BACKGROUND OF THE INVENTION The present invention relates to an adjuvant supplement for oncological patients to be administered simultaneously to or separately from conventional cancer treatments, (chemo/radiotherapy), according to a sequential administration.

The field of the invention is that of adjuvant treatment for tumours in gen- eral, in particular of solid tumours, such as tumours of the lung, colon, liver and the like.

Conventional cancer treatments normally consist of surgery, chemo and/or radiotherapy with significant side effects, which generally cause poor quality of life and limited survival due to metastasis of cancer stem cells that in- evitably survive each treatment. In any case, while greatly sacrificing the quality of life of the patient, conventional cancer treatments obtain results that are far from satisfactory even in terms of survival.

This led to the idea to propose an oncological supplement that helps to limit the spread of the cancer cells that survived the initial therapy.

SUMMARY OF THE INVENTION

The main object of the present invention is to provide a supplement for the adjuvant treatment of tumours to be administered separately or simultane- ously to known conventional cancer therapies with the aim of significantly improving the quality of life of the patient, while maintaining and/or improving the results obtained with conventional therapies (in terms of survival).

These and other objects are achieved with the supplement of claim 1 . Preferred embodiments of the invention are set forth in the remaining claims.

In relation to known radio and chemotherapy treatments in the cancer field, the supplement of the invention allows the effectiveness of the therapeutic effects obtained to be enhanced and maintained over time and prevents all the side effects related to known cancer treatments, improving the quality of life and survival of the patient even in the presence of (stable) neoplastic diseases. The adherence of the oncological patient to the consumption of the supplement is facilitated by the availability of its active ingredients in a single container represent- ing the exact dosing sequence of administration.

A further advantage is represented by the possibility of home application of the treatment with the supplement of the invention, thereby without the need for the traditional hospitalisation and with evident psychological, logistic and financial advantages for the patient.

DESCRIPTION OF PREFERRED EMBODIMENTS

According to the invention, the supplement utilised for the treatment of tumours in general, in particular solid tumours such as cancer of the lung, liver, prostate, pancreas, colon and others, is composed of a combination of active ingredients, functionally grouped in three different preparations made up in the form of respective kits to be administered according to a precise and strategic sequence with the aim of limiting the percentage of cancer cells that inevitably survived each treatment.

In particular, the supplement of the invention comprises a first preparation, made up into a corresponding Kit (1 ), containing active ingredients adapted for producing Radical Oxygen Species - ROS, highly reactive for selective damaging cancer cells.

According to a preferred embodiment of the invention, the first preparation comprises a 100 ml polysaline solution, containing 4 to 10 grams of vitamin C (on average 4 g) for intravenous administration. The same preparation also contains (with oral administration): citrulline, salified iron, an extract of Boswellia Serrata (such as the product Kymera® manufactured by the company Neo G Pharma), products based on omega 3 (such as the product Eskim® manufac- tured by the company Sigma Tao), melatonin (such as the product Circadin® manufactured by the company Fidia), polyphenols preferably glycosylated, DHEA (dehydroepiandrosterone), bitter almonds (two per day on alternate weeks), calcium ascorbate, all by oral administration.

A preferred example of formulation of the first preparation of the suppl ment of the invention is the following, where other fatty acids can be used place of omega 3, while other a-amino acids can be used in place of citrulline:

The supplement of the invention further includes a second preparation, grouped in a respective Kit (2), adapted to produce firstly the differentiation (first two weeks) and subsequently the apoptosis (subsequent two weeks) of the neo- plastic cells that survived the biological damage induced by Kit (1 ). This second preparation is administered at the end of the administration cycle of the preparation of Kit (1 ) for a total duration of 1 month.

Said second preparation comprises glycosylated flavonoids (in cps form for oral administration), in particular polydatin, quercetin (rutin), DHEA (dehy- droepiandrosterone), glucosinolates (epigallocatechin gallate) and capsaicinoids (capsaicin), and polyphenols.

Preferably, besides the active ingredients indicated above, Kit (2) can also include astragalus, (vitamin A: retinoic acid), vitamin D (dihydrotachysterol), li- poic acid, chondroitin sulphate, bitter almonds (two per day on alternate weeks), glucosamine, citrulline, melatonin, calcium ascorbate, myrrh (dried extracts), protease (bromelain), immunostimulants (organic germanium, betaglucanes), alka- lising substances (such as calcium salts), citrulline, polyphenols, DHEA (dehy- droepiandrosterone), chondroitin sulphate, anti-inflammatories (Boswellia Serrata, omega 3), calcium ascorbate, all in cps form for oral administration.

Administration of the preparation of Kit (2) takes place after the admin i- stration of Kit (1 ), for the duration of one month, preferably with the following sequence:

A) for 2 weeks (treatment for the induction of apoptosis): polydatin, sul- foraphane, myrrh (dried extracts), capsaicin, bromelain, betaglucanes, organic germanium, alkalising substances, melatonin, citrulline, epigallocatechin gallate, astragalus.

