Nutraceutical or pharmaceutical composition comprising an extract of pelargonium sidoides

Abstract

This invention concerns a composition of substances effective in the prevention and / or treatment of infectious diseases in the dermatological, gynecological, urological, respiratory fields. The composition of the invention includes an extract of Pelargoniuum sidoides, phosphatidylserine, phosphatidylcholine and starch. This formulation gives the composition properties of gastro-resistance, increased permeability across membranes, controlled release and a high bioavailability of Pelargonium sidoides extract. The composition of the invention is prepared in solid, semi-solid or liquid pharmaceutical dosage form, preferably by oral administration.

Description

[0001] “Nutraceutical or pharmaceutical composition comprising an extract of Pelargonium sidoides”

[0002] *************

[0003] DESCRIPTION

[0004] This invention concerns a nutraceutical or pharmaceutical composition effective in the prevention and / or treatment of infectious diseases in the dermatological, urological, gynecological and respiratory fields both in humans and animals.

[0005] Background of the invention

[0006] INFECTIOUS DISEASES

[0007] An infectious disease derives from the presence of pathogens that establish a parasitic relationship with the host organism.

[0008] Pathogens belong to different categories such as bacteria, viruses and fungi and are called parasites because they require some vital functions of the host organism for their survival.

[0009] The human body may also be subject to infections by pathogens, which can affect the skin or extend the infection to the urinary tract or respiratory system.

[0010] In dermatology, the main bacteria responsible for skin infections are three: Staphylococcus aureus, Staphyloccocus epidermidis and Streptococcus pyogenes.

[0011] Bacterial infections of the superficial layers of the skin are divided into impetigo and folliculitis, while those that affect the deeper layers are ectima, erisipela and necrotizing fascitis. Diagnosis requires the correct location of the site of infection with subsequent topical or systemic medical treatment.

[0012] Skin infections can also be of viral origin, as is the case for herpes simplex virus infections. Herpes is a contagious infectious disease, which causes the formation of inflammatory vesicles, which occur at the lips (HSV-1) or manifest in a widespread manner in the genital area (HSV-2). It represents a very frequent pathology that occurs when there is a decrease in the immune system, especially due to strong stress and physical fatigue. Treatment of the disease involves the use of specific antivirals in order to relieve the symptoms associated with herpes. In the gynecological field, bacterial infections can induce kidney stones and localized inflammatory states as cystitis.

[0013] As for kidney stones, pathogenic microorganisms that colonize the urinary tract determine the formation of struvite stones. The main pathogenic microorganisms of the female urinary tract are Proteus mirabilis and Klebsiella pneumoniae. The latter are producers of ammonia, which in the presence of urine determines the formation of magnesium ammonium phosphate hexahydrate crystals. It is possible to diagnose the pathology through urine analysis, in order to identify the pathogen responsible for the infection and then resort to appropriate therapy with antibiotics.

[0014] In the case of cystitis, the latter represents an acute or chronic inflammation of the bladder caused by infections of the female urinary tract. The main pathogenic agent is Escherichia coli, which passing through the urethra, can subsequently infect the bladder. Urinoculture can be used to diagnose the disease by detecting the presence of esterase and nitrite in the urine. Antibiotics are used to reduce the proliferation of these pathogens. Vaginal infections include various pathologies such as: bacterial vaginosis, cervicitis, vaginitis from Trichomonas vaginalis and vaginal Candida.

[0015] Bacterial vaginosis is a vaginitis that results from an increased growth of bacterial pathogens of the female urinary tract, resulting in alteration of normal vaginal flora. One of the main pathogens responsible for this disease is Gardnerella vaginalis. Bacterial vaginosis is characterized by greyish and malodorous secretions, associated with strong itching and irritation. It is possible to diagnose this pathology, analyzing vaginal secretions. The use of antibiotics promotes a reduction in the number of urinary tract pathogens, restoring the vaginal flora.

[0016] Cervicitis is an infectious inflammatory process that affects the cervix. The bacterial infections of the cervix can be caused by Chlamydia trachomatis and Neisseria gonorrhea. In this particular case, vaginal discharge and vaginal bleedingoccur between menstrual periods or after coitus. Diagnosis is made by using vaginal swabs, identifying the formation of purulent cervical exudate or observing cervical friability. Treatment of the disease involves the use of antibiotics associated with a temporary cessation of sexual activities.

