ITMI20091358A1 - COMPOSITIONS BASED ON LIPOPHILUS EXTRACT OF ZINGIBER OFFICINAL AND CYNARA SCOLYMUS EXTRACT FOR THE PREVENTION AND TREATMENT OF EXOPHAGEAL REFLOW AND IRRITABLE COLON SYNDROME - Google Patents

COMPOSITIONS BASED ON LIPOPHILUS EXTRACT OF ZINGIBER OFFICINAL AND CYNARA SCOLYMUS EXTRACT FOR THE PREVENTION AND TREATMENT OF EXOPHAGEAL REFLOW AND IRRITABLE COLON SYNDROME Download PDF

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ITMI20091358A1
ITMI20091358A1 IT001358A ITMI20091358A ITMI20091358A1 IT MI20091358 A1 ITMI20091358 A1 IT MI20091358A1 IT 001358 A IT001358 A IT 001358A IT MI20091358 A ITMI20091358 A IT MI20091358A IT MI20091358 A1 ITMI20091358 A1 IT MI20091358A1
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extract
cynara scolymus
zingiber officinale
compositions according
lipophilic
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IT001358A
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Italian (it)
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Ezio Bombardelli
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Indena Spa
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Priority to ITMI2009A001358A priority Critical patent/IT1395119B1/en
Application filed by Indena Spa filed Critical Indena Spa
Priority to MX2011007686A priority patent/MX2011007686A/en
Priority to DK10702411.9T priority patent/DK2379092T3/en
Priority to JP2011545687A priority patent/JP5769634B2/en
Priority to PCT/EP2010/000205 priority patent/WO2010083968A1/en
Priority to RU2011129991/15A priority patent/RU2521250C2/en
Priority to SG2011052248A priority patent/SG173053A1/en
Priority to CA2750030A priority patent/CA2750030C/en
Priority to SI201030524T priority patent/SI2379092T1/en
Priority to KR1020117016830A priority patent/KR101762388B1/en
Priority to CN2010800048142A priority patent/CN102281886A/en
Priority to PT107024119T priority patent/PT2379092E/en
Priority to US13/145,141 priority patent/US10220065B2/en
Priority to EP10702411.9A priority patent/EP2379092B1/en
Priority to BRPI1006915A priority patent/BRPI1006915B8/en
Priority to AU2010206327A priority patent/AU2010206327B2/en
Priority to PL10702411T priority patent/PL2379092T3/en
Priority to ES10702411.9T priority patent/ES2451346T3/en
Publication of ITMI20091358A1 publication Critical patent/ITMI20091358A1/en
Priority to CL2011001752A priority patent/CL2011001752A1/en
Priority to IL214160A priority patent/IL214160A/en
Publication of IT1395119B1 publication Critical patent/IT1395119B1/en
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Priority to HRP20140197AT priority patent/HRP20140197T1/en

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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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea

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Description

“COMPOSIZIONI A BASE DI ESTRATTO LIPOFILO DI ZINGIBER OFFICINALE E DI ESTRATTO DI CYNARA SCOLYMUS PER LA PREVENZIONE E IL TRATTAMENTO DEL RIFLUSSO ESOFAGEO E DELLA SINDROME DEL COLON IRRITABILE†⠀ œCOMPOSITIONS BASED ON LIPOPHILIC EXTRACT OF ZINGIBER OFFICINALE AND EXTRACT OF CYNARA SCOLYMUS FOR THE PREVENTION AND TREATMENT OF ESOPHAGEUS REFLUX AND IRRITABLE COLON SYNDROMEâ €

Descrizione dell’invenzione Description of the invention

La presente invenzione riguarda composizioni costituite da un’associazione di estratto lipofilo di Zingiber officinale e di un estratto di Cynara scolymus, utili per la prevenzione e il trattamento del riflusso esofageo e della sindrome del colon irritabile, e per la riduzione del sonno post-prandiale. The present invention relates to compositions consisting of an association of lipophilic extract of Zingiber officinale and an extract of Cynara scolymus, useful for the prevention and treatment of esophageal reflux and irritable bowel syndrome, and for the reduction of post-sleep prandial.

Stato della Tecnica State of the art

Il cancro del tratto gastro-intestinale à ̈ il secondo per diffusione ed à ̈ anche la seconda causa di morte quando questa zona viene colpita. Il cancro all’esofago e allo stomaco nei paesi industrializzati, sebbene non molto diffusi, sono estremamente letali. Cancer of the gastrointestinal tract is the second most common and is also the second leading cause of death when this area is affected. Cancer of the esophagus and stomach in industrialized countries, although not widespread, are extremely lethal.

