DE1809119C3 - Heart attack prophylactic - Google Patents

Description

Mg

Η —C-H

Η —C-NH, HCl

is a colorless crystalline substance (crystal clear plates and columns), which in the form of a 1% aqueous solution gives a pH of 4.5 to 4.8 and as a 6% 1 N HCl solution a specific rotation of +12, 5 ± 2 possesses. The mixed melting point of this compound with dicyandiamide is 188 ^C C. The solubility

ability in water is 1: 5 (cold) while the compound difficult in alcohol, acetone and chloroform

is soluble.
Magnesium monoaspartate hydrochloride can be omitted

Prepare magnesium diaspartate by adding hydrogen chloride according to the following reaction scheme

H ₂ NCC

H ₂ CC

H ₂ CC

H, N-C-C

OU

O O

Mg + HCl

CH ₂

HCl · H ₂ NCH

Mg +

OH CH ₂

CH-NH ₂

// C \ OH

H OH

The hydrochloric acid must be the solution of the The reaction is most convenient in one

Magnesium diaspartate can be added quickly, because 65 aqueous medium using the stoichio-

as soon as aspartic acid precipitates, a thixometric amount of the reactants is carried out. the

tropic mass, which is difficult to mix, precipitated aspartic acid is finished after

^lyRt reaction filtered off. After concentrating the filtrate

the magnesium monoaspartate hydrochloride according to the invention crystallizes out. The compound can by customary methods, for example by recrystallization, getting cleaned.

Magnesium monoaspartate hydrochloride stands out in a surprising way by a very high complex stability. This fact is special in this respect Surprisingly, a significantly lower one than the corresponding magnesium glutamate hydrochloride Possesses complex stability. Magnesium monoaspartate hydrochloride is therefore suitable in an excellent way for magnesium therapy, as this compound, due to the properties described, the Guarantee for extensive absorption and good organ distribution of magnesium offers and in this Is superior to all previously known inorganic and organic compounds.

Magnesium compounds are used for heart attack prophyiaxis recommended for several years. The degree of the therapeutically expected effect is depending on the amount of magnesium that can be brought into the body. As a result of the high The complex constant is magnesium monoaspartate hydrochloride considerably better sls all known so far Magnesium compounds are absorbed, so that the efficiency of this compound is above that of all previously known magnesium compounds, as shown in the following comparative studies it emerges:

There were resorptious versions in rats with magnesium diaspartate and mapagnesium monoaspartate hydrochloride carried out in the following way:

The studies were carried out on male Sprague-Dawley rats (110 to 210 g) carried out with normal animal feed and tap water ad libitum were fed.

The animals received distilled water via a gavage in a liquid volume of 1.0 ml per 100 g of body weight magnesium diaspartate (Mg-A) or magnesium monoaspartate HCl (Mg-A-HCl) in doses of 250 mg / kg, each based on magnesium. The controls received the same Amounts of distilled water.

IV2 hours after the administration of the solutions, the Animals under anesthesia (sodium salt of 5-ethyl-5- (l-methylbutyl) -barbituric acid) (100 mgkg) bleeding through puncture of the abdominal aorta; the 5 ml glass syringes used each contained heparin as sodium salt (equivalent to 500 IU) to inhibit blood coagulation.

The magnesium content was determined in the plasma. In addition to the magnesium content, the fluorimetric was detected, the blood sugar (colorimetrically) was also determined, as shown on cats in in-vivo experiments it could be shown that under acute stress (e.g. asphyxia due to anesthesia) the magnesium content increases; under such conditions it is known about an excretion of epinephrine hyperglycaemia to be expected at the same time.

The static evaluation of the tests was carried out according to the Student test (Diehl-Combitron-S with Dilector).

The following results were obtained:

Reliable resorptions were only found after a dose of 250 mg / kg (Tab. 1). Obviously high magnesium amounts are required in rats because S e 1 y e (cf.The Pluricausal Cordiopathies, Charles C. Thomas Publ., 1960) also states that it was performed on rats for the prevention of metabolic myocardial necrosis fed 1 millimole of magnesium chloride twice a day.

Compared to the controls, after administration of 250 mg / kg Mg-A or Mg-A-HCl, the plasma magnesium is increased from 2.05 ± 0.28 mg% to 2.93 ± 0.38 or 3.53 ( p <0.001). A comparison of the animals that received Mg-A and Mg-A-HCl shows that Mg-A-HCl is better absorbed. A static significance of ρ <0.05 was found.