[0017] T. vaginalis vaginitis is an infectious disease caused by entry of the protozoan in the vagina.

[0018] This type of infection occurs exclusively through sexual transmission. The production of yellowish and foamy vaginal secretion is often associated with vaginitis, as well as a strong sensation of pain during urination and sexual intercourse. By analysis of vaginal secretions and cervical fluid, it is possible to identify the pathogen. To reduce the damage from infection of T. vaginalis it is necessary to resort to the use of antiparasitic medicaments.

[0019] The female urinary tract can be prone to fungal infections, as is the case for the fungus Candida albicans. In this case, an uncontrolled proliferation of the fungus occurs at the vagina. The vaginal Candida involves discomfort and itching at the level of the vulva, as well as generating pain during urination and sexual intercourse. The urinalysis or the use of a vaginal tampon, promotes the recognition of pathology and its treatment involves the use of antifungals.

[0020] In the gynecological field, viruses are also responsible for common diseases such as papilloma virus (HPV) which is commonly characterized by the appearance of warts; conventional treatment includes creams based on salicylic acid or antiviral creams.

[0021] In the urological field there are several diseases caused by viruses, bacteria or fungi such as: contagious mollusc, balanitis, postitis, balanoposthitis, genital herpes. Pathogenic microorganisms can also affect the respiratory system, developing mainly upper airway infections. Among them, there are nasopharyngitis, sinusitis, pharyngitis, tonsillitis, laryngitis, tracheitis, bronchitis and pneumonia.

[0022] Nasopharyngitis, known as a cold, manifests by nasal secretions, frequent sneezing, throat irritation, coughing and hoarseness. To relieve the symptoms, we resort to the use of decongestants and expectorants when the colds is more marked and annoying. The common cold can also result from viral infection such as E229 coronavirus, which affects the human respiratory tract. Also in this case, the main symptoms of colds are nasal secretions and irritation of the throat.

[0023] The treatment of this condition of malaise involves the use of specific antivirals in the most serious cases.

[0024] Sinusitis, on the other hand, represents an acute or chronic inflammation of the mucosa that covers the paranasal sinuses, with more marked and persistent symptoms over time.

[0025] The origin of the infection is due to the presence of major pathogens such as Streptococcus pneumoniae and Haemophilus influenzae. For the treatment of sinusitis, antibiotics with antibacterial activity are used, as well as avoiding exposure to agents that trigger allergic reactions.

[0026] Pharyngitis is also known as sore throat and manifests as an inflammatory process caused by the presence of Streptococcus pyogenes. The symptoms associated with pharyngitis are pain during the swallowing process, enlarged lymph nodes, reddened tonsils, hoarseness and in severe cases fever and muscle pain. The treatment of sore throat can take place using hot drinks and natural remedies in addition to the use of anti-inflammatory medicaments and painkillers.

[0027] Acute tonsillitis commonly refers to inflammation of the palatine tonsils, or lymphatic tissue of ovoid shape visible in oropharynx, laterally to the uvula. Usually, the disease is caused by viral infections such as Rhinovirus or Adenovirus if the infection lasts more than 72 hours it is generally of bacterial origin.

[0028] Conventional therapy includes anti-inflammatory or if necessary broad-spectrum antibiotics. Other respiratory diseases that can lead to microbial infection are laryngitis and tracheitis.

[0029] Bronchitis and pneumonia, on the other hand, are the most common infections of the lower respiratory tract and can also be of viral or bacterial origin and are commonly treated with anti-inflammatory, antiviral or antibiotic medicaments.

[0030] The use of antibiotics, antivirals or antifungals in an inappropriate way, together with the high adaptive capacity of microorganisms, has led to a significant increase in resistance to conventional therapies.

[0031] For this reason, it is interesting to have alternative treatments of natural origin useful as a complement or replacement of common antibiotics, antivirals or antifungals in order to maximize therapeutic effectiveness.

[0032] GLOSSARY

[0033] The terms used in this description are as generally understood by the technician, unless otherwise stated.

[0034] The term "extract", in the context of this description, means any product attributable to a vegetable medicament, including all products derived from mechanical treatments (pulverization, shredding, mixing and / or other methods) or from extractive treatments (solvent extraction, distillation, and / or other specific methods) performed on a drug.

