ITRM20080668A1 - FORMULATION FOR VAGINAL ADMINISTRATION BASED ON OMEGA-3 POLYSATURATED FATTY ACIDS AND MAGNESIUM COMPOUNDS. - Google Patents
FORMULATION FOR VAGINAL ADMINISTRATION BASED ON OMEGA-3 POLYSATURATED FATTY ACIDS AND MAGNESIUM COMPOUNDS. Download PDFInfo
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- ITRM20080668A1 ITRM20080668A1 IT000668A ITRM20080668A ITRM20080668A1 IT RM20080668 A1 ITRM20080668 A1 IT RM20080668A1 IT 000668 A IT000668 A IT 000668A IT RM20080668 A ITRM20080668 A IT RM20080668A IT RM20080668 A1 ITRM20080668 A1 IT RM20080668A1
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- Prior art keywords
- formulation
- magnesium
- vaginal administration
- omega
- administration according
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Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
Description
Descrizione dell'invenzione avente per titolo: Description of the invention entitled:
“FORMULAZIONE PER LA SOMMINISTRAZIONE VAGINALE A BASE DI ACIDI GRASSI POLINSATURI OMEGA-3 E DI COMPOSTI DEL MAGNESIO†⠀ œFORMULATION FOR VAGINAL ADMINISTRATION BASED ON OMEGA-3 POLYUNSATURATED FATTY ACIDS AND MAGNESIUM COMPOUNDSâ €
DESCRIZIONE DESCRIPTION
Settore della tecnica Technical sector
La presente domanda di brevetto per invenzione si riferisce in generale al settore delle formulazioni per la somministrazione vaginale, più in particolare, l’invenzione riguarda una formulazione per la somministrazione vaginale a base di acidi grassi polinsaturi omega-3 e di composti del magnesio. The present patent application for invention relates in general to the field of formulations for vaginal administration, more particularly, the invention relates to a formulation for vaginal administration based on omega-3 polyunsaturated fatty acids and magnesium compounds.
L’invenzione à ̈ applicabile a qualsiasi settore, dove un tale tipo di formulazione può essere vantaggiosamente utilizzata, ma preferibilmente essa riguarda la branca medica relativa all’ostetricia e alla ginecologia. The invention is applicable to any sector, where this type of formulation can be advantageously used, but preferably it concerns the medical branch relating to obstetrics and gynecology.
Tecnica nota Known technique
Come à ̈ noto il magnesio appartiene alla categoria dei macro elementi, ossia quei componenti inorganici della dieta che devono essere assunti ogni giorno in quantità piuttosto elevate, dal momento che il nostro organismo ne contiene quantità relativamente alte. Circa metà del magnesio corporeo à ̈ immobilizzato nello scheletro, mentre il resto à ̈ presente nei liquidi cellulari. Il magnesio à ̈ il cofattore in circa 300 reazioni enzimatiche necessarie per il metabolismo di tutto l’organismo. As is known, magnesium belongs to the category of macro elements, that is, those inorganic components of the diet that must be taken every day in rather high quantities, since our body contains relatively high quantities. About half of the body's magnesium is immobilized in the skeleton, while the rest is present in cell fluids. Magnesium is the cofactor in about 300 enzymatic reactions necessary for the metabolism of the whole organism.
