MXPA06001818A - Enhancement of magnesium uptake in mammals - Google Patents

Abstract

Disclosed are methods and complexes for increasing magnesium uptake in mammals. Increasing magnesium uptake in mammals is accornfishedd by concurrently administering one or more magnesium salts with one or more quaternary amines and/or phosphatides and one or more di- or tri-carboxylic acids.

Description

IMPROVEMENT OF THE MAGNESIUM CAPTATION IN THE MAMMALS FIELD OF THE INVENTION The present invention relates to the increase of magnesium uptake in mammals. More particularly, the present invention relates to the increase of magnesium uptake in mammals by simultaneously administering one or more magnesium salts, with one or more quaternary amines or phosphatides and one or more di- or tri-carboxylic acids. BACKGROUND OF THE INVENTION Magnesium is an important mineral in the nutrition of mammals. As part of adenosine triphosphate (ATP), magnesium is used for all processes of biosynthesis, glycolysis, formation of cyclic adenosine monophosphate (Cyclic AMP), is involved in energy metabolism and energy-dependent membrane transport and is used for the synthesis of ribonucleic acid (RNA) and the transmission of the genetic code. Magnesium, as a cation, is involved in approximately 10,000 enzymatic actions (cellular catalyst). Magnesium is especially important for enzymes related to oxidative phosphorylation. Magnesium is also an important component of intracellular and extracellular fluids. The intracellular magnesium is Ref: 170392 believed to control the cellular metabolism by modulating the activity of the enzymes that limit the speed. Extracellular magnesium is important for the maintenance of the electrical potentials of the nerve and muscle membranes and for the transmission of impulses through the neuromuscular joints. Magnesium has been shown to be important in maintaining the homeostasis of smooth and cardiac muscle tissues. Magnesium is the fourth most common cation in the human body. For example, a typical human body contains on average 25 grams of magnesium. Approximately 59% of the magnesium is in the body's skeleton and bone structures, approximately 40% is in the body's musculature and soft body tissues and approximately 1% (around 2 to 2.8 grams) is in the extracellular fluid of the body. Whereas magnesium is an activator for many important bodily functions, it is not surprising that the deficiency can lead to a variety of serious physical and mental problems. Health conditions, such as spasms and muscle tremors are associated with magnesium deficiency. In addition, nervous irritability, mood instability, high blood pressure (Essential, otherwise unexplained), angina (chest pain in exertion), cardiac arrhythmias (magnesium is the "calcium channel blocker"). nature "), loss of calcium / risk of osteoporosis and insomnia are also associated with magnesium deficiency. Toxic metals (lead, mercury, cadmium, arsenic and nickel) can accumulate more quickly when magnesium stores are slow and the replacement of magnesium in the body accelerates the removal of toxic metals from the body. Magnesium is inorganic and is not produced by the human body. Humans have to rely on dietary sources to provide the body with magnesium requirements. Magnesium uptake in the diet has been decreased in the United States, with a per capita decline in magnesium in the U.S. food supply. (estimated as the flow of food through the food distribution system) from 408 mg / day in 1909 to 329 mg / day in 1986, almost a 20% decline. This decline has been attributed to the increase in the consumption of processed foods. For example, "white foods" such as refined flour, sugar, fat, and processed or synthesized foods contain relatively little magnesium. In those with normal digestion and assimilation, the magnesium absorption of the food is believed to be approximately 40 to 60% of what is ingested. However, there are many factors that can inhibit the body's ability to absorb magnesium. For example, phosphoric acid, which is present in most light beverages, and oxalates in foods, such as spinor and chocolate, combine with magnesium in the intestines and form insoluble compounds that are not absorbed by the body. Other factors that can reduce the function of the magnesium uptake system include: toxic minerals such as lead, mercury, arsenic, cadmium and nickel; imitators of the biocidal hormone; metabolic cellular acidosis; phytates in ingested food; caffeine uptake; consumption of alcohol; some medications, such as steroids and oral contraceptives; discomfort; enteropathy and other intestinal disorders and poor digestion and digestive diseases. The oral uptake of magnesium is difficult for the body to absorb. It is believed that only 3 to 12% of the elemental magnesium, usually in the form of magnesium oxide, is absorbed for use by the body. Attempts have been made to make complexes to improve the absorption of magnesium in the human body. For example, U.S. No. 5,849,337 by Dixon discloses a complex containing magnesium, protein amino acids and ascorbic acid. As described above and in Dixon, there is a need for a method for increasing magnesium uptake in mammals, particularly in humans. BRIEF DESCRIPTION OF THE INVENTION This invention includes magnesium complexes and methods for administering magnesium to a mammal. The magnesium complex includes a magnesium salt, a quaternary amine or phosphatide and a dicarboxylic or tri-carboxylic acid. Preferably, the magnesium complex of claim 1, wherein the complex further includes a solution of water and glycerol. Preferably, the magnesium salt is magnesium glycinate, magnesium ascorbate, magnesium chloride, magnesium sulfate, magnesium orotate, magnesium citrate, magnesium fumarate, magnesium t malate, magnesium succinate, magnesium tartrate, carbonate of magnesium or a similar magnesium salt. Preferably, the quaternary amine is choline and / or the phosphatide is phosphatidyl choline and the do- or tri-carboxylic acid is citrate. The method for enhancing magnesium uptake in mammals includes administering to a mammal a magnesium salt, a quaternary amine or a phosphatide and a dicarboxylic acid or tri-carboxylic acid. Preferably, the administration is oral and the mammal is a human.

