Histaminase of vegetable origin for use in the treatment of allergic and septic shock and of allergic asthma

Abstract

The present invention relates to a histaminase of vegetable origin to be used in the treatment of allergic and septic shock and inallergic asthma. The invention also regards the preparation of the histaminase for pharmaceutical use and the corresponding pharmaceutical compositions.

Description

[0001] The present invention relates to a histaminase of vegetable origin to be used in the treatment of allergic and septic shock and of allergic asthma. The invention also regards the preparation of the histaminase for pharmaceutical use and the corresponding pharmaceutical compositions.PRIOR ART[0002] Histaminase is an enzyme of the family of the amine oxidases. A method for its preparation is described in the U.S. Pat. No. 4,725,540, where histaminase is produced by micro-organisms and used for removing or degrading the histamine present in animal feed and in those foods that may be responsible for allergies, such as milk and its derivatives, so as to stem allergic phenomena affecting humans. Afterwards, histaminase is removed or in some way deactivated by the above-mentioned types of food.[0003] Allergy is a complex phenomenon that may even affect internal organs, such as the heart and the lungs, causing bronchospasm, dyspnoea, asthma and shock. In particular, asthma is a chron...

AI Technical Summary

Benefits of technology

[0015] A further object of the invention is the use of a particular histaminase (Enzyme Commission EC 1.4.3.6) of vegetable origin that presents, amongst its innumerable advantages, a considerable ease of production, a high stability and a high level of activity.

Problems solved by technology

Allergy is a complex phenomenon that may even affect internal organs, such as the heart and the lungs, causing bronchospasm, dyspnoea, asthma and shock.

However, the above drugs present negative side effects.

However, these drugs must be considered only symptomatic, in so far as they induce relaxation of smooth bronchial muscle without affecting at all the pathogenic mechanism of the allergic reaction.

In addition, the effect of inhibition of the release of mediators of mast cells, which has been demonstrated for salbutamol in vitro and in vivo, is not, however, detectable in clinical use, given the acute conditions under which the drug is administered, as well as the brief duration of its action.

Another drug indicated both in attacks of asthma and in anaphylactic shock on account of its marked .beta..sub.2-agonist action is adrenaline, a drug which is certainly effective and frequently a life-saver in emergency situations, but which also presents dangerous side effects (hyperglycaemia, dyspnoea, tachycardia, arrhythmias, cephalea, vomiting, and dizziness, up to the point of triggering attacks of angina in cardiac patients), which relegate its use only to life-threatening situations (Hoffman B. B., Lefkowitz R. J., Catecholamines, sympathomimetic drugs and adrenergic receptor antagonists.

The use of methyl xanthines via parenteral route, which are useful above all in the state of asthmatic illness, is extremely dangerous owing to the considerable systemic effects (risk of arrhythmias, panic attacks, convulsions), which limit their use to the more serious situations and involve the need for careful monitoring of the patient (Nasser S. S., Rees P. J., Theophylline.

Their efficacy is beyond doubt both in attenuating the phenomenon in the acute phase and in the prevention of long-term relapse; however, in this case, the numerous side-effects of these drugs inevitably emerge (hyperglycaemia, osteoporosis, suppression of the hypothalamus-pituitary--adrenal axis, dysphoria / depression, increase in weight, hydro-saline retention, gastro-duodenal ulcer, cataract, hypertension, immuno-suppression, suspension syndrome) (Lipworth B. J., Clinical pharmacology of corticosteroids in bronchial asthma.

From the foregoing it emerges how, notwithstanding the constant endeavour aimed at countering allergic phenomena, given their enormous negative impact on the world population, so far no effective means have come available.

The above results, albeit encouraging, are, however, not resolutive.

Although it is absolutely indispensable to obtain positive results in laboratory animals before administration of potentially active molecules to a healthy volunteer for pathological situations, it is not at all certain that in man there will be the same results, in so far as there exist pharmacokinetic diversities (of absorption, distribution and accumulation in blood cells and in the organs) that may modify significantly the bioavailability of the drug, its pharmacological activity and hence its therapeutic effect.

Furthermore, the possible untoward side effects fail absolutely to be inferable.

The tests on guinea pigs are therefore not a direct and unequivocal proof of the efficacy of the enzyme in humans in so far as the human immuno-allergic disease is far more complex than any experimental model (e.g., isolated organ in vitro) since it is characterized by a complex pathogenic model that involves more than one mediator responsible for the clinical symptoms and signs.

In addition, there exists a technical prejudice according to which histaminase does not present any protective effect against allergies (Lessico Universale Italiano Treccani--Istituto Enciclopedico Italiano Vol.