EP3160459A1 - New mineral composition - Google Patents

New mineral composition

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Publication number
EP3160459A1
EP3160459A1 EP15736059.5A EP15736059A EP3160459A1 EP 3160459 A1 EP3160459 A1 EP 3160459A1 EP 15736059 A EP15736059 A EP 15736059A EP 3160459 A1 EP3160459 A1 EP 3160459A1
Authority
EP
European Patent Office
Prior art keywords
mineral composition
magnesium
composition according
depression
taurine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP15736059.5A
Other languages
German (de)
French (fr)
Inventor
Eduard Antonius Joannes Arnoldussen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dedraf Holding BV
Original Assignee
Dedraf Holding BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dedraf Holding BV filed Critical Dedraf Holding BV
Publication of EP3160459A1 publication Critical patent/EP3160459A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the invention relates to the field of therapies for and prevention of mental disorders, more particularly therapies for depression, burn-out and cognitive disorders, and more specifically for a new mineral composition useful in such therapies.
  • depressive will have symptoms that may be considered to be a pre-stage of depression. Especially in the elderly, depression is often not recognized, but depression related suicide is manifest in aged people. Cognitive impairment is among the classic features of depression, such as e.g. major depressive disorder. Cognitive disorders may to some extent be secondary to depression in the sense that an improvement in the depressive state will also lead to an improvement of the cognitive impairment.
  • Depression is a condition which has links to may other conditions.
  • High blood pressure, high cholesterol levels, diabetes, osteoporosis, asthma, atherosclerosis, arthritis or cardiovascular diseases have a high comorbidity figure with depression.
  • all kinds of psychic disorders such as cognitive deficits, anxiety, ADHD, Alzheimer's disease, dementia and stress disorders are often found together with depression.
  • Magnesium deficiency will accelerate a vicious cycle and amplify the effects of chronic stress, leading to more anxiety, irritability, fatigue and insomnia— many of the symptoms of adrenal exhaustion— as well as to hypertension and heart pains— symptoms of heart disease.
  • Magnesium is utilized by the body for all sorts of detoxification pathways and is necessary for the neutralization of toxins, overly acidic conditions that arise in the body, and for protection from heavy metals. It plays a vital role in protecting us from the onslaught of man-made
  • Glutathione an antioxidant normally produced by the body and a detoxifier of mercury, lead and arsenic among others, requires magnesium for its synthesis.
  • a deficiency of magnesium increases free radical generation in the body and "causes glutathione loss, which is not affordable because glutathione helps to defend the body against damage from cigarette smoking, exposure to radiation, cancer chemotherapy, and toxins such as alcohol and just about everything else.
  • Serotonin the "feel good” hormone, requires magnesium in its delicate balance of release and reception by cells in the brain. Only when adequate levels are present can we enjoy mental and emotional equilibrium. A recent
  • the present inventors found that a mineral composition comprising magnesium glycinate, zinc glycinate and selenium methionine is effective in the prevention and/or treatment of depression and various other psychic and physiologic disorder.
  • the mineral composition further comprises a chromium compound, preferably as chromium picolinate or chromium nicotinate. More preferably, the composition also comprises taurine and even more preferably vitamin B6.
  • the mineral composition comprises > 200 mg
  • the composition also comprises > 0.2 mg chromium picolinate or > 0.2 mg chromium nicotinate and/or > 250 mg taurine, preferably the amount of magnesium glycinate is > 400 mg, more preferably >500 mg, while preferably the amount of zinc glycinate is >4 mg, more preferably >5 mg.
  • composition comprises minerals in the following amounts (+/- 5%, preferably +/- 1%): - magnesium glycinate 625 mg
  • the inventors have found that the mineral composition, when dosed in a therapeutic effective dose is effective for the prevention and/or treatment of depression and various other psychic and physiologic disorder.
  • the mineral compositions according to the present invention can be used in therapy of disorders such as cognitive impairment, depression, burn-out, ADHD, autism, memory loss, Alzheimer's disease, dementia, migraine, loss of IQ, craving for drugs or nicotine, post-menstrual syndrome or of post-traumatic stress disorder.
  • the mineral composition according to the present invention can also be used in the therapy of disorders such as diabetes, osteoporosis, fatigue, asthma, high blood pressure, allergic diseases such as hay fever, eczema, muscular spasm, conditions associated with high cholesterol levels, and heart and vascular diseases.
  • disorders such as diabetes, osteoporosis, fatigue, asthma, high blood pressure, allergic diseases such as hay fever, eczema, muscular spasm, conditions associated with high cholesterol levels, and heart and vascular diseases.
  • the mineral composition can be used in a method for treatment or prevention of cognitive impairment, depression, burn-out, ADHD, autism, memory loss, Alzheimer's disease, dementia, migraine, loss of IQ, craving for drugs or nicotine, post-menstrual syndrome or of post-traumatic stress disorder by treating a subject in need thereof with a mineral composition according to the present invention.
  • the mineral composition can be used in a method for treatment or prevention of diabetes, osteoporosis, fatigue, asthma, allergic diseases such as hay fever, eczema, muscular spasm, conditions associated with high cholesterol levels, and heart and vascular diseases, high blood pressure by treating a subject in need thereof with a mineral composition according to the present invention.
  • the effectiveness of the treatment or prevention according to the present invention can be determined by regularly measuring changes in biomarker values wherein said biomarkers are chosen from substance P, aldosterone, thromboxane, endothelin 1, EGF, vitamin D and telomerase. A full description of these markers can be found in PCT/NL2014/050054. Further biomarkers for use in such a method to determine the effectiveness of the treatment or prevention may be all enzymes that use Mg 2+ as a cofactor.
  • composition comprising specific salts of magnesium, chromium and selenium is effective in the prevention and/or treatment of depression and various other psychic and physiologic disorders.
  • magnesium is often provide in the form of magnesium oxide. It has been submitted that magnesium oxide is poorly absorbed by the body in contrast to e.g. magnesium citrate (Lindberg, J.S. et al., 1990, J. Am. Coll. Nutr. 9:48-55). The recommended dietary allowance for magnesium is 350 mg/day for a male adult and 280 mg/day for a female. However, for therapeutic purposes higher dosages are needed, but the therapeutic window for magnesium is wide and rarely side- effects of magnesium intoxication are found (Saris, N.-E. et al., 2000, Clin. Chim. Acta, 294: 1-26).