Per questi due tumori sono state individuate varie concause, quali l’abuso di superalcolici, spesso abbinati al fumo, una dieta ricca di nitrati e/o prodotti o abitudini che inducono la rottura della barriera di muco a livello di stomaco ed esofago. In base all’esame delle abitudini alimentari e della carenza di alcuni oligoelementi in popolazioni di continenti diversi (Sindromi di Plummer-Vinson o di Paterson-Kelly) si à ̈ cercato di porre rimedio all’insorgenza del carcinoma dello stomaco e dell’esofago correndo le concause individuate, modificando le abitudini alimentari e lo stile di vita, utilizzando farmaci o prodotti dietetici. Sebbene molte di queste concause siano state eliminate, l’incidenza globale à ̈ aumentata perché à ̈ incrementato il numero delle persone affette da riflusso gastro-esofageo, legato spesso all’alimentazione e/o ernia iatale, che costituisce una delle concause principali di tumore esofageo. L’adenocarcinoma si manifesta infatti nell’epitelio colonnare displastico della parte distale dell’esofago quasi sempre in presenza di riflusso cronico e di metaplasia gastrica dell’epitelio (Esofago di Barrett), comuni nelle persone obese, e in più del 50% dei casi diventa maligno. Various contributing causes have been identified for these two tumors, such as the abuse of spirits, often combined with smoking, a diet rich in nitrates and / or products or habits that induce the breakdown of the mucus barrier in the stomach and esophagus. Based on the examination of dietary habits and the deficiency of some trace elements in populations of different continents (Plummer-Vinson or Paterson-Kelly Syndromes), an attempt was made to remedy the onset of stomach and stomach cancer. ™ esophagus by running the identified contributing causes, changing eating habits and lifestyle, using drugs or dietary products. Although many of these contributing causes have been eliminated, the global incidence has increased because the number of people suffering from gastroesophageal reflux, often linked to nutrition, and / or hiatal hernia, which is one of the contributing causes, has increased. principal of esophageal tumor. In fact, adenocarcinoma occurs in the dysplastic columnar epithelium of the distal part of the esophagus almost always in the presence of chronic reflux and gastric metaplasia of the epithelium (Barrett's esophagus), common in obese people, and more than 50% of cases become malignant.

Pertanto appare evidente l’estrema importanza di cercare di ridurre questa patologia. Therefore the extreme importance of trying to reduce this pathology is evident.

Di conseguenza, la ricerca si à ̈ orientata verso farmaci in grado di ridurre il riflusso, in modo particolare agendo sullo svuotamento gastrico. In particolare, si cerca di sviluppare procinetici naturali ben tollerati, in considerazione del fatto che il potenziale farmaco va assunto cronicamente per molti anni come preventivo o in modo discontinuo a seconda della necessità digestiva. Consequently, research has focused on drugs capable of reducing reflux, in particular by acting on gastric emptying. In particular, we try to develop well-tolerated natural prokinetics, in consideration of the fact that the potential drug must be taken chronically for many years as a preventive or discontinuously depending on the digestive need.

Tuttavia, molti farmaci ad azione sullo svuotamento gastrico utilizzati negli ultimi tempi presentavano spesso gravi effetti collaterali a livello del SNC o azione tumorigena, per cui sono stati ritirati dal commercio o lo saranno a breve. Attualmente il riflusso gastro-esofageo viene curato con cocktail di farmaci quali inibitori della pompa protonica (ranitidina, prazoli o semplici antiacidi), enzimi, digestivi vari e procinetici quali il domperidone. Tuttavia spesso l’uso prolungato di inibitori della pompa protonica comporta notevoli problemi di carattere digestivo. However, many drugs acting on gastric emptying used in recent times often had serious side effects at the level of the CNS or tumorigenic action, so they have been withdrawn from the market or will soon be. Currently gastroesophageal reflux is treated with cocktail of drugs such as proton pump inhibitors (ranitidine, prazoles or simple antacids), enzymes, various digestives and prokinetics such as domperidone. However, the prolonged use of proton pump inhibitors often leads to considerable digestive problems.

La ricerca à ̈ quindi orientata verso nuovi approcci terapeutici. The research is therefore oriented towards new therapeutic approaches.

