Pharmacological preparation composed of a quinoxaline derivative mixed with sodium bicarbonate

A pharmacological preparation for use in animal husbandry, consists essentially of sodium bicarbonate and an active ingredient which is either 2-methyl-3 (.beta.-hydroxyethylcarbamoyl) quinoxaline-1,4-di-N-oxide or N.sub.1, N.sub.4 -dioxo-quinoxaline-2-methyleneimino-N-methylurethane. The sodium bicarbonate imparts fireproofness to what would otherwise be a highly flammable preparation.

The present invention relates to a product obtained by conditioning and 
supporting a quinoxaline derivative, known for its pharmacological 
activity and for its use in the field of animal husbandry, with sodium 
bicarbonate. 
The said conditioning and support are extremely useful inasmuch as they 
make it easy to handle, mix and store a substance which is otherwise very 
dangerous in that it is unstable, highly flammable and also explosive. 
The product supported according to the invention can be marketed, and the 
end-user can further mix it with animal feed in the required proportions 
with absolutely no risk of flammability. 
The quinoxaline derivatives currently used in animal husbandry are of two 
types and their structure is similar. They are 
2-methyl-3(.beta.-hydroxyethylcarbamoyl)quinoxaline1,4-di-N-oxide and 
N.sub.1,N.sub.4 -dioxo-quinoxaline-2-methyleneimino-N-methylurethane. 
Their structural formulas are as follows: 
##STR1## 
These two substances are also similar pharmacologically: they possess 
particular chemotherapeutic properties which make them effective urinary 
tract antiseptics, but are also systemic disinfectant agents, combat 
chronic respiratory diseases in poultry, certain bacterial infections in 
pigs and are particularly effective as animal feed supplements and are 
thus useful as animal growth promoters. However, the major disadvantage of 
these two substances, resulting from their labile chemical structure, is 
their high flammability. 
To overcome this serious problem, the present invention proposes to mix the 
quinoxaline derivative to be employed with sodium bicarbonate in a 50% 
proportion, or also in other proportions in the range 20:80. This addition 
of sodium bicarbonate to the quinoxaline derivative decreases or, if the 
proportion of sodium bicarbonate added is at least 50%, totally eliminates 
all risk of fire due to friction, impact or any other cause, thus allowing 
these quinoxaline derivatives to be handled with absolute safety. 
When either of these otherwise highly flammable substances is mixed in 
equal parts with sodium bicarbonate it will no longer catch fire even if 
primed with a naked flame. The antifire properties of sodium bicarbonate, 
already known in other fields, are thus in the present instance absolutely 
decisive, more exactly because sodium bicarbonate is a support which 
effects a chemical mediation of particular efficacy for the purpose in 
question as a result of the evolution of carbon dioxide resulting from the 
known reaction: 
EQU 2NaHCO.sub.3 .fwdarw.Na.sub.2 CO.sub.3 +CO.sub.2 +H.sub.2 O 
These concepts find endorsement in various laboratory trials which aimed to 
identify the substance or substances most suitable for the purpose in 
question, but which at the same time took all due account of the fact that 
the selected additive must be compatible with the two quinoxaline 
derivatives as regards chemical interaction and pH. Selection of the most 
suitable substance was also conditioned by the fact that, as well as 
requiring to be an antifire and stabilizing agent, it will be ingested by 
animals for long periods, even if in small doses, and must therefore be 
nontoxic. The trials mentioned showed that sodium bicarbonate is the most 
effective and least toxic substance available for the purpose. It is a 
nontoxic substance. 
Moreover, it has the further advantage of allowing a readier digestibility 
of the two quinoxaline derivatives. 
The quantitative ratio of the two components of the mixture, i.e. the 
quinoxaline derivative and sodium bicarbonate, can therefore be 50:50, or 
in a range of between 80% of one component and 20% of the other, though it 
is more advisable to use 50% or more sodium bicarbonate. 
The mixing of the two components can be carried out in the quinoxaline 
synthesis reactor, at the end of the reaction, when the sodium bicarbonate 
can be added in the desired ratio so as to protect the quinoxaline in the 
subsequent steps of isolation, centrifugation, drying and grinding.

The following example, which is not limiting as regards other types of 
mixing, is illustrative of the kind mentioned. 
EXAMPLE 
To a reaction flask containing 100 g of 
2-methyl-3(.beta.-hydroxyethylcarbamoyl)quinoxaline1,4-di-N-oxide, and in 
the presence of the reaction solvent, addition was made of 100 g of sodium 
bicarbonate. The whole was vacuum filtered and transferred to a vacuum 
dryer. 200 g of 
2-methyl-3-(.beta.-hydroxyethylcarbamoyl)quinoxaline1,4-di-N-oxide 
containing 50% sodium bicarbonate was obtained. Even if primed with a 
naked flame, this mixture was non-flammable and did not decompose.