  • magnesium oxide In order to provide for a sufficient therapeutic dose, it is recommended not to use magnesium oxide. Therefor, in the present mineral composition the glycinate salt of magnesium is used. Because salts based on amino acids are much better-tolerated by the digestive system and do not have the side-effects of the older compounds used. Since magnesium glycinate is a relatively large molecule, it is not standardly included in multi-prep ar ations .
  • magnesium preparations seem to be a valuable addition to the pharmacological armamentarium for management of depression. Apart from being administered as components of dietary supplements, magnesium preparations also perceived as the effective agents in treatment of migraine, alcoholism, asthma, heart diseases, arrhythmias, renal calcium stones, premenstrual tension syndrome etc. Magnesium preparations have an essential place in homeopathy as a remedy for a range of mental health problems. (Serefko, A., et al., 2013, Pharmacol. Rep.
  • Zinc is an NMDA receptor antagonist and thus inhibits the transfer of stimuli and loss of magnesium. Zinc deficiency leads to decreased zinc in the nerve synapse, which results in an increase in the NMDA receptors. These receptors respond to glutamate, an excitatory neurotransmitter that can be responsible for toxic effects in the brain if there is too much. At the same time, the inhibitory (in this case, neuroprotective) neurotransmitter GABA is decreased, along with BDNF and another nerve growth factor, NGF. The glutamate level in the synapse is higher, so calcium mediated stimulation of the nerves is primed. This same mechanism is thought (in acute vs chronic and in differing areas of the brain) to be responsible for seizures, migraines, dementia, anxiety, depression, and bipolar disorder (and is why
  • GABA receptor modulators such as valium and anti-seizure medicines
  • zinc supplementation (together with normal medication of serotonin reuptake inhibitors) significantly improves the condition of patients with major depression (Ranibar, E., et al., 2013, Iran. J. Psychiatry 8:73-79).
  • Selenium methionine (or selenomethionine) also has been abundantly used in food supplements in order to achieve the daily
  • the mineral composition of the present invention may optionally comprise taurine and/or chromium picolinate.
  • the amino acid taurine is known for its many advantageous effects, especially on depression, anxiety, fatigue, etc. It generally is advocated as an anti-stress cure, because taurine calms the nervous system by
  • taurine By helping to raise GABA levels, taurine will allow the body to manage anxiety. Taurine is stored in the gallbladder in bile, and it helps the body digest food, particularly fats. Taurine helps the body metabolize fat, making it essential for energy production and a lean physique. But, it is also necessary for many aspects of health because "good" fats play a role in the health of every cell in the body. Partly because of this effect, taurine is a well known supplement for preventing diabetes and improving insulin sensitivity. Taurine makes the cells more sensitive to insulin binding and glucose uptake by multiple mechanisms. First, taurine has an anorexigenic effect on the hypothalamus gland, meaning that it minimizes feelings of hunger by improving energy production and metabolism.
  • taurine enhances the role of insulin in the control of food intake and helps stall body fat gain (Solon, C.S. et al., 2012, Amino Acids 42:2403- 2410). Because of the fact that insulin has a role in the storage of magnesium in the cell, addition of taurine enhances the effects of
  • Taurine has many other proven therapeutic effects: it is one of the main nutrients for the heart musculature and it could help against heart rhythm disorders. It has also been proved to be effective against high blood pressure by inhibiting the antidiuretic hormone. It is also one of the important components of the eye lens and retina.
  • taurine also facilitates the intracellular availability of magnesium and thus the therapeutic effects of magnesium.
  • the organism appears to stimulate taurine mobilization. This compensatory action is known to occur e.g. during migraine.
  • the taurine in the mineral composition of the present invention may also be present as the magnesium salt, i.e. as magnesium taurate.
  • Chromium picolinate is mainly provided to inhibit chromium deficiency, but it is also heavily used for its beneficial effects against insulin resistance, diabetes type II and metabolic syndrome.
  • Insulin resistance is a physiological condition in which cells fail to respond to the normal actions of the hormone insulin.
  • the picolinate salt is more effective to achieve absorption of chromium than other salts.
  • the picolinate salt may have some adverse effects (especially cancer promoting effects: Stearns, D.M. et al., 1995, FASEB J. 9: 1643-1648), and for this reason the use of the nicotinate salt of chromium has been proposed as an alternative, but this has not yet been tested as frequently as the picolinate salt.
  • Insulin resistance also has the effect that magnesium no longer can be stored in the cells. Accordingly, addition of chromium to the mineral composition of the invention has the effect that magnesium still can be taken up and stored in the cell.
  • the invention may also comprise mineral compositions where additional minerals, vitamins or salts have been added. Such additions are - of course - only beneficial if they do not interfere with the above indicated effects of magnesium, zinc, chromium, selenium and taurine. In this case, it should be repeated that it would not be advisable to increase calcium uptake (e.g. by addition of Ca-salts in the present mineral composition), because calcium negatively affects the uptake of magnesium and zinc.
  • treatment and “treating” refer to any and all uses which remedy a condition or disease or symptoms thereof, prevent the establishment of a condition or disease or symptoms thereof, or otherwise prevent or hinder or reverse the progression of a condition or disease or other undesirable symptoms in any way whatsoever.
  • the term "therapeutically effective amount” includes within its meaning a non-toxic amount of each of the indicated compounds, alone or in combination, sufficient to provide the desired therapeutic effect. The exact amount will vary from subject to subject depending on the age of the subject, their general health, the severity of the disorder being treated and the mode of administration. It is therefore not possible to specify an exact “therapeutically effective amount", however one skilled in the art would be capable of determining a
  • the present invention relates to a method for the treatment of depression and cognitive deficits or cognitive impairment, said method comprising the administration of a mineral composition of the present invention to a patient in need thereof.
  • Cognitive deficits include a decline in cognitive functions or cognitive domains, e.g. working memory, attention and vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving e.g. executive function, speed of processing and/or social cognition.
