IT201800009741A1 - ASSOCIATION OF ALPHA-LIPOIC ACID, CITICOLINE, LUTEOLINE AND PHYSETIN FOR NERVOUS SYSTEM DISEASES AND FOR THE CONTROL OF ASSOCIATED PAIN - Google Patents
ASSOCIATION OF ALPHA-LIPOIC ACID, CITICOLINE, LUTEOLINE AND PHYSETIN FOR NERVOUS SYSTEM DISEASES AND FOR THE CONTROL OF ASSOCIATED PAIN Download PDFInfo
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- IT201800009741A1 IT201800009741A1 IT102018000009741A IT201800009741A IT201800009741A1 IT 201800009741 A1 IT201800009741 A1 IT 201800009741A1 IT 102018000009741 A IT102018000009741 A IT 102018000009741A IT 201800009741 A IT201800009741 A IT 201800009741A IT 201800009741 A1 IT201800009741 A1 IT 201800009741A1
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- polyvinylpyrrolidone
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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
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Description
Descrizione dell’invenzione avente per titolo: Description of the invention entitled:
“ASSOCIAZIONE DI ACIDO ALFA-LIPOICO, CITICOLINA, LUTEOLINA E FISETINA PER LE AFFEZIONI DEL SISTEMA NERVOSO E PER IL CONTROLLO DEL DOLORE ASSOCIATO” "ASSOCIATION OF ALPHA-LIPOIC ACID, CITICOLINE, LUTEOLINE AND PHYSETIN FOR NERVOUS SYSTEM DISEASES AND FOR THE CONTROL OF ASSOCIATED PAIN"
Descrizione Description
Campo dell’Invenzione Field of the Invention
La presente domanda di brevetto per invenzione descrive e rivendica un’innovativa associazione di acido α-lipoico, citicolina, luteolina e fisetina per le affezioni del sistema nervoso e per il controllo del dolore associato, facendo riferimento in generale al settore dei prodotti alimentari destinati a integrare la comune dieta e che costituiscono una fonte concentrata di sostanze nutritive e più in particolare al settore degli integratori alimentari. The present patent application for invention describes and claims an innovative combination of α-lipoic acid, citicoline, luteolin and fisetin for diseases of the nervous system and for the control of associated pain, referring in general to the sector of food products intended for supplement the common diet and constitute a concentrated source of nutrients and more particularly to the food supplement sector.
Stato dell’Arte State of the art
Le affezioni del sistema nervoso (S.N.) in generale, denominate anche malattie neurologiche, comprendono essenzialmente i disturbi che colpiscono il sistema nervoso centrale, così come la sclerosi multipla, le malattie cerebrovascolari, la malattia di Alzheimer, il morbo di Parkinson, l’epilessia, le malattie eredodegenerative, le patologie infiammatorie-infettive e così via, e i disturbi che colpiscono il sistema nervoso periferico, come le polineuropatie, la miastenia, le miopatie, ecc. Diseases of the nervous system (NN) in general, also called neurological diseases, essentially include disorders affecting the central nervous system, as well as multiple sclerosis, cerebrovascular diseases, Alzheimer's disease, Parkinson's disease, epilepsy , heredodegenerative diseases, inflammatory-infectious diseases and so on, and disorders affecting the peripheral nervous system, such as polyneuropathies, myasthenia, myopathies, etc.
A tutt’oggi la rilevanza di queste patologie, anche in relazione ai relativi costi sociali ed emotivi, è molto importante; si pensi che solo in Italia circa 700.000 persone devono convivere con il morbo di Alzheimer, con 8.000 nuovi casi stimati ogni anno, per non parlare poi delle neuropatie periferiche che colpiscono più del 13% della popolazione oltre i 55 anni. To date, the relevance of these pathologies, also in relation to the related social and emotional costs, is very important; just think that in Italy alone about 700,000 people have to live with Alzheimer's disease, with 8,000 new cases estimated every year, not to mention peripheral neuropathies that affect more than 13% of the population over 55 years of age.