BRIEF DESCRIPTION OF THE FIGURES The invention will be better understood with reference to the Detailed Description of the Invention when taken in conjunction with the accompanying Figure 1, wherein Figure 1 is a graph showing the influence of choline citrate on the concentration of ionized magnesium in plasma. DETAILED DESCRIPTION OF THE INVENTION This invention includes the magnesium complexes and methods for administering magnesium to a mammal. It has been found that administration to a mammal of a magnesium salt, a quaternary amine or phosphatide and a dicarboxylic acid or tri-carboxylic acid, the magnesium uptake in the patient can be improved. The magnesium salt may be any of the known magnesium salts or a combination of several known magnesium salts. Preferred magnesium salts include magnesium glycinate, magnesium ascorbate, magnesium chloride, magnesium sulfate, magnesium orotate, magnesium citrate, magnesium fumarate, magnesium malate magnesium succinate, magnesium tartrate and magnesium carbonate. The quaternary amine or phosphatide can include any quaternary amine, phosphatide or a combination of the quaternary amines and phosphatides. A preferred quaternary amine is choline.

The di-carboxylic acid or tri-carboxylic acid can include any di-carboxylic acid, tri-carboxylic acid, or a combination of the dicarboxylic acids and tricarboxylic acids. A preferred di-carboxylic acid is citrate. Preferably, the magnesium salt, the quaternary amine or phosphatide and the dicarboxylic acid or tri-carboxylic acid are administered simultaneously. Simultaneously, as used herein, means administered within the same day. Preferably, they are administered together either as part of the same complex, which may include, for example, a solution or a pill containing all the components, or administered one after the other, so that they can be metabolized together. Preferably, the magnesium salt, the quaternary amine or phosphatide and the dicarboxylic acid or tri-carboxylic acid are administered as part of a complex in an aqueous glycerol solution. More preferably, the magnesium salt, the quaternary amine or phosphatide and the dicarboxylic acid or tri-carboxylic acid are administered as part of a complex in a solution containing both water and glycerol. Preferably, the solution contains approximately the same amount of water as glycerol. The invention will be better understood with reference to the following examples in which patients who had diseases associated with low magnesium levels were administered a variety of combinations of the compounds to determine their effectiveness. Patients in the examples were selected according to signs of magnesium deficiency including muscle irritability and fasciculation, benign cardiac irritability and / or moderate fibromyalgia pain that had not previously been sensitive to magnesium therapy. Example 1 A 26-year-old man suffering from supraventricular arrhythmias was insensitive to medication and, despite detailed medical elaboration, was determined to be "idiopathic". The clinical assessments were made during periods of one month. The magnesium salts were administered to the patient for one month followed by one month of choline citrate alone, followed by one month of magnesium salts together with the concurrent administration of choline citrate. During this time the patient was instructed to count the number of irregular heartbeats (IHBs) for a period of 2 minutes upon rising and before. to go to bed The average number of irregular heartbeats counted during the three-month period can be found in Table 1: Table 1 AM PM Total Month 1 (prom.) 13 22 35 Month 2 (prom.) 11 27 38 Month 3 (prom.) 1 3 4 As shown in table 1, the average number of irregular heartbeats decreased drastically when the magnesium salts were administered together with the simultaneous administration of choline citrate. Example 2 A 72-year-old woman suffering from ectopic heartbeat who was not sensitive to medication and, despite detailed medical elaboration, was found to be "idiopathic". The clinical assessments were made during periods of one month. The magnesium salts were administered to the patient for one month followed by one month of choline citrate alone, followed by one month of magnesium salts together with the concurrent administration of choline citrate. During this time the patient was instructed to count the number of irregular heartbeats (IHB) for a period of 2 minutes standing and before going to bed.

