pg of selenocysteine (or equivalent to between about 75 pg selenium from high selenium yeast and about 75 pg selenium from selenocysteine per unit dosage form), about 400 mg of Silybum marianum and about 62 mg of lecithin per unit dosage form.

[0011] In embodiments of the first aspect, the high selenium yeast and the selenocysteine may each contribute between about 20 pg and about 120 pg of selenium, per unit dosage form. The composition may provide between about 30 pg and 120 pg of selenium from high selenium yeast and about 30 pg to about 120 pg of selenium from selenocysteine per unit dosage form, between about 20 pg to about 80 pg of selenium from high selenium yeast and about 20 pg to about 80 pg of selenium from selenocysteine, about 50 pg of selenium from high selenium yeast and about 50 pg of selenium from selenocysteine, or about 75 pg of selenium from high selenium yeast, about 75 pg of selenium from selenocysteine.

[0012] In embodiments of the disclosure, the selenium from high selenium yeast is at a ratio of 1:1, 1:2, 1:3 or 1:4 to the selenium from selenocysteine. In further embodiments, the selenium from selenocysteine is at a ratio of 1:2, 1:3 or 1:4 to the selenium from high selenium yeast.

[0013] In a second aspect, the present disclosure provides a composition comprising about 37.5 mg of high selenium yeast and about 174.5 pg of selenocysteine per unit dosage form. Typically the high selenium yeast and the selenocysteine each provide about 75 pg of selenium per unit dosage form, the composition therefore providing a total of about 150 pg of selenium per unit dosage form. In an embodiment the selenium provided by the high selenium yeast is between about 30 pg and about 120 pg and the selenium provided by the selenocysteine is between about 30 pg and about 120 pg per unit dosage form. In an embodiment of this aspect, the selenium from high selenium yeast is at a ratio of 1:1,1:2,1:3 or 1:4 to the selenium from selenocysteine. In further embodiments, the selenium from selenocysteine is at a ratio of 1:2, 1:3 or 1:4 to the selenium from high selenium yeast.

[0014] In a third aspect, the present disclosure provides a composition comprising about 25 mg of high selenium yeast, which provides approximately 50 pg of selenium, about 116 pg of selenocysteine, which provides about 50 pg of selenium, and about 300 mg of Momordica charantia per unit dosage form. In an embodiment the Momordica charantia is in the form of an extract. In an embodiment the selenium provided by the high selenium yeast is between about 20 pg and about 80 pg, the selenium provided by the selenocysteine is between about 20 pg and about 80 μg and the Momordica charantia is between about 100 mg and about 300 mg per unit dosage form. In an embodiment of this aspect, the selenium from high selenium yeast is at a ratio of 1:1, 1:2, 1:3 or 1:4 to the selenium from selenocysteine. In further embodiments, the selenium from selenocysteine is at a ratio of 1:2, 1:3 or 1:4 to the selenium from high selenium yeast.

[0015] In a fourth aspect, the present disclosure provides a composition comprising about 37.5 mg of high selenium yeast, which provides approximately 75 pg of selenium, about 174.5 pg of selenocysteine, which provides about 75 pg of selenium, about 400 mg of Silybum marianum and about 62 mg of lecithin per unit dosage form. In an embodiment the Silybum marianum is in the form of an extract. In an embodiment the selenium provided by the high selenium yeast is between about 30 pg and about 120 pg, the selenium provided by the selenocysteine is between about 30 pg and about 120 pg, the Silybum marianum is between about 200 mg and about 500 mg and the lecithin is between about 50 mg and about 100 mg per unit dosage form. In an embodiment of this aspect, the selenium from high selenium yeast is at a ratio of 1:1, 1:2, 1:3 or 1:4 to the selenium from selenocysteine. In further embodiments, the selenium from selenocysteine is at a ratio of 1:2, 1:3 or 1:4 to the selenium from high selenium yeast.

[0016] Compositions of the present disclosure are typically in a form suitable for oral administration. The composition may be a solid or liquid composition. In one embodiment, the composition may be in the form of a capsule, tablet or powder. The composition may be in the form of a beverage or food supplement.

