DE1809119B2 - INFARM PROPHYLACTIC - Google Patents

Description

Mg

/ Η — C-H

\ Η —C-NH ₂ HCl
O

is a colorless crystalline substance (crystal clear plates and columns) that comes in the form of a 1% aqueous Solution gives a pH of 4.5 to 4.8 and, as a 6% 1N HCl solution, a specific rotation of +12.5 Owns ± 2. The mixed melting point of this compound with dicyandiamide is 188 ° C. The solution

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 ₃ NCC

H, C-C

H ₂ CC

H ₂ NCC
H

\
O

O
"ΟΗ

OH

CH ₂ \

Mg + HCl

HCl · H ₂ NCH

Mg +

CH ₂

CH-NH ₂

y \

OH

The hydrochloric acid must be added to 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 is obtained, a thixometric amount of the reactants is carried out. the

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

leaves. Implementation filtered off. After concentrating the filtrate

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

Magnesium monoaspartate hydrochloride is surprisingly characterized by a very high complex stability the end. This fact is particularly surprising as the corresponding magnesium glutamate hydrochloride has a significantly lower 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 have been recommended for heart attack prophylaxis for several years. Of the The degree of the expected therapeutic effect depends on the amount of magnesium in the Body can be introduced. As a result of the high complex constant, magnesium monoaspartate hydrochloride becomes absorbed considerably better than all previously known magnesium compounds, so that the The efficiency of this compound is higher than that of all previously known magnesium compounds, as can be seen from the following comparative studies:

Absorption tests were carried out on rats with magnesium diaspartate and magnesium monoaspartate hydrochloride carried out in the following manner:

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 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 mg / kg) bled by puncture of the abdominal aorta; the 5 tul 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). Apparently 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 MiUimol Magnesium-Chlorid twice a day.

Compared to the controls, after administration of vpn 250 mg / kg Mg-A or Mg-A-HCl reduced the plasma magnesium from 2.05 ± 0.28 mg% to 2.93 ± 0.38 or 3.53 increased (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 was found <0.05.

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 (? I = 8)

Mg-A (n = 8)

Mg-A-HCl (n = 7)

Magnesium / plasma glucose / plasma

2.05 ± 0.28 223.0 ± 23.5

2.93 ± 0.385 ^{XX 230} ' ^{9 ± 27} > ⁵ 3.53 ± 0.60 £ ^x * 223.8 ± 15.1

x = P <0.001 versus 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 in the. Inhibition of blood coagulation 2000 UU / kg heparin or 75 mg / kg pentosan sodium polysulfuric acid 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.

2. Arterial pressure, pulse rate and breathing. The intravascular 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 substance after 30 minutes Average
after 60 minutes after 120 minutes Magnesium chloride
Magnesium di-aspartate
Magnesium mono aspartate
Hydrochloride + 0.19 mg%
+ 0.18 mg%
+ 0.15 mg% + 0.25 mg%
+ 0.29 mg%
+ 0.36 mg% + 0.31 mg%
+ 0.44 mg%
+ 0.57 mg %

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

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 experiments on humans with magnesium mono-aspartate-hyi'rochloride 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. Others come too, of course

Administration forms in question, for example tablets, capsules, coated tablets, 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 which is characterized by a content of magnesium monoaspartate hydrochloride.
Magnesium monoaspartate hydrochloride of the formula