The average number of irregular heartbeats counted during the three-month period can be found in Table 2: Table 2 AM PM Total Month 1 (prom.) 18 20 38 Month 2 (prom.) 22 19 41 Month 3 (prom.) 1 2 3 As shown in Table 2, the average number of irregular heartbeats decreased drastically when the magnesium salts were administered together with the concurrent administration of choline citrate. Example 3 A 59-year-old man suffered from "restless legs" and intermittent leg cramps during sleep. Clinical assessments were made with the patient taking the magnesium salts during weeks 1 and 2, then with the patient taking choline citrate only during weeks 3 and 4, then with the patient taking the magnesium salts together with the simultaneous administration of choline citrate in weeks 5-9. Each week the patient was asked to classify the intensity of the problem according to a consistent classification scale, with "0" indicating no problems and "1" indicating the most serious expression of the condition. The results can be found in table 3. Table 3 Average intensity of difficulty related to leg cramps Week 1--2 88 Week 3--4 83 Week 5 63 Week 6 44 Week 7 29 Week 8 12 Week 9 7 As shown in Table 3, the average intensity of difficulty related to leg cramps decreased drastically when the magnesium salts were administered together with the concurrent administration of choline citrate. The clinical ratings shown in Examples 1-3 are consistent with the improved magnesium uptake when the correct magnesium salts are appropriately combined with high purity choline citrate.

Example 4 Patients were selected according to the signs of magnesium deficiency including muscle irritability and fasciculation, benign cardiac irritability and / or moderate fibromyalgia pain that had not previously been sensitive to magnesium therapy. Patients were given a fixed dose of magnesium salts, 2 capsules with each meal (6 per day) for one month. For the second month, the same regimen was continued plus the addition of 1 tablespoon of choline citrate in juice or water taken at the same time as the magnesium supplement. For the third month, the patient continued the magnesium regimen, but without the addition of choline citrate. Diet and fluid uptake remained consistent during the study interval. The amount of magnesium in each patient was measured at the end of each week using a specific ion electrode. The reference interval for the ionized magnesium using this ion-specific electrode (NOVA) is 0.43-0.59 mmol / L. The results can be found below in table 4.

Table 4 Figure 1 is a graphic representation of the data in Table 4. As shown in Figure 1 and Table 4, the amount of magnesium in the patient's plasma increased to its highest values after weeks 5-8. when the patients were taking choline citrate together with the magnesium salts. In other studies, the role of choline citrate on magnesium levels in the absence of magnesium supplementation was evaluated. A modest but statistically significant increase in magnesium was observed during a 30-day evaluation period. The examples show that a previously unknown and unanticipated benefit is seen in the form of facilitated uptake of magnesium when choline citrate is administered simultaneously. Choline citrate alone does not substantially raise the ionized magnesium levels. In some people in need of clinical magnesium, even the most soluble and ionized forms of magnesium are less available, possibly due to the inhibition of the Ca / Mg ATPase pump. A possible mechanism of action is the formation of micelles containing 2 molar equivalents of magnesium and choline together with 3 molar equivalents of citrate, thus forming an electrically neutral complex. The above description is presented to enable a person skilled in the art to make and use the invention, and is provided in the context of a particular request and its requirements. Various modifications to the preferred embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments and applications without departing from the spirit and scope of the invention. Thus, this invention is not intended to be limited to the modes shown, but will be in accordance with the broadest scope consistent with the principles and features described herein. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (22)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. A magnesium complex, characterized porgue consists of: a magnesium salt; a quaternary amine or phosphatide; and a di-carboxylic or tricarboxylic acid; and a solution of water and glycerol or a solution similar to water and glycerol.