[0035] DETAILED DESCRIPTION OF THE INVENTION

[0036] Pelargonium sidoides is a perennial herbaceous plant that belongs to the Geraniaceae family, widely spread in the south-eastern region of southern Africa. It is well known also with the name of African geranium and prefers grassy areas and neutral or alkaline stony soils for the growth. The name of the plant comes from the Greek term "pelargos" which means stork and refers in particular to the stem of the plant, whose elongated shape reminds precisely the beak of the stork.

[0037] This shrub can grow up to 50 centimeters tall, characterized by the presence ofheart- shaped leaves, having a very strong and penetrating smell. In addition, there are also flowers with five petals with purple-pink shades.

[0038] According to traditional uses of the plant by African tribes, P. sidoides is used for the treatment of infections of the gastro-intestinal tract and the upper respiratory tract, including the common cold, bronchitis and sinusitis.

[0039] The portion of the plant responsible for the therapeutic effects of P. sidoides is the root, rich in several active substances including: coumarins, gallic acid and polyphenols (proanthocyanidins A and B and tannins).

[0040] Scientific studies have also shown that the beneficial effects derived from the use of the root of P. sidoides favor the treatment of different pathologies on an infectious basis in the dermatological, gynecological and respiratory fields.

[0041] P. sidoides root extracts are particularly effective in limiting the growth of several skin pathogens, such as S. aureus and Staphylococcus epidermidis at a concentration of 80 pg / ml and 70 pg / ml.

[0042] The mechanism of action behind the inhibition of bacterial growth depends on the presence of proanthocyanidins, contained in the root extract of the plant. In fact, it has been reported in the literature that proanthocyanidins can enhance the bactericidal action of antibiotics, influencing the permeability of the bacterial cell, following interaction with the efflux pumps present along the plasma membrane. 30 In addition, an in vitro study on the micro-organism S. pyogenes has shown that proanthocyanidins can limit the degree of cellular bacterial adhesion, in order to reduce the infection process of the host, using a concentration of plant extract of 30 pg / ml.

[0043] As for the pathologies on an infectious basis of viral origin in dermatology, it has been reported that the root extract of P. sidoides is effective in the treatment of infections caused by herpes virus (HSV).

[0044] In particular, it has been observed that the antiviral action of the plant is useful in the treatment of HSV-1 and HSV-2 that cause respectively skin lesions at the oral cavity and genitals. The antiviral mechanism of action is based on the ability of proanthocyanidins and gallic acid to inhibit the formation of the viral shell, thus preventing infection of the host cell by the obligate endocellular parasite.

[0045] The antiseptic action of the P. sidoides plant has also been analyzed for pathologies related to the female urinary tract, observing how the use of this plant species can reduce the incidence of cases of kidney stones, cystitis and vaginal Candida.

[0046] In the specific case of kidney stones, it has been observed that the pathogenic bacteria Klebsiella pneumoniae and Proteus mirabilis can infect the female urinary tract and generate infection stones commonly known as struvite stones. This type of stone represents about 10-15% of kidney stones in general and often patients suffering from kidney stones may be subject to recurrence phenomena.

[0047] Moreover, in vitro studies have confirmed that the growth of K. pneumoniae and P. mirabilis is inhibited, using the respective MIC (Minimum Inhibitory Concentration) of 10 mg / ml and 3.3 mg / ml of P. sidoides root extracts.

[0048] The antiseptic action of P. sidoides extract is determined by the activation of macrophages and monocytes resulting in the production of nitric oxide, which has an inhibitory effect on the growth of pathogenic bacterial strains.

[0049] The bactericidal action of P. sidoides is also useful in the treatment of cystitis of bacterial origin, which involve pelvic pain and increased urination frequency.

[0050] In this particular case, the bacterium responsible for the infection and thesubsequent inflammatory state of the bladder is Escherichia coli, which populates the terminal tract of the intestine and from which it can then propagate to the bladder through the urethra.

[0051] In vitro studies on the bacterial strain of E. coli showed a P. sidoides concentration higher than 80 pg / ml can be useful to reduce the growth of the bacterium.

[0052] In addition, the intake of P. sidoides root extracts also promotes increased phagocytic activity of immune system cells, located tothe site of infection. In the literature it has been seen that the use of P. sidoides determined an increase in the process of phagocytosis, following vaginal infection caused by the fungus Candida albicans.

