ITUB20154158A1 - Association of glycosaminoglycans and magaldrate and compositions containing it. - Google Patents
Association of glycosaminoglycans and magaldrate and compositions containing it. Download PDFInfo
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- ITUB20154158A1 ITUB20154158A1 ITUB2015A004158A ITUB20154158A ITUB20154158A1 IT UB20154158 A1 ITUB20154158 A1 IT UB20154158A1 IT UB2015A004158 A ITUB2015A004158 A IT UB2015A004158A IT UB20154158 A ITUB20154158 A IT UB20154158A IT UB20154158 A1 ITUB20154158 A1 IT UB20154158A1
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- IT
- Italy
- Prior art keywords
- association
- chondroitin sulfate
- sodium
- magahydrate
- pharmaceutical composition
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims description 43
- 229920002683 Glycosaminoglycan Polymers 0.000 title description 8
- 229960004018 magaldrate Drugs 0.000 title description 2
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- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 25
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 17
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- 239000011777 magnesium Substances 0.000 description 1
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- 229960002216 methylparaben Drugs 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- SPPNVMTVMQOKSC-UHFFFAOYSA-A pentaaluminum decamagnesium hentriacontahydroxide disulfate hydrate Chemical compound O.[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg++].[Mg++].[Mg++].[Mg++].[Mg++].[Mg++].[Mg++].[Mg++].[Mg++].[Mg++].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O SPPNVMTVMQOKSC-UHFFFAOYSA-A 0.000 description 1
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- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
“Associazione di glicosamminoglicani e magaldrato e composizioni che la contengono” "Association of glycosaminoglycans and magaldrate and compositions containing it"
Descrizione Description
Riassunto dell’invenzione Summary of the invention
La presente invenzione riguarda un'associazione di acido ialuronico, condroitin solfato e magaidrato nella prevenzione o nel trattamento dell'iperacidità gastrica e nelle patologie ad essa correlate. Più in particolare, Γ associazione viene utilizzata per la preparazione di composizioni orali con almeno un veicolo fannaceutico e comprendono vantaggiosamente anche un agente bioadesivo. The present invention relates to an association of hyaluronic acid, chondroitin sulphate and magahydrate in the prevention or treatment of gastric hyperacidity and in the pathologies related thereto. More particularly, the association is used for the preparation of oral compositions with at least one pharmaceutical vehicle and advantageously also comprise a bioadhesive agent.
Contesto Tecnico Technical context
L’iperacidità gastrica (o bmciore di stomaco o pirosi) è un sintomo molto comune ed è cosi frequente che quasi tutta la popolazione adulta ne soffre. L'aumento dell'acidità può essere legata a diversi fattori. Può rappresentare un problema occasionale, legato a pasti troppo abbondanti, alimenti difficili da digerire, stress, farmaci o a un eccesso di alcol e di fumo di sigaretta. Può invece anche però rappresentare un problema costante, qualora ci si trovi in presenza di una gastrite cronica o, peggio, di un ulcera. Gastric hyperacidity (or heartburn or heartburn) is a very common symptom and is so frequent that almost the entire adult population suffers from it. The increase in acidity can be linked to several factors. It can be an occasional problem, linked to too large meals, hard-to-digest foods, stress, medications, or excessive alcohol and cigarette smoking. However, it can also represent a constant problem, if you are in the presence of chronic gastritis or, worse, of an ulcer.
I glicosamminoglicani sono una famiglia di polisaccaridi formata dalla ripetizione di un acido uronico, acido glucuronico o iduronico, un 1 →4 or β 1 →3 legati ad un residuo di esosammina, glucosammina o galattosammina. I residui di esosammina e di acido uronico possono essere solfatati in modo vario. Nella famiglia dei glicosamminoglicani oltre all' eparin solfato ed all’eparan solfato, sono inclusi anche l’acido ialuronico ed il condroitin solfato. Dal punto di vista fisiologico, i glicosamminoglicani sono organizzati in proteoglicani, formati da un nucleo proteico a cui il glicosamminoglicano è legato da una regione di collegamento. Queste strutture Iranno un molo di controllo di reazioni biochimiche mediante la captazione ed il rilascio di proteine e di fattori di crescita. Glycosaminoglycans are a family of polysaccharides formed by the repetition of a uronic acid, glucuronic or iduronic acid, a 1 → 4 or β 1 → 3 linked to a residue of hexosamine, glucosamine or galactosamine. The residues of hexosamine and uronic acid can be sulfated in various ways. In addition to heparin sulfate and heparan sulfate, the family of glycosaminoglycans also includes hyaluronic acid and chondroitin sulfate. From a physiological point of view, glycosaminoglycans are organized into proteoglycans, formed by a protein core to which the glycosaminoglycan is bound by a connecting region. These structures will play a role in controlling biochemical reactions through the uptake and release of proteins and growth factors.
In particolare, il condroitin solfato è localizzato nelle cartilagini e nella porzione epiteliale della mucosa gastrica o nell' urotelio. Alle cartilagini esso conferisce la caratteristica di elasticità e ne controlla la resistenza, mentre nella mucosa e nell’epitelio protegge l’epitelio stesso dall’ aggressione acida nel caso dell’epitelio gastrico e dal potassio nel caso dell’urotelio. Nelle patologie in cui la quantità di condroitin solfato è bassa come ad esempio la gastrite o la cistite interstiziale la somministrazione di condroitin solfato aiuta a mitigare l'infiammazione e i danni correlati dovuti al basso contenuto di condroitin solfato. Il condroitin solfato di estrazione di norma ha un peso molecolare medio compreso fra 10.000 e 50.000 Da. Il condroitin solfato biosintetico si può ottenere a partire dal polisaccaride K4, per esempio, secondo il metodo descritto nel Documento EP 1304338. Il suo peso molecolare medio è compreso fia 12.000 e 15.000 Da, sebbene si possano anche preparare dei prodotti che hanno un peso molecolare più basso opiù alto. In particular, chondroitin sulfate is localized in the cartilages and in the epithelial portion of the gastric mucosa or in the urothelium. It gives the cartilage the characteristic of elasticity and controls its resistance, while in the mucosa and epithelium it protects the epithelium itself from acid aggression in the case of the gastric epithelium and from potassium in the case of the urothelium. In diseases where the amount of chondroitin sulfate is low such as gastritis or interstitial cystitis, the administration of chondroitin sulfate helps to mitigate inflammation and related damage due to the low content of chondroitin sulfate. The extraction chondroitin sulfate usually has an average molecular weight between 10,000 and 50,000 Da. The biosynthetic chondroitin sulfate can be obtained starting from polysaccharide K4, for example, according to the method described in EP Document 1304338. Its average molecular weight is including 12,000 and 15,000 Da, although products having a lower or higher molecular weight can also be prepared.
