PHARMACEUTICAL COMPOSITION COMPRISING ECBALLIUM ELATERlUM JUICE AND THEIR USE IN MEDICAL FIELD

The present invention concerns a pharmaceutical composition comprising Ecballium Elaterium juice and uses thereof in medical field. In particular, the present invention concerns a pharmaceutical composition comprising Ecballium Elaterium juice and uses thereof in medical field for the treatment of the infectious and allergic rhinitis, rhino-sinusitis and nasal clogging. The oedema of nasal mucosa, provoking narrowing or occlusion of para.-nasal sinus ostium, interrupts the normal transit of oxygen thereto, thus resulting in strong cephalea and general malaise due to the occurrence of ex vacuo sinusitis (negative pressure in the paranasal sinus resulting from oxygen deficiency previously absorbed by mucosal vessels). If the vacuum persists in the mucosa transudate is formed which fills the sinus; transudate acts as a culture medium for bacteria entering sinus through ostium or diffused cellulites or thromboflebitis of mucosa lamina propria. Serum exudates, leukocyte rich, is formed in order to treat the infection and, in the obstructed sinus a positive pressure is developed resulting in increased pain. The mucosa becomes hyperemic and edematous.

Up to now used therapies for the treatment of infectious, allergic mucus - purulent rhinitis and rhino-sinusitis involve the use of cortisone based drugs, decongestants or vasoconstrictors, mucolytics, antihistamines, sulphur crenotherapy, antibiotics, surgery. However, this type of therapies is not suitable to reduce the oedema of nasal and paranasal mucosa and above all facilitate the outwardly flow of mucus-pus formed in the paranasal sinus as a result of rhino-sinusitis.

Moreover, it is known that the drugs up to now used for the therapies of rhinitis display various disadvantages and drawbacks. As an example, cortisone based drugs result in water retention (swelling), weight increase, reduce the immune system thus exposing the patient to the risk of acquiring other diseases, topical formulations are not effective during acute steps, must be used for long periods, do not contribute to the elimination of the mucus-pus.

Decongestants or vasoconstrictors display an as immediate as short effect, are not selective, i.e. they act not only on the nose but all the organism, provoke the occurrence of the "so-called" rebound, i.e. opposite

to desired, effect, can increase the arterial pressure values, can be used for few days even if administered together as topical formulations (nasal spray), do not contribute to the elimination of the mucus-pus formed in para-nasal sinus. As to mucolytic drugs, it is known that they display disadvantages, for example they are contraindicated for asthmatic patients, their effectiveness is displayed only after 10-15 days of therapy, are not able to penetrate para-nasal sinus and therefore do not fluidize mucus-pus therein contained, these drugs, due to the above mentioned reasons, do not contribute to the elimination of the mucus-pus formed in para-nasal sinus.

Antihistaminic drugs do not display an immediate effect, the main side-effect is sleepiness, resulting in effects on attention condition and reflex quickness, therefore these drugs are not suitable for driver or people carrying out potentially dangerous job, often they are marketed in association with vasoconstrictors resulting in an increase of the probability of side-effects occurrence, do not contribute to the elimination of mucus- pus formed in the paranasal sinus.

Also sulphur crenotherapy displays disadvantages, in fact it requires long therapeutic cycles (minimal 12 days), it is necessary to reach thermal treatment centres (often distant from residence place), it does not exert an immediate effect on painful symptomatology, even if it subsidised by SSN, it is possible to be very expensive because of necessity to stay in a thermal centre (hotel, travel etc), it is not within common possibilities involving the absence for long time periods from job, school or family.

Antibiotics display only antibacterial activity, therefore they are not effective for viral or fungine rhino-sinusitis, in some cases do not penetrate para-nasal cavities, if broad spectrum antibiotics are used it is possible to promote, during long period, an indiscriminate antibacterial activity, on the other hand, if narrow spectrum antibiotics are used, when a resistant bacterial strain is present, long therapies are necessary and they do not contribute to the elimination of the mucus-pus formed in para-nasal sinus.

Finally the surgery involves that the patient is subjected to a surgical operation, it can results in an alteration of the mucociliary tissue, high probability of relapse occurrence and therefore the need of carrying

out a new surgical operation, it is not indicated neither for the acute occurrences nor for symptom remission in the same.

In the light of above, it is therefore apparent the need to provide new therapeutic compositions suitable to overcome the disadvantages of known therapies for the treatment of rhinitis and principally of rhino- sinusitis.

Ecballium Elaterium belongs to the Cucurbitacee family. The plant is typical in the Mediterranean countries, it originates from arid regions of North Africa. In antiquity, this plant has been used by Egyptians, Greeks and Romans as drastic laxative, it is 20-40 cm high and grows on uncultivated lands, at the margins of crop fields, everywhere in coastal peninsular regions and islands. Ecballium Elaterium is a perennial herbaceous, crawling plant with rough hair covered prostrate stalk. Flowers of the plant are yellowish, green streaked, similar to those of the melon, and are situated at the axilla of the leaves. It is very characteristic for this plant the mode through which the fruit separation occurs. At maturation time, in fact, gases inside of the fruit reach a critical pressure and the fruit, shaped as a large green acorn, detaches abruptly from peduncle, spontaneously or at minimum contact; seeds and mucillagineous substance containing the same, are sprayed at a distance, while the empty capsule, by reaction, is thrown in opposite direction

The juice of this cucurbitaceae member exerts a strong attraction for liquids, for this reason many Mediterranean inhabitants used and still today use this substance for the therapy of costiveness. In fact, the plant, orally administered, attracts liquids in the intestine, thus increasing the feces volume and stimulating intestinal motility and therefore evacuation.

