DE19964116A1 - Increasing bioavailability of magnesium ions by co-administration of vitamin K, allowing reduction of dosage in the treatment of magnesium deficiency syndrome - Google Patents

Abstract

Increasing the bioavailability of magnesium ions in an organism involves administration of vitamin K (I). An Independent claim is included for a pharmaceutical packaging unit comprising: (i) magnesium ions, preferably formulated in granular form; (ii) vitamin K, preferably formulated in aqueous emulsion; and (iii) instruction for dosing.

Description

The invention relates to a method for increasing the bioavailability of magnesium ions in the Organism and a pharmaceutical packaging unit on this basis. Areas of application of the invention are medicine and the pharmaceutical industry.

Minerals and trace elements form an important part of human nutrition. she have essential functions as components and cofactors of enzymes or as components of Chromoproteins, hormones or membrane and structural proteins. They come in all tissues suggests that withdrawal of an element leads to element-specific deficiency symptoms, the Changes in physiological and structural terms at the molecular level circumscribed biochemical defect can be assigned. All specific Symptoms of deficiency or the biochemical changes that occur with the withdrawal prevented or normalized by the supply of the element (Wolffram 1996). The changes can affect the entire metabolism or partial metabolism (e.g. the metabolism of proteins, fats, carbohydrates, energy or membrane metabolism). Changes and damage to the entire organism or its subsystems (e.g. central and peripheral nervous system, cardiovascular, gastrointestinal, kidney, skeletal and Muscular system) can result.

One of the most important quantity and trace elements is magnesium, which is in one in the organism Amount of 21-28 g (0.03-0.04% of body weight) occurs. Magnesium is in the diet of humans especially in foods of plant origin (e.g. cereals, vegetables, fruits) available. Mg suppliers are u. a. Nuts, chocolate, whole grain bread, oatmeal, magnesium rich mineral waters, fish, bananas (Holtmeier 1988).

On the magnesium balance of animals and humans

The magnesium balance is mainly through absorption from the intestine and through. Reabsorption regulated by the urinary organs. Absorption in the intestine is the only way the organism can get out of metabolism Elimination to replace lost magnesium. The mechanism of reabsorption is only able to control the degree of magnesium loss by reducing urine output (Rude 1998).

For absorption

Magnesium ions are in the form of inorganic and organic salts by humans and animals ingested through food. Magnesium is largely ionized in the intestinal lumen. Magnesium ions are absorbed depending on the existing body stock. Transport through the intestinal mucosa takes place through active and passive transport. The bioavailability fluctuates between 20 and 80%: the smaller the supply, the greater is the share of active transportation. Obviously, active transportation can become saturated.

Active transport takes place using transport proteins. Neither those responsible Transport proteins are still the fine mechanism of active transport of magnesium ions previously known (Rude 1998).  

For magnesium substitution

Some patients who have symptoms of magnesium deficiency syndrome (e.g. magnesium deficiency tetanie) suffer (Hanna et al. 1960), have so far required up to 3-4 times daily magnesium Dose compared to the average recommended diet of 300-350 mg magnesium / day, to achieve the overall magnesium balance (a so-called magnesium homeostasis).

On the one hand, this is due to the possibility of a magnesium loss kidney, characterized by a increased renal excretion offset by an increased oral magnesium supply on the other hand due to the reduced transport capacity through the luminal intestinal cells.

Some patients even received magnesium intravenously to make up for the losses balance because oral intake through the luminal intestinal cells is not sufficient Supply allows more.

The disadvantage of the high magnesium dose is that an above-average oral Magnesium often leads to the appearance of soft stools or even diarrhea (Classen et al. 1986). Furthermore, due to the previously necessary multiple intakes per day (3-4 ×) necessary insight (so-called compliance) of the patient is often not given.

Object of the invention

The object of the invention was to cause various types of magnesium deficiency syndromes eliminate without a significant overdose of magnesium.

It was found that vitamin K1 administration surprisingly enables a lower dosage of magnesium ions without reducing the therapeutic or substitution effect. The method according to the invention is derived from this finding. It is characterized in that the bioavailability of magnesium in the organism through the simultaneous or timely administration of naturally occurring vitamin K, e.g. B. Vitamin K1, is increased. Vitamin K, in particular vitamin K1, is preferably taken in by the oral route. The invention also relates to pharmaceutical packaging units

• Magnesium ions, preferably prepared in granular form,
• - Vitamin K, preferably prepared in an aqueous emulsion, and one
• - Package insert

characterized.

