IT202000029747A1 - COMPOSITION WITH PROTECTIVE ACTIVITY ON NEURON CELLS TO PREVENT AND TREAT A NEUROCOGNITIVE DISORDER - Google Patents
COMPOSITION WITH PROTECTIVE ACTIVITY ON NEURON CELLS TO PREVENT AND TREAT A NEUROCOGNITIVE DISORDER Download PDFInfo
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- IT202000029747A1 IT202000029747A1 IT102020000029747A IT202000029747A IT202000029747A1 IT 202000029747 A1 IT202000029747 A1 IT 202000029747A1 IT 102020000029747 A IT102020000029747 A IT 102020000029747A IT 202000029747 A IT202000029747 A IT 202000029747A IT 202000029747 A1 IT202000029747 A1 IT 202000029747A1
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- catechins
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- cocoa
- salidroside
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- 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
- A61K31/352—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 condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/41—Crassulaceae (Stonecrop family)
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- Alternative & Traditional Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
Deposito di una domanda di brevetto per invenzione industriale dal titolo: Filing of a patent application for an industrial invention entitled:
COMPOSIZIONE AD ATTIVITA? PROTETTIVA SU CELLULE NEURONALI PER PREVENIRE E TRATTARE UN DISTURBO NEUROCOGNITIVO. ACTIVITY COMPOSITION? PROTECTIVE ON NEURON CELLS TO PREVENT AND TREAT A NEUROCOGNITIVE DISORDER.
DESCRIZIONE DESCRIPTION
CAMPO DELL'INVENZIONE FIELD OF THE INVENTION
La presente invenzione concerne una composizione ad attivit? protettiva su cellule neuronali per prevenire e/o trattare un disturbo neurocognitivo. The present invention relates to a composition with active protective effect on neuronal cells to prevent and/or treat a neurocognitive disorder.
In particolare, la presente invenzione riguarda un integratore per la somministrazione orale comprendente una combinazione di ingredienti biologicamente attivi provvista di attivit? neuroprotettiva sulle cellule neuronali, idonea a prevenire o trattare disturbi neurocognitivi e/o il declino cognitivo correlato all?avanzamento dell?et?. In particular, the present invention relates to a supplement for oral administration comprising a combination of biologically active ingredients having neuroprotective on neuronal cells, suitable for preventing or treating neurocognitive disorders and/or age-related cognitive decline.
La presente invenzione origina nel settore dei prodotti ad azione biologica che non richiedono prescrizione medica e che trovano utilizzo nel trattamento dei disturbi neurocognitivi. The present invention originates in the sector of products with a biological action which do not require a medical prescription and which are used in the treatment of neurocognitive disorders.
Con disturbi neurocognitivi si intendono i disturbi neurologici o della sfera psichica in cui si riscontra un deterioramento delle capacit? intellettive, dell'apprendimento e/o della memoria, eventualmente associati ad alterazioni del comportamento e/o dell?orientamento spazio-temporale. With neurocognitive disorders we mean neurological disorders or psychic sphere in which there is a deterioration of the abilities? intellectual, learning and/or memory, possibly associated with alterations of behavior and/or space-time orientation.
TECNICA ANTERIORE PRIOR TECHNIQUE
L?innalzamento dell?et? media di vita nei paesi occidentali ha portato negli ultimi decenni ad una maggiore diffusione ed incidenza di disturbi neurocognitivi e di patologie neurodegenerative la cui comparsa determina una involuzione delle principali funzioni cognitive del soggetto interessato. The raising of the age? life expectancy in Western countries has led in recent decades to a greater diffusion and incidence of neurocognitive disorders and neurodegenerative pathologies whose appearance determines a decline of the main cognitive functions of the person concerned.
Le funzioni intellettive maggiormente interessate dal declino cognitivo sono rappresentate dalla memoria, capacit? di apprendimento, di linguaggio e di orientamento spazio-temporale. The intellectual functions most affected by cognitive decline are represented by memory, ability to of learning, language and spatio-temporal orientation.
Le forme lievi di disturbi neurocognitivi hanno una sintomatologia lieve e non impediscono, ai soggetti che ne soffrono, di svolgere le pi? comuni attivit? quotidiane e di mantenere normali relazioni interpersonali e di condurre una vita autonoma. The mild forms of neurocognitive disorders have a mild symptomatology and do not prevent the subjects who suffer from carrying out the most important tasks. common activities daily life and to maintain normal interpersonal relationships and to lead an independent life.
Queste forme lievi interessano principalmente la fascia di popolazione con et? superiore ai 60 anni. Nella fascia di et? introno ai 60 anni questi disturbi possono essere parzialmente reversibili se opportunamente trattati mentre nella popolazione con et? superiore a 80 anni i margini di miglioramenti sono pressoch? nulli. These mild forms mainly affect the age group of the population? over 60 years old. In the age range? around the age of 60 these disorders can be partially reversible if properly treated while in the population with age? more than 80 years the margins for improvements are almost? null.
Le forme di declino cognitivo generalmente sono di origine vascolare e/o neurodegenerative. The forms of cognitive decline are generally of vascular and/or neurodegenerative origin.
Il declino cognitivo, avendo una matrice a degenerazione progressiva non lascia grossi margini di miglioramento e quindi la terapia ? solitamente di tipo conservativo. Cognitive decline, having a matrix of progressive degeneration does not leave much room for improvement and therefore the therapy? usually conservative.
Un lieve miglioramento o un rallentamento nella progressione del declino cognitivo rappresenta gi? indice della adeguatezza delle misure e interventi presi. A slight improvement or a slowdown in the progression of cognitive decline already represents? index of the adequacy of the measures and interventions taken.
Il rallentamento del declino cognitivo ? tanto pi? efficace quanto prima vengono prese adeguate misure. I possibili interventi sull?individuo spaziano da una regolazione del regime dietetico, all?adozione di uno stile di vita appropriato alle condizioni di salute, al trattamento terapeutico con specifici prodotti o medicinali. Esistono diverse forme e gradi di disturbo neurocognitivo, analoghe per manifestazioni, ma indotte da meccanismi differenti. Tutte le forme di disturbo neurocognitivo sono legate alla presenza di un danno cerebrale che pu? essere conseguenza di un evento acuto, come nel caso dell'ictus, oppure essere un processo involutivo progressivo che diventa evidente quando viene superata una certa "soglia", oltre la quale viene meno la capacit? di compensare le funzioni cognitive. Slowing Cognitive Decline? all the more effective as soon as appropriate measures are taken. The possible interventions on the individual range from adjusting the diet, to adopting a lifestyle appropriate to the health conditions, to therapeutic treatment with specific products or medicines. There are different forms and degrees of neurocognitive disorder, similar in manifestations, but induced by different mechanisms. All forms of neurocognitive disorder are related to the presence of brain damage that can be the result of an acute event, as in the case of a stroke, or be a progressive involutionary process that becomes evident when a certain "threshold" is exceeded, beyond which the ability to to compensate for cognitive functions.
Nella maggior parte dei casi il declino cognitivo ? associato all'invecchiamento dell?organismo, e le manifestazioni sono compatibili con la fase iniziale di degenerazione neuronale. In most cases the cognitive decline ? associated with the aging of the organism, and the manifestations are compatible with the initial phase of neuronal degeneration.
Agli esordi queste forme iniziali di decadimento cognitivo sono trattate instaurando idonei regimi dietetici e somministrando specifici prodotti nutrizionali provvisti di una azione cerebrovascolare e/o neuroprotettiva. At the outset, these initial forms of cognitive impairment are treated by establishing suitable dietary regimens and administering specific nutritional products with a cerebrovascular and/or neuroprotective action.
In questi casi vengono somministrati integratori nutrizionali contenenti vitamine, composti ad attivit? antiossidante quali selenio, vitamina E oppure prodotti contenenti sostanze a matrice fosfolipidica come fosfatidilserina, fosfatidilcolina o fosfatidilinositolo o sostanze associate a effetti benefici sulla salute dell'apparato cardiovascolare e del sistema nervoso quali gli acidi polinsaturi omega-3 e omega-6. In these cases, nutritional supplements containing vitamins, compounds with antioxidant such as selenium, vitamin E or products containing phospholipid matrix substances such as phosphatidylserine, phosphatidylcholine or phosphatidylinositol or substances associated with beneficial effects on the health of the cardiovascular system and nervous system such as omega-3 and omega-6 polyunsaturated acids.