Pertanto, considerando che dette condizioni morbose comprendono un vasto gruppo di patologie di diversa gravità, a volte reversibili e a volte croniche e degenerative, nella maggior parte dei casi, indipendentemente dalle cause scatenanti, queste sono invalidanti e possono causare dolore più o meno intenso e comunque risulteranno, sempre per diversi gradi, compromettenti la qualità della vita del paziente. Therefore, considering that said morbid conditions include a large group of pathologies of different severity, sometimes reversible and sometimes chronic and degenerative, in most cases, regardless of the triggering causes, these are disabling and can cause more or less intense pain and in any case will result, again in varying degrees, compromising the patient's quality of life.
Complicanze metaboliche e vascolari, fenomeni di neurodegenerazione ascrivibili a varie cause, squilibri dei neurotrasmettitori e neuromodulatori, perossidazione dei lipidi di membrana, fenomeni di ipossia dei nervi, produzione di radicali liberi e di mediatori pro-infiammatori rappresentano parte di un quadro patologico talora ancora di difficile comprensione. Metabolic and vascular complications, phenomena of neurodegeneration attributable to various causes, imbalances of neurotransmitters and neuromodulators, peroxidation of membrane lipids, phenomena of hypoxia of the nerves, production of free radicals and pro-inflammatory mediators represent part of a pathological picture that is sometimes still of difficult to understand.
Quindi, partendo dal presupposto che la classificazione di dette variegate condizioni morbose è molto difficile e che l'approccio terapeutico, laddove possibile, sia esso di tipo chirurgico o di tipo farmacologico o fisiatrico, varierà in base alla tipologia di malattia, la presente invenzione nasce proprio dall’esigenza di rivendicare un prodotto, la cui formulazione sia in grado di fornire sostanze di interesse fisiologico e dotate nel complesso di un effetto neurotrofico, neuroprotettivo e con un’eccellente attività antiinfiammatoria e antiossidante, in grado di migliorare il metabolismo e le funzioni fisiologiche dell’organismo connesse prevalentemente con le affezioni del sistema nervoso in generale e al controllo del dolore a queste associato. Therefore, starting from the assumption that the classification of said various morbid conditions is very difficult and that the therapeutic approach, where possible, be it of a surgical or pharmacological or physiatric type, will vary according to the type of disease, the present invention is born precisely from the need to claim a product, whose formulation is able to provide substances of physiological interest and with a complex neurotrophic, neuroprotective effect and with an excellent anti-inflammatory and antioxidant activity, able to improve metabolism and functions physiological conditions of the organism mainly connected with the affections of the nervous system in general and the control of pain associated with them.
A tali scopi detta associazione, risultante in un’innovativa formulazione, è dotata di un’attività dei costituenti altamente sinergica e favorente la guarigione nei confronti di molte delle affezioni che interessano il sistema nervoso in generale. Di conseguenza detta associazione inventiva, facente parte a tutti gli effetti anche della categoria degli integratori alimentari, rappresenterebbe un valido contributo, non soltanto nella cura e come adiuvante terapeutico, ma anche nella profilassi delle malattie del sistema nervoso in generale. For these purposes, said association, resulting in an innovative formulation, has a highly synergistic activity of the constituents and promotes healing against many of the diseases that affect the nervous system in general. Consequently, said inventive association, which in all respects also belongs to the category of food supplements, would represent a valid contribution, not only in the treatment and as a therapeutic adjuvant, but also in the prophylaxis of diseases of the nervous system in general.
Descrizione dell’Invenzione Description of the Invention
La presente domanda di brevetto per invenzione intende descrivere e rivendicare l’innovativa associazione tra l’acido α-lipoico, la citicolina, la luteolina e la fisetina. This patent application for invention intends to describe and claim the innovative association between α-lipoic acid, citicoline, luteolin and fisetin.