The dosage leaflet can be found in the package insert, which is in the range of 250-350 mg / day Magnesium ions and 0.8-1.2 mg / day of vitamin K. A preferred dosage for Migraine prophylaxis is 300 mg / day magnesium ions and 1.0 mg / day vitamin K.

There was no connection between vitamin K and the transport of magnesium ions known; it is the basis of the method according to the invention and the packaging unit. How Further attempts by the applicant prove the magnesium transport of one or dependent on several intestinal gamma-carboxylated transport proteins.

The existence of gamma-carboxylated proteins (Gla proteins)

The gamma carboxylation of proteins is dependent on vitamin K. Gamma-carboxylated proteins  (Gla proteins) can bind divalent cations (e.g. calcium). The importance of gamma Carboxylation is only known for a few proteins, e.g. B. regulating blood clotting Proteins (including coagulation factors II, VII, IX and X and protein C and S) and for certain Bone proteins (including osteocalcin, Gla matrix protein) (Ferland 1998).

The importance of vitamin K1

This is the natural and nutritionally important vitamin of the vitamin K group vegetable vitamin K, which is called vitamin K1 (phylloquinone). By optimizing vitamin K intake through food, it is possible to control the degree of Affect gamma carboxylation of proteins.

The invention will be explained in more detail below by means of exemplary embodiments.

Examples

• 1. Magnesium deficient patients, previously on a continuous dose of 900 mg magnesium / day (given as organic or inorganic salts) need under one Continuous intake of 1 mg vitamin K1 / day only 600 mg magnesium / day or fewer.
• 2. Patients who previously had a continuous dose of 600 mg magnesium / day for migraine prophylaxis receipts, need only 300 mg with a continuous intake of 1 mg vitamin K1 / day Magnesium / day or less.
• 3. Patients who previously had a continuous dose of 600 mg magnesium / day for prophylaxis of Taking tension headaches require 1 mg of vitamin K1 / day only 300 mg magnesium / day or less.
• 4. A pharmaceutical packaging unit is composed of several bags Granules with 300 mg magnesium ions each and a bottle of vitamin K1 emulsion containing 20 mg Contains vitamin K1 per ml, where 20 drops correspond to one ml (corresponds to 1 mg / drop), as well as an instruction leaflet (e.g. for dosing).
• 5. A pharmaceutical packaging unit is put together from
  • - 100 sachets of granules, each with 300 mg of magnesium ions
  • - 1 bottle of 5 ml vitamin K1 emulsion with 20 mg / ml (20 drops / ml; corresponds to 1 mg / drop) and one
  • - Package insert (for dosage, among other things).

bibliography

Classen, HG et al .: Magnesium: Indications for Diagnostics and Therapy in Human Medicine. Magnesium Bulletin 8 127-135 (1986)
Ferland, G .: The Vitamin K-dependent Proteins: An Update. Nutrition Rev. 56, 223-230 (1998)
Hanna, S. et al .: The syndrome of magnesium deficiency in man. Lancet ii 172-176 (1960)
Holtmeier, H.-J .: "Magnesium deficiency syndrome - meaning for humans, animals and plants". Hippokrates Verlag, 1988
Rude, RK: Magnesium deficiency: A Gause of Heterogeneous Disease in Humans. J. Bone Mineral Res. 13 (4), 749-758 (1998)
Wolffram, S .: Trace elements. In: Forth, W. et al. (Ed.) "General and special pharmacology and toxicology", 7th edition, pp. 657-663, Spectrum Academic Publishing House Heidelberg, Berlin, Oxford (1996)

Claims (6)

1. Process for increasing the bioavailability of magnesium ions in the organism Administration of vitamin K. 2. The method according to claim 1, characterized by administration of vitamin K1. 3. The method according to claim 1 and 2, characterized in that the administration takes place orally. 4. Pharmaceutical packaging unit consisting of

• Magnesium ions, preferably prepared in granular form,
• - Vitamin K, preferably prepared in an aqueous emulsion, and one
• - Package insert for dosing.

5. Pharmaceutical packaging unit consisting of

• - several sachets of granules, each with 300 mg magnesium ions
• - a bottle of vitamin K1 emulsion with 20 mg / ml and
• - Package insert for dosing.

6. Pharmaceutical packaging unit consisting of

• - 100 sachets of granules, each with 300 mg of magnesium ions
• - 1 bottle of 5 ml vitamin K1 emulsion with 20 mg / ml and
• - Package insert for dosing.