La terapia farmacologica viene invece riservata al trattamento di forme di media ed elevata gravit? quali le forme di demenza senile e il morbo di Alzheimer, nella quali la sintomatologia collegata al decadimento cognitivo inizia a condizionare la qualit? della vita e lo svolgimento delle attivit? quotidiane dell?individuo. Pharmacological therapy is instead reserved for the treatment of forms of medium and high severity such as forms of senile dementia and Alzheimer's disease, in which the symptoms connected to cognitive impairment begin to affect the quality of life and the performance of activities? daily life of the individual.
In queste forme pi? avanzate di decadimento cognitivo sono somministrati inibitori dell'acetilcolinesterasi ad esempio come il donepezil, la rivastigmina e la galantamina. In these forms more? advanced cognitive impairment are given acetylcholinesterase inhibitors such as donepezil, rivastigmine and galantamine.
Altri farmaci come la memantina sono riservati al trattamento delle forme pi? gravi di patologie neurodegenerative e del morbo di Alzheimer. Other drugs such as memantine are reserved for the treatment of the more severe forms. serious neurodegenerative diseases and Alzheimer's disease.
Si ? tuttavia riscontrato che la somministrazione di questi farmaci si accompagna, nella maggior parte dei casi, alla comparsa di effetti secondari che possono diventare importanti nel caso delle terapie farmacologiche croniche. Yup ? however, it has been found that the administration of these drugs is accompanied, in most cases, by the appearance of secondary effects which can become important in the case of chronic pharmacological therapies.
Inoltre, i prodotti nutraceutici attualmente sul mercato indicati per il trattamento delle forme lievi o moderate dei disturbi cognitivi forniscono una risposta terapeutica inadeguata. Furthermore, the nutraceutical products currently on the market indicated for the treatment of mild or moderate forms of cognitive disorders provide an inadequate therapeutic response.
Attualmente si sente l?esigenza di disporre di nuovi prodotti ad azione neuroprotettiva o nootropa per il trattamento delle malattie involutive e dei disturbi cognitivi di lieve entit? Currently there is a need for new products with a neuroprotective or nootropic action for the treatment of involutionary diseases and mild cognitive disorders.
? uno scopo generale della presente invenzione fornire un medicinale o prodotto nutraceutico idoneo a migliorare il quadro clinico e/o la sintomatologia connessa con le forme lievi o moderate di un disturbo neurocognitivo. ? a general purpose of the present invention is to provide a medicinal or nutraceutical product suitable for improving the clinical picture and/or the symptoms associated with the mild or moderate forms of a neurocognitive disorder.
Un altro scopo della presente invenzione consiste nel fornire una composizione per prevenire o trattare patologie neurodegenerative e disturbi neurocognitivi la cui somministrazione cronica non si accompagni ad effetti collaterali severi e che consenta il trattamento a lungo termine delle patologie neurodegenerative. Another object of the present invention consists in providing a composition for preventing or treating neurodegenerative pathologies and neurocognitive disorders whose chronic administration is not accompanied by severe side effects and which allows the long-term treatment of neurodegenerative pathologies.
Rappresenta un ulteriore oggetto della presente invenzione un metodo per prevenire o trattare patologie neurodegenerative o disturbi neurocognitivi in un individuo in necessit? di trattamento. A further object of the present invention represents a method for preventing or treating neurodegenerative pathologies or neurocognitive disorders in an individual in need? of treatment.
SOMMARIO DELL'INVENZIONE SUMMARY OF THE INVENTION
Nel corso dell?attivit? di ricerca in ambito neurologico, la Richiedente ha osservato che la combinazione di due specifici ingredienti biologicamente attivi ha un?azione protettiva sulle cellule neuronali e sulla loro funzionalit?. Questo effetto rende la combinazione idonea a trattare i disturbi neurocognitivi, in particolare le forme lievi in sostanziale assenza di effetti collaterali anche a seguito di somministrazione cronica. During the activity? of research in the neurological field, the Applicant has observed that the combination of two specific biologically active ingredients has a protective action on neuronal cells and their functionality. This effect makes the combination suitable for treating neurocognitive disorders, in particular the mild forms in the substantial absence of side effects even following chronic administration.
L?effetto riscontrato su modello sperimentale che utilizza cellule neuronali ? inatteso poich? i due componenti base della composizione dell?invenzione hanno target biologici diversi ed agiscono a livello centrale attraverso meccanismi di azione diversi che non sembrerebbero giustificare un?azione neuroprotettiva sinergica. The effect found on an experimental model that uses neuronal cells? unexpected because? the two basic components of the composition of the invention have different biological targets and act centrally through different mechanisms of action which would not seem to justify a synergistic neuroprotective action.
La Richiedente ha osservato che i flavan-3-oli, in particolare selezionate catechine provviste di spiccata attivit? antiossidante, possono superare la barriera ematoencefalica e possono localizzarsi nel cervello in aree cruciali per l?apprendimento e la memoria come l?ippocampo, la corteccia cerebrale, il cervelletto e il nucleo striato. Queste aree sono risulte particolarmente colpite in caso di neurodegenerazione, una delle principali concause dei disturbi neurocognitivi. In presenza di flavan-3-oli, in particolare di certe catechine, l?ippocampo aumenta l?espressione del fattore neurotrofico cerebrale (BDNF), elemento fondamentale per la sopravvivenza neuronale, per la trasmissione sinaptica e la neurogenesi. L?uso di flavanoli, aumentando l?espressione di BDNF, migliora le capacit? cognitive. L?invenzione origina dall?avere trovato che l?entit? di questo miglioramento aumenta quando i flavanoli e catechine qui descritte, sono combinate con salidroside. Questo ? un composto di origine vegetale che ha una pathway diversa da quelle delle catechine e che agisce aumentando nel cervello i livelli di monoamine, in particolare serotonina, attraverso un'inibizione dell'enzima responsabile della loro degradazione. The Applicant has observed that the flavan-3-ols, in particular selected catechins provided with marked antioxidant, can cross the blood brain barrier and can locate in the brain in areas crucial for learning and memory such as the hippocampus, cerebral cortex, cerebellum and striatum. These areas are particularly affected in case of neurodegeneration, one of the main causes of neurocognitive disorders. In the presence of flavan-3-ols, especially certain catechins, the hippocampus increases the expression of brain neurotrophic factor (BDNF), a fundamental element for neuronal survival, synaptic transmission and neurogenesis. The use of flavanols, by increasing the expression of BDNF, improves the ability cognitive. The invention originates from having found that the entity? This improvement is increased when the flavanols and catechins described herein are combined with salidroside. This ? a compound of vegetable origin which has a different pathway from those of catechins and which acts by increasing the levels of monoamines, in particular serotonin, in the brain through an inhibition of the enzyme responsible for their degradation.
Forma quindi oggetto della presente invenzione una composizione ad attivit? neuroprotettiva per l?uso nella prevenzione o nel trattamento di un disturbo neurocognitivo e/o correlata sintomatologia, in cui la composizione comprende una combinazione di Therefore, the object of the present invention is a composition with active neuroprotective for use in the prevention or treatment of a neurocognitive disorder and/or related symptoms, wherein the composition comprises a combination of
i) salidroside o un estratto da pianta Rhodiola rosea L. che la contiene, i) salidroside or a Rhodiola rosea L. plant extract containing it,
ii) flavanoli, in particolare catechine o un estratto di cacao che le contiene e un veicolo commestibile, fisiologicamente accettabile. ii) flavanols, in particular catechins or a cocoa extract containing them, and an edible, physiologically acceptable vehicle.
La Richiedente osservando gli effetti di flavanoli, catechine e salidroside su modelli di cellule neuronali in vitro ha inaspettatamente osservato che la combinazione dei due principi attivi ha un effetto di riduzione dell?apoptosi indotta da beta-amiloide. Questa ? una delle cause delle patologie neurodegenerative pi? ampiamente studiata in letteratura al fine di individuare i meccanismi che determinano sofferenza neuronale e la comparsa dei disturbi neurocognitivi. By observing the effects of flavanols, catechins and salidroside on in vitro neuronal cell models, the Applicant unexpectedly observed that the combination of the two active ingredients has a reduction effect on apoptosis induced by beta-amyloid. This ? one of the causes of neurodegenerative diseases pi? extensively studied in the literature in order to identify the mechanisms that determine neuronal suffering and the appearance of neurocognitive disorders.