A comparison of the blood sugar values of all collectives regularly reveals hyperglycaemia around 200 mg%. On the one hand, this is due to the fact that the animals were not sober. The animals were deliberately not to go hungry, since magnesium supplements usually do not go on an empty stomach either be taken. On the other hand, the increase in blood sugar is due to the stress during bleeding. However, since the BG values are raised in the same range in all groups, there are controls and animals that received magnesium face the same conditions.

These findings clearly show that magnesium monoaspartate HCl is better absorbed as magnesium diaspartate.

Table 1

Feeding 250 mg / kg magnesium in the form of magnesium diaspartate and magnesium aspartate hydrochloride with the gavage

on rats

Determination of the magnesium and glucose content
in mg% in the plasma after 90 minutes

Controls (/ 1 = 8)

Mg-A (/ 1 = 8)

Mg-A-HCl (»1 = 7)

Magnesiun / Plasma Glucose / Plasma

2.05 ± 0.28
2.93 ± 0.385
3.53 ± 0.60a

223.0 ± 23.5 * ^x 230.9 ± 27.5 ^xx 223.8 ± 15.1

> χ x = ρ <O'.OOl compared to the controls.
O = P < 0.05.

There were also further comparative studies on the absorption of magnesium chloride, Magnesium di-aspartate and magnesium mono-aspartate hydrochloride from the cat's small intestine in carried out in the following way:

Experimental set-up
Laboratory animals

Cats of both sexes around 3.0 kg body weight. Body temperature 37 ° C (electric heating pad, control via a relay with a contact thermometer in the rectum). Anesthesia: hexobarbital IM Inhibition of blood coagulation 2000 UU / kg heparin or 75 mg / kg pentosan polysulfuric acid sodium i.v. Cannulation of a femoral vein for injections and infusions.

The following processes were recorded on recorders:

1. Magnesium in whole blood:

Flame photometric determination with the auto analyzer. Blood withdrawal 0.3 ml / min.

Arterial pressure, pulse rate, and breathing. The intruvasal volume was kept constant by infusion - a 6% aqueous solution of a dextran.
In each case, 10 mg / kg Mg ^{+ +} (in the form of the various compounds) in 5 ml of demineralized water was administered using the duodenal probe.

At least five cats were used for each of the experiments. The values given are mean values in each case.

Research results on the absorption rate after administration of 10 mg / kg Mg ⁺⁺ with the duodenal probe in cats.

Test subscription

Magnesium chloride

Magnesium di-aspartate ....

Magnesium mono-aspartate hydrochloride

after 30 minutes

+ 0.19 mg% + 0.18 mg%

+ 0.15 mg% mean
after 60 minutes

+ 0.25 mg%
+ 0.29 mg%

+ 0.36 mg%

after 120 minutes

+ 0.31 mg% + 0.44 mg %

+ 0.57 mg%

The values each give the mean value of the increase in magnesium in whole blood in certain time periods on.

The test results show that magnesium mono-aspartate hydrochloride is also found in the cat's small intestine is better absorbed than magnesium di-aspartate and magnesium chloride.

For carrying out resorption tests on humans with magnesium mono-aspartate hydrochloride the following galenic preparation was used:

Magnesium mono-aspartate hydrochloride -
corresponding to 121.56 mg magnesium

Magnesium mono aspartate

Hydrochloride 1242.9 mg

Thiamine Hydrochloride 2.0 mg

Riboflavin 3.0 mg

Pyridoxine hydrochloride 3.0 mg

Sugar 3219.1 mg

Saccharin 75% 10.0 mg

Mandarin flavor 20.0 mg

Citric acid 500.0 mg

5000.0 mg

The galenic preparation shown is a drinking granulate that is consumed by the patient per dosi was dissolved in half a glass of water. Administration was on an empty stomach Stomach. Of course, other forms of administration are also possible, for example tablets, Capsules, Dragoes, etc.

The determination of the blood serum concentration of magnesium was made with an atomic absorption photometer carried out by L e i t ζ.

It was found that magnesium monoaspartate hydrochloride is absorbed significantly better as magnesium di-aspartate, which is included in the same pharmaceutical preparation in the same amount was administered under identical conditions.

Claims (1)

Claim: Orally administrable infarct prophylactic, characterized in that it contains magnesium monoaspartate hydrochloride contains as an active ingredient. The present invention relates to an orally administrable infarct prophylactic treatment which is characterized by a content of magnesium monoaspartate hydrochloride.
Magnesium monoaspartate hydrochloride of the formula