The authors of the present invention now have found that the Ecballium Elaterium juice attracts the mucus and liquids in the para-nasal and nasal sinus, thus reducing oedemas, congestion and nasal clogging. The mucosa oedemas, major responsible of the nasal clogging and congestion, as well as of the narrowing or occlusion of para-nasal sinus ostium, are remarkably reduced as result of the loss of liquids strongly attracted from Ecballium Elaterium juice. Also mucus-pus occurring in nasal and para-nasal fossa is attracted outwardly due to the strong action resulting from this substance. As a result of the restoration of the ostium

accessibility, normal oxygen flow in the para-nasal sinus and therefore the disappearance of aforesaid painful symptomatology are obtained

Rhinitis and rhino-sinusitis, which disclose by means of above described symptomatology onset, resulting from the formation of nasal and para-nasal mucosa oedema, as well as mucus-pus formation in nasal fossa and para-nasal sinus, therefore can be treated with Ecballium

Elaterium juice.

Particularly, Ecballium Elaterium juice is prepared according to a particular method provided by the authors of the invention comprising cold squeezing of Ecballium Elaterium plant berry (peponide), which is harvested from June to November, i.e. during the full maturation period.

After the squeezing the juice is micro-filtered with appropriate system with

0.1 micron porosity; thus the solid is separated from the liquid and the microbial flora is completely separated For the preparation of the solution to be used for the treatment of said pathologies only the liquid part of the juice is used. The latter is diluted with water at 1 :3,5 ratio (1 liquid part of ecballium elatrium juice for

3,5 parts of water). The solution thus obtained is used to prepare nasal spray or vial for aerosol therapy. Therefore it is an object of the present invention the juice of

Ecballium Elaterium obtainable by means of the method comprising or consisting of the following steps: a) cold squeezing of Ecballium Elaterium berries; b) filtering with elimination of the solid, for example by means of 0,1 micron size pore filter. In particular, the filtration is carried out by using sequential filters with different size pores, i.e. beginning from large and having, at the end of the filter set, 0,1 micron size pore filter. This final porosity represents a pore size not allowing the passage of bacteria, yeasts and fungi into the final solution. Moreover, the present invention relates to a solution of

Ecballium Elaterium juice comprising or consisting of Ecballium Elaterium juice and water at 1 :5, preferably 1 :4, more preferably 1 :3,5 ratio.

A pharmaceutical composition comprising or consisting of Ecballium Elaterium juice or Ecballium Elaterium juice solution as above defined as active principle in association with one or more pharmaceutically acceptable co-adjuvant and/or excipient represent a further object of the present invention. The pharmaceutical composition

can be in a form suitable for nasal administration like, for example, nasal sprays or vials for aerosol therapy.

The present invention concerns moreover the use of Ecballium Elaterium juice, solution of Ecballium Elaterium juice or pharmaceutical composition as above defined for the preparation of a medicament for the treatment of infectious or allergic rhinitis, rhino-sinusitis or nasal clogging.

The present invention now will be described by illustrative, but not limitative, way, according to preferred embodiments thereof.

EXAMPLE 1 : Clinical study on subjects affected by rhino- sinusitis and subjected to treatment with Ecballium Elaterium juice

Objectives: evaluation of the treatment effectiveness with Ecballium Elaterium juice administered to subjects affected by acute or relapsed chronic rhino-sinusitis;

Study criterion: administration of the solution at different doses based on the case severity;

Methodology: 72 patients (2/3 male and 1/3 female), 80% with 34 year average age and 20% under 16 year old (minimum 6 year old), all suspected of acute or chronic relapsed rhino-sinusitis, as identified by family doctor, have been subjected to diagnostic exams. 60 out of 72 patients subjected to diagnostic exams, were found to be affected by acute or chronic relapsed rhino-sinusitis, and all were included in the study.

Depending on the case severity, the following doses have been administered: - 32 patients with symptomatology defined as "common" were subjected to administration of two daily doses over 3 days;

- 21 patients with symptomatology defined as "pronounced" were subjected to administration of daily doses for 6 days;

- 7 patients with symptomatology defined as "critical" were subjected to administration of two daily doses for 10 days;,

Sinusitis time course was evaluated 24 hours after the last administration of the solution with score based on the symptoms, objectivity and therapy protocol.

Study results: in 90% of the cases (n° 54) the patients considered and therefore subjected to the treatment with the solution containing Ecballium Elaterium juice evidenced the disappearance of the sinusitis symptomatology, previously identified by the family doctor. Only

for 13 (thirteen) subjects, during the treatment, the occurrence of side- effects was present, like throat irritation, rhinorrhea and nasal mucosa irritation.

Conclusions: from reported study it is apparent that the solution containing Ecballium Elaterium juice used for the treatment of the acute and chronic relapsed rhino-sinusitis proved to be the unique medical application suitable, in so high case number, to result in, before of the last administration, total symptomatology disappearance (cephalea, general malaise, nasal clogging, frontal and maxillary oedemas, etc).