L’acido ialuronico di solito si trova come una regolare macromolecola non solfatata fonnata da una sequenza lineare disaccaridica di acido glucuronico 1-3 legato a N-acetilglucosammina, mentre il condroitin solfato è principalmente presente in due forme distinte il condroitin-4-solfato (o ChSA) ed il condroitin-6 -solfato (o ChSC). Il condroitin solfato è formato dalla ripetizione disaccaridica contenente acido glucuronico β 1→3 legato a galattosammina che è solfatata o in posizione 4 o in posizione 6. Nella stessa molecola sono presenti gruppi sia di ChSA che di ChSC. Occasionalmente possono essere presenti anche piccole quantità di disaccaridi disolfatati e non solfatati nella catena polisaccaridica. I proteoglicani contenenti il condroitin solfato sono fonnati da uno scheletro di acido ialuronico su cui sono inserite le catene proteiche (nucleo proteico) che portano i bracci delle catene di condroitin solfato. Si fonna quindi una macromolecola con viscosità molto elevata, viscosità che è dovuta alla massa molecolare molto elevata ed anche alle caratteristiche strutturali dei suoi componenti. Hyaluronic acid is usually found as a regular unsulfated macromolecule formed from a linear disaccharide sequence of glucuronic acid 1-3 bound to N-acetylglucosamine, whereas chondroitin sulfate is mainly present in two distinct forms, chondroitin-4-sulfate ( or ChSA) and chondroitin-6 -sulfate (or ChSC). Chondroitin sulfate is formed by the disaccharide repeat containing glucuronic acid β 1 → 3 bound to galactosamine which is sulfated either in position 4 or in position 6. In the same molecule there are groups of both ChSA and ChSC. Occasionally, small amounts of disulfated and unsulfated disaccharides may also be present in the polysaccharide chain. The proteoglycans containing chondroitin sulfate are formed by a hyaluronic acid skeleton on which the protein chains (protein nucleus) that carry the arms of the chondroitin sulfate chains are inserted. A macromolecule with very high viscosity is then formed, viscosity which is due to the very high molecular mass and also to the structural characteristics of its components.
L’acido ialuronico di estrazione ha un peso molecolare medio dell’ordine di 10<5>-10<6>Da. Il magaidrato è la Denominazione Comune Intemazionale dell’ alluminato di magnesio monoidrato, ed è comunemente usato come farmaco antiacido, per il trattamento di ulcera duodenale, ulcera gastrica e esofagite da reflusso. Extraction hyaluronic acid has an average molecular weight of the order of 10 <5> -10 <6> Da. Magahydrate is the International Common Name of magnesium aluminate monohydrate, and is commonly used as an antacid drug, for the treatment of duodenal ulcer, gastric ulcer and reflux esophagitis.
Scopi dell’ invenzione Aims of the invention
E uno scopo dell’ invenzione fornire una associazione di principi attivi utile per il riattamento dell’iperacidità gastrica e delle patologie ad essa connesse, che sia ben tollerata e che contestualmente svolga un’azione citoprotettiva. It is an aim of the invention to provide an association of active ingredients useful for the reactivation of gastric hyperacidity and related diseases, which is well tolerated and which simultaneously performs a cytoprotective action.
E un altro scopo dell’invenzione fornire delle composizioni farmaceutiche comprendenti detta associazione e il loro uso in terapia. It is another object of the invention to provide pharmaceutical compositions comprising said association and their use in therapy.
E un ulteriore scopo dell’invenzione fornire una associazione di principi attivi utile per il riattamento dell’iperacidità gastrica e delle patologie ad essa connesse, che permette di somministrare una dose di antiacido inferiore a quelle comunemente impiegate. It is a further purpose of the invention to provide an association of active ingredients useful for the reactivation of gastric hyperacidity and associated pathologies, which allows the administration of a lower dose of antacid than those commonly used.
Descrizione dell’invenzione Description of the invention
Si è trovato che un’associazione di acido ialuronico, condroitin solfato e magaidrato può essere utile in terapia, in particolare per la preparazione di composizioni farmaceutiche destinate al riattamento dell’iperacidità gastrica e delle patologie ad essa correlate. It has been found that an association of hyaluronic acid, chondroitin sulfate and magahydrate can be useful in therapy, in particular for the preparation of pharmaceutical compositions intended for the restoration of gastric hyperacidity and related pathologies.
Così secondo uno dei suoi aspetti, l’invenzione ha per oggetto una associazione di acido ialuronico o un suo sale farmaceuticamente accettabile, condroitin solfato o un suo sale farmaceuticamente accettabile, e magaidrato. Thus, according to one of its aspects, the invention relates to an association of hyaluronic acid or a pharmaceutically acceptable salt thereof, chondroitin sulfate or a pharmaceutically acceptable salt thereof, and magahydrate.
L’acido ialuronico ed il condroitin solfato della presente formulazione sono preferibilmente usati come loro sali alcalini come ad esempio come sale di sodio o sale di potassio, preferendo il sale di sodio. The hyaluronic acid and the chondroitin sulfate of the present formulation are preferably used as their alkaline salts such as sodium salt or potassium salt, preferring the sodium salt.