[0053] Finally, it has been seen that the antibacterial action of P. sidoides is very useful also in the treatment of pathologies affecting the upper respiratory tract. It has been found that the main components of P. sidoides extracts responsible for antibacterial activity are gallic acid and coumarins, which inhibit the growth of pathogenic bacteria. These two organic compounds reduce the cellular adhesion of bacteria to the mucous membranes of the respiratory tract, since they determine a reduction in the expression of the anchoring proteins of the cell membranes and at the same time induce an increase in the expression of the defence proteins of the host.

[0054] In particular, several in vitro studies have been conducted to determine the MIC value of the root extract (between 200-1600 pg / ml) on different respiratory pathogens such as S. aureus, Staphylococcus pneumoniae, Neisseriae spp. and Haemophilus influenzae.

[0055] Then, the powerful antibacterial action of P. sidoides was also demonstrated through several clinical trials in which the administration of plant root extracts favored the reduction of the severity of symptoms associated with acute bronchitis, colds and rhinosinusitis.

[0056] Recently, it has been seen that P. sidoides root extracts also exhibit good antiviral activity, particularly against HCo-229E coronavirus. The latter is responsible for the common cold, the use of P. sidoides extract preserves the state of health of the host and increases its immune defenses. In addition, it prevents viral infection by the coronavirus since it interferes with the proper formation of viral capsid. Considering the high similarity of SARS-CoV2 to other coronaviruses, characterized by the presence of a single strand of RNA and a lipid shell, it could be hypothesized a possible antiviral activity of the extracts of P. sidoides on the main cause of Covid-19. The object of this invention is a technologically innovative formulation containing an extract of Pelargonium sidoides in association with phosphatidylserine, phosphatidylcholine and starch, in particular modified starch, which can promote the stability of the extract in the gastric environment, improve its absorption and bioavailability with consequent optimization of its therapeutic effect.

[0057] This formulation that is the subject of this invention guarantees gastro-protection and controlled release of the active components of the extract thanks to the combination with three functional excipients such as phosphatidylcholine, phosphatidylserine and starch.

[0058] In particular, starch, preferably modified acetylated starch, protects thephospholipid- binding extract of Pelargonium sidoides from the gastric environment and allows its arrival in high concentrations in the intestine where thanks to the presence of phosphatidylcholine and phosphatidylserine the functional components of the extract are optimally absorbed.

[0059] The aim of this invention is therefore to provide a nutraceutical or pharmaceutical composition capable of conveying the functional components of Pelargoniumsidoides extract to improve efficacy, safety and compliance in patients with infectious diseases. The invention shall also include a pharmaceutical product or a food supplement including the nutraceutical or pharmaceutical composition according to the invention. In addition to the extract of Pelargonium sidoides and the functional excipients starch, phosphatidylcholine and phosphatidylserine, the pharmaceutical product or dietary supplement of the invention may optionally include additional active ingredients and functional excipients, which are easily chosen by the industry expert according to the needs of the case. The choice of vehicles, excipients and / or diluents required for the formulation of the pharmaceutical product or food supplement in an appropriate dosage form is also within the normal capabilities of the industry expert.

[0060] The nutraceutical or pharmaceutical composition according to the invention is as defined in the attached claim 1 .

[0061] Additional features and advantages of the invention are defined in the dependent claims. The claims form an integral part of this description.

[0062] In the following part, it is provided a detailed description of some preferred implementations of the invention.

[0063] As indicated, the nutraceutical or pharmaceutical composition of this invention includes Pelargonium sidoides extract as an active ingredient and a combination of functional excipients that provide the composition with properties of gastro-resistance, increased resistance to degradation, controlled release and increased bioavailability. Such a combination of functional excipients includes phosphatidylcholine, phosphatidylserine and starch.

[0064] The nutraceutical or pharmaceutical composition of the invention is therefore particularly effective for conveying the functional components of the extract of Pelargonium sidoides for the prevention and / or treatment of infectious diseases. Examples of such infectious diseases are impetigo, folliculitis, ectima, erysipelas, fasciitis, herpes simplex, cystitis, kidney stones, vaginitis, vaginosis, cervicitis, vaginal Candida, papilloma virus, contagious mollusc, balanitis, postitis, balanoposthitis, genital herpes, nasopharyngitis, sinusitis, pharyngitis, tonsillitis, laryngitis, tracheitis, bronchitis and pneumonia.