L’esistenza di quadri clinici legati alla carenza di magnesio à ̈ nota sin dall’inizio del secolo, ma solo negli ultimi 25 anni si sono sviluppati studi per definire gli aspetti clinici e fisiopatologici di questa sindrome. Le deficienze di magnesio sembrano essere correlate principalmente con una serie di patologie riguardanti la cardiopatia ischemica, l’ipertensione, l’osteoporosi, l’intolleranza al glucosio, l’infarto del miocardio, le manifestazioni neuropsichiche e le manifestazioni neuromuscolari. Principalmente, le espressioni cliniche di un deficit di detto minerale si manifestano con debolezza muscolare, mancanza di coordinazione, tremori, contrazioni muscolari, crampi addominali, depressione, irritabilità , modificazioni dell’elettrocardiogramma. Stati di carenza, anche lievi, favorirebbero la dismenorrea, la sindrome premestruale, l’infertilità inspiegabile, l’osteoporosi, l’ipertensione e le malattie cardiovascolari. The existence of clinical pictures linked to magnesium deficiency has been known since the beginning of the century, but only in the last 25 years have studies been developed to define the clinical and pathophysiological aspects of this syndrome. Magnesium deficiencies seem to be mainly correlated with a series of pathologies concerning ischemic heart disease, hypertension, osteoporosis, glucose intolerance, myocardial infarction, neuropsychic manifestations and neuromuscular manifestations. Mainly, the clinical expressions of a deficiency of this mineral are manifested by muscle weakness, lack of coordination, tremors, muscle contractions, abdominal cramps, depression, irritability, changes in the electrocardiogram. Even mild states of deficiency would favor dysmenorrhea, premenstrual syndrome, unexplained infertility, osteoporosis, hypertension and cardiovascular diseases.
Anche nella pratica ginecologica il magnesio svolge un ruolo di elezione nella regolazione di molti dei processi fisiologici associati. Nell’arco della sua esistenza la donna subisce notevoli modificazioni fisiologiche e ormonali, per le quali il magnesio gioca un ruolo chiave. In particolare, un corretto apporto di detto minerale à ̈ determinante nella sindrome premestruale, nella dismenorrea e nella gravidanza. Even in gynecological practice, magnesium plays an important role in the regulation of many of the associated physiological processes. Over the course of her existence, women undergo considerable physiological and hormonal changes, for which magnesium plays a key role. In particular, a correct intake of this mineral is crucial in premenstrual syndrome, dysmenorrhea and pregnancy.
A tale riguardo diversi studi clinici hanno messo in luce la correlazione tra la carenza di magnesio e la comparsa del quadro sintomatologico tipico della sindrome pre-mestruale, associato all’ovulazione o alla fase successiva del ciclo. Tale stato di deficit associato a una ridotta produzione di dopamina e a un picco della quota di serotonina, spiegherebbe stati ansiosi, irritabilità , difficoltà a concentrarsi, ritenzione idrica. È stato inoltre appurato che i sintomi neuropsichici potrebbero essere espressione di uno stato di ipereccitabilità neuronale. Il trattamento preventivo con composti del magnesio riesce a ridurre notevolmente il grado di eccitabilità delle cellule nervose attenuandone i sintomi. Fin dal 1962 sono stati messi in luce gli effetti benefici del magnesio nel trattamento della dismenorrea primitiva, patologia che colpisce circa il 50-60% delle donne tra i 15 e i 40 anni. Tale condizione risulta caratterizzata dall’insorgenza di dolori crampiformi in concomitanza del periodo mestruale, che nel 30% dei casi si protrae per più giorni. Sembra che siano sostanze chiamate prostaglandine, in grado di ipersensibilizzare le terminazioni del dolore, a esercitare un ruolo primario nell’insorgere della sindrome. Nelle donne che soffrono di dismenorrea, infatti, la produzione di dette sostanze raddoppia, aumentando la contrattilità dell’utero. Gli antinfiammatori non steroidei efficaci sui sintomi, ma spesso gravati da effetti collaterali pesanti, possono essere sostituiti con successo dalla somministrazione di magnesio per sei giorni, a partire da 3 giorni prima del ciclo. Il magnesio, infatti, agisce sulla contrattilità uterina e contrasta efficacemente il dolore. Alcuni studi hanno calcolato che determinate quantità di magnesio riescono a ridurre il dolore nel primo giorno del ciclo, in modo ancora più significativo nel secondo e terzo giorno. Sembra, inoltre, che l’aumento delle dosi di magnesio introdotte, anche di pochi mg (circa 13) al giorno, possa già espletare effetti