Sebbene predetta nuova associazione possa essere anche annoverata come una vera e propria composizione farmacologica, ovvero, quale composizione indirizzata a una specifica finalità terapeutica, scopo della presente invenzione è quella di considerare predetta associazione come una formulazione in grado di svolgere un ruolo diretto a favorire lo stato di benessere dell’organismo, agendo sia come coadiuvante terapeutico e sia agendo di per sé da prodotto dotato di un’attività favorente determinate funzioni e processi fisiologici, connessa con la profilassi, oppure, con l’alleviamento o la scomparsa dei sintomi e del dolore, o nei casi più favorevoli con la guarigione di molte delle affezioni a carico del S.N. centrale e periferico. Although the aforementioned new association can also be counted as a real pharmacological composition, that is, as a composition addressed to a specific therapeutic purpose, the purpose of the present invention is to consider the aforementioned association as a formulation capable of playing a direct role in favoring the state of well-being of the organism, acting both as a therapeutic adjuvant and acting in itself as a product endowed with an activity that favors certain physiological functions and processes, connected with prophylaxis, or, with the alleviation or disappearance of symptoms and pain, or in the most favorable cases with the healing of many of the affections affecting the S.N. central and peripheral.
L’acido α-lipoico (ALA), che rappresenta il primo costituente dell’associazione secondo l’invenzione, noto anche come acido α-tioctico, è entrato a pieno titolo nella terapia delle neuropatie periferiche, delle malattie neurodegenerative e delle problematiche neurotossiche e neurosensoriali, grazie alle sue molteplici funzioni. Α-lipoic acid (ALA), which represents the first constituent of the association according to the invention, also known as α-thioctic acid, has fully entered the therapy of peripheral neuropathies, neurodegenerative diseases and neurotoxic problems and sensorineural, thanks to its multiple functions.
Le caratteristiche dell’ALA, tra cui la possibilità di superare la barriera ematoencefalica nonché l'ampia diffusione tissutale, lo rendono: The characteristics of ALA, including the ability to overcome the blood-brain barrier as well as the wide tissue diffusion, make it:
- un antiossidante con una spiccata versatilità, in grado di agire in compartimenti cellulari lipofili e idrofili, di rigenerare i sistemi di difesa endogeni (vit. C ed E, coenzima Q10, glutatione) e di presentare un ampio spettro d’azione verso differenti specie radicaliche; - an antioxidant with a marked versatility, able to act in lipophilic and hydrophilic cellular compartments, to regenerate the endogenous defense systems (vitamins C and E, coenzyme Q10, glutathione) and to present a broad spectrum of action towards different species radicals;
- un regolatore del metabolismo energetico e glucidico in grado di partecipare, come cofattore enzimatico, ai processi deputati alla produzione di ATP (ciclo di Krebs), al catabolismo del glicogeno e degli acidi grassi e di esercitare, inoltre, un’azione ipoglicemizzante, mimando l’azione dell’insulina e stimolando l’uptake del glucosio; - a regulator of energy and carbohydrate metabolism capable of participating, as an enzymatic cofactor, in the processes responsible for the production of ATP (Krebs cycle), in the catabolism of glycogen and fatty acids and also to exert a hypoglycemic action, mimicking the action of insulin and stimulating glucose uptake;
- un chelante naturale di metalli pesanti; - a natural chelator of heavy metals;
- un antinfiammatorio neuronale, centrale e periferico, in grado di modulare la biosintesi di citochine infiammatorie, di ridurre l’attivazione della microglia NF-ĸB dipendente e l’espressione di molecole di adesione e di metalloproteasi. - a central and peripheral neuronal anti-inflammatory, capable of modulating the biosynthesis of inflammatory cytokines, reducing the activation of NF-ĸB dependent microglia and the expression of adhesion and metalloprotease molecules.
La citicolina, che rappresenta il secondo composto dell’associazione inventiva, nota anche come CDP-colina, partecipa alla biosintesi dei fosfolipidi di membrana cellulare e mitocondriale, in particolar modo della fosfatidilcolina. Presenta un’ampia diffusione tissutale, anche nel sistema nervoso centrale. In particolare: Citicoline, which is the second compound of the inventive association, also known as CDP-choline, participates in the biosynthesis of cell membrane and mitochondrial phospholipids, especially phosphatidylcholine. It has a wide tissue diffusion, including in the central nervous system. In particular:
- influenza la disponibilità di alcuni neurotrasmettitori rappresentando una fonte di colina, un precursore dell'acetilcolina e incrementando i livelli di dopamina e di noradrenalina; - influences the availability of some neurotransmitters representing a source of choline, a precursor of acetylcholine and increasing the levels of dopamine and noradrenaline;
- potenzia la neuroplasticità ed è utile per migliorare l’apprendimento e la memoria, tanto da essere un noto supporto nel trattamento di malattie caratterizzate da perdita, lenta ma progressiva, delle funzioni cerebrali (per es. sindromi parkinsoniane); - it enhances neuroplasticity and is useful for improving learning and memory, so much so that it is a well-known support in the treatment of diseases characterized by slow but progressive loss of brain functions (eg. Parkinsonian syndromes);
- esercita un’azione neuroprotettiva, accelerando il riassorbimento dell’edema cerebrale, riducendo il volume della lesione ischemica, contrastandone i processi apoptotici derivati. - exerts a neuroprotective action, accelerating the reabsorption of cerebral edema, reducing the volume of the ischemic lesion, counteracting its derived apoptotic processes.