B) for two weeks (cell differentiation treatment): polydatin, quercetin, palmitoyl ethanol amide, retinoic acid, dihydrotachysterol (vitamin D), lipoic acid, organic germanium, epigallocatechin gallate, potassium ascorbate, melatonin, calcium ascorbate, Boswellia Serrata.

According to the invention, the aforesaid Kit (2) comprises the following compounds, where other proteolytic enzymes can be used in place of bromelain, other fatty acids can be used in place of omega 3, other polyphenols can be used in place of capsaicin, other isothiocyanates can be used in place of sul- foraphane and other a-amino acids can be used in place of citrulline:

After concluding the administration of the second preparation of the supplement of the invention, the adjuvant treatment of the oncological patient pro- vides for administration of a third preparation made up in a respective Kit (3) and also forming part of the supplement of the invention.

This third preparation performs the function of metastatic blockage of the neoplastic cells that survived the preceding treatments with Kit (1 ) and Kit (2).

Kit (3) is also administered orally for a duration of six months and mainly comprises glycosaminoglycans (preferably chondroitin sulphate), amino monosaccharides, (preferably glucosamine), amino acids (preferably lysine and proline), alkalising substances, Boswellia Serrata, polyphenols (glycosylated), melatonin, myrrh, calcium ascorbate, bitter almonds, according to the following preferred example of the invention:

The total amounts of active ingredients that make up the respective Kits (1 ), (2) and (3) is that necessary to cover the whole period of approximately 8 months of administration of the supplement of the invention, in the sequence: Kit (1 ) one month, Kit (2) one month, Kit (3) at least 6 months.

In this way, Kit (1 ) causes selective damages at various levels of the cancer cell (DNA, RNA, ion pumps of the cytoplasmic and mitochondrial membrane, protein enzymes and phospholipids), through the production of ROS. This dam- age is highly selective towards the cancer cells and leads them to necrosis as these latter, unlike normal cells, do not have efficient ROS neutralisation systems, such as catalase, glutathione peroxidase, superoxide dismutase. Apop- tosis must be induced in the surviving cells after differentiation with arrest in phase gO. It is underlined in particular that the ROS of the supplement of the invention selectively damage the cancer cell in any stage of the cell cycle, unlike chemotherapy, which instead acts prevalently on cells in mitosis. This allows a larger number of neoplastic cells to be damaged, therefore enhancing the effec- tiveness of radio/chemotherapy and leaving healthy tissue intact.

Apoptosis is subsequently induced in the cells that survived the aforesaid treatment with Kit (1 ) through administration of Kit (2). The object of Kit (2) consists in inhibiting the glycolysis pathway of pentoses and causing apoptosis through activation of the natural killer lymphocytes.

For its part, Kit (3) performs the function of obstructing metastatic spread, through inhibition of neo-angiogenesis, strengthening and inhibiting collagen degradation, activating the innate immune system (LNK) and facilitating its antineoplastic action through destruction of the fibrin coating that surrounds and conceals the tumour from the attack of the natural killer lymphocytes by prote- ases, alkalizing and inhibiting the inflammatory process of the extracellular matrix and obstructing the Warburg effect (prevalent in cancer cells).

In the table below some examples of the supplement of the invention are provided, where the percentages are by weight with respect to the total weight of the preparation.

The table illustrated below represents a range of recommended doses with the related maximum and minimum doses. The percentages relating to the KIT refer to the amount of product with respect to the total of the substances contained in the Kit in question, while the percentages relating to the total refer to the amount of product with respect to the total of the substances contained in all three Kits (KIT1 +KIT2+KIT3). Percentage re¬

Dose Range of doses Percentage related

Subject lated to the KIT

(g) (MI N/MAX) to the TOTAL (%)

(%)

M IN

(g) MAX (g)

* The doses are related to the amount of substances administered in one month ** The administration of 4 g of Vit. C takes place on alternate days through a 100ml polysaline solution drip, included in the kit

*** The doses are related to the amount of substances administered in 6 months

Clinical case: patient with right lung neoplasm

The present document describes application of the therapy in question to the patient A.R. who was diagnosed with right lung neoplasm.

The patient was initially treated with the therapy proposed with the first preparation+second preparation+third preparation plan followed by second preparation+third preparation plan. The patient is currently continuing solely with the third preparation. The patient in question refused conventional cancer therapies, hence undergoing only the therapy in question.

The CT scans performed on the patient are indicated below and show that the disease, initially aggressive with rapid proliferation, has evolved into a stable disease, confirming the efficiency of the sequential therapy proposed.

The patient is enjoying good health and good quality of life, achieving unexpected survival without conventional therapies.