A meno che non altrimenti specificato, i dosaggi riportati per l’acido ialuronico e il condroitin solfato qui di seguito si riferiscono quindi a ialuronato di sodio e a condroitin solfato di sodio. Preferibilmente l’associazione dell’invenzione è una associazione fissa di ialuronato di sodo/condroitin solfato sodico/magaidrato. Le quantità relative dei principi attivi nell’associazione possono variare. A titolo di esempio, rispetto allo ialuronato di sodio è possibile utilizzare da 1,5 a 5 volte in peso il condroitin solfato di sodio, ad esempio circa 2-3 volte in peso e da 3 a 20 volte in peso di magaidrato, ad esempio da 5 a 15 volte in peso. Delle associazioni preferite consistono nell’associazione di ialuronato di sodio/condroitin solfato sodico/magaidrato in un rapporto ponderale reciproco di approssimativamente di 1/2,5/12-13. Altri rapporti ponderali possono comunque essere utilizzati e rientrano tutti nell’ambito di protezione della presente invenzione. Unless otherwise specified, the dosages indicated for hyaluronic acid and chondroitin sulfate below therefore refer to sodium hyaluronate and sodium chondroitin sulfate. Preferably the association of the invention is a fixed association of sodium hyaluronate / sodium chondroitin sulfate / magahydrate. The relative quantities of the active ingredients in the combination may vary. By way of example, with respect to sodium hyaluronate it is possible to use from 1.5 to 5 times by weight the sodium chondroitin sulfate, for example about 2-3 times by weight and from 3 to 20 times by weight of magahydrate, for example 5 to 15 times by weight. Preferred associations consist of the association of sodium hyaluronate / sodium chondroitin sulfate / magahydrate in a reciprocal weight ratio of approximately 1 / 2.5 / 12-13. Other weight ratios can still be used and all fall within the scope of protection of the present invention.
Secondo un altro dei suoi aspetti, l’invenzione ha per oggetto delle composizioni farmaceutiche che comprendono l’associazione come sopra definita e il loro uso in terapia, specialmente per il trattamento dell’iperacidità gastrica e delle patologie connesse. According to another of its aspects, the invention relates to pharmaceutical compositions which include the association as defined above and their use in therapy, especially for the treatment of gastric hyperacidity and related pathologies.
Per l’uso destinato, l’associazione dell’invenzione è fonnulata con i veicoli farmaceutici comunemente usati per la preparazione di composizioni per la sonimi ni strazione orale. For its intended use, the association of the invention is formulated with the pharmaceutical vehicles commonly used for the preparation of compositions for oral sonication.
L’acido ialuronico, vantaggiosamente in forma di sale di sodio, ha preferibilmente un peso molecolare medio non inferiore a 10<S>Da. Hyaluronic acid, advantageously in the form of sodium salt, preferably has an average molecular weight of not less than 10 <S> Da.
Il condroitin solfato ha vantaggiosamente un peso molecolare medio da 5.000 a 50.000, vantaggiosamente da 10.000 a 50.000, preferibilmente da 12.000 a 30.000. The chondroitin sulfate advantageously has an average molecular weight from 5,000 to 50,000, advantageously from 10,000 to 50,000, preferably from 12,000 to 30,000.
Le composizioni delfinvenzione sono preferibilmente in unità di dosaggio orali appropriate, come ad esempio unità di dosaggio solide, quali compresse, polveri, o granulati in bustine, o in unità di dosaggio liquide quali soluzioni o sospensioni orali. Dette forme unitarie contengono preferibilmente da 30 mg a 200 mg di acido ialuronico o un suo sale farmaceuticamente accettabile, da 50 mg a 500 mg di condroitin solfato o un suo sale farmaceuticamente accettabile e da 300 a 1000 mg di magaidrato. The compositions of the invention are preferably in appropriate oral dosage units, such as for example solid dosage units, such as tablets, powders, or granulates in sachets, or in liquid dosage units such as oral solutions or suspensions. Said unitary forms preferably contain from 30 mg to 200 mg of hyaluronic acid or a pharmaceutically acceptable salt thereof, from 50 mg to 500 mg of chondroitin sulfate or a pharmaceutically acceptable salt thereof and from 300 to 1000 mg of magahydrate.
Secondo una forma di realizzazione preferita, le composizioni dell’invenzione comprendono da 30 a 100 mg di ialuronato di sodio, da 80 a 200 mg di condroitin solfato sodico e da 400 a 600 mg di magaidrato. According to a preferred embodiment, the compositions of the invention comprise from 30 to 100 mg of sodium hyaluronate, from 80 to 200 mg of sodium chondroitin sulfate and from 400 to 600 mg of magahydrate.
Delle composizioni preferite comprendono circa 40 mg di ialuronato di sodio, circa 100 mg di condroitin solfato sodico e circa 500 mg di magaidrato. Preferred compositions comprise about 40 mg of sodium hyaluronate, about 100 mg of sodium chondroitin sulfate and about 500 mg of magahydrate.
I veicoli per le compresse includono per esempio amidi, cellulosa e loro derivati; lubrificanti come ad esempio talco, acido stearico o stearato di magnesio; diluenti come ad esempio talco, cellulosa in polvere, lattosio, polietilenglicole, amidi come ad esempio mais o amido di mais, mannitolo, sorbitolo; agenti disaggreganti come ad esempio cellulosa microcristallina o crospovidone; leganti come ad esempio metilcellulosa, carbossimetilcellulosa di sodio; edulcoranti, come ad esempio saccarosio, destrosio, mannitolo, saccalina; o agenti aromatizzanti come ad esempio oli naturali o di sintesi. Carriers for tablets include, for example, starches, cellulose and derivatives thereof; lubricants such as for example talc, stearic acid or magnesium stearate; diluents such as for example talc, powdered cellulose, lactose, polyethylene glycol, starches such as for example corn or corn starch, mannitol, sorbitol; disaggregating agents such as microcrystalline cellulose or crospovidone; binders such as for example methylcellulose, sodium carboxymethylcellulose; sweeteners, such as sucrose, dextrose, mannitol, saccaline; or flavoring agents such as natural or synthetic oils.