La luteolina, che rappresenta il terzo composto dell’associazione secondo la presente invenzione, è tra i più potenti ed efficaci polifenoli, in grado di: Luteolin, which represents the third compound of the association according to the present invention, is one of the most powerful and effective polyphenols, capable of:
- inibire la produzione di citochine proinfiammatorie nel cervello, contribuendo ai processi di apprendimento e di mantenimento della memoria; - inhibit the production of proinflammatory cytokines in the brain, contributing to the processes of learning and memory maintenance;
- ridurre i livelli di proteine amiloidi responsabili dei processi neurodegenerativi; - reduce the levels of amyloid proteins responsible for neurodegenerative processes;
- favorire l’attivazione di antiossidanti endogeni, potenziando le difese cellulari; - favor the activation of endogenous antioxidants, enhancing cellular defenses;
- regolare numerosi complessi enzimatici e modulare alcuni meccanismi epigenetici. - regulate numerous enzymatic complexes and modulate some epigenetic mechanisms.
La fisetina, che rappresenta il quarto e ultimo composto dell’associazione inventiva, appartiene a un sottogruppo di flavonoidi ed è salita alla ribalta negli ultimi anni soprattutto grazie ad alcuni studi, che ne hanno evidenziato un coinvolgimento nei processi di formazione della memoria a lungo termine. Fisetin, which represents the fourth and last compound of the inventive association, belongs to a subgroup of flavonoids and has risen to prominence in recent years mainly thanks to some studies, which have highlighted its involvement in the formation processes of long-term memory. .
Oltre alla suddetta stimolazione cognitiva, alla fisetina sono state attribuite le seguenti attività: In addition to the aforementioned cognitive stimulation, the following activities have been attributed to fisetin:
- neurotrofica favorente il differenziamento neuronale e la sopravvivenza cellulare soprattutto in caso di stress ossidativo. Potenzia la via proteasoma ubiquitina-dipendente, uno dei maggiori processi cellulari coinvolti nell’omeostasi proteica, importante per la formazione iniziale degli assoni ma notevolmente compromessa in patologie neurodegenerative; - neurotrophic favoring neuronal differentiation and cell survival especially in the case of oxidative stress. It enhances the ubiquitin-dependent proteasome pathway, one of the major cellular processes involved in protein homeostasis, important for the initial formation of axons but significantly impaired in neurodegenerative diseases;
- neuroprotettiva per le cellule del ganglio della retina, proponendola per il trattamento del glaucoma e di retinopatie oculari; - neuroprotective for the retinal ganglion cells, proposing it for the treatment of glaucoma and ocular retinopathies;
- antiossidante comportandosi sia da scavenger sia da induttore di livelli intracellulari di glutatione; - antioxidant acting both as a scavenger and as an inducer of intracellular levels of glutathione;
- antiallergica poiché inibisce la produzione di citochine rilasciate dai linfociti T helper, modulando il rilascio di istamina e leucotrieni da parte di mastociti attivati; - antiallergic as it inhibits the production of cytokines released by T helper lymphocytes, modulating the release of histamine and leukotrienes by activated mast cells;
- antinfiammatoria in quanto sopprime gli effetti infiammatori e la neurotossicità microgliale. - anti-inflammatory as it suppresses inflammatory effects and microglial neurotoxicity.