Sulla base di queste premesse la somministrazione di flavanoli, specialmente catechine o epicatechine qui descritte in combinazione con salidroside ha un effetto neuroprotettivo che ? alla base del miglioramento delle capacit? cognitive del soggetto trattato. Based on these premises, the administration of flavanols, especially catechins or epicatechins described herein in combination with salidroside, has a neuroprotective effect which ? the basis of the improvement of capabilities? knowledge of the treated subject.
In accordo ad un aspetto, la presente invenzione quindi prevede una composizione di combinazione per la prevenzione e/o il trattamento di patologie neurodegenerative e/o disturbi neurocognitivi in un individuo in necessit? di trattamento. According to one aspect, the present invention therefore provides a combination composition for the prevention and/or treatment of neurodegenerative pathologies and/or neurocognitive disorders in an individual in need of of treatment.
In accordo ad un ulteriore aspetto viene qui descritto un metodo per la prevenzione o il trattamento delle patologie neurodegenerative e/o disturbi cognitivi comprendente la somministrazione ad un individuo in necessit? di trattamento di una composizione ad attivit? neuroprotettiva comprendente flavanoli, in particolare catechine in combinazione con salidroside. In accordance with a further aspect, a method for the prevention or treatment of neurodegenerative pathologies and/or cognitive disorders is described herein comprising the administration to an individual in need of of treatment of a composition to activity? neuroprotective comprising flavanols, especially catechins in combination with salidroside.
Vantaggiosamente, gli inventori hanno inoltre individuato che il cacao, specialmente in forma di polvere, ? una fonte di idonei flavanoli, in particolare di catechine che trovano utilizzo negli usi qui descritti e/o rivendicati. Advantageously, the inventors have also identified that cocoa, especially in the form of powder, is a source of suitable flavanols, in particular of catechins which find use in the uses described and/or claimed herein.
Tipicamente i principi biologicamente attivi della composizione di combinazione dell?invenzione sono forniti in un quantitativo farmaceuticamente, nutraceutico, o dietetico efficace e sono dispersi in un idoneo veicolo fisiologicamente acettabile. La composizione di combinazione ? idonea nella prevenzione o nel trattamento di un disturbo neurocognitivo, in particolare di lieve entit? e/o della sintomatologia associata a questo disturbo. Typically the biologically active ingredients of the combination composition of the invention are provided in a pharmaceutically, nutraceutically, or dietetically effective amount and are dispersed in a suitable physiologically acceptable carrier. The combination composition ? suitable for the prevention or treatment of a neurocognitive disorder, especially a minor one and/or the symptoms associated with this disorder.
Secondo alcune forme di realizzazione, la composizione dell'invenzione ? un nutraceutico, un integratore, un alimento ai fini medici speciali dispensabile senza ricetta medica che pu? essere introdotto nel regime dietetico di un individuo affetto da un disturbo neurocognitivo. According to some embodiments, the composition of the invention is a nutraceutical, a supplement, a food for special medical purposes dispensable without a medical prescription that can? be introduced into the dietary regimen of an individual with a neurocognitive disorder.
Secondo alcuni aspetti l'invenzione fornisce un kit contenente flavanoli, specialmente catechine in combinazione con salidroside ed un veicolo fisiologicamente accettabile come preparazione combinata per un uso simultaneo, separato o successivo nella prevenzione o trattamento di disturbi neurocognitivi. DESCRIZIONE DETTAGLIATA DELL'INVENZIONE In some aspects the invention provides a kit containing flavanols, especially catechins in combination with salidroside and a physiologically acceptable carrier as a combined preparation for simultaneous, separate or successive use in the prevention or treatment of neurocognitive disorders. DETAILED DESCRIPTION OF THE INVENTION
In accordo ad alcuni aspetti dell'invenzione, gli inventori hanno osservato che la combinazione di flavanoli, in particolare catechine qui descritte con salidroside ha un effetto protettivo sulle cellule neuronali ascrivibile ad un aumento dell?espressione del fattore neurotrofico cerebrale (BDNF) ed una inibizione dei processi che portano alla formazione e deposito di placche ?-amiloide e di ?amiloide. Quest?ultima ? una proteina che si organizzano in depositi proteici fibrillari extracellulari da cui origina la placca amiloide nelle strutture cerebrali a cui ? attribuito un ruolo rilevante nell?origine delle patologie neurodegenerative e dei disturbi cognitivi. In accordance with some aspects of the invention, the inventors have observed that the combination of flavanols, in particular catechins described herein, with salidroside has a protective effect on neuronal cells attributable to an increase in the expression of brain neurotrophic factor (BDNF) and an inhibition of the processes leading to the formation and deposition of ?-amyloid and ?amyloid plaques. The latter ? a protein that are organized in extracellular fibrillar protein deposits from which the amyloid plaque originates in the brain structures to which ? attributed an important role in the origin of neurodegenerative diseases and cognitive disorders.
In accordo ad un la presente invenzione ha ad oggetto una composizione di combinazione ad attivit? neuroprotettiva per l?uso come definito nella acclusa rivendicazione 1. According to one the object of the present invention is a combination composition with active neuroprotective for use as defined in the appended claim 1.
Si ? osservato che l?utilizzo della composizione di combinazione, in particolare in un periodo lungo almeno 3 mesi, previene il deposito nelle strutture cerebrali delle proteine amiloidogeniche, un gruppo di proteine che si organizzano in depositi proteici fibrillari extracellulari da cui origina la placca amiloide. Poich? la deposizione extracellulare di queste proteine, in particolare la proteina ?-amiloide, in alcune regioni del cervello e la presenza delle placche ? uno dei segnali tipici presente nel decadimento delle funzioni cognitive, la composizione di combinazione trova utilizzo nella prevenzione e trattamento di disturbi neurocognitivi, grazie all?effetto inibitorio sulla formazione di queste placche. Yup ? observed that the use of the combination composition, particularly over a period of at least 3 months, prevents the deposition in brain structures of amyloidogenic proteins, a group of proteins that organize themselves into extracellular fibrillar protein deposits from which amyloid plaque originates. because the extracellular deposition of these proteins, in particular the ?-amyloid protein, in some regions of the brain and the presence of ? one of the typical signals present in the decay of cognitive functions, the combination composition finds use in the prevention and treatment of neurocognitive disorders, thanks to the inhibitory effect on the formation of these plaques.
Forme di realizzazione della composizione per gli usi qui descritti sono definiti nelle accluse rivendicazioni dipendenti 2-9. Embodiments of the composition for the uses described herein are defined in the attached dependent claims 2-9.
La composizione di combinazione dell?invenzione contiene flavanoli (flavan-3-oli), quali catechine, ad esempio epicatechine, come principio biologicamente attivo. The combination composition of the invention contains flavanols (flavan-3-ols), such as catechins, for example epicatechins, as a biologically active ingredient.
Tra i flavanoli, alcune catechine sono state selezionati dalla richiedente per il loro effetto sui meccanismi antiossidanti cellulari. A livello cellulare le catechine riducono l'eccesso di radicali liberi dell?ossigeno circolanti come il radicale idrossile OH<- >e l?anione superossido O2-. Inoltre, le catechine riducono le specie non radicaliche quali il perossido di idrogeno H2O2, contribuendo a ristabilire l?equilibrio tra produzione ed eliminazione di specie chimiche ossidanti, prevenendo lo stress ossidativo cellulare ed equilibrando la funzionalit? mitocondriale. Among the flavanols, some catechins have been selected by the Applicant for their effect on cellular antioxidant mechanisms. At the cellular level, catechins reduce excess circulating oxygen free radicals such as the hydroxyl radical OH<- > and the superoxide anion O2-. Furthermore, catechins reduce non-radical species such as hydrogen peroxide H2O2, helping to restore the balance between production and elimination of oxidant chemical species, preventing cellular oxidative stress and balancing cell functionality. mitochondrial.
Vantaggiosamente nella composizione dell?invenzione possono essere utilizzati selezionati flavanoli quali le catechine contenute in cacao, preferibilmente in polvere ottenuta da pianta Theobroma cacao. Advantageously, selected flavanols such as the catechins contained in cocoa, preferably in powder obtained from the Theobroma cacao plant, can be used in the composition of the invention.
Vantaggiosamente le catechine sono contenute in polvere di semi di cacao, da Theobroma cacao. Advantageously, the catechins are contained in cocoa bean powder, from Theobroma cacao.
I flavanoli, le catechine in particolare quelle selezionate secondo alcuni aspetti dell?invenzione, attivano il metabolismo energetico a livello cellulare e la biogenesi mitocondriale. Flavanols, catechins in particular those selected according to some aspects of the invention, activate energy metabolism at the cellular level and mitochondrial biogenesis.