CT CHEST SCAN WITHOUT AND WITH CONTRAST

Compared to the previous exam, in known case history of emphysema and chronic bronchitis of the chest, the known nodule with irregular spiculated margins within the lower left lung lobe appears thicker and slightly increased in volume.

Minimum bilateral pleural effusion.

Presence of multiple lymph nodes, of unspecified size, in the Barety lodge, at the origin of the supra aortic trunk SAT, at the aortopulmonary window and, more numerous, in the subcarinal region.

No pericardial effusion.

CT OF UPPER ABDOMEN WITHOUT AND WITH CONTRAST

Detects the finding of non-homogeneous solid tumefaction of the left adrenal (approximately 6 x 5 cm) indicative of the secondary site.

No other significant findings; in particular no hepatic focal lesions with suspected metastatic significance. BRAIN CT WITH CONTRAST

Marked widespread right frontal gliotic-malacic sequelae close to the vertex.

Non-pathological areas of contrast enhancement of the encephalic paren- chyma.

Median structures in axis.

CHEST with patient seated through necessity

The findings were apparently substantially stable compared with the previous exam. In particular: apparent faint nodule with a diameter of approximately 20 mm observed in the medial left lung field in the mantle zone, apparently already known from the previous CT.

Moreover, in senile chest hilar-perihilar vascular hyperaemia with pleural effusion at the bases, slightly prevalent on the left.

Calcified aortic sclerosis of the aortic disc.

Q.D.: lung ca examination

Exam performed with spiral technique in basal conditions as per specific request.

Previous investigations available.

FIRST BASAL CHEST CT

Increase in the size of the solid nodule with spiculated margins located in the apical segment of the lower left lobe, with maximum diameter of approximately 2.4 cm.

Appearance of suspect solid nodule of approximately 0.6 cm in the mantle area at the level of the basal segment of the same lobe.

Unchanged calcified nodule with "traction lines", as a result, in the apical segment of the upper left lobe.

No further parenchymal foci in lung in known, prevalently centrilobular, emphysema of the chest.

Explorable area of the trachea and main bronchial branches permeable. Suspected residues of mucous along the back wall of the tracheal band, to the carina.

Infracentimetric layer of decubitus pleural effusion in left medial-basal segment.

No right pleural effusion or pericardial effusion.

Lymph node with generally rounded shape, pathologically suspicious, of approximately 1 .4 cm in the right paratracheal region. Further suspicious lymph nodes are highlighted in the subcarinal region, the largest of approximately 2.3 cm.

Lymph nodes with prevalently elongated morphology are highlighted in the right hilar region (1 .5 cm) at the level of the aortopulmonary window (1 .2 cm) and in the Barety lodge (1 .1 cm).

Substantially no change to the solid tumefaction of approximately 6 cm at the level of the left adrenal, and to the remaining findings.

SECOND BASAL CHEST CT

At follow-up a slight increase is observed in the size of the nodule formations of the left lobe, which measure 2.1 cm vs. 1 .9 cm and 0.7 cm vs. 0.4 cm, respectively.

There is also a slight increase in the size of the mediastinal lymph nodes.

Appearance of minimum right pleural effusion.

No change to the findings regarding the left adrenal.

THIRD BASAL CHEST CT

At follow-up, no increases are observed in the sizes of the nodule formations previously indicated and of the mediastinal lymph nodes.

Right pleural effusion no longer appreciable.

Appearance of minimal left pleural effusion with maximum thickness of 7 mm is noted.

FOURTH BASAL CHEST CT

At follow-up, appearance of non-homogeneous alveolar and interstitial parenchymal thickenings at the level of the basal segment of the lower left lobe and in the ventral basal segment of the lower right lobe, these latter more circumscribed. The findings require clinical correlation and possibly re-evaluation after therapy, to exclude their inflammatory nature.

No substantial changes detected in the size of the known solid nodule with irregular margins in the apical segment of the lower left lobe, currently with maximum axial diameters of approximately 23x22 mm. The further subpleural nodule indicated in the antero-medial segment of the same lobe (6 mm) is also stable. Known very extensive centrilobular and paraseptal emphysema. Widespread thickening of the walls of the airways. Slight increase in the moderate left pleural effusion with a maximum thickness of approximately 15 mm in the medial-dorsal region. No right pleural effusion or pericardial effusion.

Substantially no change to the multiple mediastinal lymph nodes (the largest in the subcarinal region with short axis up to approximately 15 mm).

Collaterally in the scans through the abdomen, known enlarged left adre- nal of approximately 50 mm, unchanged.

Stable hypodense nodule of approximately 15 mm in the cutaneous- subcutaneous region at the level of the anterior thoracic wall in the right paramedian region at the height of the xiphoid process of the sternum.

Fracture of the anterior arch of the left 9th rib, in the healing stage, re- quires correlation of the medical history to evaluate the origin of the trauma.