I veicoli per compresse per uso orale disgregabili (da masticare) includono per esempio agenti lubrificanti, aggreganti, edulcoranti, aromatizzanti, bioadesivi o disaggreganti. Carriers for disintegrating (chewable) oral tablets include, for example, lubricating, aggregating, sweetening, flavoring, bioadhesive or disaggregating agents.
I veicoli per le sospensioni o le soluzioni liquide, di norma acquose includono per esempio antiossidanti, come ad esempio metabisolfito di sodio o solfito di sodio, agenti addensanti, come ad esempio cellulosa microcristallina, 1 di ossipropil cellulosa, car bossime tilcellulosa o poli vinilpirr oli done, gomme, come la gomma xantano, i conservanti come ad esempio metil paraben, etil paraben, etilenediaminotetracetato di sodio, benzoato di sodio o un sale alcalino dell’acido sorbico, cosi come agenti aromatizzanti ed edulcoranti. Vehicles for liquid, usually aqueous suspensions or solutions include, for example, antioxidants, such as sodium metabisulfite or sodium sulphite, thickening agents, such as microcrystalline cellulose, oxypropyl cellulose, carboxypropyl cellulose or polyvinylpyrene. done, gums, such as xanthan gum, preservatives such as methyl paraben, ethyl paraben, sodium ethylenediaminotetraacetate, sodium benzoate or an alkaline salt of sorbic acid, as well as flavoring and sweetening agents.
Gli edulcoranti contenuti nelle compresse per uso orale masticabili e le sospensioni o le soluzioni liquide possono essere zuccheri naturali, a scelta ridotti, come ad esempio saccarosio, destrosio, xilitolo, mannitolo o sorbitolo, o un prodotto di sintesi come ad esempio la saccarina sodica o raspartame. Possono anche essere aggiunti agenti acidificanti. The sweeteners contained in the chewable tablets for oral use and the suspensions or liquid solutions can be natural sugars, optionally reduced, such as sucrose, dextrose, xylitol, mannitol or sorbitol, or a synthetic product such as sodium saccharin or raspartame. Acidifying agents can also be added.
Gli agenti aromatizzanti sono degli aromi e dei gusti accettabili dal punto di vista farmaceutico di oh di sintesi o di oh naturali, questi ultimi estratti da piante, fiori, frutti e loro combinazioni, come ad esempio cannella, menta, anice, e foghe di agrumi, mandorle amare, agrumi, in particolare oh di arancia e/o limone, tiglio e pompeimo. Si possono usare in modo vantaggioso anche aromi di cioccolato, vaniglia o eucalipto ed essenze di frutta, in particolare mela, pera, pesca, fragola, albicocca, arancia, limone e uva. Flavoring agents are pharmaceutically acceptable aromas and tastes of synthetic oh or natural oh, the latter extracted from plants, flowers, fruits and their combinations, such as cinnamon, mint, anise, and citrus leaves. , bitter almonds, citrus, especially oh of orange and / or lemon, lime and pompeii. Aromas of chocolate, vanilla or eucalyptus and fruit essences, in particular apple, pear, peach, strawberry, apricot, orange, lemon and grape can also be used advantageously.
Le composizioni della presente invenzione sono formulate in una composizione orale, vantaggiosamente liquida, in cui gli principi attivi sono miscelati con un agente bioadesivo che è in grado di aderire alla parete dell’esofago insieme con l’associazione di principi attivi dell’ invenzione, proteggendo quindi o cicatrizzando l’epitelio danneggiato. The compositions of the present invention are formulated in an oral composition, advantageously liquid, in which the active ingredients are mixed with a bioadhesive agent which is able to adhere to the wall of the esophagus together with the association of active ingredients of the invention, protecting therefore or by healing the damaged epithelium.
Pertanto, secondo una forma di realizzazione preferita, le composizioni dell’ invenzione comprendono acido ialuronico, condroitin solfato (entrambi preferibilmente in forma di sale di sodio) e magaidrato, insieme ad un veicolo farmaceutico comprendente almeno un agente bioadesivo solubile in acqua. L’impiego dell’agente bioadesivo fornisce delle nuove composizioni liquide orali con una viscosità particolarmente adatta all’impiego terapeutico dell’ invenzione. Therefore, according to a preferred embodiment, the compositions of the invention comprise hyaluronic acid, chondroitin sulfate (both preferably in the form of sodium salt) and magahydrate, together with a pharmaceutical vehicle comprising at least one water-soluble bioadhesive agent. The use of the bioadhesive agent provides new oral liquid compositions with a viscosity particularly suitable for the therapeutic use of the invention.
L’associazione e le composizioni dell’invenzione sono vantaggiosamente prive di proteine, dove l’espressione “prive di proteine” indica che gli principi attivi qui contenuti sono dei prodotti purificati, contenenti meno dell<1>1 % di proteine. In questo modo si riduce drasticamente il rischio di insorgenza di allergie nei soggetti a cui detta associazione o composizioni vengono somministrate. The association and compositions of the invention are advantageously protein-free, where the expression "protein-free" indicates that the active ingredients contained herein are purified products, containing less than <1> 1% protein. In this way the risk of onset of allergies in the subjects to whom said combination or compositions are administered is drastically reduced.
Le molecole bioadesive sono sostanze molto ben conosciute per la loro capacità di far si che i principi attivi aderiscano ai siti di azione per la somministrazione locale di farmaci o per rivestire alcune parti del corpo. The bioadhesive molecules are very well known substances for their ability to ensure that the active ingredients adhere to the sites of action for the local administration of drugs or to coat certain parts of the body.