Per quanto appena esposto, l’acido α-lipoico, la citicolina, la luteolina e la fisetina risultano già di per sé, ovvero in forma non associata, particolarmente adatti per le affezioni del sistema nervoso in generale. As described above, α-lipoic acid, citicoline, luteolin and fisetin are already in themselves, or in an unassociated form, particularly suitable for diseases of the nervous system in general.
Tuttavia, scopo principale della presente invenzione è quello di sfruttare un’innovativa azione sinergica, che si verifica attraverso la formulazione dell’associazione dei predetti quattro principi attivi, intesa a originare un’attività avente per risultato un amplificato effetto neurotrofico, neuroprotettivo e nel contempo dotata di una sorprendente attività antiinfiammatoria e antiossidante, che nel complesso è in grado di migliorare il metabolismo e le funzioni fisiologiche dell’organismo connesse prevalentemente con le affezioni del sistema nervoso in generale. However, the main purpose of the present invention is to exploit an innovative synergistic action, which occurs through the formulation of the association of the aforementioned four active ingredients, intended to originate an activity resulting in an amplified neurotrophic, neuroprotective and at the same time effect. endowed with a surprising anti-inflammatory and antioxidant activity, which on the whole is able to improve the metabolism and physiological functions of the organism mainly connected with diseases of the nervous system in general.
Più specificatamente approfonditi studi clinici, eseguiti dagli inventori della seguente privativa, hanno chiaramente dimostrato che la somministrazione di detta innovativa associazione, eseguita da sola o in combinazione con una terapia farmacologica mirata per l’affezione da trattare, ha mostrato una sorprendente e amplificata attività agendo come coadiuvante ovvero come un’associazione dotata di un’attività favorente determinate funzioni e processi fisiologici connessi con la scomparsa o l’alleviamento dei sintomi, oppure nei casi più favorevoli con la positiva risoluzione o il netto miglioramento di molte delle patologie, che a scopo esemplificativo e non limitativo, verranno riportate di seguito, nonché con il controllo del dolore connesso a dette patologie: More specifically, in-depth clinical studies, carried out by the inventors of the following patent, have clearly shown that the administration of said innovative combination, performed alone or in combination with a drug therapy targeted for the disease to be treated, has shown a surprising and amplified activity by acting as an adjuvant or as an association endowed with an activity favoring certain physiological functions and processes connected with the disappearance or alleviation of symptoms, or in the most favorable cases with the positive resolution or clear improvement of many of the pathologies, which for the purpose exemplary and not limitative, will be reported below, as well as with the control of pain associated with these pathologies:
• patologie neurodegenerative centrali e periferiche, così come morbo di Parkinson, malattia di Alzheimer, SLA, sclerosi multipla e malattie demielinizzanti in genere; • central and peripheral neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, ALS, multiple sclerosis and demyelinating diseases in general;
• riabilitazione post stroke e post traumatica; • post stroke and post traumatic rehabilitation;
• demenza senile e vascolare; • senile and vascular dementia;
• neuropatia diabetica e post erpetica, paralisi di Bell, nevralgia del trigemino; • diabetic and post herpetic neuropathy, Bell's palsy, trigeminal neuralgia;
• lombosciatalgia, cruralgie, cervicobrachialgia, radicolopatie, sindrome del tunnel carpale; • lumbosciatalgia, cruralgia, cervicobrachialgia, radiculopathies, carpal tunnel syndrome;
• dolori neuronali e neuropatici cronici, consentendo la riduzione della posologia di farmaci antidolorifici, come pregabalin e ossicodone, con i quali può essere usata in combinazione; • chronic neuronal and neuropathic pain, allowing the reduction of the dosage of painkilling drugs, such as pregabalin and oxycodone, with which it can be used in combination;
• oculopatie come retinopatia diabetica, degenerazione maculare senile, glaucoma; • oculopathies such as diabetic retinopathy, age-related macular degeneration, glaucoma;
• dolore pelvico cronico di origine neurologica (neuropatia del pudendo), ginecologica (endometriosi, vulvodinia, infezioni pelviche), urologica (cistite cronica, uretrite, prostatite cronica, penodinia), muscoloscheletrica (disfunzioni del pavimento pelvico); • chronic pelvic pain of neurological origin (pudendal neuropathy), gynecological (endometriosis, vulvodynia, pelvic infections), urological (chronic cystitis, urethritis, chronic prostatitis, penodynia), musculoskeletal (pelvic floor dysfunction);
• low grade non resolving inflammation: dolore cronico nell’anziano e nella donna in menopausa; • low grade non resolving inflammation: chronic pain in the elderly and in postmenopausal women;
• neuropatie iatrogene indotte da chemioterapici, da terapie radianti o sostitutive, da immunosoppressori, alleviando il dolore oncologico e migliorando la neurotossicità da cisplatino; • iatrogenic neuropathies induced by chemotherapy, by radiation or replacement therapies, by immunosuppressants, relieving cancer pain and improving cisplatin neurotoxicity;
• sindrome della bocca urente caratterizzato da bruciore, fastidio e dolore del cavo orale; • burning mouth syndrome characterized by burning, discomfort and pain of the oral cavity;
• emicrania. • migraine.