[0017] Compositions of the present disclosure may be employed as nutritional supplements. Typically, compositions of the disclosure are administered as nutritional supplements to humans. The compositions may also be administered as an adjunct to one or more other treatments or therapies for a disease, such as cancer, diabetes or liver disease, or conditions associated therewith.

[0018] In a fifth aspect, the present disclosure provides the use of a high selenium yeast in combination with selenocysteine in the manufacture of a composition for treating or preventing DNA damage and/or for promoting DNA repair.

[0019] In an exemplary embodiment of this aspect, the composition comprises about 37.5 mg of high selenium yeast, which provides approximately 75 pg of selenium, and about 174.5 pg of selenocysteine, which provides approximately 75 pg of selenium, per unit dosage form.

[0020] In an embodiment, the selenium provided by the high selenium yeast is between about 30 pg and about 120 pg and the selenium provided by the selenocysteine is between about 30 pg and about 120 pg per unit dosage form.

[0021] In an embodiment, the composition promotes DNA repair and may treat or prevent conditions associated with DNA damage, for example through the production of selenoproteins that may have antioxidant effects or be useful in DNA repair.

[0022] In a sixth aspect the present disclosure provides the use of a high selenium yeast in combination with selenocysteine and a Momordica charantia extract in the manufacture of a composition for treating or preventing diabetes, or for reducing blood glucose levels.

[0023] In particular embodiments, the composition may treat or prevent elevated blood glucose levels, promote normal glucose homeostasis and/or prevent conditions associated with diabetes, such as diabetic ketoacidosis, heart disease, stroke, kidney failure and diabetic neuropathy.

[0024] In an exemplary embodiment, the composition comprises about 25 mg of high selenium yeast, which provides approximately 50 pg of selenium, about 116 pg of selenocysteine, which provides about 50 pg of selenium, and about 300 mg of Momordica charantia extract per unit dosage form.

[0025] In a seventh aspect the present disclosure provides the use of a high selenium yeast in combination with selenocysteine, a Silybum marianum extract and lecithin in the manufacture of a composition for use in liver protection or for the treatment or prevention of conditions associated with abnormal liver function.

[0026] In particular embodiments, the compositions promote liver protection by promoting normal liver function. In other particular embodiments the compositions treat or prevent diseases associated with abnormal liver function, such as liver fibrosis, cirrhosis, biliary disease, cholelithiasis, cholesystitis, hepatitis, hemochromatosis, glycogen storage abnormalities and steatohepatitis.

[0027] In an exemplary embodiment, the composition comprises about 37.5 mg of high selenium yeast, which provides approximately 75 pg of selenium, about 174.5 pg of selenocysteine, which provides about 75 pg of selenium, about 400 mg of Silybum marianum extract and about 62 mg of lecithin per unit dosage form.

[0028] Also provided herein in an eighth aspect of the present disclosure, is a method of treating or preventing a disease or condition by administering an effective amount of a composition as defined in any one of the first to the seventh aspects. In an embodiment, the disease or condition is associated with DNA damage, diabetes or liver disease. A particular embodiment provides a method for promoting DNA repair, for treating or preventing DNA damage, or for treating or preventing a condition associated with DNA damage by administering to a subj ect a composition of the first, second or fifth aspects. A particular embodiment provides a method for treating or preventing diabetes, or for reducing blood glucose levels by administering to a subject a composition of the first, third or sixth aspects. Another particular embodiment provides a method for promoting liver protection or for treating or preventing diseases associated with abnormal liver function by administering to a subject a composition of the first, fourth or seventh aspects.

Detailed Description of the Disclosure [0029] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, typical methods and materials are described.

[0030] The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0031] In the context of this specification, the term "about" is understood to refer to a range of numbers that a person of skill in the art would consider equivalent to the recited value in the context of achieving the same function or result.