La composizione liquida preferita secondo l’invenzione dovrà avere anche una viscosità utile per la somministrazione del principio attivo usando un contenitore semplice o monodose in una forma riproducibile immediatamente pronto per rutilizzatore. Preferibilmente, la viscosità della composizione liquida sarà compresa tra 6.000 e 7.000 centipoise, con un valore medio di 6.500 centipoise (misurata come indicato nella Sezione Sperimentale). The preferred liquid composition according to the invention must also have a viscosity useful for administering the active ingredient using a simple or single-dose container in a reproducible form immediately ready for the user. Preferably, the viscosity of the liquid composition will be between 6,000 and 7,000 centipoises, with an average value of 6,500 centipoises (measured as indicated in the Experimental Section).
Quindi, secondo questa forma di realizzazione preferita la presente invenzione fornisce una composizione orale liquida acquosa comprendente l’associazione dell’invenzione come sopra definita, specialmente l’associazione indicata come preferita secondo l’invenzione, e un bioadesivo il quale è vantaggiosamente presente in una concentrazione totale che va da 0,5 a 4% in peso rispetto al peso totale della composizione, vantaggiosamente intorno a 2,5-3%. Dal momento che l’acido ialuronico ed il condroitin solfato sono essi stessi dei polimeri con elevate proprietà viscose ed elevata attività bioadesiva, è auspicabile usare dei polimeri che siano del tutto compatibili con questi principi attivi. Therefore, according to this preferred embodiment the present invention provides an aqueous liquid oral composition comprising the association of the invention as defined above, especially the association indicated as preferred according to the invention, and a bioadhesive which is advantageously present in a total concentration ranging from 0.5 to 4% by weight with respect to the total weight of the composition, advantageously around 2.5-3%. Since hyaluronic acid and chondroitin sulfate are themselves polymers with high viscous properties and high bioadhesive activity, it is desirable to use polymers that are fully compatible with these active ingredients.
Detti polimeri bioadesivi compatibili sono ad esempio selezionati dal gruppo consistente dei polossameri come ad esempio i copolimeri dell’ossido di etilene e di propilene, in particolare il polossamero 407, i polimeri del vinilpirrolidone, come ad esempio il polivinilpirrolidone Kw 24-32, corrispondenti ad un peso molecolare di 40.000, e derivati della cellulosa come ad esempio l'idrossipropilcellulosa. Said compatible bioadhesive polymers are for example selected from the group consisting of the poloxamers such as for example the copolymers of ethylene and propylene oxide, in particular the poloxamer 407, the polymers of vinylpyrrolidone, such as for example the polyvinylpyrrolidone Kw 24-32, corresponding to a molecular weight of 40,000, and cellulose derivatives such as hydroxypropylcellulose.
Preferibilmente, detti agenti di viscosità idrosolubili aventi delle elevate proprietà bioadesive, come ad esempio il polossamero 407, il polivinilpirrolidone o ridrossipropilcellulosa, sono miscelati con acido ialuronico avente un peso molecolare fra 100 e 3.000 Kdalton e condroitin solfato con un peso molecolare fra 5 e 40 Kdalton e magaidrato, per ottenere una soluzione limpida. Detta soluzione può essere facilmente usata come fonna farmaceutica liquida che ha un ottima attività antiacido. Preferably, said water-soluble viscosity agents having high bioadhesive properties, such as for example poloxamer 407, polyvinylpyrrolidone or redroxypropylcellulose, are mixed with hyaluronic acid having a molecular weight between 100 and 3,000 Kdalton and chondroitin sulfate with a molecular weight between 5 and 40 Kdalton and magahydrate, to obtain a clear solution. Said solution can be easily used as a liquid pharmaceutical form which has an excellent antacid activity.
Accanto ai principali componenti e al bioadesivo, le composizioni preferite della presente invenzione possono contenere agenti conservanti per aumentare la stabilità della composizione cosi come agenti edulcoranti, aromatizzanti e, a scelta, agenti coloranti per aumentare e per ottimizzare le caratteristiche organolettiche della preparazione orale liquida. Alongside the main components and the bioadhesive, the preferred compositions of the present invention may contain preservative agents to increase the stability of the composition as well as sweetening agents, flavoring agents and, optionally, coloring agents to increase and optimize the organoleptic characteristics of the liquid oral preparation.
I conservanti, come il benzoato di sodio, l’acido sorbico e suoi sali, in particolare il sorbato di potassio, l’EDTAoi suoi sali, e parabeni come il metri el’etilparabene possono essere presenti aduna concentrazione dallo 0,01 allo 0,4% in peso. Preservatives, such as sodium benzoate, sorbic acid and its salts, in particular potassium sorbate, EDTA or its salts, and parabens such as meters and ethyl paraben can be present at a concentration from 0.01 to 0, 4% by weight.
Gli agenti edulcoranti possono essere zuccheri naturali, a scelta ridotti, come ad esempio saccarosio, destrosio, xilitolo, mannitolo o sorbitolo, o un prodotto di sintesi come ad esempio la saccarina sodica o l' aspartame. The sweetening agents can be natural sugars, optionally reduced, such as sucrose, dextrose, xylitol, mannitol or sorbitol, or a synthetic product such as sodium saccharin or aspartame.
