DE2454164A1 - Injections against magnesium tetany in ruminants - contg. a basic magnesium salt of acetylglutamic acid - Google Patents

Abstract

In Ca- and Mg-contg. injection- or infusion solns. against magnesium tetany (hypomagnesaemia) in ruminants, the Mg is present as a basic salt or acetylglutamic acid. The solns. are used against magnesium tetany, such as field-, stable- or transport tetany in ruminants esp. cattle. They re-instate the acutely disturbed ion-equilibrium in the blood so that acute symptoms quickly disappear. They also remove excess NH3, caused by eating spring grasses, via the urea cycle. The N-acetylglutamate present stabilises the enzyme protein necessary for the reaction of excess NH3 with ornithine to form carbamylphosphate with enduring effect. The solns. are very well tolerated and have no side-effects on heart and circulation.

Description

Solution for injection or infusion to combat tetany Ruminants and Methods for Making Same The present invention is on an injection resp.

Infusion solution aimed at the control of tetany in ruminants, which contains calcium and magnesium as active ingredients. It also relates the invention relates to a method for producing such an injection or

Infusion solution.

With the beginning of the pasture uplift the cattle will be on pastures with a well-developed grass growth regularly observed the increased occurrence of pasture tetany. Since Stedefelder (Berlin veterinarian Scher. 41, 807, 1925) and Sjollema (Tijdschr. Diergeneesk. 55, 1017, 1085, 1121, 1187, 1928; German veterinarian Wschr. 37, 17-24, 1929; Tijdschr. Diergenessk. 57, 67-69, 1930) a drop in the serum magnesium level (Hypomagnesaemia) was recognized as a characteristic feature of this disease, was the goal of all treatments is to restore the ionic balance in the blood restore.

For the development of the tetania caused by hypomagnesaemia internal and external factors are responsible for cattle. In the pasture tetany alone represents the transition from stable to pasture husbandry with a radical change in feed and possible extreme temperature fluctuations place a great strain on adaptability and the metabolism of the animals. The most important factor aetiologically, however, is to name the excessive ammonia production in the rumen of the animals, caused by the Ingestion of young pasture grass with its high N content and low proportion of Crude fiber. Due to the increased formation of NH3, it comes about as a result of a blockage of the magnesium in the form of insoluble ammonium magnesium phosphate for the development of hypomagnesaemia with their well-known, often life-threatening symptoms, such as cramps, being stuck, Heart and circulatory failure.

The fall cases are due to the fact that the At this time, due to the climate, grass often regains the character of young pasture grass accepts.

From 1930 to 1936 (e.g. Tijdschr. Diergeneesk. 56, 979-989, 1929) for the control of tetany in cattle the administration of calcium-magnesium salts in general therapy.

The salts are given to the animals in the form of an injection or

Infusion solution administered. This treatment has proven itself and preserved to this day.

As a result of their poor local tolerance, calcium-magnesium-chloride solutions are but can only be used intravenously. With paravenous infusion there is a risk of Thrombophlebitis. They are also not without danger in the presence of circulatory damage apply. Not least for these reasons, Allcroft (Vet. J. 103, 157-176, 1947) propose the use of magnesium sulfate. However, this also causes this Magnesium sulphate significant local irritation symptoms.

The recent administration of anesthetics such as E.g. Ohloralhydrat and from tranquilizers as well as from barbiturates represents a symptomatic Treatment. It calms the patient down and is said to be safe Enable causal therapy.

Because of the side effects associated with the treatment methods mentioned Magnesium gluconate was introduced into therapy. (Fischer, German veterinarian. Wschr. 75, 8-11, 1968).

There are also references to this in American literature, e.g. in Witherspoon (Mod.Vet.Pract. 42: 4,49, 1961). Wehner (Veterinarian Umschau 19, 553-565, 1964) reports on the use of magnesium gluconate together with calcium gluconate and methionine against the cows getting stuck.