[0032] Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0033] The term "optionally" is used herein to mean that the subsequently described feature may or may not be present or that the subsequently described event or circumstance may or may not occur. Hence the specification will be understood to include and encompass embodiments in which the feature is present and embodiments in which the feature is not present, and embodiments in which the event or circumstance occurs as well as embodiments in which it does not.

[0034] In the context of this specification, the term "associated with" means a condition, illness or disorder that is caused by, results from or is otherwise characteristic of or associated with DNA damage or with abnormal liver function.

[0035] The term "subject" as used herein refers to any mammal, including, but not limited to, livestock and other farm animals (such as cattle, goats, sheep, horses, pigs and chickens), performance animals (such as racehorses), companion animals (such as cats and dogs), laboratory test animals and humans. Typically the subject is a human.

[0036] As used herein, the term "effective amount" refers to an amount of an active agent, such as selenium, that is sufficient to effect one or more beneficial or desired outcomes. An “effective amount” can be provided in one or more administrations. The exact amount required will vary depending on factors such as the subject being treated, the age and general health of the subject, and the form in which the composition is administered. Thus, it is not possible to specify an exact “effective amount”. However, for any given case, an appropriate “effective amount” may be determined by one of ordinary skill in the art using only routine experimentation.

[0037] As used herein the term “extract” refers to a preparation comprising a plant or plant part or derived from a plant or plant part. Thus, in one embodiment, an extract may comprise one or more plant parts (such as, for example, roots, shoots, leaves, flowers, seeds etc.), while in another embodiment, an extract may be obtained by a process of “extraction” from one or more plant parts (such as, for example, roots, shoots, leaves, flowers, seeds etc.), which process will be understood by those skilled in the art as, in general terms, comprising treating plant material with a solvent, a liquid, or a supercritical fluid to dissolve the preparation and separate the same from residual unwanted plant material. An extract may be in liquid form (for example as a decoction, solution, infusion or tincture) or solid form (for example as a powder or granules).

[0038] In the context of this specification, the terms "promote" and "promoting" and variations thereof as used herein refer to the ability of a composition of the present disclosure to achieve or assist in achieving a benefit, either directly or indirectly, in relation to DNA repair, blood glucose levels, insulin production, insulin resistance, diabetes symptoms, liver function, liver glucose synthesis or storage, liver hormone production, storage of fat in the liver, or to improve the ability to achieve or assist in achieving a measurable benefit, either directly or indirectly, in relation to one or more of these parameters. Thus the terms "promote" and "promoting" and the like are to be considered in their broadest context.

[0039] As used herein the terms "treating", “treatment”, "preventing" and "prevention" refer to any and all uses which remedy a condition or symptom, prevent the establishment of a condition or symptom, otherwise prevent, hinder, retard, or reverse the progression of a condition or symptom in any way whatsoever, or improve a condition or symptom. Thus the terms "treating" and "preventing" and the like are to be considered in their broadest context. For example, treatment does not necessarily imply that the subject is treated until total recovery. In conditions which display or are characterized by multiple symptoms, the treatment or prevention need not necessarily remedy, prevent, hinder, retard, or reverse all of said symptoms, but may prevent, hinder, retard, or reverse one or more of said symptoms. The term "protection" refers herein to maintaining a healthy state and preventing disease or deterioration of function. For example "liver protection" herein refers to maintaining a healthy state, such as promoting normal glycogen storage and gluconeogenesis, and preventing disease or deterioration of normal liver function.

[0040] Provided herein for the first time are compositions comprising a combination of a high selenium yeast and selenocysteine. Selenocysteine can be reduced to hydrogen selenide and converted to selenophosphate, contributing to the production of selenoproteins. In particular embodiments of the present disclosure the selenocysteine is present in the compositions in the form of L-Se-methylselenocysteine. L-Se-methylselenocysteine is readily converted to selenocysteine in vivo body and has the same functions as selenocysteine. However the use of L-Se-methylselenocysteine offers advantages, including a higher stability and resistance to oxidation at room temperature, making it particularly suitable for manufacturing. In the disclosure hereinbelow reference is made to generally to selenocysteine, and while those skilled in the art will appreciate that the scope of the disclosure encompasses selenocysteine in a number of forms, a particularly preferred embodiment of the disclosure makes use of L-Se-methylselenocysteine and reference below to selenocysteine can be interpreted as reference to L-Se-methylselenocysteine.