Si ? inoltre osservato che idonei flavanoli/catechine, quali quelli estratti o contenute nel cacao preservano i livelli organici degli acidi grassi polinsaturi omega 3 e 6, sostanze biologicamente attive che riducono i processi infiammatori a livello corticale, espressione di una sofferenza cerebrale che prelude a disturbi neurocognitivi. Yup ? further noted that suitable flavanols/catechins, such as those extracted or contained in cocoa, preserve the organic levels of omega 3 and 6 polyunsaturated fatty acids, biologically active substances that reduce inflammatory processes at the cortical level, an expression of cerebral suffering that heralds neurocognitive disorders .
Nell?ambito dell?invenzione, idonei flavanoli sono catechine selezionate tra epicatechina, epigallocatechina, epicatechina gallato, epigallocatechina gallato e loro miscele. In una forma di realizzazione l?epicatechina ? epigallocatechina gallato. Within the scope of the invention, suitable flavanols are catechins selected from epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate and mixtures thereof. In one embodiment, epicatechin ? epigallocatechin gallate.
Le catechine possiedono due anelli di benzene ed un eterociclo di diidropirano con un gruppo OH sul carbonio 3. Tipicamente esistono due centri chirali sulla molecola sui carboni 2 e 3. Pertanto, le catechine hanno 4 diastereoisomeri. Due degli isomeri sono in configurazione trans e sono detti catechine mentre gli altri due sono in configurazione cis e sono detti epicatechine. Le epicatechine sono un sottogruppo idoneo di flavanoli ai fini degli utilizzi dell?invenzione. Catechins possess two benzene rings and a dihydropyran heterocycle with an OH group on carbon 3. Typically, there are two chiral centers on the molecule at carbons 2 and 3. Therefore, catechins have 4 diastereoisomers. Two of the isomers are in the trans configuration and are called catechins while the other two are in the cis configuration and are called epicatechins. Epicatechins are a suitable subgroup of flavanols for uses of the invention.
In accordo ad alcune forme di realizzazione, idonei flavanoli sono scelti dal gruppo consistente in (+)-catechin, (?)-epicatechin, (+)-gallocatechin, (?)-epigallocatechin, (+)-catechin-3-O-gallate, (?)-epicatechin-3-O-gallate, (?)-gallocatechin-3-O-gallate, (?)-epigallocatechin-3-O-gallate, procyanidin A2, and procyanidin B2 e loro miscele. According to some embodiments, suitable flavanols are selected from the group consisting of (+)-catechin, (?)-epicatechin, (+)-gallocatechin, (?)-epigallocatechin, (+)-catechin-3-O- gallate, (?)-epicatechin-3-O-gallate, (?)-gallocatechin-3-O-gallate, (?)-epigallocatechin-3-O-gallate, procyanidin A2, and procyanidin B2 and mixtures thereof.
In accordo a certe forme di realizzazione flavanoli idonei sono scelti tra (+)-catechin-3-O-gallate, (?)-epicatechin-3-O-gallate, (?)-gallocatechin-3-O-gallate, (? )-epigallocatechin-3-O-gallate, procyanidin B2 e loro miscele. According to certain embodiments suitable flavanols are selected from (+)-catechin-3-O-gallate, (?)-epicatechin-3-O-gallate, (?)-gallocatechin-3-O-gallate, (?)-gallocatechin-3-O-gallate, (?)-epicatechin-3-O-gallate, )-epigallocatechin-3-O-gallate, procyanidin B2 and mixtures thereof.
Secondo alcune forme di realizzazione la composizione dell?invenzione comprende una componente o estratto di origine vegetale che contiene epicatechine in particolare da cacao, preferibilmente polvere di semi di cacao. In accordo a certe forme di realizzazione idonee catechine sono contenute in cacao in polvere avente un contenuto di catechine maggiore di 7 g/kg, preferibilmente maggiore di 12 g/kg titolato come acido gallico. According to some embodiments, the composition of the invention comprises a component or extract of vegetable origin which contains epicatechins in particular from cocoa, preferably cocoa bean powder. According to certain embodiments suitable catechins are contained in cocoa powder having a catechin content greater than 7 g/kg, preferably greater than 12 g/kg titrated as gallic acid.
Vantaggiosamente, un idoneo cacao in polvere avente un contenuto di catechine preferibilmente epicatechine maggiore di 7 g/kg, preferibilmente maggiore di 12 g/kg titolato come acido gallico, pu? essere ottenuto partendo da fave di cacao fermentate o non, avente un contenuto di umidit? inferiore al 20% in peso e riscaldando le fave di cacao ad una temperature da 70 a 120 ?C per un periodo di tempo da 1 a 30 minuti. Advantageously, a suitable cocoa powder having a content of catechins, preferably epicatechins greater than 7 g/kg, preferably greater than 12 g/kg titrated as gallic acid, can be obtained starting from fermented or non-fermented cocoa beans, having a humidity content? less than 20% by weight and by heating the cocoa beans at a temperature of from 70 to 120°C for a period of time from 1 to 30 minutes.
Ad esempio, un idoneo cacao in polvere avente un contenuto di catechine/epicatechine maggiore di 7 g/kg, preferibilmente maggiore di 12 g/kg titolato come acido gallico pu? essere ottenuto con un processo che comprende le seguenti fasi: For example, a suitable cocoa powder having a catechin/epicatechin content greater than 7 g/kg, preferably greater than 12 g/kg titrated as gallic acid can be obtained with a process that includes the following steps:
a) fornire fave di cacao fermentate o non fermentate; a) supply fermented or unfermented cocoa beans;
b) drenare/sgocciolare le fave della fase a) b) drain/drain the beans of phase a)
c) seccare le fave sgocciolate; c) dry the drained broad beans;
d) scaldare le fave di cacao a temperatura da 70 a 120 ?C per un periodo di tempo idoneo a rimuovere il guscio delle fave, ad esempio per 1 - 30 minuti, ad esempio ad infrarossi o aria calda, ad esempio a 30-70?C, 45.60?C. d) heating the cocoa beans at a temperature ranging from 70 to 120 ?C for a period of time suitable for removing the shell of the beans, for example for 1 - 30 minutes, for example with infrared or hot air, for example at 30-70 ?C, 45.60?C.
e) vagliare/separare le fave scaldate per separare granella/chicchi/semi di cacao dal guscio; e) sifting/separating the heated beans to separate cocoa nibs/beans/beans from the shell;
f) macinare chicchi/granella/semi di cacao in un brodo fluido marrone scuro contenente le particelle macinate di solidi di cacao parzialmente senza lipidi (parzialmente delipidati) sospesi nel burro di cacao; f) grinding cocoa beans/nibs/beans into a dark brown fluid broth containing the ground particles of partially lipid-free (partially delipidated) cocoa solids suspended in the cocoa butter;
g) Separare i solidi di cacao dal burro di cacao. g) Separate the cocoa solids from the cocoa butter.
Secondo alcune forme di realizzazione il quantitativo di cacao che contiene catechine nella composizione dell?invenzione varia da 10 a 1000mg, preferibilmente da 50 a 500 mg, pi? preferibilmente da 100 a 300 mg ad esempio 200 mg per unit? di dosaggio. According to some embodiments, the quantity of cocoa which contains catechins in the composition of the invention varies from 10 to 1000mg, preferably from 50 to 500mg, more? preferably from 100 to 300 mg for example 200 mg per unit? of dosage.
In accordo ad alcune forme di realizzazione, la quantit? di epicatechine varia da 0,01% a 20%, pi? preferibilmente dal 0,1 al 10%, ancor pi? preferibilmente dallo 0,05 al 5% in peso, rispetto al peso totale della composizione. According to some embodiments, the quantity of epicatechins varies from 0.01% to 20%, pi? preferably from 0.1 to 10%, even more? preferably from 0.05 to 5% by weight, with respect to the total weight of the composition.
Secondo alcune forme di realizzazione il quantitativo di cacao, preferibilmente in polvere, che contiene epicatechine nella composizione dell?invenzione varia da 10 a 1000mg, preferibilmente da 50 a 500 mg, pi? preferibilmente da 100 a 300 mg, ad esempio 200 mg per unit? di dosaggio. According to some embodiments, the quantity of cocoa, preferably in powder form, which contains epicatechins in the composition of the invention varies from 10 to 1000mg, preferably from 50 to 500mg, more? preferably from 100 to 300 mg, for example 200 mg per unit? of dosage.