  • cognitive deficits or cognitive impairment may indicate deficits in attention, disorganized thinking, slow thinking, difficulty in understanding, poor concentration, impairment of problem solving, poor memory, difficulties in expressing thoughts and/or difficulties in integrating thoughts, feelings and behavior, or difficulties in extinction of irrelevant thoughts.
  • cognitive deficits and
  • Cognitive impairment are intended to indicate the same and are used interchangeably. Cognitive impairment is a particularly important consideration in the elderly. Cognitive impairment normally increases with age, and further with depression.
  • the patient to be treated for cognitive impairment is elderly, and in particular elderly with depression.
  • next to patients suffering from psychological disorders, such as depression, and/or cognitive disorders also patients suffering from various physiological diseases may benefit of treatment with the mineral composition according to the invention.
  • diseases are diabetes, insulin resistance, osteoporosis, vascular diseases, high blood pressure, rheumatoid arthritis, muscular spasms, fatigue, premenstrual stress syndrome, allergic rhinitis, eczema, allergic diseases, such as hay fever, COPD and asthma.
  • the mineral composition of the present invention may be administered in any acceptable way. Preferably, administration is dealt with orally or topically,
  • compositions may be packed in e.g. gelatin capsules or may be tableted in the form of tablets or may be given in liquid compositions.
  • active compound may be administered with excipients and e.g. used in the form of powders, sachets, tablets, pills, pastilles or capsules.
  • compositions may be prepared by conventional means with
  • binding agents e.g., binding agents
  • pregelatinised maize starch tragacanth gum, gelatine, polyvinylpyrrolidone or hydroxypropyl methylcellulose
  • fillers e.g. lactose, microcrystalline cellulose, mannitol or calcium hydrogen phosphate
  • lubricants e.g.
  • Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g.
  • sorbitol syrup cellulose derivatives or hydrogenated edible fats
  • emulsifying agents e.g. lecithin or acacia
  • non- aqueous vehicles e.g.
  • preparations may also contain buffer salts, flavoring, coloring and sweetening agents as appropriate.
  • Preparations for oral administration may be suitably formulated to give controlled release of the active compound.
  • compositions may take the form of tablets or lozenges formulated in conventional manner.
  • compositions may be in the form of dispersions (solutions, suspensions) in an aqueous or oil solution or dispersed into an emulsion, wherein said emulsion may be water-in-oil, oil- in-water or any double emulsion.
  • the formulation may take the form of an oil, a creme, an ointment, a lotion, a paste, a gel, a jelly, a foam, a spray, a (dermal) patch,
  • formulatory agents such as suspending, stabilizing and/or dispersing agents.
  • the active ingredient may be in powder form for constitution with a suitable vehicle, e.g. sterile pyrogen-free water, before use.
  • the capsule When dosing is in the form of a capsule, the capsule may comprise apart from the elements mentioned above a liquid carrier such as an oil. Dosage form may further be provided with coatings of sugar, shellac or other agents.
  • the components of the pharmaceutical composition are preferably chosen such that they do not reduce the desired working of the active compound.
  • compositions can further comprise flavoring sweetening, coloring and/or preservative agents.
  • a mineral composition according to the invention or a
  • pharmaceutically acceptable salt thereof may also be administered in the form of e.g. an elixir, a suspension, a syrup, a waffle or a chewing gum.
  • the total of active minerals and further therapeutically active compounds, such as the amino acid taurine will be present in an amount of from 0.01 to 99.9 % by weight, preferably from 10 to 90 wt.%, and more preferably from 30 to 80 wt.%.
  • the present invention further relates to a method for the preparation of a mineral composition for use as medicament, comprising processing or incorporating a mineral composition according to the invention, as an active substance, together with a pharmaceutically acceptable carrier in a pharmaceutical composition.
  • the preparation of a pharmaceutical composition may very suitably occur by mixing all separate ingredients such as fillers, binders, lubricants and optionally other excipients together with one or more of the minerals and /or taurine, and processing the mixture obtained to a pharmaceutical preparation.
  • PCT/NL2014/050054 may be used. In order to obtain a good overview of the improvement of the depression over the treatment time a regular assay as described in PCT/NL2014/050054 should be performed.
  • Monitoring of the treatment of cognitive disorders may be performed by regularly performing questionnaires as are described in the DSM manual, or by using the Alzheimer Questionnaire (Malek-Ahmadi, M. et al., 2012, Age Ageing 41:396-399) or other comparable diagnostic systems (such as the 4-item Abbreviated Mental Test described in. Schofield, I. et al., 2010, Eur. J. Emerg. Med. 17:340-342).
  • pharmaceutically acceptable carriers can be either solid or liquid.
  • Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules.
  • a solid carrier can be one or more substances which may also act as diluents, flavouring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.
  • the carrier is a finely divided solid which is in a mixture with the finely divided active component.
  • the active component is mixed with the carrier having the necessary binding capacity in suitable proportions and compacted in the shape and size desired.
  • the powders and tablets preferably contain from five or ten to about seventy percent of the active compound.
  • Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like.
  • the term "preparation” is intended to include the formulation of the active compound with encapsulating material as carrier providing a capsule in which the active component, with or without carriers, is surrounded by a carrier, which is thus in association with it.
  • cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid forms suitable for oral administration.
  • Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water-propylene glycol solutions.
  • the compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilising and/or dispersing agents.
  • the active ingredient may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilisation from solution, for constitution with a suitable vehicle, e.g. sterile, pyrogen-free water, before use.
  • Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavours, stabilizing and thickening agents, as desired.
  • Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium
  • liquid form preparations which are intended to be converted, shortly before use, to liquid form preparations for oral administration.
  • liquid forms include solutions, suspensions, and emulsions.
  • preparations may contain, in addition to the active component, colorants, flavours, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.
  • the pharmaceutical preparations are preferably in unit dosage forms.
  • the preparation is subdivided into unit doses containing appropriate quantities of the active component.
  • the unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules.
  • the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.
  • magnesium glycinate >200 mg, pref. >400 mg, more pref. >500 mg zinc glycinate > 2 mg, pref. >4 mg, more pref. >5 mg
  • composition may also additionally comprises
  • taurine 300 mg The amounts here are indications and may differ + or - 5%, more preferably +/- 1%.