[0041] The compositions may optionally further comprise one or more of Momordica charantia, Silybum marianum and lecithin.

[0042] In embodiments of the present disclosure, the high selenium yeast contains approximately 80% selenomethionine and a small amount of selenocysteine, plus selenium nucleic acids, selenium polysaccharides and selenium polypeptides. This is combined with a high supplemental dose of selenocysteine. The active centres of at least 25 selenoproteins, which have been found in humans or animals, contain selenocysteine. In particular embodiments, each dose of a composition of the present disclosure provides approximately 150 μg, close to the midrange of the World Health Organization recommendations for a desired dose of 60-400 μg selenium per day for the adult population. Compositions of the present disclosure are therefore suitable for a wide range of human populations. By contrast, prior art products which contain only selenomethionine are not suitable for all people, for example those with certain metabolic disorders liver-related illnesses.

[0043] In exemplary embodiments, the high selenium yeast comprises Saccharomyces cerevisiae. In a particular embodiment, the yeast, preferably Saccharomyces cerevisiae, is grown in a selenium enriched medium and produces selenomethionine, used in protein production in the yeast.

[0044] The amounts of high selenium yeast included in compositions disclosed herein may depend on a variety of factors including the identity and number of individual strains employed and the form in which the composition is to be administered. By way of example only, the high selenium yeast may be present in the composition in an amount from about 10 mg to about 60 mg per unit dosage form (comprising from about 20 pg to about 120 pg per unit dosage form of selenium to the composition). For example, the composition may comprise about 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 45 mg, 50 mg, 55 mg or 60 mg of high selenium yeast per unit dosage form. Exemplary compositions comprise about 25 mg or about 37.5 mg high selenium yeast per unit dosage form.

[0045] Compositions of the present disclosure may comprise selenocysteine in an amount from about 100 pg to about 200 pg per unit dosage form. For example, the composition may comprise about 100 pg, 105 pg, 110 pg, 115 pg, 120 pg, 125 pg, 130 pg, 135 pg, 140 pg, 145 pg, 150 pg, 155 pg, 160 pg, 165 pg, 170 pg, 175 pg, 180 pg, 185 pg, 190 pg, 195 pg or 200 pg selenocysteine per unit dosage form. Exemplary compositions comprise about 116 pg or about 174.5 pg selenocysteine per unit dosage form.

[0046] In particular embodiments of the present disclosure, the composition comprises high selenium yeast that contributes between about 20 pg and about 120 pg of selenium per unit dosage form, for example, about 20 pg, 25 pg, 30 pg, 35 pg, 40 pg, 45 pg, 50 pg, 55 pg, 60 pg, 65 pg, 70 pg, 75 pg, 80 pg, 85 pg, 90 pg, 95 pg, 100 pg, 105 pg, 110 pg, 115 pg or 120 pg of selenium per unit dosage form. In particular embodiments, the composition comprises selenocysteine that contributes between about 20 pg and about 120 pg of selenium per unit dosage form, for example, about 20 pg, 25 pg, 30 pg, 35 pg, 40 pg, 45 pg, 50 pg, 55 pg, 60 pg, 65 pg, 70 pg, 75 pg, 80 pg, 85 pg, 90 pg, 95 pg, 100 pg, 105 pg, 110 pg, 115 pg or 120 pg of selenium per unit dosage form.

[0047] In exemplary embodiments, the composition may comprise about 120 pg selenium from high selenium yeast and about 30 pg selenium from selenocysteine, about 112.5 pg selenium from high selenium yeast and about 37.5 pg selenium from selenocysteine, about 100 pg selenium from high selenium yeast and about 50 pg selenium from selenocysteine, about 75 pg selenium from high selenium yeast and about 75 pg selenium from selenocysteine, about 50 pg selenium from high selenium yeast and about 100 pg selenium from selenocysteine, about 37.5 pg selenium from high selenium yeast and about 112.5 pg selenium from selenocysteine or about 30 pg selenium from high selenium yeast and about 120 pg selenium from selenocysteine, per unit dosage form.