However, one disadvantage of calcium-magnesium-gluconate is the bad Solubility in water, which, however, is improved by the addition of boric acid can. Another disadvantage is that compared to the inorganic crystalline Solutions of calcium and magnesium salts have the therapeutic effect of magnesium gluconate occurs more slowly (Fischer, Dtsch. Tierärztl. Scher. 75, 8-11, 1968). A reassurance the animals enter within 20 - 45 minutes after the infusion of magnesium gluconate, Get up after 30 minutes to 6 hours.

Because of the often life-threatening condition mentioned at the beginning however, a rapid onset of action is desirable. It also affects the relatively large infusion volume of 490-500 ml per animal as a result of the Disease-related alarming of the animals is often very detrimental.

The present invention is based on the object of an injection or to create infusion solution to combat tetany in ruminants, with which avoids the disadvantages described above and with which in particular a faster onset of action and the side effects of the well-known calcium-magnesium salt solutions can be switched off.

This task is achieved by an injection or injection process mentioned at the outset. Infusion solution solved, which is characterized in that the magnesium as a basic salt the acetylglutamic acid is present.

The new composition of the calcium-magnesium solution represents according to the invention new ways in the therapy of tetany in ruminants, especially cattle. This composition eliminates the disadvantages of the well-known calcium-magnesium salt solutions, and it is a much better effectiveness and tolerance to calcium respectively.

Magnesium gluconate or borogluconate solutions detectable.

These advantages are achieved in particular by the fact that for the production the solution according to the invention N-acetyl-glutamic acid is used. This acid is used for the first time for therapeutic purposes in veterinary medicine.

According to a further embodiment of the invention, the calcium is located as calcium gluconate. However, since calcium gluconate is known to be bad in water is soluble, injection or infusion solutions are advantageously used, in which the calcium is present as calcium borogluconate. Calcium borogluconate dissolves very good in water (The Merck Index 1968, p. 190); which has 20% solution but a pH of 3.5, which can be achieved by adding before using these solutions brings Ca0 to pH 7.

The injection or infusion solution according to the invention has an effect on the disease process opposed to tetany in two ways. First is the acutely disturbed ion balance restored in the blood so that the acute symptoms of the disease quickly subside. Furthermore, the N-acetyl Glutamic acid the excess NH3 is introduced into the urea cycle and removed from the organism with the urine.

This stabilizes the healing process and prevents recurrences or reduced.

N-acetylglutamic acid intervenes in the urea cycle in the following way: The urea formation is of an intact, energizing Metabolism dependent. To react with ornithine, a CO2 molecule must first be used and an NH3 molecule brought into a reactive form, the carbamyl phosphate will. In addition to carbamyl phosphate synthetase, N-acetyl glutamate is involved in this reaction involved as an activator, which does not act as a substrate, but the enzyme protein stabilized.

The N-acetylglutamic acid used for the first time in the solution according to the invention has a lasting effect in terms of eliminating the excess NH3 and thus contributes significantly to overcoming the disease process. Next to The solution is extremely well tolerated by this two-phase effect for the heart and circulation.

The present invention also relates to a method of manufacture the injection or described above. Infusion solution. This procedure is characterized by the following steps: (1) Making a clear solution from a basic Magnesium compound and acetylglutamic acid; (2) Prepare an aqueous suspension of calcium gluconate, add boric acid until a clear solution is obtained; (3) Mixing the prepared according to (1) and (2) Solutions; and (4) filtering, filling and sterilizing the according to in the usual way (3) final product obtained.

The solution obtained is stable, can be sterilized or hot also with preservatives, for example methyl p-hydroxybenzoate or Nipagin, to be preserved.

According to another embodiment of the method according to the invention the solution prepared according to step (1) is boric acid and calcium gluconate directly added.

The preferred basic magnesium compound is magnesium carbonate, Magnesium hydroxide or magnesium hydroxide carbonate (basic carbonate magnesia) used. The solutions formed according to step (1) and / or (2) are preferred under Stirring made at room temperature.

The boric acid has a calcium gluconate: boric acid ratio of 1: 1.6 used. Accordingly, the molar ratio of boric acid and calcium gluconate corresponds not that of calcium borogluconate.