La composizione di combinazione oggetto della presente invenzione comprende salidroside in aggiunta ai selezionati flavanoli qui descritti. The combination composition object of the present invention comprises salidroside in addition to the selected flavanols described herein.
Salidoroside nota con il nome IUPAC 2-(4-Hydroxyphenyl)ethyl ?-D-glucopyranoside ha la seguente formula : Salidoroside known by the IUPAC name 2-(4-Hydroxyphenyl)ethyl ?-D-glucopyranoside has the following formula:
Salidroside pu? essere di origine naturale o sintetica. Salidroside can? be of natural or synthetic origin.
Vantaggiosamente salidroside contenuta nella composizione ? di origine vegetale ed ? contenuta o estratta dalla pianta Rhodiola rosea L., genere appartenente alla famiglia delle Crassulaceae. Advantageously salidroside contained in the composition ? of vegetable origin and ? contained or extracted from the Rhodiola rosea L. plant, a genus belonging to the Crassulaceae family.
La composizione dell'invenzione pu? contenere Rhodiola rosea L. come tale, ad esempio una sua porzione da una parte della pianta, o come estratto da una parte della pianta. In certe forme di realizzazione ? previsto l?uso della pianta in combinazione con le epicatechine qui descritte o con cacao in polvere che le contiene. The composition of the invention can contain Rhodiola rosea L. as such, for example a portion thereof from a part of the plant, or as an extract from a part of the plant. In certain embodiments ? the use of the plant is foreseen in combination with the epicatechins described here or with cocoa powder which contains them.
Con l?uso della pianta si intende la pianta intera o una sua porzione contenente componenti biologicamente attiva. La pianta pu? essere utilizzata intera, macinata, o come estratto. Parti della pianta includono foglie, semi, frutti, radici o lo stelo/fusto. Nel caso della Rhodiola rosea L. ? preferito l?uso di radici. The use of the plant means the whole plant or a portion thereof containing biologically active components. The plant can be used whole, ground, or as an extract. Parts of the plant include leaves, seeds, fruit, roots, or the stem/stem. In the case of Rhodiola rosea L. ? the use of roots is preferred.
Preferibilmente l?efficacia della pianta qui descritta viene ottenuta con l?uso della pianta intera o di un suo estratto piuttosto che con l?uso di isolate componenti/ingredienti biologicamente attivi e derivati. Preferably, the efficacy of the plant described herein is obtained with the use of the whole plant or an extract thereof rather than with the use of isolated biologically active components/ingredients and derivatives.
Preferibilmente viene utilizzato un estratto secco, vantaggiosamente da radice della pianta. Preferably a dry extract is used, advantageously from the root of the plant.
Ad esempio, una fase iniziale della preparazione di un idoneo estratto secco prevede che la pianta o sue porzioni preferibilmente le radici, siano pulite, essiccate e opzionalmente tagliate in pezzi o sminuzzate, macinate o polverizzate. In una fase successiva questo materiale viene estratto utilizzando metodi convenzionali. For example, an initial step in the preparation of a suitable dry extract provides that the plant or portions thereof, preferably the roots, are cleaned, dried and optionally cut into pieces or comminuted, ground or pulverized. At a later stage this material is extracted using conventional methods.
Un solvente idoneo per ottenere l?estratto vegetale di Rhodiola rosacea ? un liquido fisiologicamente accettabile in cui le componenti biologicamente attive sono solubili ed in cui non subiscono una alterazione che le privi di attivit?. A suitable solvent to obtain Rhodiola rosacea plant extract? a physiologically acceptable liquid in which the biologically active components are soluble and in which they do not undergo an alteration that deprives them of activity.
Ad esempio, l?estrazione pu? essere realizzata con idoneo solvente come acqua o un alcool come etanolo o una miscela idroalcolica ad esempio acqua-etanolo. A titolo di esempio, il solvente idroalcolico pu? contenere dal 10% al 70% in volume di alcool, preferibilmente etanolo, preferibilmente dal 20% al 60% in volume, ancor preferibilmente dal 30% al 50% in volume, ad esempio il 40% in volume. For example, the extraction pu? be made with a suitable solvent such as water or an alcohol such as ethanol or a hydroalcoholic mixture such as water-ethanol. By way of example, the hydroalcoholic solvent can? contain from 10% to 70% by volume of alcohol, preferably ethanol, preferably from 20% to 60% by volume, still preferably from 30% to 50% by volume, for example 40% by volume.
L?estrazione pu? essere fatta a freddo o a caldo, ad esempio a 40-70 gradi centigradi. The extraction can? be made cold or hot, for example at 40-70 degrees Celsius.
Il liquido estratto pu? essere filtrato se necessario. In una fase successiva l?estratto liquido ? essiccato per ottenere la componente biologicamente attiva in forma di polvere secca. L?essiccamento pu? essere realizzato con tecniche convenzionali ad esempio ad aria, riscaldamento o spray-drying. The extracted liquid can be filtered if necessary. In a subsequent phase, the liquid extract? dried to obtain the biologically active component in dry powder form. Drying can be made with conventional techniques such as air, heating or spray-drying.
Ulteriori metodi per ottenere l?estratto vegetale di Rhodiola rosea titolato in Salidroside includono tecniche di estrazione mediante digestione, infusione, spremitura, decozione, percolazione, estrazione controcorrente, soxhlet, estrazione con gas supercritici o ultrasuoni. Additional methods for obtaining Salidroside titrated Rhodiola rosea plant extract include extraction techniques by digestion, infusion, squeezing, decoction, percolation, counter-current extraction, soxhlet, supercritical gas extraction or ultrasound.
In alternativa, estratti liquidi da Rhodiola rosea contenenti salidroside possono essere ottenuti utilizzando come mezzo di estrazione un solvente fisiologicamente accettabile, ad esempio scelto tra acqua, etanolo, o loro miscele. Alternatively, liquid extracts from Rhodiola rosea containing salidroside can be obtained using a physiologically acceptable solvent as extraction medium, for example selected from water, ethanol, or mixtures thereof.
In certe forme di realizzazione l?estrazione di una o pi? componenti biologicamente attive avviene per macerazione di una porzione o matrice vegetale di Rhodiola rosea, preferibilmente radice, in un idoneo solvente, ad esempio una miscela idroalcolica. In certain embodiments? The extraction of one or more? biologically active components takes place by maceration of a portion or vegetable matrix of Rhodiola rosea, preferably root, in a suitable solvent, for example a hydroalcoholic mixture.
Secondo alcune forme di realizzazione, nel processo di estrazione, una porzione o matrice vegetale, preferibilmente da radice di pianta di Rhodiola rosea, viene immersa in un idoneo solvente, ad esempio una miscela acqua-etanolo (ad esempio dal 40 all?80% in etanolo), per un tempo idoneo ad arricchire il solvente di una o pi? componenti biologicamente attive tra cui salidroside. In queste condizioni l?estrazione nel solvente delle componenti biologicamente attive presenti nei tessuti vegetali della pianta avviene per diffusione ed osmosi. According to some embodiments, in the extraction process, a portion or vegetable matrix, preferably from Rhodiola rosea plant root, is immersed in a suitable solvent, for example a water-ethanol mixture (for example from 40 to 80% in ethanol), for a time suitable for enriching the solvent with one or more? biologically active components including salidroside. Under these conditions, the extraction of the biologically active components present in the plant tissues in the solvent takes place by diffusion and osmosis.
Tipicamente nella macerazione la matrice di pianta di Rhodiola rosea viene tenuta a contatto con il solvente per un tempo variabile ad ottenere l?estrazione di un quantitativo efficace di componente biologicamente attiva, in particolare salidroside. In certe forme di realizzazione il tempo di macerazione pu? variare tra 10 minuti e 48 ore, 1 e 5 ore. Typically in maceration the Rhodiola rosea plant matrix is kept in contact with the solvent for a variable time to obtain the extraction of an effective quantity of biologically active component, in particular salidroside. In certain embodiments the steeping time can vary between 10 minutes and 48 hours, 1 and 5 hours.
Secondo alcune forme di realizzazione l?estratto secco di Rhodiola ? un estratto secco dalla pianta intera o preferibilmente da radici titolato in salidroside. According to some embodiments the dry extract of Rhodiola is a dry extract from the whole plant or preferably from roots titrated in salidroside.