La sindrome del colon irritabile nei paesi industrializzati colpisce fino al 9% della popolazione. Si tratta di una patologia di tipo psicosomatico e viene curata con antidepressivi, antinfiammatori, probiotici ed altro a seconda della gravità e del suo perdurare. Le esacerbazioni dell’intestino irritabile avvengono prevalentemente in caso stress, di alimentazione inadeguata e di stati infiammatori di varia origine. L’intestino irritabile inoltre à ̈ influenzato anche dallo stato dello stomaco. La presenza di riflusso esofageo costituisce sovente un motivo di peggioramento delle condizioni legate alla sindrome del colon irritabile. Irritable bowel syndrome in industrialized countries affects up to 9% of the population. It is a psychosomatic pathology and is treated with antidepressants, anti-inflammatories, probiotics and more depending on the severity and its persistence. The exacerbations of the irritable bowel occur mainly in case of stress, inadequate nutrition and inflammatory states of various origins. Furthermore, the irritable bowel is also influenced by the state of the stomach. The presence of esophageal reflux is often a reason for the worsening of conditions related to irritable bowel syndrome.

Descrizione dell’invenzione Description of the invention

Si à ̈ ora trovato che un’associazione a base di estratto lipofilo di Zingiber officinale preparato per estrazione con anidride carbonica in condizioni supercritiche e di un estratto di Cynara scolymus esercita una sorprendente attività procinetica e antidispeptica, accelerando lo svuotamento gastrico, eliminando la flatulenza e migliorando la funzione digestiva. L’associazione dell’invenzione risulta quindi utile per la prevenzione e il trattamento del riflusso esofageo e della sindrome del colon irritabile. It has now been found that an association based on the lipophilic extract of Zingiber officinale prepared by extraction with carbon dioxide under supercritical conditions and an extract of Cynara scolymus exerts a surprising prokinetic and antidispeptic activity, accelerating gastric emptying, eliminating flatulence and improving digestive function. The combination of the invention is therefore useful for the prevention and treatment of esophageal reflux and irritable bowel syndrome.

Pertanto la presente invenzione riguarda composizioni comprendenti: a) estratto lipofilo di Zingiber officinale, e Therefore the present invention relates to compositions comprising: a) lipophilic extract of Zingiber officinale, e

b) estratto di Cynara scolymus, b) Cynara scolymus extract,

per la prevenzione e il trattamento del riflusso esofageo, dello svuotamento gastrico e dell’intestino irritabile. Inoltre, la capacità di aumentare lo svuotamento gastrico riduce significativamente la sonnolenza post-prandiale evitando i problemi ad essa connessi. for the prevention and treatment of esophageal reflux, gastric emptying and irritable bowel. Furthermore, the ability to increase gastric emptying significantly reduces post-prandial sleepiness avoiding the problems associated with it.

Più specificamente, secondo la presente invenzione, l’estratto lipofilo di Zingiber officinale sarà preparato per estrazione delle radici e dei rizomi della pianta con anidride carbonica in condizioni supercritiche estraendo la polvere della radice a pressioni comprese fra 230 e 260 bar nell’estrattore, preferibilmente 235 bars e ad una temperatura compresa fra 40 e 60°C, preferibilmente 50°C per un tempo variabile da 1 a 10 ore, preferibilmente sette ore; l’estratto viene raccolto nel condensatore e disidratato in gas inerte sciolto in n-esano od eptano e concentrato nel vuoto ad una temperatura non superiore a 40°C. Questo estratto contiene circa un 30% di gingeroli e può essere usato direttamente nelle formulazioni della presente invenzione. L’estratto di Cynara scolymus sarà preparato secondo metodi convenzionali, ad esempio per estrazione delle parti aeree della pianta con un solvente alcolico o idroalcolico e opzionale frazionamento su resina. More specifically, according to the present invention, the lipophilic extract of Zingiber officinale will be prepared by extraction of the roots and rhizomes of the plant with carbon dioxide in supercritical conditions by extracting the root powder at pressures between 230 and 260 bar in the extractor , preferably 235 bars and at a temperature comprised between 40 and 60 ° C, preferably 50 ° C for a time ranging from 1 to 10 hours, preferably seven hours; the extract is collected in the condenser and dehydrated in inert gas dissolved in n-hexane or heptane and concentrated in vacuum at a temperature not exceeding 40 ° C. This extract contains about 30% of gingerols and can be used directly in the formulations of the present invention. The Cynara scolymus extract will be prepared according to conventional methods, for example by extraction of the aerial parts of the plant with an alcoholic or hydroalcoholic solvent and optional fractionation on resin.