[0048] In other exemplary embodiments, the composition may comprise about 20 pg selenium from high selenium yeast and about 80 pg selenium from selenocysteine, about 25 pg selenium from high selenium yeast and about 75 pg selenium from selenocysteine, about 33.3 pg selenium from high selenium yeast and about 66.7 pg selenium from selenocysteine, about 50 pg selenium from high selenium yeast and about 50 pg selenium from selenocysteine, about 80 pg selenium from high selenium yeast and about 20 pg selenium from selenocysteine, about 75 pg selenium from high selenium yeast and about 25 pg selenium from selenocysteine or about 66.7 pg selenium from high selenium yeast and about 33.3 pg selenium from selenocysteine, per unit dosage form.

[0049] In other exemplary embodiments, the composition may comprise about 30 pg selenium from high selenium yeast and about 120 pg selenium from selenocysteine, about 37.5 pg selenium from high selenium yeast and about 112.5 pg selenium from selenocysteine, about 50 pg selenium from high selenium yeast and about 100 pg selenium from selenocysteine, about 75 pg selenium from high selenium yeast and about 75 pg selenium from selenocysteine, about 100 pg selenium from high selenium yeast and about 50 pg selenium from selenocysteine, about 112.5 pg selenium from high selenium yeast and about 37.5 pg selenium from selenocysteine or about 120 pg selenium from high selenium yeast and about 30 pg selenium from selenocysteine, per unit dosage form.

[0050] In embodiments of the disclosure, the selenium from high selenium yeast is in a ratio of 1:1,1:2,1:3 or 1:4 with the selenium from selenocysteine. In further embodiments, the selenium from selenocysteine is in a ration of 1:2, 1:3 or 1:4 with the selenium from high selenium yeast.

[0051] Momordica charantia, also known as bitter melon, has a hypoglycemic effect when administered to a subject. In an embodiment of the present disclosure, the composition comprises Momordica charantia or an extract thereof. The Momordica charantia or extract thereof may be present in the composition at a dose between about 100 mg and about 300 mg per unit dosage form. For example, the composition may comprise about 100 mg, 120 mg, 140 mg, 160 mg, 180 mg, 200 mg, 220 mg, 240 mg, 260 mg, 280 mg 300 mg Momordica charantia or extract thereof per unit dosage form. In exemplary embodiments in which a composition of the present disclosure is formulated for reducing blood glucose levels or preventing or treating diabetes, the composition may comprise 300 mg Momordica charantia or extract thereof per unit dosage form.

[0052] Silyhum marianum, also known as milk thistle, promotes treatment of liver diseases, such as cirrhosis, jaundice and hepatitis. Silyhum marianum may also protect liver cells against toxins. In an embodiment of the present disclosure, the composition comprises Silyhum marianum or an extract thereof. The Silyhum marianum or extract thereof may be present in the composition at a dose of between about 200 mg and about 500 mg per unit dosage form. For example, the the composition may comprise about 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 450 mg, 475 mg, or 500 mg Silyhum marianum or extract thereof per unit dosage form. In exemplary embodiments in which a composition of the present disclosure is formulated for promoting liver protection or for the prevention or treatment of diseases associated with liver diseases, the composition may comprise 400 mg Silyhum marianum or extract thereof per unit dosage form.

[0053] The compositions of the present disclosure find use generally in promoting DNA repair or for the prevention or treatment of conditions associated with DNA damage in a subject; in the prevention or treatment of diabetes, for reducing blood glucose levels; for promoting liver function, or for the prevention or treatment of diseases associated with abnormal liver function.