[0065] Starch is an organic compound of a polysaccharide nature consisting of the repetition of glucose units bound by a-glycosidic bonds. It consists of two types of polymers: amylose, which generally amounts to about 20%, and amylopectin, which generally amounts to about 80%. Amylose forms the central part of the starch granules, is soluble in very hot water and consists of glucose molecules bound by a-1 ,4 glycosidic bonds. Amylopectin is a polymer with a high degree of branching that forms the outer part of the granules. The monomeric units that compose it are joined, at the branching points, by a-1 ,6 glycosidic bonds. In nature it forms in the green parts of the plants, and then it accumulated in the reserve organs, such as tubers, seeds and roots. Due to its properties and characteristics, it has used for numerous industrial purposes.

[0066] Starch is particularly important in the food industry, which uses it as a thickening agent and in the production of sweeteners such as maltitol and sorbitol. Thanks to its adhesive properties, it is also used in the production of paper and glues, in the form of a starch weld. In the pharmaceutical industry starch has always been used as an excipient and for the formation of coatings, thanks to its binding properties.

[0067] Although starch is also used in its natural form, the interest of companies is mainly focused on modified starches, that is starch molecules suitably modified to meet the needs of the various production processes in which it is used. Such modified starches may be obtained from plants which have undergone natural or induced genetic mutations and which therefore produce starches with altered characteristics. Another strategy is to modify starch, generally derived from corn, tapioca and rice, by chemical treatments (addition of functional groups, treatment with acids and bases), physical (gelatinization) or enzymatic (partial hydrolysis). Dextrins are an example of modified starches obtained by hydrolysis and re-polymerization. These reactions can be performed either by simple thermal degradation or by acid catalysis. The result is the obtaining of molecules characterized by shorter chains and therefore partially or totally soluble in water. Examples of dextrins are cyclodextrins and maltodextrins, excipients widely used in the nutraceutical and pharmaceutical fields.

[0068] The nutraceutical and pharmaceutical industry has shown great interest in modified starches with a high amylose starch (HAS - high amylose starch). A starch, to be defined as such, must have an amylose percentage of at least 50%. Starch with a high amylose content can be obtained from genetically modified plants or by enriching starches with low amylose content. The strategies employed by different companies involve the use of HAS for the preparation of solid pharmaceutical forms or in coating processes. HAS have several advantages over other types of starch, such as better consistency, greater thermal stability and greater resistance to moisture and adhesion. Various strategies have been implemented to exploit the advantages of HAS in the most appropriate way.

[0069] At Scherer Corporation, for example, is attributed the use of soft gel capsules in which a certain percentage of gelatin is replaced with the aforementioned starch. The capsules thus obtained have a better appearance and greater resistance. The Dow Chemical Company can boast the use of capsules more uniform and with greater stability in water and at high temperatures thanks to the use of hydroxyalkylated HAS. Upjohn Company boasts the use of amylose acetate phthalate as a coating agent in gastro-resistant preparations.

[0070] Different types of starch can be used in this invention. Examples include: a non chemically modified pregelatinized corn starch, or an acetylated pregelatinized corn starch with a high amylose content, which in this case can reach up to 90% by weight. The percentage of acetyl groups is between 0.5% and 2.5%.

[0071] Acetylation is carried out, for example, with acetic anhydride, which guarantees to reach a percentage of acetyl groups greater than 0.5% but not more than 2-.5%.

[0072] The starch pregelatinization treatment consists in dispersing the acetylated starch in water and subjecting the resulting dispersion to temperatures between 100 and 130 degrees and at high pressures. Starch granules subjected to this procedure explode and form a gel with a moisture content between 5 and 10%. Once solidified and removed, the modified starch thus obtained can be used in thecoating processes of rigid, soft and microgranules capsules and ensures the obtaining of a coating that is resistant and adequately viscous at the same time, which is capable of masking unpleasant odours and tastes and can also be used if a modified release or gastroresistant pharmaceutical form is to be obtained. The features of the pharmaceutical form can be modulated by changing the amount of starch used in the coating. Tests conducted using the aforementioned starch showed the g astro- resista nt action, moisture protection and the ability to release the active ingredient after a few minutes in the intestinal environment.