Ad esempio, un estratto secco da Rhodiola rosea contiene dallo 0,5% al 5%, dall?1 al 3% di salidroside, che rappresenta il principale ingrediente biologicamente attivo contenuto nella pianta. For example, a dry extract from Rhodiola rosea contains 0.5% to 5%, 1 to 3% salidroside, which is the main biologically active ingredient contained in the plant.
Vantaggiosamente, nella composizione pu? essere usato un estratto secco da radice di Rhodiola titolato al 3% in salidroside. Advantageously, in the composition can? a dry extract from Rhodiola root titrated at 3% in salidroside should be used.
In certe forme di realizzazione l?estratto vegetale di Rhodiola rosea ? presente nella composizione in un quantitativo da 0,1 a 30% da 0,5 a 20%, da 1 a 10% ad esempio 5% in peso rispetto al peso totale della composizione. In certain embodiments the plant extract of Rhodiola rosea is present in the composition in an amount from 0.1 to 30% from 0.5 to 20%, from 1 to 10% for example 5% by weight with respect to the total weight of the composition.
In alcune forme di realizzazione un estratto secco di Rhodiola di 1000 mg, ha un contenuto di salidroside di 30 mg ovvero nella composizione il rapporto estratto secco Rhodiola : salidroside (principio attivo) pu? essere pari a 100 : 3 (+/- 10%). In una forma di realizzazione preferita la composizione contiene una combinazione di cacao in polvere contenente epicatechine qui descritte ed un estratto di Rhodiola rosacea contenente salidroside come qui descritto. In some embodiments a dry extract of Rhodiola of 1000 mg, has a salidroside content of 30 mg or in the composition the ratio dry extract Rhodiola : salidroside (active ingredient) can? be equal to 100 : 3 (+/- 10%). In a preferred embodiment the composition contains a combination of epicatechin-containing cocoa powder described herein and a salidroside-containing Rhodiola rosacea extract as described herein.
In certe forme di realizzazione la composizione dell?invenzione contiene un estratto secco di Rhodiola rosacea in un quantitativo compreso da 30 a 3000mg, da 100 a 2000, da 400 a 1200mg, ad esempio 800 mg. In certain embodiments the composition of the invention contains a dry extract of Rhodiola rosacea in an amount ranging from 30 to 3000mg, from 100 to 2000, from 400 to 1200mg, for example 800mg.
In certe forme di realizzazione la composizione dell?invenzione contiene un estratto da Rhodiola rosacea in una quantit? compresa da 1 al 60% in peso, da 3 a 30% in peso o dal 5% a 15% in peso. In certain embodiments the composition of the invention contains an extract from Rhodiola rosacea in an amount ranging from 1 to 60% by weight, from 3 to 30% by weight or from 5% to 15% by weight.
In certe forme di realizzazione, la composizione dell'invenzione comprende ulteriori sostanze biologicamente attive o ingredienti attivi, ad esempio come vitamine, minerali, micronutrienti ed altre sostanze o estratti biologicamente attive di origine vegetale. In certain embodiments, the composition of the invention comprises further biologically active substances or active ingredients, for example such as vitamins, minerals, micronutrients and other biologically active substances or extracts of plant origin.
Ad esempio, la composizione pu? includere una o pi? vitamine, ad esempio vitamine del gruppo B come B2, B3 o nicotinammide, B5, B6, B12, vitamina A, vitamina C, vitamina D e vitamina E, quest?ultima essendo preferita. For example, the composition can include one or more vitamins, for example B vitamins such as B2, B3 or nicotinamide, B5, B6, B12, vitamin A, vitamin C, vitamin D and vitamin E, the latter being preferred.
Secondo alcune forme di realizzazione la composizione dell?invenzione comprende ulteriormente una sostanza provvista di attivit? antiossidante cellulare. Nell?ambito della presente invenzione la misura dell?attivit? antiossidante pu? essere realizzata con il metodo ?Oxygen-Radical Absorbance Capacity? (ORAC)(Cao, G.; et al, (1993) Free Radic. Biol. Med. 14(3):303-11), oppure con la metodica Total Radical-Trapping Antioxidant Parameter (TRAP) (Ghiselli, A.; et al (1995) Free Radic. Biol. Med. 18(1):29-36; Wayner, D. D et al (1985) FEBS Lett. According to some embodiments, the composition of the invention further comprises a substance having active activity. cellular antioxidant. Within the scope of the present invention, the measurement of the activity? antioxidant can be made with the ?Oxygen-Radical Absorbance Capacity? (ORAC)(Cao, G.; et al, (1993) Free Radic. Biol. Med. 14(3):303-11), or with the Total Radical-Trapping Antioxidant Parameter (TRAP) method (Ghiselli, A. ; et al (1995) Free Radic. Biol. Med. 18(1):29-36; Wayner, D. D et al (1985) FEBS Lett.
187(1):33-7) i quali determinano la capacit? delel sostanze di ritardare o spegnere ROS prodotti mediante generatori di radicali liberi. 187(1):33-7) which determine the capacity? delel substances to retard or extinguish ROS produced by free radical generators.
Nell?ambito dell?invenzione, una idonea sostanza provvista di attivit? antiossidante cellulare comprende la vitamina E e suoi derivati. Within the scope of the invention, a suitable substance having an active Cellular antioxidant includes vitamin E and its derivatives.
Nell?ambito della presente, con il termine vitamina E e derivati si intende comprendere i tocoferoli (?, ?, ?, ?), i tocotrienoli (?, ?, ?, ?). Un tocoferolo di impiego preferito nell?ambito dell?invenzione ? l??-tocoferolo. In the context of the present, the term vitamin E and derivatives is intended to include tocopherols (?, ?, ?, ?), tocotrienols (?, ?, ?, ?). A tocopherol of preferred use within the scope of the invention ? l??-tocopherol.
In alcune forme di realizzazione, la composizione dell'invenzione contiene vitamina E, ad esempio alfa tocoferolo, in un quantitativo compreso da 0,01 a 300mg, da 0,1 a 50mg, da 1 a 30mg per unit? di dosaggio. In some embodiments, the composition of the invention contains vitamin E, for example alpha tocopherol, in an amount ranging from 0.01 to 300mg, from 0.1 to 50mg, from 1 to 30mg per unit. of dosage.
In certe forme di realizzazione la composizione dell?invenzione contiene vitamina E in un quantitativo compreso da 0,05 a 10% in peso, da 0,1 a 5% in peso o da 0,5 a 3% in peso. In certain embodiments the composition of the invention contains vitamin E in an amount ranging from 0.05 to 10% by weight, 0.1 to 5% by weight or 0.5 to 3% by weight.
Secondo alcune forme di realizzazione, la composizione dell'invenzione comprende inoltre uno o pi? micronutrienti e/o minerali come sali di Zn, Mg, K, Na, Fe, Cr, Se, Mn, Ca, Se e relative miscele. According to some embodiments, the composition of the invention further comprises one or more? micronutrients and/or minerals such as salts of Zn, Mg, K, Na, Fe, Cr, Se, Mn, Ca, Se and relative mixtures.
In alcune forme di realizzazione, la composizione dell'invenzione comprende ulteriori sostanze o principi attivi. In some embodiments, the composition of the invention comprises further active substances or ingredients.
La composizione dell'invenzione pu? assumere un'ampia variet? di forme di preparazione, secondo la via di somministrazione desiderata. The composition of the invention can take on a wide variety of preparation forms, according to the desired route of administration.
La composizione dell'invenzione pu? essere in forma solida. The composition of the invention can be in solid form.
Quando la composizione dell'invenzione ? presentata in forma solida, pu? essere sotto forma di una compressa, capsula, polvere, granuli, pastiglia da sciogliere in bocca e polvere o soluzione/sospensione. When is the composition of the invention ? presented in solid form, pu? be in the form of a tablet, capsule, powder, granule, lozenge and powder or solution/suspension.
Le preparazioni in forma solida possono comprendere uno o pi? eccipienti/come ad esempio amidi, zuccheri, cellulosa microcristallina e opzionalmente diluenti, agenti di granulazione, lubrificanti, aggreganti, agenti di disintegrazione. The preparations in solid form can include one or more? excipients/such as starches, sugars, microcrystalline cellulose and optionally diluents, granulating agents, lubricants, binders, disintegrating agents.