[0054] As used herein, the term "DNA repair" may refer to any mechanisms within a cell that identify and correct damage or mutations to DNA molecules. DNA damage or mutations may occur due to processes such as production of reactive metabolic byproducts in the cell, free radical damage, ultraviolet damage, radiation damage, replication errors, thermal disruption, toxins, mutagens or viruses. DNA damage may result in chemical modification of the DNA bases. As referred to herein, DNA repair may include, but is not limited to photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, non-homologous end joining, microhomology-mediated end joining, homologous recombination, and translesion synthesis.

[0055] DNA damage can occur as a result of various insults, including the production of metabolic products such as reactive oxygen species, reactive nitrogen species, lipid peroxidation products, exposure to ultraviolet light, ionizing radiation and chemical agents. DNA damage can result from hydrolysis of chemical bonds within the DNA molecule which may contribute to ageing or cell death, or, if further errors are introduced in replication, mutations may be introduced which may alter the function of a gene or contribute to the development of cancer. In humans, it is estimated that in the order of 10 000 oxidative hits occur per cell daily (Ames et al 1993 PNAS 90:7915-22). Cells have DNA repair mechanisms to minimize the effect of DNA damage, such as excision repair mechanisms, base-pair alterations, and repair of DNA strand breaks. However, DNA repair may not be completely efficient and deficiencies in DNA repair may be associated with ageing and risk of cancer.

[0056] In the context of the present disclosure, DNA damage typically comprise mutations, damage caused by reactive metabolic byproducts in the cell, free radical damage, ultraviolet damage, radiation damage, replication errors, thermal disruption, or damage induced by toxins, mutagens or viruses. DNA repair may comprise mechanisms within a cell that identify and correct damage or mutations to DNA molecules.

[0057] Diabetes mellitus (diabetes) is characterised by high levels of glucose in the blood for a prolonged period. If the condition is not treated, diabetes can lead to several complications, such as diabetic ketoacidosis, heart disease, stroke, kidney failure, and diabetic neuropathy. Diabetes is associated with a lack of production of insulin or a lack of ability to respond to circulating insulin by promoting uptake and storage of glucose. Prevention and management of diabetes includes diet, exercise, maintaining a healthy weight range. Type I diabetes (wherein sufficient insulin is not produced) and some type II diabetes (wherein the condition develops from insulin resistance and progresses to non-production of insulin) can be managed by administering insulin, however this can lead to hypoglycaemia. Type II diabetes is usually managed with exercise weight loss and diet.

[0058] Diabetes is often associated with liver disease and it is possible that diabetes may contribute to, or result from, abnormal liver function. The functions of the liver include in glucose homeostasis in storage of glycogen, use of glucose, and production of glucose (gluconeogenesis). Other roles of the liver include detoxification of metabolites and ingested or other foreign substances in the blood, metabolism of plasma proteins and red blood cells, hormone production, excretion and production of bile for digestion and absorption of fats, cholesterol and vitamins. The liver plays a vital role in metabolism and homeostasis in the body and complications arising from liver disease may comprise fibrosis, cirrhosis, biliary disease, cholelithiasis, cholesystitis, hepatitis, hemochromatosis, glycogen storage abnormalities, steatohepatitis.

[0059] In some embodiments, the present disclosure provides the use of (i) a high selenium yeast in combination with (ii) selenocysteine in the manufacture of a composition for use in DNA repair or for the prevention or treatment of conditions associated with DNA damage in a subject. In such embodiments, the composition may comprise about 37.5 mg of high selenium yeast, which provides approximately 75 pg of selenium, and about 174.5 pg of selenocysteine, which provides about 75 pg of selenium per unit dosage form. The composition may therefore comprise a total of about 150 pg of selenium in one dosage of the composition, which is the Australian recommended daily dosage. In an embodiment the selenium provided by the high selenium yeast is between about 30 pg and about 120 pg and the selenium provided by the selenocysteine is between about 30 pg and about 120 pg per unit dosage form.