Le radici e i rizomi dello zenzero (Zingiber officinale) variamente trattati sono utilizzati, soprattutto nei paesi asiatici e del medio oriente, come spezie e in medicina popolare per il trattamento dell’indigestione, della flatulenza, della diarrea, della tosse e, in minor misura, per la protezione delle mucose, contro l’infiammazione, per l’incontinenza urinaria ecc. The roots and rhizomes of ginger (Zingiber officinale) variously treated are used, especially in Asian and Middle Eastern countries, as a spice and in folk medicine for the treatment of indigestion, flatulence, diarrhea, cough and, to a lesser extent measure, for the protection of the mucous membranes, against inflammation, for urinary incontinence, etc.

I principi attivi presenti nell’estratto lipofilo di Zingiber officinale, sono costituti principalmente dai gingeroli (generalmente presenti in concentrazioni dal 10 al 15%), che possiedono attività antidispeptica, antinausea e antivomito, utili per il trattamento della nausea da cinetosi, delle eruttazioni, dell’indigestione, delle coliche, del vomito, della dispepsia e dei dolori dello stomaco e del colon. Tuttavia, studi clinici recenti hanno dimostrato che l’estratto lipofilo di Zingiber officinale preparato secondo i metodi tradizionali presenta scarsa attività, data la ben nota instabilità chimica dei gingeroli, al punto che la stessa farmacopea americana consiglia una completa revisione delle proprietà attribuite alla pianta per mancanza di documentazione convincente. Infatti i gingeroli contenuti nell’estratto lipofilo di Zingiber officinale preparato secondo i metodi tradizionali si degradano rapidamente dando origine a una serie di composti, come lo shogaolo e altri prodotti di ossidazione, che sono privi di efficacia. Tali dati contrastanti sono in parte da attribuire all’instabilità dei principi attivi negli estratti normalmente impiegati. Al contrario, l’estratto impiegato nella presente invenzione à ̈ un estratto lipofilo, stabilizzato e preparato con anidride carbonica in condizioni supercritiche ben definite. L’estratto di Zingiber officinale accelera lo svuotamento gastrico eliminando nausea postprandiale bilanciando l’effetto negativo della prima e completando l’effetto terapeutico. The active ingredients present in the lipophilic extract of Zingiber officinale, are mainly constituted by gingerols (generally present in concentrations from 10 to 15%), which possess antidispeptic, antinausea and antivomiting activities, useful for the treatment of nausea from motion sickness, of belching , indigestion, colic, vomiting, dyspepsia and stomach and colon pains. However, recent clinical studies have shown that the lipophilic extract of Zingiber officinale prepared according to traditional methods has little activity, given the well-known chemical instability of gingerols, to the point that the American pharmacopoeia itself recommends a complete review of the properties attributed to the plant. for lack of convincing documentation. In fact, the gingerols contained in the lipophilic extract of Zingiber officinale prepared according to traditional methods degrade rapidly giving rise to a series of compounds, such as shogaol and other oxidation products, which are ineffective. These conflicting data are partly attributable to the instability of the active ingredients in the extracts normally used. On the contrary, the extract used in the present invention is a lipophilic extract, stabilized and prepared with carbon dioxide under well-defined supercritical conditions. Zingiber officinale extract accelerates gastric emptying eliminating postprandial nausea, balancing the negative effect of the former and completing the therapeutic effect.

Gli estratti di carciofo (Cynara scolymus) sono noti per la loro azione coleretica, colagoga e antidispeptica, ma spesso non possono essere impiegati in caso di intestino irritabile in quanto peggiorano l’alternarsi di stitichezza e diarrea come conseguenza dell’effetto coleretico; inoltre rallentano lo svuotamento gastrico e la funzione digestiva. Artichoke extracts (Cynara scolymus) are known for their choleretic, cholagogue and antidispeptic action, but often cannot be used in case of irritable bowel as they worsen the alternation of constipation and diarrhea as a consequence of the choleretic effect; they also slow down gastric emptying and digestive function.