Gli agenti aromatizzanti saranno scelti dall’esperto nel ramo in relazione alle proprietà organolettiche della composizione. Gli agenti aromatizzanti possono essere selezionati dal gruppo consistente da aromi accettabili dal punto di vista farmaceutico e dal punto di vista nutrizionale e da gusti di oh di sintesi o di oh naturali, questi ultimi estratti da piante, foghe, fiori, frutti e loro combinazioni, come ad esempio cannella, menta, anice, e foghe di agrumi, mandorle amare, agrumi, in particolare oh di arancia e/o limone, tiglio e pompelmo. Si possono usare in modo vantaggioso anche aroma di cioccolato, vaniglia o eucalipto ed essenze di frutta, in particolare mela, pera, pesca, fragola, albicocca, arancia, limone e uva. Gli agenti aromatizzanti preferiti sono quelli conferiti da menta o da frutti, come ad esempio, uva, ciliegia 0 agrumi, in particolare arancia e limone, da aromi o loro miscele. The flavoring agents will be chosen by the skilled in the art in relation to the organoleptic properties of the composition. Flavoring agents can be selected from the group consisting of pharmaceutically and nutritionally acceptable flavors and flavors of synthetic oh or natural oh, the latter extracted from plants, leaves, flowers, fruits and combinations thereof, such as cinnamon, mint, anise, and citrus leaves, bitter almonds, citrus fruits, especially oh orange and / or lemon, lime and grapefruit. Flavors of chocolate, vanilla or eucalyptus and fruit essences, in particular apple, pear, peach, strawberry, apricot, orange, lemon and grape can also be used advantageously. The preferred flavoring agents are those conferred by mint or fruits, such as, for example, grapes, cherries or citrus fruits, in particular orange and lemon, by flavorings or mixtures thereof.
Vantaggiosamente, le composizioni orali liquide di glicosamminoglicani preferite della presente invenzione sono le miscele acquose preferibilmente in forma di dosaggio unitaria, ciascuna comprendente: Advantageously, the preferred liquid oral compositions of glycosaminoglycans of the present invention are the aqueous mixtures preferably in unit dosage form, each comprising:
(a) ialuronato di sodio in una quantità da 30 a 100 mg; (a) sodium hyaluronate in an amount of 30 to 100 mg;
(b) condroitin solfato sodico in una quantità da 80 a 200 mg; (b) sodium chondroitin sulfate in an amount of 80 to 200 mg;
(c) magaidrato in una quantità da 400 a 600 mg; e (c) magahydrate in an amount of 400 to 600 mg; And
(c) almeno un polimero bioadesivo in una quantità totale da 100 a 400 mg, (c) at least one bioadhesive polymer in a total amount of 100 to 400 mg,
insieme a veicoli e eccipienti convenzionali, essendo detta unità di dosaggio complessivamente di circa 10 mi. together with conventional vehicles and excipients, said dosage unit being a total of about 10 ml.
Le composizioni liquide dell’invenzione hanno un pH vantaggiosamente compreso fra 7,8 e 8,4. The liquid compositions of the invention have a pH advantageously between 7.8 and 8.4.
Delle composizioni particolarmente preferite sono riportate nella sezione sperimentale che segue. Un a composizione particolannente preferita è la composizione dell’Esempio 1. Particularly preferred compositions are reported in the experimental section that follows. A particularly preferred composition is the composition of Example 1.
Le unità di dosaggio possono essere bustine, piccole bottiglie di vetro o di plastica o qualsiasi altro contenitore disponibile in attuale tecnologia fannaceutica, inclusi i contenitori multidose, anche se le unità di dosaggio monodose sono preferite secondo l’invenzione. The dosage units can be sachets, small glass or plastic bottles or any other container available in current pharmaceutical technology, including multidose containers, although single-dose dosage units are preferred according to the invention.
Le composizioni in forma di unità di dosaggio in bustine da assumere direttamente. The compositions in the form of dosage units in sachets to be taken directly.
Le composizioni orali liquide preferite della presente invenzione si possono preparare mediante 1 metodi conosciuti in tecnologia fannaceutica. The preferred liquid oral compositions of the present invention can be prepared by the methods known in pharmaceutical technology.
Secondo un ulteriore aspetto, l’invenzione fornisce un procedimento per la preparazione di una composizione orale liquida, caratterizzata dal fatto che si carica dell’acqua depurata in un reattore opportuno e si riscalda fino a 60°C. Si aggiunge, sotto agitazione, gli eventuali polimeri cellulosici e le gomme e si lascia sotto agitazione fino a completa solubilizzazione. Si aggiungono il sodio ialuronato e la condroitina solfato e si mantiene in agitazione. Si aggiungono il magaidrato e l’agente bioadesivo e successivamente i conservanti e gli aromi desiderati e si lascia in agitazione per qualche decina di minuti. According to a further aspect, the invention provides a process for the preparation of a liquid oral composition, characterized in that it is loaded with purified water in a suitable reactor and heated up to 60 ° C. Any cellulosic polymers and gums are added under stirring and left under stirring until complete solubilization. Sodium hyaluronate and chondroitin sulphate are added and the mixture is kept stirred. Add the magahydrate and the bioadhesive agent and then the desired preservatives and aromas and leave to stir for a few tens of minutes.
Le composizioni orali liquide preferite secondo la presente invenzione sono utili per la somministrazione agevole dell’associazione dell’invenzione anche a dosaggi elevati in fonna liquida aventi delle proprietà bioadesive adeguate. In particolare, esse sono composizioni per il trattamento o per la prevenzione dell’iperacidità gastrica e delle patologie ad essa correlate quali ulcera duodenale e gastrica, esofagite da reflusso, gastriti e gastro-duodeniti. The preferred liquid oral compositions according to the present invention are useful for the easy administration of the association of the invention even at high dosages in liquid form having adequate bioadhesive properties. In particular, they are compositions for the treatment or prevention of gastric hyperacidity and related diseases such as duodenal and gastric ulcer, reflux esophagitis, gastritis and gastro-duodenitis.