[0060] In further embodiments, the present disclosure provides the use of (i) a high selenium yeast in combination with (ii) selenocysteine and (iii) Momordica charantia, or an extract thereof, in the manufacture of a composition for use in prevention or treatment of diabetes, or for reducing blood glucose levels in a subject. In such embodiments, the composition may comprise about 25 mg of high selenium yeast, which provides approximately 50 pg of selenium, about 116 pg of selenocysteine, which provides about 50 pg of selenium, and about 300 mg of Momordica charantia or extract thereof per unit dosage form. In an embodiment the selenium provided by the high selenium yeast is between about 20 pg and about 80 pg, the selenium provided by the selenocysteine is between about 20 pg and about 80 pg and the Momordica charantia or extract thereof is present at between about 100 mg and about 300 mg per unit dosage form.

[0061] Further embodiments of the present disclosure comprises the use of (i) a high selenium yeast in combination with (ii) selenocysteine, (iii) Silyhum marianum, or an extract thereof, and (iv) lecithin in the manufacture of a composition for use in liver protection or for the prevention or treatment of diseases associated with abnormal liver function. In such embodiments, the composition may comprise about 37.5 mg of high selenium yeast, which provides approximately 75 μg of selenium, about 174.5 pg of selenocysteine, which provides about 75 pg of selenium, about 400 mg of Silybum marianum or extract thereof and about 62 mg of lecithin per unit dosage form. In an embodiment the selenium provided by the high selenium yeast is between about 30 pg and about 120 pg, the selenium provided by the selenocysteine is between about 30 pg and about 120 pg, the Silybum marianum or extract thereof is present at between about 200 mg and about 500 mg and the lecithin is between about 50 mg and about 100 mg per unit dosage form.

[0062] Compositions of the present disclosure may additionally include any suitable additives, carriers, additional therapeutic agents, bioavailability enhancers, side-effect suppressing components, diluents, buffers, flavouring agents, colouring agents, binders, preservatives or other ingredients that are not detrimental to the efficacy of the composition.

[0063] Compositions of the disclosure can be readily manufactured by those skilled in the art using known techniques and processes. For example, the yeast can be seeded from standard stock into a reactor and grown in media comprising selenium. Yeast material and selenocysteine and, optionally Momordica charantia ox Silybum marianum, or extracts thereof, and lecithin can then be blended with the carrier medium and the resulting mixture can be pressed into tablets, filled into foil pouches as a granular solid, or introduced into gelatin capsules as a particulate material.

[0064] Compositions of the present disclosure may be suitably formulated for oral administration, and may be prepared according to conventional methods well known in the pharmaceutical and nutraceutical industries, such as those described in Remington’s Pharmaceutical Handbook (Mack Publishing Co., NY, USA) using suitable excipients, diluents and fillers.

[0065] Compositions may be dried to form, for example, a powder, granules, capsules or tablets. For oral administration, the composition may then be mixed with a suitable volume of an aqueous medium, typically with agitation, to dissolve the components, or produce a suspension, suitable for ingestion. Thus, the compositions may be provided to a user in a powder form, which powder may then be added by the user to any type of aqueous medium (for example water or fruit juice) and consumed there after. Alternatively, the composition may be provided as a beverage, pre-mixed with an aqueous medium such as water. In another embodiment the compositions may be added in powder form by the user to any type to a food product and consumed there after. In another embodiment, the compositions may simply be consumed as a powder in the absence of a drink or additional food product.

[0066] For the various circumstances in which a composition of the present disclosure maybe administered, those skilled in the art will appreciate that the amount of the consumed, and the number of discreet consumptions per unit time will vary depending on the actual use to which the composition is put, the condition of the subject who will consume the composition, the subject's age, sex, weight and general health.

[0067] All publications mentioned in this specification are herein incorporated by reference. The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

[0068] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the disclosure without departing from the spirit or scope of the disclosure as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

[0069] The present disclosure will now be described with reference to the following specific examples, which should not be construed as in any way limiting the scope of the disclosure.

Examples

Example 1 - Formulation for DNA repair [0070] By way of example only a suitable composition for use in accordance with the present disclosure in relation to DNA repair is outlined below. The following is to be construed as merely an illustrative example of a composition and not as a limitation of the scope of the disclosure in any way.