[0073] As indicated, additional functional excipients present in the nutraceutical or pharmaceutical composition of the invention are phosphatidylcholine andphosphatidylserine. These compounds are part of the vast class of phospholipids. Phospholipids are structurally very similar to triglycerides. They are composed of an esterified glycerol molecule in position 1 and 2 with fatty acids. Fatty acids that are involved in the composition of natural phospholipids can have a length between 12 and 22 carbon atoms; in position 1 is generally present a saturated fatty acid, in position 2 unsaturated fatty acids are found; in position 3 there is a phosphate group which, in turn, is esterified with a complex molecule of various nature such as choline, serine, ethanolamine or inositol. Such molecules are those that give the phospholipid its name (phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol) and affect its physical properties as they determine whether the molecule is anionic (such as phosphatidylserine) or zwitterionic (such as phosphatidylcholine).

[0074] The peculiar chemical structure makes the phospholipids amphiphilic molecules, which are able to interact both with polar solvents and with apolar solvents. More precisely, the carbonyl chains of fatty acids represent the apolar portion that interacts with the apolar solvents, while the head of the phospholipid, composed by the phosphate group and the molecule linked to it, represents the polar part which interacts with water and other polar solvents.

[0075] This structural characteristic makes them molecules with surfactant properties that above a certain temperature, defined as a critical micellar concentration, aggregate forming characteristic complexes that can vary in shape and size depending on the conditions of the environment in which they form and the length of the chains of the fatty acids that make them up. For example, if dispersed in aqueous solution, they form typical micelles, with the polar heads facing outwards towards the aqueous environment and the hydrophobic tails facing inwards. If dispersed in organic solvents, they instead form the so-called inverse micelles, in which the heads are turned inwards and the tails towards the external apolar environment. As for the dimensions, they vary according to the length of the carbon chains of the fatty acids that make up the phospholipids.

[0076] Phospholipids are molecules with a very important biological significance, mainly because they take part in the composition of biological membranes and, secondly, because they are involved in several complex mechanisms such as transduction of intracellular signals, regulation of intracellular concentration of certain ions and mediation of inflammatory processes as sources of arachidonic acid. Phospholipids are interesting molecules also from the technological point of view and, therefore, are used in pharmaceutical and nutraceutical field as technological adjuvants in the formulation of delivery systems for various active ingredients.

[0077] Many active ingredients can have a low bioavailability caused by the difficulty of crossing the biological barriers and membranes of many areas of the body. Phospholipids, and in particular phosphatidylcholine and phosphatidylserine, represent a valuable aid in the framework of technological strategies for the release of various active ingredients. One of the advantages of phospholipid-based vehicle systems is the compatibility of phospholipids with cell membranes, both at the mucosal and skin level.

[0078] Phosphatidylcholine and phosphatidylserine, therefore, act as enhancers of intestinal and topical absorption and this action can be ascribed to the following mechanisms of action:

[0079] - thanks to their properties and their structure, they can merge with the lipids of the stratum corneum and of the membranes and disrupt their structure allowing the passage of various substances;

[0080] - in contact with intestinal fluids form micelles that help increase the absorption of the active of interest as they extract lipids from membranes and alter the rheological properties, fluidity and composition of membranes increasing the permeability;

[0081] - the aforementioned micelles protect the active substances from chemical and enzymatic degradation and can be absorbed in the enteroepathic circle of bile salts, together with the mixed micelles of the diet, and be transported in the bloodstream where they release the embedded active substances.

[0082] This invention therefore makes it possible to obtain:

[0083] - Gastroresistance;

[0084] - Increased permeability through biological membranes; - Controlled release of functional components of Pelargonium sidoides extract; Increased bioavailability of functional components of Pelargonium sidoides extract. This invention is a valid strategy useful for the prevention and / or treatment of infectious diseases. This effect is attributed to the combined action of its constituent substances. The starch used in this invention, allows to protect the functional components of the extract of Pelargonium sidoides from the acidic Ph of the stomach and from enzymatic degradation, guaranteeing its controlled release at the intestinal level. Phosphatidylcholine and phosphatidylserine increase the bioavailability of the aforementioned functional components thanks to the multi-mechanism action at the level of the intestinal mucosa.

[0085] The efficacy of the nutraceutical or pharmaceutical composition covered by this invention shall be assessed by the experimental protocol described below.