In aggiunta, la composizione descritta nella presente invenzione raggiunge i suoi scopi nel trattamento affezioni del sistema nervoso centrale e periferico che comprendono le patologie neurodegenerative centrali e periferiche, così come il morbo di Parkinson, la malattia di Alzheimer, la SLA, la sclerosi multipla e le malattie demielinizzanti in genere, la demenza senile e vascolare, la neuropatia diabetica e post erpetica, la paralisi di Bell, la nevralgia del trigemino, la lombosciatalgia, le cruralgie, la cervicobrachialgia, le radicolopatie, la sindrome del tunnel carpale e tarsale, le oculopatie così come retinopatia diabetica, degenerazione maculare senile e glaucoma, le neuropatie iatrogene indotte da chemioterapici, da terapie radianti/sostitutive, da immunosoppressori e dal fatto di riuscire ad alleviare i dolori oncologici, migliorando la neurotossicità da cisplatino, i dolori neuronali e neuropatici cronici, il dolore pelvico cronico di origine neurologica e segnatamente la neuropatia del pudendo, la composizione descritta nella presente invenzione è particolarmente efficace in ginecologia e segnatamente nell’endometriosi, vulvodinia e nelle infezioni pelviche, in urologia per il trattamento della cistite cronica, nelle uretriti e nelle prostatiti croniche e nella penodinia, La presente composizione è altresì efficace nelle muscoloscheletrie e segnatamente nelle disfunzioni del pavimento pelvico, nel low grade non resolving inflammation, ovvero, nel trattamento del dolore cronico nell’anziano e nella donna in menopausa, nel dolore nella sindrome della bocca urente, nell’emicrania e infine consente la riduzione della posologia di farmaci antidolorifici con i quali detta associazione può essere usata in combinazione. In aggiunta, la composizione descritta nella presente invenzione raggiunge i suoi scopi principali descrivendo e rivendicando anche la via di somministrazione di detta inventiva associazione, che in base al tipo di affezione da trattare può essere opportunamente formulata per la somministrazione enterale, per la somministrazione parenterale e per la somministrazione topica. In addition, the composition described in the present invention achieves its purposes in the treatment of diseases of the central and peripheral nervous system which include central and peripheral neurodegenerative diseases, as well as Parkinson's disease, Alzheimer's disease, ALS, multiple sclerosis and demyelinating diseases in general, senile and vascular dementia, diabetic and post-herpetic neuropathy, Bell's palsy, trigeminal neuralgia, lumbosciatalgia, cruralgia, cervicobrachialgia, radiculopathies, carpal and tarsal tunnel syndrome, oculopathies as well as diabetic retinopathy, age-related macular degeneration and glaucoma, iatrogenic neuropathies induced by chemotherapy, radiant / replacement therapies, immunosuppressants and the fact of being able to relieve oncological pain, improving neurotoxicity from cisplatin, chronic neuropathic and neuronal pain , chronic pelvic pain of neurological origin and in particular the pudendal neuropathy, the composition described in the present invention is particularly effective in gynecology and in particular in endometriosis, vulvodynia and pelvic infections, in urology for the treatment of chronic cystitis, in chronic urethritis and prostatitis and in penodynia. also effective in musculoskeletons and in particular in pelvic floor dysfunctions, in low grade non resolving inflammation, that is, in the treatment of chronic pain in the elderly and in menopausal women, in pain in burning mouth syndrome, in migraine and finally allows the reduction of the dosage of painkilling drugs with which said combination can be used in combination. In addition, the composition described in the present invention achieves its main purposes by also describing and claiming the route of administration of said inventive association, which according to the type of condition to be treated can be suitably formulated for enteral administration, for parenteral administration and for topical administration.