  • composition as defined above may additionally comprise magnesium stearate as lubricant > 5mg and silicium dioxide as anticoagulant > 5 mg.
  • Example 1 Preparation of a mineral composition.
  • silicium dioxide as SYLOID® AL-1 FP from W.R. Crace&Co.-Conn
  • Chromium picolinate (minimally 12% chromium) 6.1
  • Zinc Glycinate Chelate (minimally 20% Zn) 8.3 Selenomethionine (5000 pg/g Se) 1.8
  • Crystalline microcellulose (Microcel MCC 101) 531.7
  • the tablets were coated in a normal tablet coating machine (FC 39 from NR Group, 97200 tablets per batch) with the following composition (amounts average per tablet):
  • depression may be treated by oral administration of the mineral composition.

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Abstract

The invention relates to the field of therapies for and prevention of mental disorders, more particularly therapies for depression, burn-out and cognitive disorders. Specifically, the invention relates to a new mineral composition comprising magnesium glycinate, zinc glycinate and selenium methionine, possibly combined with chromium picolinate, taurine and/or vitamin B6, useful in such therapies.

Description

Title: New mineral composition
FIELD OF THE INVENTION
The invention relates to the field of therapies for and prevention of mental disorders, more particularly therapies for depression, burn-out and cognitive disorders, and more specifically for a new mineral composition useful in such therapies. BACKGROUND
Depression is a highly abundant condition in the current society. Next to that, also many people that are officially not diagnosed as
depressive will have symptoms that may be considered to be a pre-stage of depression. Especially in the elderly, depression is often not recognized, but depression related suicide is manifest in aged people. Cognitive impairment is among the classic features of depression, such as e.g. major depressive disorder. Cognitive disorders may to some extent be secondary to depression in the sense that an improvement in the depressive state will also lead to an improvement of the cognitive impairment.
Depression is a condition which has links to may other conditions.
High blood pressure, high cholesterol levels, diabetes, osteoporosis, asthma, atherosclerosis, arthritis or cardiovascular diseases have a high comorbidity figure with depression. Further, all kinds of psychic disorders, such as cognitive deficits, anxiety, ADHD, Alzheimer's disease, dementia and stress disorders are often found together with depression.
One of the theories is that stress underlies the development of depression. One of the phenomena in stress is that cells get depleted of magnesium. A first reason that magnesium leaves the cell is because of the action of epinephrine, which is one of the hormones that is overproduced in stress situations. Mental and physical stress, with its related continuous flow of adrenaline, uses up magnesium rapidly, as adrenaline affects heart rate, blood pressure, vascular constriction and muscle contraction— actions that all demand steady supplies of magnesium for smooth function. The nervous system depends upon sufficient magnesium for its calming effects, including restful sleep. Hibernating animals, by the way, maintain very high levels of magnesium. Magnesium deficiency will accelerate a vicious cycle and amplify the effects of chronic stress, leading to more anxiety, irritability, fatigue and insomnia— many of the symptoms of adrenal exhaustion— as well as to hypertension and heart pains— symptoms of heart disease.
A second reason is because of the stress that is related to our modern feeding habits and our pharmaceutical usage. We consume too much sugars, coffee, alcohol, dairy products, and certain pharmaceuticals as specified in the book "Magnesium muggers" from Suzy Cohen. With these modern foods and pharmaceuticals, the intracellular magnesium stores are getting depleted.
Magnesium is utilized by the body for all sorts of detoxification pathways and is necessary for the neutralization of toxins, overly acidic conditions that arise in the body, and for protection from heavy metals. It plays a vital role in protecting us from the onslaught of man-made
chemicals all around us. Glutathione, an antioxidant normally produced by the body and a detoxifier of mercury, lead and arsenic among others, requires magnesium for its synthesis. A deficiency of magnesium increases free radical generation in the body and "causes glutathione loss, which is not affordable because glutathione helps to defend the body against damage from cigarette smoking, exposure to radiation, cancer chemotherapy, and toxins such as alcohol and just about everything else.
When our bodies are replete with magnesium (and in balance with the other essential minerals) we are protected from heavy metal deposition and the development of associated neurological diseases. Research indicates that ample magnesium will protect brain cells from the damaging effects of aluminum, beryllium, cadmium, lead, mercury and nickel. We also know that low levels of brain magnesium contribute to the deposition of heavy metals in the brain that heralds Parkinson's and Alzheimer's. It appears that the metals compete with magnesium for entry into the brain cells.
Depression is related to stress and magnesium deficiency as well. Serotonin, the "feel good" hormone, requires magnesium in its delicate balance of release and reception by cells in the brain. Only when adequate levels are present can we enjoy mental and emotional equilibrium. A recent
Norwegian study showed a relation between a magnesium deficit and depression relating to food habits (Jacka, F.N. et al., 2009, Aust N Z J Psychiatry. 43(l):45-52).
Accordingly, there is a need for a simple, cheap and therapeutically effective treatment for preventing or treating depression and many of the psychic and physiologic disorders that are found together with depression.
SUMMARY OF THE INVENTION
The present inventors found that a mineral composition comprising magnesium glycinate, zinc glycinate and selenium methionine is effective in the prevention and/or treatment of depression and various other psychic and physiologic disorder.
Preferably, the mineral composition further comprises a chromium compound, preferably as chromium picolinate or chromium nicotinate. More preferably, the composition also comprises taurine and even more preferably vitamin B6.
Preferably, the mineral composition comprises > 200 mg
magnesium glycinate, > 2 mg zinc glycinate and >1 selenium methionine. More preferably, the composition also comprises > 0.2 mg chromium picolinate or > 0.2 mg chromium nicotinate and/or > 250 mg taurine, preferably the amount of magnesium glycinate is > 400 mg, more preferably >500 mg, while preferably the amount of zinc glycinate is >4 mg, more preferably >5 mg.
In a preferred embodiment of the present invention the composition comprises minerals in the following amounts (+/- 5%, preferably +/- 1%): - magnesium glycinate 625 mg
- zinc glycinate 8.3 mg
- selenium methionine 1.8 mg
- chromium picolinate 0.06 mg
- taurine 300 mg.