[0086] In order to assess gastro-resistance, a disintegration test is performed, as prescribed by Pharmacopoeia. A sample of the pharmaceutical form to be tested is placed in a suitable device containing 0.1 N hydrochloric acid. The gastro-resistant pharmaceutical form, in contact with the pH 2 buffer for two hours, does not undergo disintegration. The sample is then transferred to a pH 6.8 buffer in which it breaks down within ten minutes.

[0087] Gastro-resistance can also be assessed by a Pharmacopoeia dissolution test, according to which the pharmaceutical form is in contact with a 0.1 N solution of hydrochloric acid and to meet the test it must release a quantity of the functional components of the extract less than about 20% after 2 hours.

[0088] To assess intestinal permeability, an in vitro test is performed, for example, on Caco- 2 cells. The cultured cells, are prepared using an appropriate growth medium (for example, containing FBS, bovine foetal serum) and kept under controlled conditions (for example, 37° C, in an atmosphere of 5% CO2 and 100% humidity). After several steps the cells are washed and pre-incubated with PBS.

[0089] After treatment with the formulations of interest, the samples are subjected to analysis to quantify the functional components of the extract.

[0090] The effectiveness of this invention can be evaluated by monitoring the activity of the P. sidoides extract against the main microbial strains responsible for the infectious diseases covered by this invention such as bacteria, viruses, fungi using techniques known to the branch expert such as MIC, diffusion method or disk method, evaluation of inhibition of the stages of the replicative cycle of a virus (such as fixing, cell entry, replication).

[0091] As indicated above, the nutraceutical or pharmaceutical composition of this invention is inserted into a pharmaceutical product or food supplement, which is formulated in a suitable dosage form, the composition and preparation of which is the competence of the expert in the field.

[0092] In a preferred implementation, P. sidoides extract in the nutraceutical or pharmaceutical composition of the invention is present in an amount between 0.1 and 90%, preferably between 0.5 and 80%, even more preferably between 1 and 70%, with respect to the total weight of the composition covered by this invention. As an example, additional percentages of P. sidoides extract used in the composition of the invention are: 2%, 3%, 4%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, or 85%.

[0093] In another preferred implementation, starch in the nutraceutical or pharmaceutical composition of the invention is present in an amount preferably between 0.1 and 90%, more preferably between 0.5 and 80%, even more preferably between 1 and 70% compared to the total weight of the composition object of this invention. As an example, additional percentages of starch used in the composition of the invention are: 2%, 3%, 4%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, or 85%.

[0094] In yet another preferred implementation, phosphatidylcholine in the nutraceuticalor pharmaceutical composition of the invention is present in an amount between 0.01 and 50%, preferably between 0.05 and 30%, even more preferably between 0.01 and 10% of the total weight of the composition object of this invention.

[0095] As an example, further percentages of phosphatidylcholine that can be used in the composition of the invention are: 0.02%, 0.03%, 0.04%, 0.06%, 0.07%, 0.08%, 0.09%, 0.2%, 0.3%, 0.4%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 15%, 20%, 25%, 35%, 40%, or 45%. In yet another preferred implementation, phosphatidylserine in the nutraceutical or pharmaceutical composition of the invention is present in an amount between 0.01 and 50%, preferably between 0.05 and 30%, even more preferably between 0.1 and 10% of the total weight of the composition covered by this invention. As an example, further percentages of phosphatidylserine that can be used in the composition of the invention are: 0.02%, 0.03%, 0.04%, 0.06%, 0.07%, 0.08%, 0.09%, 0.2%, 0.3%, 0.4%, 0.6%, 0.7%, 0.8%, 0.9%, 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 15%, 20%, 25%, 35%, 40%, or 45%.

[0096] All of the above preferred implementations are combinable with each other.

[0097] The pharmaceutical product or dietary supplement, which includes the pharmaceutical or nutraceutical composition of the invention, is formulated in a preferably oral pharmaceutical form, which can be solid, semisolid or liquid.

[0098] Examples include a powder, a soluble powder, a granulate, a rigid capsule, a soft gel capsule, a tablet, a sachet, a solution, a syrup, a suspension or an emulsion.