La Richiedente ha condotto dei test sulla composizione dell’Esempio 1 che segue, che hanno dimostrato che l’associazione dell’invenzione, in particolare l’associazione formulata con l’agente bioadesivo come sopra indicato, si è dimostrata particolarmente efficace nel trattamento dell’iperacidità e delle patologie correlate. L’associazione ha inoltre permesso di diminuire la dose del magaidrato nelle unità di dosaggio rispetto alle dosi comunemente impiegate in terapia, che prevedono circa 800 mg per unità di dosaggio da assumere 4 volte al giorno. Difatti, nei test condotti, la composizione dell’Esempio 1 è stata somministrata solo due volte al giorno. The Applicant has carried out tests on the composition of Example 1 which follows, which have shown that the association of the invention, in particular the association formulated with the bioadhesive agent as indicated above, has proved to be particularly effective in the treatment of hyperacidity and related pathologies. The association also made it possible to reduce the dose of magahydrate in the dosage units compared to the doses commonly used in therapy, which provide about 800 mg per dosage unit to be taken 4 times a day. In fact, in the tests conducted, the composition of Example 1 was administered only twice a day.
La presenza dei glicosamminoglicani, in particolare di acido ialuronico ha portato ad ottenere un effetto citoprotettore, promuovendo la guarigione delle cellule della mucosa gastroesofagea danneggiate dall’iperacidità. The presence of glycosaminoglycans, in particular hyaluronic acid, has led to a cytoprotective effect, promoting the healing of the cells of the gastroesophageal mucosa damaged by hyperacidity.
Secondo un altro dei suoi aspetti, l’invenzione ha per oggetto un metodo per il trattamento e la prevenzione dell’iperacidità e le patologie ad essa connesse, che comprende somministrare a un soggetto che lo necessita l’associazione o le composizioni secondo l’invenzione. According to another of its aspects, the invention relates to a method for the treatment and prevention of hyperacidity and the pathologies connected to it, which comprises administering the association or compositions according to the invention to a subject who needs it. .
Gli esempi che seguono illustrano l’invenzione. In detti esempi, si è usato ialuronato di sodio purificato, di estrazione avente un peso molecolare medio di circa 10<6>Da e condroitin solfato di sodio purificato, di estrazione avente un peso molecolare medio di circa 30.000 Da. The following examples illustrate the invention. In said examples, purified sodium hyaluronate, by extraction having an average molecular weight of about 10 <6> Da, and purified sodium chondroitin sulfate, by extraction having an average molecular weight of about 30,000 Da, was used.
Esempio 1 Example 1
Si prepara una composizione liquida in bustine monodose da 10 mi ciascuna A liquid composition is prepared in single-dose sachets of 10 ml each
Ingredienti mg/10 mi Ingredients mg / 10 ml
gomma xantano 28 xanthan gum 28
idrossipropil-metil cellulosa 165 hydroxypropyl methyl cellulose 165
sodio ialuronato 41 sodium hyaluronate 41
sodio condroitin solfato 103 sodium chondroitin sulfate 103
xilitolo C 2473 xylitol C 2473
Polossamero 407 297 Poloxamer 407 297
polivinilpirrolidone 275 polyvinylpyrrolidone 275
magaidrato 500 magahydrate 500
parametri parabene 11 paraben parameters 11
paraetil parabene 11 paraethyl paraben 11
aroma q.b. aroma to taste
acidificante q.b. acidifier to taste
acqua q.b. water q.s.
Esempio 2 Example 2
Si prepara una composizione liquida in bustine monodose da 10 mi ciascuna A liquid composition is prepared in single-dose sachets of 10 ml each
Ingredienti mg/10 mi Ingredients mg / 10 ml
ialuronato di sodio 68,926 sodium hyaluronate 68.926
condroitin solfato di sodio 172,288 sodium chondroitin sulfate 172,288
xilitoloplv (xilisorb 300) 2481,132 xylitoloplv (xylisorb 300) 2481,132
poi ossamero 407 148,889 then oxamer 407 148,889
polivinilpirrolidone 275,683 polyvinylpyrrolidone 275,683
sodio benzoato 10,342 sodium benzoate 10.342
potassio sorbato 20,672 potassium sorbate 20.672
aroma 2,296 flavor 2,296
magaidrato 529,671 magahydrate 529.671
acqua q.b. water q.s.
Esempio 3 Example 3
Procedimento di preparazione della composizione deirEsempio 1 Preparation process of the composition of Example 1
Caricare l’acqua depurata in idoneo mescolatore perfettamente pulito e sanitizzato. Accendere il riscaldamento impostando la temperatura a 60°C. A 60°C gradi aggiungere sotto agitazione idrossipropil-metil cellulosa e gomma xantano e lasciare sotto agitazione fino a completa solubilizzazione. Procedere addizionando sodio ialuronato e condroitina solfato. Mantenere in agitazione e aggiungere polossamero, polivinlpirrolidone e magaidrato. Addizionare lo xilitolo e lasciare in agitazione per altri 40 minuti. Successivamente far raffreddare e aggiungere i parabeni e gli aromi, sotto agitazione. Regolare il pH del prodotto con acidificante e mantenere in agitazione per almeno 15 minuti. Load the purified water into a suitable, perfectly clean and sanitized mixer. Turn on the heating by setting the temperature to 60 ° C. At 60 ° C, add hydroxypropyl-methyl cellulose and xanthan gum while stirring and leave under stirring until completely dissolved. Proceed by adding sodium hyaluronate and chondroitin sulfate. Keep stirring and add poloxamer, polyvinylpyrrolidone and magahydrate. Add xylitol and leave to stir for another 40 minutes. Then let it cool and add the parabens and flavorings, while stirring. Adjust the pH of the product with an acidifier and keep stirring for at least 15 minutes.
Esempio 4 Example 4
Misurazione della viscosità della composizione dell’Esempio 1 Measurement of the viscosity of the composition of Example 1
Preparazione del campione Sample preparation
Viene prelevato dal batch un campione (200 mi) di prodotto e viene condizionato ad una temperatura di 25 - 26°C . A sample (200 ml) of product is taken from the batch and conditioned at a temperature of 25-26 ° C.
Strumenti Instruments
Brookfield DV - II plus Brookfield DV - II plus
Misurazione con Brookfield DV-II plus Measured with Brookfield DV-II plus
Il viscosimetro deve essere calibrato con gli standard di Controllo Qualità . The viscometer must be calibrated with Quality Control standards.