The magnesium complex according to claim 1, characterized in that the magnesium salt is selected from the group consisting of magnesium glycinate, magnesium ascorbate, magnesium chloride, magnesium sulfate, magnesium orotate, magnesium citrate, magnesium fumarate, magnesium malate, magnesium succinate, magnesium tartrate, magnesium carbonate or a similar magnesium salt.

3. The magnesium complex according to claim 1, characterized in that it consists of the phosphatide.

4. The magnesium complex according to claim 1, characterized in that it consists of dicarboxylic acid.

5. A method for increasing magnesium uptake in a mammal, characterized in that it comprises administering to the mammal a magnesium complex consisting essentially of: a magnesium salt; a quaternary amine or phosphatide; and a di-carboxylic or tricarboxylic acid.

6. The method according to claim 5, characterized in that the administration is oral.

The method according to claim 5, characterized in that the magnesium salt, the quaternary amine or phosphatide, and the dicarboxylic acid or tri-carboxylic acid are in a solution of water and glycerol.

The method according to claim 5, characterized in that the magnesium salt is selected from the group consisting of magnesium glycinate, magnesium ascorbate, magnesium chloride, magnesium sulfate, magnesium orotate, magnesium citrate, fumarate magnesium, magnesium malate, magnesium succinate, magnesium tartrate, magnesium carbonate or a similar magnesium salt.

9. The method according to claim 5, characterized in that it consists of the phosphatide.

10. The method according to claim 5, characterized in that it consists of the dicarboxylic acid.

11. The method according to claim 5, characterized in that the mammal is a human.

The method according to claim 5, characterized in that the magnesium salt, the quaternary amine or the phosphatide and the dicarboxylic acid or tri-carboxylic acid are administered together.

13. The magnesium complex according to claim 3, characterized in that the phosphatide is phosphatide choline.

14. The magnesium complex according to claim 4, characterized in that the dicarboxylic acid is dicarboxylic acid citrate.

15. The method according to claim 9, characterized in that the phosphatide is phosphatide choline.

16. The method according to claim 10, characterized in that the dicarboxylic acid is dicarboxylic acid citrate.

17. The method according to claim 5, characterized in that the mammal has a disease associated with magnesium deficiency.

18. The method according to claim 17, characterized in that the disease is one or more diseases selected from the group consisting of muscular irritability, fasciculation, benign cardiac irritability, fibromyalgia pain and restless legs syndrome.

19. A magnesium complex for use in increasing magnesium uptake in a mammal, characterized in that it consists essentially of: a magnesium salt; a quaternary amine or phosphatide; and a di-carboxylic or tricarboxylic acid; where the magnesium complex is in a solution of water and glycerol or a solution similar to water and glycerol.

20. A kit for increasing the uptake of magnesium in a mammal, characterized in that it comprises: a container comprising: i. a magnesium salt; ii. a quaternary amine or phosphatide; iii. a di-carboxylic acid or tricarboxylic acid; and iv. an aqueous solution; and instructions for use, wherein the magnesium salt and the quaternary amine or phosphatide and a di-carboxylic or tricarboxylic acid are each pre-measured in a respective unit of use amount.

21. A kit for increasing uptake of magnesium in a mammal, characterized in that it comprises: a first container comprising a magnesium salt; a second container comprising: i. a quaternary amine or phosphatide; ii. a di-carboxylic acid or tricarboxylic acid; and iii. an aqueous solution; and instructions for use, wherein the magnesium salt and the quaternary amine or phosphatide and a di-carboxylic or tricarboxylic acid each are pre-measured in a respective unit of use amount, wherein the ingredients in the first container and the Second container are taken contemporaneously.

22. A kit for increasing uptake of magnesium in a mammal, characterized in that it comprises: a first container comprising a magnesium salt; a second container comprising: i. a quaternary amine or a phosphatide; ii. a di-carboxylic acid or tricarboxylic acid; and iii. an aqueous solution; and instructions for use, wherein the magnesium salt and the quaternary amine or phosphatide and a dicarboxylic or tricarboxylic acid each are pre-measured in a respective unit of use amount, wherein the components in the first container and the Second container are taken successively.