The inventors have found that the mineral composition, when dosed in a therapeutic effective dose is effective for the prevention and/or treatment of depression and various other psychic and physiologic disorder.
In particular, it was found that the mineral compositions according to the present invention can be used in therapy of disorders such as cognitive impairment, depression, burn-out, ADHD, autism, memory loss, Alzheimer's disease, dementia, migraine, loss of IQ, craving for drugs or nicotine, post-menstrual syndrome or of post-traumatic stress disorder.
Moreover, the mineral composition according to the present invention can also be used in the therapy of disorders such as diabetes, osteoporosis, fatigue, asthma, high blood pressure, allergic diseases such as hay fever, eczema, muscular spasm, conditions associated with high cholesterol levels, and heart and vascular diseases.
In a further aspect of the present invention, it was found that the mineral composition can be used in a method for treatment or prevention of cognitive impairment, depression, burn-out, ADHD, autism, memory loss, Alzheimer's disease, dementia, migraine, loss of IQ, craving for drugs or nicotine, post-menstrual syndrome or of post-traumatic stress disorder by treating a subject in need thereof with a mineral composition according to the present invention. In another embodiment, the mineral composition can be used in a method for treatment or prevention of diabetes, osteoporosis, fatigue, asthma, allergic diseases such as hay fever, eczema, muscular spasm, conditions associated with high cholesterol levels, and heart and vascular diseases, high blood pressure by treating a subject in need thereof with a mineral composition according to the present invention.
In a further aspect of the present invention, it was found that the effectiveness of the treatment or prevention according to the present invention can be determined by regularly measuring changes in biomarker values wherein said biomarkers are chosen from substance P, aldosterone, thromboxane, endothelin 1, EGF, vitamin D and telomerase. A full description of these markers can be found in PCT/NL2014/050054. Further biomarkers for use in such a method to determine the effectiveness of the treatment or prevention may be all enzymes that use Mg2+ as a cofactor.
DETAILED DESCRIPTION
The present inventors now found that a composition comprising specific salts of magnesium, chromium and selenium is effective in the prevention and/or treatment of depression and various other psychic and physiologic disorders.
Of course, a combination of these minerals is known in the art. However, such a combination, often provided in the form of or as part of a multi-preparation, wherein said multi-preparation contains a large a number of minerals and vitamins, provides for a lower amount of the minerals, since these multi-preparations are meant as an additive to the normal diet. Thus, in those cases, the components of the multi-preparation are not given for therapeutic purposes, but just to provide a sufficient amount of these ingredients, the so-called recommended daily intake.
One of the main ingredients of the present mineral composition is magnesium. In traditional mineral compositions magnesium is often provide in the form of magnesium oxide. It has been submitted that magnesium oxide is poorly absorbed by the body in contrast to e.g. magnesium citrate (Lindberg, J.S. et al., 1990, J. Am. Coll. Nutr. 9:48-55). The recommended dietary allowance for magnesium is 350 mg/day for a male adult and 280 mg/day for a female. However, for therapeutic purposes higher dosages are needed, but the therapeutic window for magnesium is wide and rarely side- effects of magnesium intoxication are found (Saris, N.-E. et al., 2000, Clin. Chim. Acta, 294: 1-26). In order to provide for a sufficient therapeutic dose, it is recommended not to use magnesium oxide. Therefor, in the present mineral composition the glycinate salt of magnesium is used. Because salts based on amino acids are much better-tolerated by the digestive system and do not have the side-effects of the older compounds used. Since magnesium glycinate is a relatively large molecule, it is not standardly included in multi-prep ar ations .
Clinical aspects of magnesium have been extensively described (see e.g. Saris et al., supra) and it forms part of many therapeutic compositions. The first information on the beneficial effect of magnesium sulfate given hypodermically to patients with agitated depression was published almost 100 years ago. Numerous pre-clinical and clinical studies confirmed the initial observations as well as demonstrated the beneficial safety profile of magnesium supplementation. Nevertheless, the mechanisms of
antidepressant action of magnesium are not fully understood yet. From a practical point of view, however, magnesium preparations seem to be a valuable addition to the pharmacological armamentarium for management of depression. Apart from being administered as components of dietary supplements, magnesium preparations also perceived as the effective agents in treatment of migraine, alcoholism, asthma, heart diseases, arrhythmias, renal calcium stones, premenstrual tension syndrome etc. Magnesium preparations have an essential place in homeopathy as a remedy for a range of mental health problems. (Serefko, A., et al., 2013, Pharmacol. Rep.
65:547-554). .
For zinc a similar argument can be developed. Again, zinc oxide is poorly taken up by the body and zinc glycinate is an excellent source to provide the necessary amount of zinc.
Zinc is an NMDA receptor antagonist and thus inhibits the transfer of stimuli and loss of magnesium. Zinc deficiency leads to decreased zinc in the nerve synapse, which results in an increase in the NMDA receptors. These receptors respond to glutamate, an excitatory neurotransmitter that can be responsible for toxic effects in the brain if there is too much. At the same time, the inhibitory (in this case, neuroprotective) neurotransmitter GABA is decreased, along with BDNF and another nerve growth factor, NGF. The glutamate level in the synapse is higher, so calcium mediated stimulation of the nerves is primed. This same mechanism is thought (in acute vs chronic and in differing areas of the brain) to be responsible for seizures, migraines, dementia, anxiety, depression, and bipolar disorder (and is why
pharmaceutical GABA receptor modulators, such as valium and anti-seizure medicines, can be effective for certain symptoms of any of those conditions). Recently, it has been reported that zinc supplementation (together with normal medication of serotonin reuptake inhibitors) significantly improves the condition of patients with major depression (Ranibar, E., et al., 2013, Iran. J. Psychiatry 8:73-79). Selenium methionine (or selenomethionine) also has been abundantly used in food supplements in order to achieve the daily
recommended dose of selenium. Selenomethionine proves to be taken up better than several forms of inorganic selenium.