Gli estratti di Cynara scolymus che possono essere vantaggiosamente utilizzati secondo l’invenzione presentano un contenuto in rapporto determinato di tre classi di sostanze, gli acidi caffeoilchinici, i flavonoidi derivati della luteolina e la cinaropicrina. Gli acidi caffeoilchinici esercitano un effetto coleretico ed epatoprotettore, i flavonoidi un’azione ipolipemizzante legata alla sintesi del colesterolo e la cinaropicrina un’azione antiinfiammatoria per l’interazione con il fattore nucleare NFkB e TNF-α. L’estratto di carciofo contiene preferibilmente non meno del 20% di acidi caffeoilchinici, non meno del 5% di flavonoidi e non meno del 5% di cinaropicrina. The extracts of Cynara scolymus which can be advantageously used according to the invention have a content in a determined ratio of three classes of substances, the caffeoylquinic acids, the flavonoids derived from luteolin and the cinaropicrin. The caffeoylquinic acids exert a choleretic and hepatoprotective effect, the flavonoids a lipid-lowering action linked to the synthesis of cholesterol and the cynaropicrin an anti-inflammatory action due to the interaction with the nuclear factor NFkB and TNF-Î ±. The artichoke extract preferably contains not less than 20% of caffeoylquinic acids, not less than 5% of flavonoids and not less than 5% of cinaropicrin.

Si à ̈ sorprendentemente trovato a livello clinico che la combinazione di questi due estratti riduce in modo imprevedibile sia il riflusso gastroesofageo sia i parametri intestinali che ne sono indirettamente concausa, accelerando lo svuotamento gastrico, l’eliminazione della flatulenza e migliorando la funzione digestiva. It has surprisingly been found at a clinical level that the combination of these two extracts unpredictably reduces both gastroesophageal reflux and the intestinal parameters that are indirectly contributing to it, accelerating gastric emptying, eliminating flatulence and improving digestive function.

Infatti, nei pazienti sofferenti di intestino irritabile con dolore e dispepsia resistente alla combinazione di probiotici e antidepressivi, in seguito a somministrazione della composizione dell’invenzione à ̈ stata osservata la rapida scomparsa della sintomatologia con un netto miglioramento della qualità della vita. Questa attività non à ̈ attribuibile a nessuno dei due componenti assunti separatamente. In fact, in patients suffering from irritable bowel with pain and dyspepsia resistant to the combination of probiotics and antidepressants, following administration of the composition of the invention, the rapid disappearance of the symptoms was observed with a clear improvement in the quality of life. This activity is not attributable to either of the two components hired separately.

Infatti, come già detto, l’azione coleretica, colagoga e antidispeptica degli estratti di carciofo spesso non può essere impiegata in presenza della sindrome del colon irritabile, in quanto l’effetto coleretico peggiora l’alternanza di episodi di stitichezza e di diarrea, e inoltre riduce la velocità di svuotamento gastrico e la funzione digestiva. In fact, as already mentioned, the choleretic, cholagogue and antidispeptic action of artichoke extracts often cannot be used in the presence of irritable bowel syndrome, as the choleretic effect worsens the alternation of episodes of constipation and diarrhea, and also reduces gastric emptying rate and digestive function.

La presente associazione ha sorprendentemente migliorato il reflusso gastroesofageo e l’intestino irritabile nei pazienti sofferenti di questa fastidiosa patologia premettendo in linea di principio di evitare il rischio di insorgenza di tumore esofageo. The present association has surprisingly improved gastroesophageal reflux and irritable bowel in patients suffering from this annoying pathology, starting in principle to avoid the risk of onset of esophageal cancer.

Secondo un aspetto preferito, le composizioni dell’invenzione conterranno i due componenti entro i seguenti intervalli ponderali: According to a preferred aspect, the compositions of the invention will contain the two components within the following weight ranges:

a) estratto lipofilo di Zingiber officinale: da 1 a 25 mg; e a) lipophilic extract of Zingiber officinale: from 1 to 25 mg; And

b) estratto di Cynara scolymus: da 50 a 200 mg. b) Cynara scolymus extract: from 50 to 200 mg.

Secondo un aspetto particolarmente preferito, le composizioni conterranno i due componenti nelle seguenti quantità ponderali: According to a particularly preferred aspect, the compositions will contain the two components in the following weight quantities:

a) estratto lipofilo di Zingiber officinale: 12,5 mg; e a) lipophilic extract of Zingiber officinale: 12.5 mg; And

b) estratto di Cynara scolymus: 100 mg. b) Cynara scolymus extract: 100 mg.

Secondo un aspetto preferito, l’estratto lipofilo di Zingiber officinale e l’estratto di Cynara scolymus saranno formulati in oli vegetali ricchi in acidi grassi poli-insaturi ω3/ω6, come per esempio l’olio di Enothera biennis. According to a preferred aspect, the lipophilic extract of Zingiber officinale and the extract of Cynara scolymus will be formulated in vegetable oils rich in polyunsaturated fatty acids Ï ‰ 3 / Ï ‰ 6, such as Enothera oil biennis.