1. Avviare lo strumento portando l'interruttore posto sul cruscotto posteriore in posizione ON ed eseguire Γ autocalibrazione. 1. Start the instrument by moving the switch located on the rear dashboard to the ON position and perform Γ self-calibration.
2. Abbassare il viscosimetro nella posizione di misurazione. 2. Lower the viscometer to the measurement position.
3. Fissare il viscosimetro girando in senso antiorario la girante adatta per misurare la viscosità secondo lo schema seguente : 3. Fix the viscometer by turning the suitable impeller to measure viscosity counterclockwise according to the following diagram:
RV1 500 - 1500 cPs RV1 500 - 1500 cPs
RV2 1500 - 5000 cPs RV2 1500 - 5000 cPs
RV3 5000 - 15000 cPs RV3 5000 - 15000 cPs
RV4 15000 - 25000 cPs RV4 15000 - 25000 cPs
RV5 25000 - 50000 cPs RV5 25000 - 50000 cPs
RV6 50000 - 150000 cPs RV6 50000 - 150000 cPs
RV7 150000 - 500000 cPs RV7 150000 - 500000 cPs
Immergere la girante nel campione. Immerse the impeller in the sample.
4. Selezionare sul display la tipologia di girante 4. Select the type of impeller on the display
5. Selezionare la velocità 5. Select the speed
6. Selezionare Punità di misura cP ( centiPoise ) 6. Select Measurement unit cP (centiPoise)
7. Premere il tasto “Motor ON / OFF misurare la viscosità a velocità 4 e velocità 10 e calcolare la viscosità come media aritmetica dei valori ottenuti espressa in Cp ( centiPoise ). 7. Press the “Motor ON / OFF” key, measure the viscosity at speed 4 and speed 10 and calculate the viscosity as the arithmetic average of the values obtained expressed in Cp (centiPoise).
I valori di viscosità ottenuti per la composizione dell’Esempio 1, variano da 6000 a 7000 centipoise, con un valore medio 6500 centipoise. The viscosity values obtained for the composition of Example 1 vary from 6000 to 7000 centipoise, with an average value of 6500 centipoise.
Claims (12)
Priority Applications (13)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITUB2015A004158A ITUB20154158A1 (en) | 2015-10-01 | 2015-10-01 | Association of glycosaminoglycans and magaldrate and compositions containing it. |
| ITUA2016A002869A ITUA20162869A1 (en) | 2015-10-01 | 2016-04-26 | Combination of glycosaminoglycans and an antacid agent and compositions containing it. |
| PCT/IB2016/001423 WO2017055909A1 (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and compositions thereof |
| CA2999411A CA2999411A1 (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and compositions thereof |
| EP16795133.4A EP3240550B1 (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and compositions thereof |
| ES16795133T ES2733634T3 (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and compositions thereof |
| US15/762,602 US11116786B2 (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and compositions thereof |
| DK16795133.4T DK3240550T3 (en) | 2015-10-01 | 2016-09-30 | COMBINATION OF GLYCOSAMINOGLYCANES AND AN ANTACIDIUM AND COMPOSITIONS THEREOF |
| MX2018003975A MX2018003975A (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and compositions thereof. |
| PT16795133T PT3240550T (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and compositions thereof |
| EA201890842A EA037070B9 (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and composition thereof |
| PL16795133T PL3240550T3 (en) | 2015-10-01 | 2016-09-30 | Combination of glycosaminoglycans and an antacid agent and compositions thereof |
| KR1020187012120A KR20180081508A (en) | 2015-10-01 | 2016-09-30 | Combinations of glycosaminoglycans and antacids and compositions thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITUB2015A004158A ITUB20154158A1 (en) | 2015-10-01 | 2015-10-01 | Association of glycosaminoglycans and magaldrate and compositions containing it. |
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| ITUB20154158A1 true ITUB20154158A1 (en) | 2017-04-01 |
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| ITUB2015A004158A ITUB20154158A1 (en) | 2015-10-01 | 2015-10-01 | Association of glycosaminoglycans and magaldrate and compositions containing it. |
| ITUA2016A002869A ITUA20162869A1 (en) | 2015-10-01 | 2016-04-26 | Combination of glycosaminoglycans and an antacid agent and compositions containing it. |
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| ITUA2016A002869A ITUA20162869A1 (en) | 2015-10-01 | 2016-04-26 | Combination of glycosaminoglycans and an antacid agent and compositions containing it. |
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|---|---|
| DK (1) | DK3240550T3 (en) |
| ES (1) | ES2733634T3 (en) |
| IT (2) | ITUB20154158A1 (en) |
| PT (1) | PT3240550T (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4676984A (en) * | 1985-08-14 | 1987-06-30 | American Home Products Corp. | Rehydratable antacid composition |
| US20140107064A1 (en) * | 2008-05-13 | 2014-04-17 | Apharm S.R.L. | Glycosaminoglycan oral use and compositions |
-
2015
- 2015-10-01 IT ITUB2015A004158A patent/ITUB20154158A1/en unknown
-
2016
- 2016-04-26 IT ITUA2016A002869A patent/ITUA20162869A1/en unknown
- 2016-09-30 PT PT16795133T patent/PT3240550T/en unknown
- 2016-09-30 DK DK16795133.4T patent/DK3240550T3/en active
- 2016-09-30 ES ES16795133T patent/ES2733634T3/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4676984A (en) * | 1985-08-14 | 1987-06-30 | American Home Products Corp. | Rehydratable antacid composition |
| US20140107064A1 (en) * | 2008-05-13 | 2014-04-17 | Apharm S.R.L. | Glycosaminoglycan oral use and compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| ITUA20162869A1 (en) | 2017-10-26 |
| ES2733634T3 (en) | 2019-12-02 |
| PT3240550T (en) | 2019-07-16 |
| DK3240550T3 (en) | 2019-07-15 |
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