No clear effects of selenium supplementation with respect to therapy in depression have been reported. It has, however, been reported that selenium levels in frail elderly people were significantly related to the occurrence of depression and anxiety disorders, but supplementation gave only limited beneficial effects (Gosney, M.A. et al., 2008, Gerontology
54:292-299). A more recent study suggests a link of selenium levels with cognitive impairment rather than depression (Gao, S. et al., 2012, BMC Psychiatry 12:72-79). However, the main purpose of including selenium in the present mineral composition is because selenium improves the uptake and storage of magnesium (and probably also zinc) in the body (Howard, J.M. et al., 1994, Magnesium Res. 7:49-57).
The mineral composition of the present invention may optionally comprise taurine and/or chromium picolinate.
The amino acid taurine is known for its many advantageous effects, especially on depression, anxiety, fatigue, etc. It generally is advocated as an anti-stress cure, because taurine calms the nervous system by
facilitating the production of the neurotransmitter GABA. By helping to raise GABA levels, taurine will allow the body to manage anxiety. Taurine is stored in the gallbladder in bile, and it helps the body digest food, particularly fats. Taurine helps the body metabolize fat, making it essential for energy production and a lean physique. But, it is also necessary for many aspects of health because "good" fats play a role in the health of every cell in the body. Partly because of this effect, taurine is a well known supplement for preventing diabetes and improving insulin sensitivity. Taurine makes the cells more sensitive to insulin binding and glucose uptake by multiple mechanisms. First, taurine has an anorexigenic effect on the hypothalamus gland, meaning that it minimizes feelings of hunger by improving energy production and metabolism. A recent study found that the anorexigenic action of taurine enhances the role of insulin in the control of food intake and helps stall body fat gain (Solon, C.S. et al., 2012, Amino Acids 42:2403- 2410). Because of the fact that insulin has a role in the storage of magnesium in the cell, addition of taurine enhances the effects of
magnesium.
Taurine has many other proven therapeutic effects: it is one of the main nutrients for the heart musculature and it could help against heart rhythm disorders. It has also been proved to be effective against high blood pressure by inhibiting the antidiuretic hormone. It is also one of the important components of the eye lens and retina.
However, next to its intrinsic actions, taurine also facilitates the intracellular availability of magnesium and thus the therapeutic effects of magnesium. In the course of a magnesium deficit, the organism appears to stimulate taurine mobilization. This compensatory action is known to occur e.g. during migraine.
It may even be that the above mentioned beneficial effects of taurine are mostly exerted through the effects of taurine on the intracellular magnesium concentration.
The taurine in the mineral composition of the present invention may also be present as the magnesium salt, i.e. as magnesium taurate.
Chromium picolinate is mainly provided to inhibit chromium deficiency, but it is also heavily used for its beneficial effects against insulin resistance, diabetes type II and metabolic syndrome. Insulin resistance is a physiological condition in which cells fail to respond to the normal actions of the hormone insulin. Here again the picolinate salt is more effective to achieve absorption of chromium than other salts. However, it has been proposed in the past that in high doses the picolinate salt may have some adverse effects (especially cancer promoting effects: Stearns, D.M. et al., 1995, FASEB J. 9: 1643-1648), and for this reason the use of the nicotinate salt of chromium has been proposed as an alternative, but this has not yet been tested as frequently as the picolinate salt. Insulin resistance also has the effect that magnesium no longer can be stored in the cells. Accordingly, addition of chromium to the mineral composition of the invention has the effect that magnesium still can be taken up and stored in the cell.
The invention may also comprise mineral compositions where additional minerals, vitamins or salts have been added. Such additions are - of course - only beneficial if they do not interfere with the above indicated effects of magnesium, zinc, chromium, selenium and taurine. In this case, it should be repeated that it would not be advisable to increase calcium uptake (e.g. by addition of Ca-salts in the present mineral composition), because calcium negatively affects the uptake of magnesium and zinc.
In the context of this specification, the terms "treatment" and "treating" refer to any and all uses which remedy a condition or disease or symptoms thereof, prevent the establishment of a condition or disease or symptoms thereof, or otherwise prevent or hinder or reverse the progression of a condition or disease or other undesirable symptoms in any way whatsoever.
In the context of this specification, the term "therapeutically effective amount" includes within its meaning a non-toxic amount of each of the indicated compounds, alone or in combination, sufficient to provide the desired therapeutic effect. The exact amount will vary from subject to subject depending on the age of the subject, their general health, the severity of the disorder being treated and the mode of administration. It is therefore not possible to specify an exact "therapeutically effective amount", however one skilled in the art would be capable of determining a
"therapeutically effective amount" by routine trial and experimentation. In one embodiment, the present invention relates to a method for the treatment of depression and cognitive deficits or cognitive impairment, said method comprising the administration of a mineral composition of the present invention to a patient in need thereof.
"Cognitive deficits" or "cognitive impairment" include a decline in cognitive functions or cognitive domains, e.g. working memory, attention and vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving e.g. executive function, speed of processing and/or social cognition. In particular, cognitive deficits or cognitive impairment may indicate deficits in attention, disorganized thinking, slow thinking, difficulty in understanding, poor concentration, impairment of problem solving, poor memory, difficulties in expressing thoughts and/or difficulties in integrating thoughts, feelings and behavior, or difficulties in extinction of irrelevant thoughts. The terms "cognitive deficits" and
"cognitive impairment" are intended to indicate the same and are used interchangeably. Cognitive impairment is a particularly important consideration in the elderly. Cognitive impairment normally increases with age, and further with depression.
Hence, in one embodiment, the patient to be treated for cognitive impairment is elderly, and in particular elderly with depression.