Pur tuttavia, come descritto più diffusamente nella descrizione dettagliata che segue, la formulazione preferita di detta associazione, secondo la presente invenzione, è quella relativa alla via enterale e più preferibilmente alla via orale. Altre caratteristiche della presente invenzione saranno descritte nella seguente descrizione particolareggiata di una o più forme specifiche di esecuzione, protette dalle varie rivendicazioni dipendenti. However, as described more fully in the detailed description that follows, the preferred formulation of said association, according to the present invention, is that relating to the enteral route and more preferably to the oral route. Other features of the present invention will be described in the following detailed description of one or more specific embodiments, protected by the various dependent claims.
Descrizione Dettagliata dell’Invenzione Detailed Description of the Invention
La presente domanda di brevetto per invenzione verrà ora descritta dettagliatamente, tramite le sue forme di realizzazioni preferite riguardanti la formulazione nonché il dosaggio dell’associazione inventiva. The present patent application for invention will now be described in detail, through its preferred embodiments regarding the formulation as well as the dosage of the inventive association.
Allo scopo, la presente domanda di brevetto per invenzione tende a descrivere e rivendicare l’associazione di acido α-lipoico, citicolina, luteolina e fisetina come coadiuvante terapeutico ovvero come un’associazione dotata di un’eccellente attività favorente determinate funzioni e processi fisiologici, connessi con la scomparsa o l’alleviamento del dolore e dei sintomi, oppure nei casi più favorevoli con la guarigione di molte delle patologie sopra accennate e riguardanti il sistema nervoso centrale e periferico. For this purpose, the present patent application for invention tends to describe and claim the association of α-lipoic acid, citicoline, luteolin and fisetin as a therapeutic adjuvant or as an association endowed with an excellent activity favoring certain physiological functions and processes, connected with the disappearance or alleviation of pain and symptoms, or in the most favorable cases with the healing of many of the aforementioned pathologies concerning the central and peripheral nervous system.
Alla luce delle predette evidenze, una forma di realizzazione preferita della presente invenzione prevede di realizzare detta associazione inventiva tramite una formulazione adatta per la via di somministrazione enterale e più specificatamente sotto forma di una qualsiasi delle forme adatte per la somministrazione orale. In light of the aforementioned evidences, a preferred embodiment of the present invention provides for the realization of said inventive association by means of a formulation suitable for the enteral route of administration and more specifically in the form of any one of the forms suitable for oral administration.
Specificatamente in un aspetto, l’invenzione si riferisce a un integratore alimentare per la somministrazione orale costituito dall’associazione, così come definita sopra, sotto forma di capsule di gelatina dura o molle, di compresse, di compresse effervescenti o masticabili, di bustine di granuli o polvere, di forme solide a rilascio controllato, di gomme da masticare, di sciroppi e simili. Specifically in one aspect, the invention relates to a food supplement for oral administration consisting of the combination, as defined above, in the form of hard or soft gelatin capsules, tablets, effervescent or chewable tablets, sachets of granules or powder, of controlled release solid forms, of chewing gums, syrups and the like.
Predette composizioni adatte per la somministrazione orale, saranno formulate e preparate secondo metodi convenzionali ben noti nella tecnica farmaceutica, utilizzando eccipienti, veicoli, fragranze e altre sostanze approvate conformemente al tipo di formulazione desiderata. Predicted compositions suitable for oral administration will be formulated and prepared according to conventional methods well known in the pharmaceutical art, using excipients, carriers, fragrances and other substances approved according to the type of formulation desired.