[0099] Some non-exclusive examples of nutraceutical or pharmaceutical compositions covered by this invention are given below. As indicated above, such nutraceutical or pharmaceutical compositions are formulated as pharmaceuticals or food supplements and administered in a suitable form of oral dosage, possibly divided into one or more dosage units, such as, for example, one capsule, a tablet or a sachet.

[0100] The following examples are provided for illustrative purposes only and not to limit the scope of the invention as defined by the attached claims.

[0101] EXAMPLES

[0102] EXAMPLE 1

[0103] EXAMPLE 2

[0104] EXAMPLE 3

[0105] EXAMPLE 4

[0106] EXAMPLE 5

[0107] EXAMPLE 6

[0108] For the preparation of the product "P. sidoides granular extract" it is possible to use, for example, fluid bed granulation technology. Below is an example of preparation, applied to the compositions of the Examples. The manufacturing process consists of the following steps: a) Mixing:

[0109] The raw materials previously loaded in the granulator basket are subjected to a first mixing phase on a fluid bed, with process air having a certain temperature (for example, 80-90 °C), until a mixture with an average temperature of about 44 °C is obtained. During this phase a homogeneous bulk shall be produced in terms of composition and temperature, indispensable prerequisite for the optimal course of the next granulation phase. b) Granulation: The granulation phase involves the grafting of an aqueous solution of a properly chosen binding or granulation agent, by direct spraying on the premixed and fluidized bulk on a fluid bed. Also in this phase process air is used, for example at 90 °C, choosing the appropriate inlet rate of the binder solution to obtain a granular structure according to expectations (grain size, bulk density, density, and smoothness) and homogeneous. c) Drying:

[0110] During the drying phase the water content of the preformed granular is reported to the conditions of the mixture of the raw materials of starting. The temperature of the process air of the granulate at the end of phase is suitably evaluated during pilot tests according to this objective. d) Calibration:

[0111] The semi-finished product obtained from the previous phase is transferred from the fluid bed granulator to an oscillating granulator where it is calibrated through a sieve for particle size reduction (particle size) of granules and agglomerates with a coarser structure.

Claims

CLAIMS1. Nutraceutical or pharmaceutical composition comprising the combination of an extract of Pelargonium sidoides, phosphatidylcholine, phosphatidylserine and starch.

2. Nutraceutical or pharmaceutical composition according to claim 1 for use in the treatment or prevention of infectious diseases in both humans and animals.

3. Nutraceutical or pharmaceutical composition for use according to claims 1 and 2, including 0.1 to 90% Pelargonium sidoides extract, preferably between 0.5 and 80%, even more preferably between 1 and 70% compared to the total weight of the above combination.

4. Nutraceutical or pharmaceutical composition for use according to any of the claims 1 to 3, including starch, preferably acetylated pregelatinized, preferably in an amount between 0.1 and 90%, more preferably between 0.5 and 80%, even more preferably between 1 and 70% compared to the total weight of the above combination.

5. Nutraceutical or pharmaceutical composition for use according to any of the claims 1 to 4, comprising a quantity of phosphatidylcholine between 0.01 and 50%, preferably between 0.05 and 30%, even more preferably between 0.1 and 10% of the total weight of the above combination and a quantity of phosphatidylserine between 0.01 and 50%, preferably between 0.05 and 30%, even more preferably between 0.1 and 10% of the total weight of the above combination.

6. Nutraceutical or pharmaceutical composition for use according to any of claims 1 to 5, where the infectious disease is related to the dermatological and / or gynecological and / or urological and / or respiratory fields.

7. Nutraceutical or pharmaceutical composition for use according to any of 1 to 6 claims, in which the infectious disease is selected from the group comprising: impetigo, folliculitis, ectima, erysipelas, fasciitis, herpes simplex, cystitis, kidney stones, vaginitis, vaginosis, cervicitis, vaginal Candida, papilloma virus, contagious mollusc, balanitis, postitis, balanoposthitis, genital herpes, nasopharyngitis, sinusitis, pharyngitis, tonsillitis, laryngitis, tracheitis, bronchitis and pneumonia.

8. Pharmaceutical product or food supplement according to claims 1 to 7, formulated in a liquid, semi-solid or solid oral dosage form.

9. Pharmaceutical product or food supplement according to claim 8, in which the dosage form is a powder, a hormonal powder, a granulate, a rigid capsule, a soft-gel capsule, a tablet, a sachet, a solution, a syrup, a suspension or an emulsion.

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