In a further part of the invention, next to patients suffering from psychological disorders, such as depression, and/or cognitive disorders also patients suffering from various physiological diseases may benefit of treatment with the mineral composition according to the invention. Such diseases are diabetes, insulin resistance, osteoporosis, vascular diseases, high blood pressure, rheumatoid arthritis, muscular spasms, fatigue, premenstrual stress syndrome, allergic rhinitis, eczema, allergic diseases, such as hay fever, COPD and asthma. The mineral composition of the present invention may be administered in any acceptable way. Preferably, administration is dealt with orally or topically,
For oral administration, the compositions may be packed in e.g. gelatin capsules or may be tableted in the form of tablets or may be given in liquid compositions. For oral therapeutic application the active compound may be administered with excipients and e.g. used in the form of powders, sachets, tablets, pills, pastilles or capsules. The pharmaceutical
compositions may be prepared by conventional means with
pharmaceutically acceptable excipients such as binding agents (e.g.
pregelatinised maize starch, tragacanth gum, gelatine, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g. lactose, microcrystalline cellulose, mannitol or calcium hydrogen phosphate); lubricants (e.g.
magnesium stearate, talc or silica); disintegrants (e.g. potato starch, sodium starch glycollate or alginate); or wetting agents (e.g. sodium lauryl sulphate). The tablets may be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g.
sorbitol syrup, cellulose derivatives or hydrogenated edible fats);
emulsifying agents (e.g. lecithin or acacia); non- aqueous vehicles (e.g.
almond oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g. methyl or propyl-p-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, flavoring, coloring and sweetening agents as appropriate. Preparations for oral administration may be suitably formulated to give controlled release of the active compound.
For buccal administration the compositions may take the form of tablets or lozenges formulated in conventional manner. For topical administration, the compositions may be in the form of dispersions (solutions, suspensions) in an aqueous or oil solution or dispersed into an emulsion, wherein said emulsion may be water-in-oil, oil- in-water or any double emulsion. As such, the formulation may take the form of an oil, a creme, an ointment, a lotion, a paste, a gel, a jelly, a foam, a spray, a (dermal) patch,
The compounds according to the present invention may be formulated for parenteral administration by injection e.g. by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form e.g. in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain
formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g. sterile pyrogen-free water, before use.
When dosing is in the form of a capsule, the capsule may comprise apart from the elements mentioned above a liquid carrier such as an oil. Dosage form may further be provided with coatings of sugar, shellac or other agents. The components of the pharmaceutical composition are preferably chosen such that they do not reduce the desired working of the active compound.
The pharmaceutical compositions can further comprise flavoring sweetening, coloring and/or preservative agents.
A mineral composition according to the invention, or a
pharmaceutically acceptable salt thereof may also be administered in the form of e.g. an elixir, a suspension, a syrup, a waffle or a chewing gum.
In a pharmaceutical composition as described above, the total of active minerals and further therapeutically active compounds, such as the amino acid taurine, will be present in an amount of from 0.01 to 99.9 % by weight, preferably from 10 to 90 wt.%, and more preferably from 30 to 80 wt.%.
The present invention further relates to a method for the preparation of a mineral composition for use as medicament, comprising processing or incorporating a mineral composition according to the invention, as an active substance, together with a pharmaceutically acceptable carrier in a pharmaceutical composition.
The preparation of a pharmaceutical composition may very suitably occur by mixing all separate ingredients such as fillers, binders, lubricants and optionally other excipients together with one or more of the minerals and /or taurine, and processing the mixture obtained to a pharmaceutical preparation.
Once given to a subject in need thereof, the development of the treatment can be monitored using diagnostic methods available in the art. Especially for the monitoring of depression an assay as described in
PCT/NL2014/050054 may be used. In order to obtain a good overview of the improvement of the depression over the treatment time a regular assay as described in PCT/NL2014/050054 should be performed.
Monitoring of the treatment of cognitive disorders may be performed by regularly performing questionnaires as are described in the DSM manual, or by using the Alzheimer Questionnaire (Malek-Ahmadi, M. et al., 2012, Age Ageing 41:396-399) or other comparable diagnostic systems (such as the 4-item Abbreviated Mental Test described in. Schofield, I. et al., 2010, Eur. J. Emerg. Med. 17:340-342).
The skilled person will know how to diagnose and monitor depression and cognitive impairment.
For the more physiological-based diseases, such as diabetes and asthma, clinical methods are available to monitor the development of the disease or improvement thereof. These are readily available to physicians. For monitoring the effects of magnesium special emphasis can be given to the biomarkers that are known to be influenced by magnesium, such as substance P, aldosteron, thromboxane, endothelin 1, EGF, Vitamin D and telomerase. A full description of the use of these biomarkers can be found in PCT/NL2014/050054. Furthermore about 325 enzymes in the human body (i.e. telomerase, insulin, glucose-6-phosphatase, hexokinase, DNA
polymerase, isocitrate dehydrogenase, maltokinase, alpha-galactosidase etc.) require magnesium as a cofactor for proper functioning. All enzymes which require magnesium as cofactor can be used as a biomarker. As described in PCT/NL2014/050054 also for diagnosing magnesium deficiency a combination of biomarkers is needed.
Monitoring the effects of magnesium through these biomarkers has the advantage that the physiological effects of magnesium are measured. As has been reported in the literature Ismail, Y. et al., 2010, Clin. Chem. Lab. Med. 48:323-327) serum concentrations of magnesium are not reliable and - as a result of that - magnesium deficiencies are under diagnosed.
For preparing pharmaceutical compositions comprising the mineral composition of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances which may also act as diluents, flavouring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.
In powders, the carrier is a finely divided solid which is in a mixture with the finely divided active component.
In tablets, the active component is mixed with the carrier having the necessary binding capacity in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain from five or ten to about seventy percent of the active compound. Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term "preparation" is intended to include the formulation of the active compound with encapsulating material as carrier providing a capsule in which the active component, with or without carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid forms suitable for oral administration.
Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water-propylene glycol solutions. The compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilising and/or dispersing agents. Alternatively, the active ingredient may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilisation from solution, for constitution with a suitable vehicle, e.g. sterile, pyrogen-free water, before use.
Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavours, stabilizing and thickening agents, as desired.
Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium
carboxymethylcellulose, or other well known suspending agents. Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These
preparations may contain, in addition to the active component, colorants, flavours, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.
The pharmaceutical preparations are preferably in unit dosage forms. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.
A preferred embodiment of the invention is formed by a mineral composition comprising:
magnesium glycinate >200 mg, pref. >400 mg, more pref. >500 mg zinc glycinate > 2 mg, pref. >4 mg, more pref. >5 mg
selenium methionine > 1 mg.
This composition may also additionally comprises
chromium picolinate > 0.2 mg or
chromium nicotinate > 0,2 mg
and/or
taurine >250 mg.