Tipicamente la composizione in forma solida pu? contenere un agente aggregante come gomma adragante, gomma, amido di mais o gelatina; eccipienti come fosfato bicalcico; un agente di disintegrazione come amido di mais, fecola di patate, acido alginico; un lubrificante come magnesio stearato; un agente dolcificante come saccarosio, lattosio o saccarina. Se lo si desidera, le compresse possono essere rivestite usando tecniche tradizionali. Typically the composition in solid form can? contain a binding agent such as tragacanth, gum, cornstarch, or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid; a lubricant such as magnesium stearate; a sweetening agent such as sucrose, lactose or saccharin. If desired, the tablets can be coated using traditional techniques.
In alcune forme di realizzazione la composizione ? un integratore in forma di compresse o di capsula, ad esempio in gelatina che preferibilmente pu? contenere un agente antiagglomerante, ad esempio Mono e digliceridi degli acidi grassi, Magnesio Stearato Vegetale, Biossido di silicio e uno o pi? agenti di carica ad esempio Calcio fosfato bibasico, Cellulosa microcristallina. In some embodiments the composition ? a supplement in the form of tablets or capsules, for example in gelatin which preferably can? contain an anti-caking agent, such as mono and diglycerides of fatty acids, vegetable magnesium stearate, silicon dioxide and one or more? bulking agents e.g. dibasic calcium phosphate, microcrystalline cellulose.
Secondo alcune forme di realizzazione, la composizione dell'invenzione contiene un eccipiente a base di cellulosa. According to some embodiments, the composition of the invention contains a cellulose-based excipient.
In alcune forme di realizzazione, la composizione dell'invenzione comprende inoltre uno o pi? componenti aggiuntivi come additivi, cariche, stabilizzanti, emulsionanti, texturizzanti, agenti filmogeni, plastificanti, agenti umettanti e addensanti. In some embodiments, the composition of the invention further comprises one or more? add-ons such as additives, fillers, stabilizers, emulsifiers, texturizers, film-forming agents, plasticizers, wetting agents and thickeners.
Preferibilmente la composizione ? in forma di capsula contenente gli estratti vegetali sopra descritti. Preferably the composition? in the form of a capsule containing the vegetable extracts described above.
Nel caso di compresse queste possono essere rivestite con gomma lacca, zucchero o entrambi. Per prevenire la rottura durante il transito attraverso la parte superiore del tratto gastrointestinale, la composizione pu? essere una formulazione con un rivestimento gastroresistente o enterico. In the case of tablets these may be coated with shellac, sugar or both. To prevent disruption during transit through the upper gastrointestinal tract, the composition can be a formulation with an enteric or enteric-coated coating.
Nella composizione o capsule possono anche esserci agenti aromatizzanti, conservanti, agenti coloranti e simili. In the composition or capsules there may also be flavoring agents, preservatives, coloring agents and the like.
Secondo alcune forme di realizzazione, la composizione ? in una forma per il rilascio modulato o controllato di ingredienti attivi. A titolo di esempio, la composizione pu? essere una formulazione a rilascio ritardato, a rilascio rapido o a rilascio lento-veloce. According to some embodiments, the composition is in a form for modulated or controlled release of active ingredients. As an example, the composition can? be a delayed-release, rapid-release, or slow-fast-release formulation.
In alcune forme di realizzazione, la composizione dell'invenzione comprende come un eccipiente, un acido grasso idrogenato, preferibilmente avente una catena con da 3 a 20 atomi di carbonio, da 14 a 18 atomi di carbonio. Un tipico esempio di un acido grasso idrogenato ? olio di palma idrogenato. In some embodiments, the composition of the invention comprises as an excipient, a hydrogenated fatty acid, preferably having a chain with 3 to 20 carbon atoms, 14 to 18 carbon atoms. A typical example of a hydrogenated fatty acid ? hydrogenated palm oil.
La composizione dell'invenzione pu? essere in forma liquida. The composition of the invention can be in liquid form.
Quando la composizione ? in forma liquida, pu? essere sotto forma di sospensione, emulsione, soluzione. In questi casi il veicolo ? liquido e pu? essere selezionato ad esempio da acqua, glicoli, oli, alcool e relative miscele. When the composition? in liquid form, can? be in the form of a suspension, emulsion, solution. In these cases the vehicle? liquid and can be selected for example from water, glycols, oils, alcohols and related mixtures.
In alcune forme di realizzazione in cui la formulazione ? in forma liquida, ad esempio in caso di sospensione pu? contenere, in aggiunta all'associazione di principi attivi, un agente dolcificante come saccarosio e/o metil e propil-parabeni come conservanti, un agente colorante e un aroma come ciliegia o arancia aromatizzanti. In some embodiments where the formulation ? in liquid form, for example in the case of suspension pu? contain, in addition to the combination of active ingredients, a sweetening agent such as sucrose and/or methyl and propyl parabens as preservatives, a coloring agent and a flavoring such as cherry or orange flavoring.
Le composizioni possono essere idoneamente presentate in un'unica forma farmaceutica e preparate usando uno qualsiasi dei metodi ben noti nello stato dell?arte farmaceutico o dietetico. The compositions may suitably be presented in a single pharmaceutical form and prepared using any of the methods well known in the pharmaceutical or dietetic state of the art.
In alcune forme di realizzazione, i principi attivi contenuti nella composizione della presente invenzione possono essere combinati o miscelati come principi attivi in miscela intima con un veicolo commestibile adatto e/o un eccipiente secondo le tecniche farmaceutiche e dell?industria alimentare o nutrizionale tradizionale. In some embodiments, the active ingredients contained in the composition of the present invention can be combined or blended as active ingredients in intimate admixture with a suitable edible carrier and/or excipient according to conventional pharmaceutical and food or nutritional industry techniques.
Le composizioni ad uso farmaceutico o nutrizionale possono essere adeguatamente presentate in singola forma farmaceutica e preparate mediante uno qualsiasi dei metodi ben noti nella tecnica farmaceutica o alimentare. The compositions for pharmaceutical or nutritional use can be suitably presented in single pharmaceutical form and prepared by any of the methods well known in the pharmaceutical or food art.
La quantit? di composto attivo nelle composizioni dell?invenzione ? tale che si otterr? un dosaggio preventivo o terapeuticamente efficace su una forma di declino cognitivo, ad esempio come la demenza senile. The quantity? of active compound in the compositions of the invention ? such that you will get? a preventive or therapeutically effective dosage on a form of cognitive decline, for example such as senile dementia.
In alcune forme di realizzazione, nelle composizioni della presente invenzione, gli ingredienti attivi sono normalmente formulati in un'unit? di dosaggio. L'unit? di dosaggio pu? contenere da 0,1 a 1.000 mg di ciascun ingrediente attivo per unit? di dosaggio per una somministrazione giornaliera. In some embodiments, in the compositions of the present invention, the active ingredients are normally formulated in a single unit. of dosage. The unit? of dosage can? contain 0.1 to 1,000 mg of each active ingredient per unit? dosage for once-daily administration.
In alcune forme di realizzazione la dose ? nell'intervallo da 0,001% in peso a circa 60% in peso della formulazione. In some embodiments the dose ? in the range of 0.001% by weight to about 60% by weight of the formulation.
Secondo alcune forme di realizzazione, la composizione dell'invenzione ? un prodotto medicinale da banco. According to some embodiments, the composition of the invention is an over-the-counter medicinal product.
Il termine "fisiologicamente accettabile" si riferisce a sostanze comunemente usate nella formulazione di prodotti nutrizionali, alimentari o farmaceutici. Un veicolo "fisiologicamente accettabile" pu? essere un veicolo farmaceuticamente accettabile. The term "physiologically acceptable" refers to substances commonly used in the formulation of nutritional, food or pharmaceutical products. A vehicle "physiologically acceptable" pu? be a pharmaceutically acceptable vehicle.
Come usato nel presente documento, il termine "edibile" significa sostanze commestibili il cui uso nella formulazione di una composizione nutrizionale o alimentare ? approvato dalle autorit? sanitarie. As used herein, the term "edible" means edible substances whose use in the formulation of a nutritional or food composition? approved by the authorities? sanitary.
Il termine "veicolo" come usato nel presente documento indica un mezzo, eccipiente, diluente con cui ? somministrata la combinazione di principi terapeutici o attivi. The term "vehicle" as used herein means a medium, excipient, diluent with which ? the combination of therapeutic or active ingredients is administered.
Qualsiasi veicolo e/o eccipiente idoneo alla forma desiderata di preparazione per una somministrazione agli esseri umani ? contemplato per uso con i composti descritti nella presente invenzione. Any vehicle and/or excipient suitable for the desired form of preparation for administration to humans? contemplated for use with the compounds disclosed in the present invention.