As previously described, the conventional calcium borogluconate injection solutions brought to pH 7, as it is in the acidic range due to incompatibilities experience has shown that they cannot be used.

The composition produced according to the invention creates a Injection solution with pH 4, i.e. in the acidic range. Unlike everyone The knowledge available to date is that produced according to the invention, despite the acidic pH Injection solution more effective and comparably more tolerable than the previously known Formulations.

The process of the invention is illustrated in more detail in the following examples explained.

Example 1 100 ml of distilled water were added at room temperature 31.2 g of 2 magnesium hydroxide carbonate were slowly suspended under rubbing and in small amounts A total of 62 g of acetyl glutamic acid were added to the portions. Everyone waited further addition of acetylglutamic acid until the foaming had subsided (C02 development when the acid is added). After he finished adding the acetyl glutamic acid was stirred for another half hour.

600 ml of distilled water were added to the resulting solution 73 g boric acid and heated to boiling.

With constant stirring, 328.8 g of calcium gluconate were poured into the warm Entered solution, whereby a clear solution was formed.

The filtered solution was filled in and sterilized in the usual way.

Example 2 584 g of magnesium hydroxide and 1890 g of acetyl glutamic acid were dissolved in 6 l of water with stirring. The solution was heated to boiling, and there were 16.7 liters of water, 10 kg of calcium gluconate, 2.22 kg of boric acid and 30 g of nipagin added. The hot clear solution was filmed, filled and hot sterilized.

The injection or infusion solution according to the invention is used for combating of tetania in ruminants, especially cattle, such as pasture, Stable, transport or Gestetania. The solution will be generally administered intravenously according to the requirements of the therapy, However, it can be used as a preventative measure in the event of particular risk or in addition to or for follow-up treatment can also be given subcutaneously.

Normally, for the treatment of a cattle (approx. 500 kg kg.) 250 ml is sufficient. In severe cases, the dose can be increased up to 500 ml will.

The following table summarizes the results of clinical trials in the form of field trials: Number d. indication beh. easy heavy dos. Thera-required add. Remarks Animals up to mid. Tetany ml pieer- derl. therapy Tetany follow% follow-up behdlg 80 --- 80 250 100 none none very good Compatible- 12 --- 12 250- at 5 at 6 2 animals emergency 400 90 animals slaughtered animals first Dexa- very good Heilg. metha- compatible- after son keit for 2.Ver- heart and abrei- cycle chung from 250 ml Cardiac opportunity 14 14 - 250 100 none none pretreated with 400-500 ml of a Ca Mg preparation

Claims (8)

P a t e n t a n s p r ü c h e: Solution for injection or infusion for Control of tetania in ruminants, which are calcium and magnesium as active ingredients contains, characterized in that the magnesium is the basic salt of 4cetylglutamic acid is present. 2. Injection or infusion solution according to claim 1, characterized in that that the calcium is present as calcium gluconate. 3. Injection or infusion solution according to claim 1, characterized in that that the calcium is present as calcium borogluconate. 4. Method of preparation of the solution for injection or infusion according to claims 1-3, characterized by the following steps: (1) create a clear solution from a basic magnesium compound and acetyl glutamic acid; (2) Prepare an aqueous suspension of calcium gluconate, add boric acid until a clear solution is obtained; (3) Mixing the prepared according to (1) and (2) Solutions; and (4) filtering, filling and sterilizing the gemass in the usual manner (3) final product obtained. 5. The method according to claim 4, characterized in that the Boric acid and calcium gluconate are added directly to the solution prepared according to step (1). 6. The method according to claim 4 or 5, characterized in that one as the basic magnesium compound, magnesium carbonate, magnesium hydroxide or magnesium hydroxide carbonate (basic carbonic acid magnesia) is used. 7. The method according to any one of claims 4 ~ 6, characterized in that that the solutions formed according to step (1) and / or (2) with stirring at room temperature getting produced. 8. The method according to any one of claims 4-7, characterized in, that the boric acid is used in a ratio of calcium gluconate: boric acid of 1: 1.6.