Tuttavia la forma preferita di realizzazione secondo la presente invenzione prevede di realizzare detta associazione sotto forma di compresse, costituenti ciascuna un’unità di dosaggio, tramite l’aggiunta ai principi attivi costituenti l’inventiva associazione di eccipienti farmaceuticamente accettabili, che a scopo esemplificativo e non limitativo comprendono amido di patate, di frumento o di mais, amido parzialmente pre-gelatinizzato, cellulosa microcristallina, idrossipropilmetilcellulosa, fosfato di calcio bibasico, carbonato di calcio, polioli come mannitolo o sorbitolo, maltodestrina, lattosio, silice colloidale, biossido di silicio altamente disperso, gliceril-behenato, propilenglicole, polivinilpirrolidone, polivinilpirrolidone reticolato, esteri ed eteri di cellulosa, carmellosa sodica, alginati, carragenina, magnesio stearato, sodio stearil fumarato, biossidio di titanio, gelatina, oli vegetali come olio di girasole o soia, poliglicerolo oleato, glicerolo, trigliceridi degli acidi grassi, lecitina, e così via. However, the preferred embodiment according to the present invention provides for the realization of said association in the form of tablets, each constituting a dosage unit, by adding to the active ingredients constituting the inventive association of pharmaceutically acceptable excipients, which for example and non-limiting include potato, wheat or corn starch, partially pre-gelatinized starch, microcrystalline cellulose, hydroxypropylmethylcellulose, dibasic calcium phosphate, calcium carbonate, polyols such as mannitol or sorbitol, maltodextrin, lactose, colloidal silica, highly silicon dioxide dispersed, glyceryl-behenate, propylene glycol, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, cellulose esters and ethers, carmellose sodium, alginates, carrageenan, magnesium stearate, sodium stearyl fumarate, titanium dioxide, gelatin, vegetable oils such as polyglycerol or soybean oil, , glycerol, triglycerides of fatty acids, lecithin, and so on.
Un ulteriore obiettivo è quello di proporre una formulazione preferita costituita da un peso per singola compressa, vale a dire per una singola unità di dosaggio costituita dall’inventiva associazione e da tutti gli eccipienti necessari per la formulazione, compreso tra 1.100 mg e 700 mg e più preferibilmente pari a 900 mg. A further objective is to propose a preferred formulation consisting of a weight per single tablet, i.e. for a single dosage unit consisting of the inventive association and all the excipients necessary for the formulation, between 1,100 mg and 700 mg and more preferably equal to 900 mg.
In un aspetto ancora più specifico, la presente invenzione propone i rapporti ponderali di ciascun principio attivo in ognuna di predetta unità di dosaggio e in particolare questi sono costituiti per quanto riguarda l’acido alfa-lipoico da un peso compreso tra il 20 % e il 46% e preferibilmente pari al 33%; per quanto riguarda la citicolina da un peso compreso tra il 15% e il 41% e preferibilmente pari al 28%; per quanto riguarda la fisetina da un peso compreso tra il 2% e il 10% e preferibilmente pari al 6% e infine per quanto riguarda la luteolina da un peso compreso tra l’1% e il 5% e preferibilmente pari al 3%, laddove tutte le sopraddette percentuali sono considerate come percentuali in peso relative complessivamente al peso totale di ciascuna unità di dosaggio. In an even more specific aspect, the present invention proposes the weight ratios of each active ingredient in each of the aforementioned dosage units and in particular these consist, as regards the alpha-lipoic acid, of a weight between 20% and 46% and preferably equal to 33%; as regards citicoline it has a weight comprised between 15% and 41% and preferably equal to 28%; as regards fisetin from a weight between 2% and 10% and preferably equal to 6% and finally as regards luteolin from a weight between 1% and 5% and preferably equal to 3%, wherein all the aforementioned percentages are considered as percentages by weight relative overall to the total weight of each dosage unit.
La presente invenzione è stata descritta a titolo illustrativo, ma non limitativo, secondo alcune forme di realizzazione preferite, ma è da intendersi che eventuali variazioni e/o modifiche potranno essere apportate dagli esperti del settore, senza per questo uscire fuori dal relativo ambito di protezione, così come definito dalle seguenti rivendicazioni dipendenti. The present invention has been described by way of illustration, but not of limitation, according to some preferred embodiments, but it is to be understood that any variations and / or modifications may be made by those skilled in the art, without thereby departing from the relative scope of protection. , as defined by the following dependent claims.
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