Secondo un ulteriore aspetto, le composizioni dell’invenzione potranno essere somministrate in concomitanza con altre sostanze ad attività utile o complementare. According to a further aspect, the compositions of the invention can be administered concomitantly with other substances with useful or complementary activity.

I dosaggi dimostratisi attivi nell’uomo saranno da 1 a 25 mg di estratto lipofilo di Zingiber officinale e da 50 a 200 mg di estratto di Cynara scolymus; più particolarmente di 100 mg di estratto di Cynara scolymus e 12,5 mg di estratto di Zingiber officinale pro dose, da assumere ad ogni pasto principale o comunque adattati alla patologia da trattare. Dosages that have been shown to be active in man will be from 1 to 25 mg of lipophilic extract of Zingiber officinale and from 50 to 200 mg of Cynara scolymus extract; more particularly, 100 mg of Cynara scolymus extract and 12.5 mg of Zingiber officinale extract per dose, to be taken with each main meal or in any case adapted to the pathology to be treated.

Le composizioni dell’invenzione saranno formulate secondo tecniche convenzionali come descritto, per esempio, in “Remington’s Pharmaceutical Handbook†, Mack Publishing Co., N.Y., USA. In particolare, le composizioni dell’invenzione saranno formulate secondo tecniche convenzionali di formulazione di ingredienti lipofili per la somministrazione orale, prevalentemente come compresse sublinguali o in capsule di gelatina molle o di cellulosa per oli a rapida dispersione nello stomaco. La forma lipofila usa come mezzo disperdente dei principi attivi oli ricchi di acidi grassi ω-3 che favoriscono un rapido assorbimento del principio attivo. Esempi di formulazioni orali sono compresse, confetti, capsule di gelatina molle e dura e capsule di cellulosa. The compositions of the invention will be formulated according to conventional techniques as described, for example, in â € œRemingtonâ € ™ s Pharmaceutical Handbookâ €, Mack Publishing Co., N.Y., USA. In particular, the compositions of the invention will be formulated according to conventional techniques for the formulation of lipophilic ingredients for oral administration, mainly as sublingual tablets or in soft gelatin or cellulose capsules for oils which are rapidly dispersed in the stomach. The lipophilic form uses oils rich in Ï ‰ -3 fatty acids as a dispersing medium for the active ingredients, which promote rapid absorption of the active ingredient. Examples of oral formulations are tablets, dragees, soft and hard gelatin capsules and cellulose capsules.

Gli esempi più sotto riportati illustreranno ulteriormente l’invenzione. The examples below will further illustrate the invention.

Esempio 1- Estrazione di Cynara scolymus Example 1- Extraction of Cynara scolymus

In un percolatore munito di camicia riscaldante si caricano 1000 g di foglie essiccate e macinate di carciofo, quindi si estrae per 5 volte con 4 L EtOH 70%, a 70°C. 1000 g of dried and ground artichoke leaves are loaded into a percolator equipped with a heating jacket, then extracted 5 times with 4 L EtOH 70%, at 70 ° C.

Si riuniscono i percolati filtrati e si concentra sotto vuoto fino al 15% ca. di residuo secco. Si lascia raffreddare a temperatura ambiente, quindi si centrifuga. The filtered percolates are collected and concentrated under vacuum up to approx. 15%. of dry residue. It is allowed to cool to room temperature, then it is centrifuged.

La soluzione surnatante à ̈ caricata su una colonna riempita con 1,5 L di resina AMBERLITEâ„¢ XADâ„¢7HP (Rohm and Haas) precedentemente ambientata in acqua. The supernatant solution is loaded onto a column filled with 1.5 L of AMBERLITEâ „¢ XADâ„ ¢ 7HP (Rohm and Haas) resin previously set in water.

Si lava la colonna con 1,5 L di acqua, quindi si eluisce con 3,75 L di EtOH 90%. L'eluato idroalcolico viene concentrato fino a molle, quindi essiccato a 50°C, sotto vuoto, per 24 ore: si ottengono 82,4 g di Carciofo foglie estratto purificato. The column is washed with 1.5 L of water, then eluted with 3.75 L of 90% EtOH. The hydroalcoholic eluate is concentrated until soft, then dried at 50 ° C, under vacuum, for 24 hours: 82.4 g of purified extracted artichoke leaves are obtained.