Secondo alcune forme di realizzazione, la composizione dell'invenzione ? un integratore nutraceutico, alimentare, un prodotto nutrizionale o un prodotto dietetico According to some embodiments, the composition of the invention is a nutraceutical, food supplement, nutritional product or dietary product
In alcune forme di realizzazione la composizione o l?integratore che la contiene sono somministrati una o due volte al giorno. In some embodiments, the composition or supplement containing it is administered once or twice daily.
Come usato nel presente documento, il termine combinazione significa che uno o pi? dei principi attivi sono aggiunti o miscelati con uno o altri ingredienti. As used herein, the term combination means that one or more of the active ingredients are added or mixed with one or other ingredients.
Il termine combinazione non intende significare che i principi attivi sono associati tra loro con la formazione di legami chimici o di altro tipo. The term combination does not intend to mean that the active ingredients are associated with each other by the formation of chemical or other bonds.
Nella presente domanda, con il termine "sinergismo o attivit? sinergica" si intende un'attivit? che ? maggiore della somma delle attivit? del singolo principio attivo. In particolare, il sinergismo si verifica quando almeno due sostanze o principi biologicamente attivi interagiscono in un modo che potenzia o aumenta uno o pi? dei loro effetti. Pertanto, due sostanze o principi attivi che producono effetti evidentemente simili talvolta produrranno effetti esagerati o ridotti quando utilizzati contemporaneamente e una valutazione quantitativa ? necessaria per distinguere questi casi da una semplice azione additiva (Tallarida RJ. Drug Synergism: its detection and applications. J Pharmacol ExpTher. 2001 Sep:298(3):865-72). In the present application, the term "synergism or synergistic activity" means an activity that ? greater than the sum of the assets? of the single active ingredient. Specifically, synergism occurs when at least two biologically active substances or ingredients interact in a way that enhances or enhances one or more substances. of their effects. Therefore, two substances or active ingredients that produce apparently similar effects will sometimes produce exaggerated or reduced effects when used together and a quantitative assessment ? necessary to distinguish these cases from a simple additive action (Tallarida RJ. Drug Synergism: its detection and applications. J Pharmacol ExpTher. 2001 Sep:298(3):865-72).
Le composizioni dell'invenzione sono idonee ad un uso alimentare, nutrizionale, dietetico o farmaceutico in mammiferi, in particolare in esseri umani. The compositions of the invention are suitable for alimentary, nutritional, dietetic or pharmaceutical use in mammals, in particular in humans.
La composizione dell?invenzione ? idonea al trattamento di un disturbo neurocognitivo in particolare lieve. The composition of the invention ? suitable for the treatment of a particularly mild neurocognitive disorder.
Ad esempio, la composizione o un integratore che la contiene trovano applicazione nei disturbi neurocognitivi in cui sono presenti uno o pi? dei seguenti componenti/fattori: For example, the composition or a supplement containing it find application in neurocognitive disorders in which there are one or more? of the following components/factors:
- fattori tossici per le cellule nervose come la proteina beta-amiloide, la proteina Tau e i corpi di Lewy in particolare localizzati nelle aree corticali responsabili della memoria e dell'apprendimento, - toxic factors for nerve cells such as beta-amyloid protein, Tau protein and Lewy bodies especially located in the cortical areas responsible for memory and learning,
- ridotta efficienza del metabolismo neuronale in particolare con ridotta efficienza di utilizzo del glucosio, - reduced efficiency of neuronal metabolism especially with reduced glucose utilization efficiency,
- riduzione di volume di alcune aree corticali e centri della memoria, apprendimento e progettualit?, in particolare ippocampo e corteccia frontale, Vantaggiosamente, la composizione o un integratore che la contiene trovano applicazione in disturbi neurocognitivi quali patologie neurodegenerative, demenza, perdita di memoria e nella protezione da danno neuronale come pu? verificarsi nel caso di un evento ischemico o di emorragia. - volume reduction of some cortical areas and centers of memory, learning and planning, in particular hippocampus and frontal cortex in the protection from neuronal damage as pu? occur in the event of an ischemic event or haemorrhage.
Queste attivit? terapeutica sono conseguenza degli effetti della composizione di combinazione sulla regolazione della risposta allo stress ossidativo, infiammazione, apoptosi, regolazione della trasmissione del segnale nervoso neuronale, rigenerazione neuronale. These activities? therapeutics are consequence of the effects of the combination composition on the regulation of the response to oxidative stress, inflammation, apoptosis, regulation of neuronal nerve signal transmission, neuronal regeneration.
La sostanziale assenza di effetti collaterali e di bassa tossicit? rende la composizione di combinazione idonea per il trattamento di una ampia popolazione di individui con et? maggiore di sessanta anni, anche in assenza di sintomi. The substantial absence of side effects and low toxicity? makes the combination composition suitable for the treatment of a large population of individuals aged over sixty years of age, even in the absence of symptoms.
I seguenti esempi sono forniti principalmente per illustrare la presente invenzione e non intendono limitare il campo di protezione come risulta dalle accluse rivendicazioni. The following examples are provided primarily to illustrate the present invention and are not intended to limit the field of protection as is apparent from the appended claims.
ESEMPIO 1 EXAMPLE 1
Composizione ad attivit? neuroprotettiva avente la seguente formulazione: Activity composition? neuroprotective having the following formulation:
Rhodiola rosea L estratto secco titolato al 3% in salidroside 800mg Rhodiola rosea L dry extract titrated at 3% in salidroside 800mg
Cacao in polvere titolato in catechine al 3% 200mg ESEMPIO 2 Cocoa powder titrated in catechins at 3% 200mg EXAMPLE 2
Integratore ad attivit? neuroprotettiva in forma di capsule in gelatina avente la seguente formulazione: Supplement to activity? neuroprotective in the form of gelatin capsules with the following formulation:
Rhodiola rosea L estratto secco titolato al 3% in salidroside 800mg Rhodiola rosea L dry extract titrated at 3% in salidroside 800mg
Cacao in polvere titolato in catechine al 3% 200mg Vitamina E, 7 mg Vitamina B5 50mg ECCIPIENTI: Cacao powder titrated in catechins at 3% 200mg Vitamin E, 7mg Vitamin B5 50mg EXCIPIENTS:
idrossi-propil-metilcellulosa hydroxypropylmethylcellulose
Maltodestrine Maltodextrins
stearato di magnesio. magnesium stearate.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013020368A1 (en) * | 2011-08-08 | 2013-02-14 | The Hong Kong University Of Science And Technology | Rhodiola rosea extracts and isolated compounds and uses thereof for treating neurodegenerative diseases |
US20130344141A1 (en) * | 2009-09-14 | 2013-12-26 | Michael Scott BUCKLEY | Concentration and mental performance amplifying formulation |
US20200316175A1 (en) * | 2016-05-27 | 2020-10-08 | Nestec S.A. | Nutritional composition for treating or preventing impaired mobility |
WO2020231906A1 (en) * | 2019-05-10 | 2020-11-19 | Bgs Holdings Llc | Sports and nutritional supplement formulations |
-
2020
- 2020-12-03 IT IT102020000029747A patent/IT202000029747A1/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130344141A1 (en) * | 2009-09-14 | 2013-12-26 | Michael Scott BUCKLEY | Concentration and mental performance amplifying formulation |
WO2013020368A1 (en) * | 2011-08-08 | 2013-02-14 | The Hong Kong University Of Science And Technology | Rhodiola rosea extracts and isolated compounds and uses thereof for treating neurodegenerative diseases |
US20200316175A1 (en) * | 2016-05-27 | 2020-10-08 | Nestec S.A. | Nutritional composition for treating or preventing impaired mobility |
WO2020231906A1 (en) * | 2019-05-10 | 2020-11-19 | Bgs Holdings Llc | Sports and nutritional supplement formulations |
Non-Patent Citations (4)
Title |
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CAO, G. ET AL., FREE RADICAL METHOD. BIOL. MED., vol. 14, no. 3, 1993, pages 303 - 11 |
GHISELLI, A. ET AL., FREE RADICAL. BIOL. MED., vol. 18, no. 1, 1995, pages 29 - 36 |
TALLARIDA RJ: "Drug Synergism: its detection and applications", J PHARMACOL EXPTHER, vol. 298, no. 3, September 2001 (2001-09-01), pages 865 - 72, XP007918154 |
WAYNER, D. D ET AL., FEBS LETT, vol. 187, no. 1, 1985, pages 33 - 7 |
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