Active Ingredient 1:

High selenium yeast (37.5 mg) - Equivalent: Selenium 75 pg Active Ingredient 2: L-Se-methylselenocysteine (174.5pg) - Equivalent: Selenium 75 pg

Total Selenium 150 μg (Australian recommend daily dose)

The composition is for administration of selenium in high selenium yeast between about 30 pg and about 120 pg, and/or selenium in L-Se-methylselenocysteine between about 30 pg and 120 pg per unit dosage form.

Ratio of ingredients

The composition is typically formulated with ratios of selenium from high selenium yeast and L-Se-methylselenocysteine as follows:

Option 1

Option 2

Example 2 -Formulation for reducing blood glucose levels [0071] By way of example only a suitable composition for use in accordance with the present disclosure in relation to lowering blood sugar is outlined below. The following is to be construed as merely an illustrative example of a composition and not as a limitation of the scope of the disclosure in any way.

Active Ingredient 1:

High selenium yeast (25 mg) - Equivalent: Selenium 50 pg

Active Ingredient 2: L-Se-methylselenocysteine (116 μg) - Equivalent: Selenium 50 qg

Active Ingredient 3:

Momordica charantia - 300mg

The composition is for administration of selenium in high selenium yeast between about 20 qg and about 80 qg, selenium in L-Se-methylselenocysteine between about 20 qg and about 80 qg and Momordica charantia between about lOOmg and about 300mg per unit dosage form.

Ratio of ingredients

The composition is typically formulated with ratios of selenium from high selenium yeast and L-Se-methylselenocysteine as follows:

Option 1

Option 2

Example 3 - Formulation for liver protection [0072] By way of example only a suitable composition for use in accordance with the present disclosure in relation to liver protection is outlined below. The following is to be construed as merely an illustrative example of a composition and not as a limitation of the scope of the disclosure in any way.

Active Ingredient 1:

High selenium yeast (37.5 mg) - Equivalent: Selenium 75 gg Active Ingredient 2: L-Se-methylselenocysteine (174.5 gg) - Equivalent: Selenium 75 gg

Active Ingredient 3:

Silybum marianum - 400mg

Active Ingredient 4:

Lecithin - 62 mg

The composition is for administration of selenium in high selenium yeast between about 30 gg and about 120 gg; selenium in L-Se-methylselenocysteine between about 30 gg and about 120 gg; Silybum marianum between about 200 mg and about 500 mg, and lecithin between about 50mg and about 100 mg per unit dosage form.

Ratio of ingredients

The composition is typically formulated with ratios of selenium from high selenium yeast and L-Se-methylselenocysteine as follows:

Option 1

Option 2

Claims (5)

1. Claims

   1. A composition comprising a combination of a high selenium yeast and selenocysteine, optionally further comprising one or more of Momordica charantia or an extract thereof, Silybum marianum or an extract thereof, and lecithin.
2. 2. A composition comprising about 37.5 mg of high selenium yeast, which provides about 75 pg of selenium, and about 174.5 pg of L-Se-methylselenocysteine, which provides about 75 pg of selenium, per unit dosage form.
3. 3. A composition comprising about 25 mg of high selenium yeast, which provides approximately 50 pg of selenium, about 116 pg of L-Se-methylselenocysteine, which provides about 50 pg of selenium, and about 300 mg of Momordica charantia or an extract thereof per unit dosage form.
4. 4. A composition comprising about 37.5 mg of high selenium yeast, which provides approximately 75 pg of selenium, about 174.5 pg of L-Se-methylselenocysteine, which provides about 75 pg of selenium, about 400 mg of Silybum marianum or an extract thereof and about 62 mg of lecithin per unit dosage form.
5. 5. Use of a high selenium yeast in combination with selenocysteine, optionally L-Se-methylselenocysteine, in the manufacture of a composition for treating or preventing DNA damage, promoting DNA repair, treating or preventing diabetes, reducing blood glucose levels, treating or preventing conditions associated with abnormal liver function, or in liver protection.