Titoli HPLC: Acidi caffeoilchinici totali 31,76%, Flavonoidi totali 14,31%, Cinaropicrina, 17,51%. HPLC Titers: Total Caffeoylquinic Acids 31.76%, Total Flavonoids 14.31%, Cynaropicrin, 17.51%.

Esempio 2 - Compresse Example 2 - Tablets

Composizione unitaria: Unitary composition:

Estratto di Cynara scolymus 150 mg Estratto lipofilo di Zingiber officinale 12,5 mg Glicerilmonostearato 30 mg Lecitina di soia 10 mg Olio di Enothera biennis q.b. a 700 mg Esempio 3 - Capsule di gelatina dura Cynara scolymus extract 150 mg Lipophilic extract of Zingiber officinale 12.5 mg Glyceryl monostearate 30 mg Soy lecithin 10 mg Enothera biennis oil to taste at 700 mg Example 3 - Hard gelatin capsules

Composizione unitaria: Unitary composition:

Estratto di Cynara scolymus 100 mg Estratto lipofilo di Zingiber officinale 12,5 mg Cellulosa microcristallina 300 mg Lattosio 170 mg Biossido di silicio 5 mg Magnesio stearato 5 mg Cynara scolymus extract 100 mg Lipophilic extract of Zingiber officinale 12.5 mg Microcrystalline cellulose 300 mg Lactose 170 mg Silicon dioxide 5 mg Magnesium stearate 5 mg

Claims (9)

RIVENDICAZIONI 1. Composizioni contenenti: a) estratto lipofilo di Zingiber officinale ottenuto per estrazione con anidride carbonica in condizioni supercritiche; e b) estratto di Cynara scolymus. CLAIMS 1. Compositions containing: a) lipophilic extract of Zingiber officinale obtained by extraction with carbon dioxide under supercritical conditions; And b) Cynara scolymus extract. 2. Composizioni secondo la rivendicazione 1, contenenti i due componenti entro i seguenti intervalli ponderali: a) estratto lipofilo di Zingiber officinale: da 1 a 25 mg; e b) estratto di Cynara scolymus: da 50 a 200 mg. 2. Compositions according to claim 1, containing the two components within the following weight ranges: a) lipophilic extract of Zingiber officinale: from 1 to 25 mg; And b) Cynara scolymus extract: from 50 to 200 mg. 3. Composizioni secondo le rivendicazioni 1 e 2, contenenti i due componenti nelle seguenti quantità ponderali: a) estratto lipofilo di Zingiber officinale: 12,5 mg; e b) estratto di Cynara scolymus: 100 mg. 3. Compositions according to claims 1 and 2, containing the two components in the following weight quantities: a) lipophilic extract of Zingiber officinale: 12.5 mg; And b) Cynara scolymus extract: 100 mg. 4. Composizioni secondo le rivendicazioni 1 e 2 in cui l’estratto di Cynara scolymus à ̈ ottenuto per estrazione delle parti aeree della pianta con un solvente alcolico o idroalcolico e frazionamento su resina. 4. Compositions according to claims 1 and 2 wherein the Cynara scolymus extract is obtained by extraction of the aerial parts of the plant with an alcoholic or hydroalcoholic solvent and fractionation on resin. 5. Composizioni secondo la rivendicazione 1, 2 o 3 in cui l’estratto di carciofo contiene non meno del 20% di acidi caffeoilchinici, non meno del 5% di flavonoidi e non meno del 5% di cinaropicrina. 5. Compositions according to claim 1, 2 or 3 wherein the artichoke extract contains not less than 20% of caffeoylquinic acids, not less than 5% of flavonoids and not less than 5% of cinaropicrin. 6. Composizioni secondo le rivendicazioni precedenti, per la somministrazione orale. 6. Compositions according to the preceding claims, for oral administration. 7. Composizioni secondo la rivendicazione 4 in forma di capsule di gelatina molle o capsule di cellulosa adatte a contenere sostanze oleose. 7. Compositions according to claim 4 in the form of soft gelatin capsules or cellulose capsules suitable for containing oily substances. 8. Uso di: a) estratto lipofilo di Zingiber officinale ottenuto per estrazione con anidride carbonica in condizioni supercritiche; e b) estratto di Cynara scolymus; per la preparazione di una composizione per la prevenzione e il trattamento del riflusso esofageo, dello svuotamento gastrico e della sindrome del colon irritabile. 8. Use of: a) lipophilic extract of Zingiber officinale obtained by extraction with carbon dioxide under supercritical conditions; And b) Cynara scolymus extract; for the preparation of a composition for the prevention and treatment of esophageal reflux, gastric emptying and irritable bowel syndrome. 9. Uso di: a) estratto lipofilo di Zingiber officinale ottenuto per estrazione con anidride carbonica in condizioni supercritiche; e b) estratto di Cynara scolymus; per la preparazione di una composizione per la riduzione del sonno post-prandiale.9. Use of: a) lipophilic extract of Zingiber officinale obtained by extraction with carbon dioxide under supercritical conditions; And b) Cynara scolymus extract; for the preparation of a post-prandial sleep reduction composition.
ITMI2009A001358A 2009-01-20 2009-07-29 COMPOSITIONS BASED ON LIPOPHILUS EXTRACT OF ZINGIBER OFFICINAL AND CYNARA SCOLYMUS EXTRACT FOR THE PREVENTION AND TREATMENT OF EXOPHAGEAL REFLOW AND IRRITABLE COLON SYNDROME IT1395119B1 (en)