Very preferred is a mineral composition comprising:
magnesium glycinate 625 mg
zinc glycinate 8.3 mg
selenium methionine 1.8 mg
chromium picolinate 0.06 mg
and
taurine 300 mg. The amounts here are indications and may differ + or - 5%, more preferably +/- 1%.
Such a composition as defined above may additionally comprise magnesium stearate as lubricant > 5mg and silicium dioxide as anticoagulant > 5 mg.
EXAMPLES
Example 1. Preparation of a mineral composition.
The individual compounds were obtained from the following sources:
Magnesium bisglycinate from Albion (Clearfield, UT, USA; #03476); zinc bisglycinate frome Albion (Clearfield, UT, USA; #03506); Crystalline microcellulose (Microcel MCC 101 ®) from Surfachem (Leeds, UK) or microcrystalline cellulose (Microcel FG- 101) from Blanver (Itapevi, Spain); AquaPolish® 094.12 MS from Biogrund (Hiinstetten, Germany); taurine from Arnold Suhr (Hilversum, the Netherlands, #A307), selenomethionine from Frutarom Belgium N.V. (Londerzeel, Belgium, #HB53520); chromium picolinate from Quimdis S.A.S. (Levollois Perret, France); magnesium stearate from Peter Greven Nederland C.V. (Venlo, the Netherlands);
silicium dioxide as SYLOID® AL-1 FP from W.R. Crace&Co.-Conn
(Lonkeren, Belgium). This resulted in a mineral composition comprising:
Name Amount (mg)
Chromium picolinate (minimally 12% chromium) 6.1
Zinc Glycinate Chelate (minimally 20% Zn) 8.3 Selenomethionine (5000 pg/g Se) 1.8
Taurine 300
Magnesium bisglycinate (minimally 10% magnesium) 625
Crystalline microcellulose (Microcel MCC 101) 531.7
Silicium dioxide 15
Magnesium stearate 18
Aqua polish® 094.12 MS 18
Total 1518
The tablets were coated in a normal tablet coating machine (FC 39 from NR Group, 97200 tablets per batch) with the following composition (amounts average per tablet):
Example 2.
A test was performed with daily administration of the mineral composition as prepared according to Example 1.
3 patients with depression (Hamilton score of 12, 14 and 26, respectively) were treated with 6 tablets per day of the mineral composition. After 6 weeks the Hamilton score of the most severely depressed patient was decreased to 22 while for the other two patients after two months values of 11 and 10, respectively, were measured.
From this preliminary finding it appears that depression may be treated by oral administration of the mineral composition.
Example 3
A test was performed with daily administration of the mineral composition as prepared according to Example 1.
3 patients with allergic symptoms (such as hay fever) were treated with an oral dose of 6 tablets per day. A first patient with general allergic reactions experienced an amelioration of the symptoms after 4 days of treatment. His energy and general condition were subjectively improved.
One patient with severe hay fever showed improvements after 10 days of treatment. After two months the symptoms were gone. For the third patient with severe hay fever the amelioration started at day 14 and the symptoms had disappeared after three months of treatment.
Example 4
A test was performed with daily administration of the mineral composition as prepared according to Example 1.
One patient suffering from arrhythmia, which also cause anxiety, was treated with 6 tablets orally per day and after two months the symptoms were completely disappeared.

Claims

1. Mineral composition comprising magnesium glycinate, zinc glycinate and selenium methionine.
2. Mineral composition according to claim 1, further comprising a
chromium compound, preferably chromium picolinate or chromium nicotinate.
3. Mineral composition according to claim 1 or claim 2, further
comprising taurine.
4. Mineral composition according to any of claims 1 -2, further
comprising vitamin B6.
5. Mineral composition according to any of the previous claims, wherein the minerals are dosed in a therapeutic effective dose.
6. Mineral composition according to any of the previous claims, wherein the mineral composition comprises:
magnesium glycinate >200 mg, preferably >400 mg, more preferably >500 mg;
zinc glycinate > 2 mg, preferably >4 mg, more preferably >5 mg;
selenium methionine > 1 mg.
7. Mineral composition according to any of the previous claims, wherein the mineral composition additionally comprises
chromium picolinate > 0.2 mg or
chromium nicotinate > 0,2 mg and/or
taurine >250 mg.
8. Mineral composition according to any of the previous claims, wherein the mineral composition comprises (+/- 5%, preferably +/- 1%):
magnesium glycinate 625 mg
zinc glycinate 8.3 mg
selenium methionine 1.8 mg
chromium picolinate 0.06 mg
and
taurine 300 mg.
9. Mineral composition according to any of the previous claims for use in therapy.
10. Mineral composition according for use according to claim 9, wherein the therapy is the therapy of cognitive impairment, depression, burnout, ADHD, autism, memory loss, Alzheimer's disease, dementia, migraine, loss of IQ, craving for drugs or nicotine, post-menstrual syndrome or of post-traumatic stress disorder.
11. Mineral composition according for use according to claim 9, wherein the therapy is the therapy of diabetes, osteoporosis, fatigue, asthma, high blood pressure, allergic diseases such as hay fever, eczema, muscular spasm, conditions associated with high cholesterol levels, and heart and vascular diseases.
12. Method for the treatment or prevention of cognitive impairment, depression, burn-out, ADHD, autism, memory loss, Alzheimer's disease, dementia, migraine, loss of IQ, craving for drugs or nicotine, post-menstrual syndrome or of post-traumatic stress disorder by treating a subject in need thereof with a mineral composition according to any of claims 1 - 8.
13. Method for the treatment or prevention of diabetes, osteoporosis, fatigue, asthma, allergic diseases such as hay fever, eczema, muscular spasm, conditions associated with high cholesterol levels, and heart and vascular diseases, high blood pressure by treating a subject in need thereof with a mineral composition according to any of claims 1 - 8.
14. Method for monitoring the effects of the method according to any of claims 12 and 13 by regularly measuring changes in biomarker values wherein said biomarkers are chosen from substance P, aldosterone, thromboxane, endothelin 1, EGF, vitamin D and telomerase.
15. Method for monitoring the effects of the method according to any of claims 12 and 13 by regularly measuring changes in biomarker values wherein said biomarkers are chosen enzymes that use magnesium as a cof actor.
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