Priority Applications (21)

Application Number Priority Date Filing Date Title
ITMI2009A001358A IT1395119B1 (en) 2009-07-29 2009-07-29 COMPOSITIONS BASED ON LIPOPHILUS EXTRACT OF ZINGIBER OFFICINAL AND CYNARA SCOLYMUS EXTRACT FOR THE PREVENTION AND TREATMENT OF EXOPHAGEAL REFLOW AND IRRITABLE COLON SYNDROME
ES10702411.9T ES2451346T3 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of Zingiber officinale and an extract of Cynara scolymus
PT107024119T PT2379092E (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus
PCT/EP2010/000205 WO2010083968A1 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus, which are useful for the prevention and treatment of oesophageal reflux and irritable bowel syndrome
RU2011129991/15A RU2521250C2 (en) 2009-01-20 2010-01-15 Compositions containing lipophilic extract of zingiber officinale and extract of cynara scolymus used for preventing and treating gastroesophageal reflux and inflammatory bowel syndrome
SG2011052248A SG173053A1 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus, which are useful for the prevention and treatment of oesophageal reflux and irritable bowel syndrome
CA2750030A CA2750030C (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus, which are useful for the prevention and treatment of oesophageal reflux and irritable bowel syndrome
SI201030524T SI2379092T1 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus
KR1020117016830A KR101762388B1 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of Zingiber officinale and an extract of Cynara scolymus, which are useful for the prevention and treatment of oesophageal reflux and irritable bowel syndrome
EP10702411.9A EP2379092B1 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus
MX2011007686A MX2011007686A (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus, which are useful for the prevention and treatment of oesophageal reflux and irritable bowel syndrome.
JP2011545687A JP5769634B2 (en) 2009-01-20 2010-01-15 Composition comprising ginger lipophilic extract and artichoke extract useful for prevention and treatment of esophageal reflux and irritable bowel syndrome
CN2010800048142A CN102281886A (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus, which are useful for the prevention and treatment of oesophageal reflux and irritable bowel syndrome
BRPI1006915A BRPI1006915B8 (en) 2009-01-20 2010-01-15 composition comprising lipophilic extract of zingiber officinale and extract of cynara scolymus, and its use
AU2010206327A AU2010206327B2 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of Zingiber officinale and an extract of Cynara scolymus, which are useful for the prevention and treatment of oesophageal reflux and irritable bowel syndrome
PL10702411T PL2379092T3 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus
DK10702411.9T DK2379092T3 (en) 2009-01-20 2010-01-15 COMPOSITIONS, INCLUDING A LIPOFIL EXTRACT OF ZINGIBER OFFICINAL AND AN EXTRACT OF CYNARA SCOLYMUS
US13/145,141 US10220065B2 (en) 2009-01-20 2010-01-15 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus, which are useful for the prevention and treatment of oesophageal reflux and irritable bowel syndrome
CL2011001752A CL2011001752A1 (en) 2009-01-20 2011-07-19 Composition containing a lipophilic extract of zingiber officinale obtained by means of extraction with carbon dioxide under supercritical conditions and extract of cynara scolymus; and its use for the prevention and treatment of esophageal reflux and irritable bowel syndrome.
IL214160A IL214160A (en) 2009-01-20 2011-07-19 Compositions comprising lipophilic extract of zingiber officinale and extract of cynara scolymus and their uses for reduction of postprandial and for prokinetic and anti-dyspeptic activities
HRP20140197AT HRP20140197T1 (en) 2009-01-20 2014-03-04 Compositions comprising a lipophilic extract of zingiber officinale and an extract of cynara scolymus

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