positivi. In this regard, several clinical studies have highlighted the correlation between magnesium deficiency and the appearance of the symptomatic picture typical of the pre-menstrual syndrome, associated with ovulation or the subsequent phase of the cycle. This state of deficit associated with a reduced production of dopamine and a peak in the amount of serotonin, would explain anxiety, irritability, difficulty concentrating, water retention. It was also ascertained that the neuropsychic symptoms could be the expression of a state of neuronal hyperexcitability. Preventive treatment with magnesium compounds is able to significantly reduce the degree of excitability of nerve cells, alleviating their symptoms. Since 1962 the beneficial effects of magnesium in the treatment of primary dysmenorrhea have been highlighted, a pathology that affects about 50-60% of women between 15 and 40 years of age. This condition is characterized by the onset of cramping pains in conjunction with the menstrual period, which in 30% of cases lasts for several days. It seems that substances called prostaglandins, able to hypersensitize the pain endings, play a primary role in the onset of the syndrome. In fact, in women suffering from dysmenorrhea, the production of these substances doubles, increasing the contractility of the uterus. Non-steroidal anti-inflammatories that are effective on symptoms, but often burdened with severe side effects, can be successfully replaced by administering magnesium for six days, starting 3 days before your period. Magnesium, in fact, acts on uterine contractility and effectively counteracts pain. Some studies have calculated that certain amounts of magnesium can reduce pain on the first day of the cycle, even more significantly on the second and third days. It also seems that the increase in the doses of magnesium introduced, even by a few mg (about 13) per day, can already have positive effects.
La gravidanza e l’allattamento sono stati fisiologici durante i quali i bisogni nutrizionali della donna aumentano, pur tuttavia la nausea e il vomito, frequenti durante i primi mesi della gravidanza, possono determinare carenze di magnesio. Per tutta la durata della gravidanza risulta, pertanto, consigliabile un aumento nell’assunzione quotidiana di magnesio. E’ stato calcolato che una dieta di 2000 calorie giornaliere comporta un apporto medio di circa 250-300 mg di magnesio, ben al di sotto del fabbisogno giornaliero. Diventano necessarie, quindi, opportune modificazioni del regime alimentare o il ricorso a integratori per sopperire le eventuali carenze. È importante, infatti, mantenere il giusto apporto di magnesio per diverse ragioni, ovvero contribuire alla salute della mamma e del bambino, diminuire il rischio di aborto del primo trimestre, di parto pretermine, di ipertensione della gravidanza, di crampi, di patologie fetali e neonatali. Pregnancy and breastfeeding are physiological states during which the nutritional needs of the woman increase, however nausea and vomiting, frequent during the first months of pregnancy, can lead to magnesium deficiencies. An increase in the daily intake of magnesium is therefore advisable for the entire duration of pregnancy. It has been calculated that a diet of 2000 calories per day involves an average intake of about 250-300 mg of magnesium, well below the daily requirement. Therefore, appropriate modifications of the diet or the use of supplements to make up for any shortcomings become necessary. It is important, in fact, to maintain the right amount of magnesium for various reasons, that is to contribute to the health of the mother and the child, to reduce the risk of abortion in the first trimester, of preterm birth, of hypertension of pregnancy, of cramps, of fetal pathologies and neonatal.
Studi recenti (The Magpie Collaborative Group, Lancet, 2002), hanno evidenziato un effetto benefico del magnesio nel caso di pre-eclampsia, ossia un disturbo caratterizzato da un notevole aumento della pressione arteriosa e della proteinuria, che compare nel 2-8% delle gravidanze e nel caso di eclampsia, ossia una crisi convulsiva generalizzata in corso di pre-eclampsia, con depressione respiratoria fino ad arresto respiratorio, cardiaco, insufficienza renale ed epatica, emorragia cerebrale ed edema polmonare. Il magnesio ha dimostrato un effetto protettivo indipendente dalla gravità dello stato pre-eclampsico, dall’età gestazionale al momento del ricovero e dal numero di figli partoriti (Belfort et Al, The Nimodipine Study Group, NEJM 384:4, 2003) Recent studies (The Magpie Collaborative Group, Lancet, 2002), have highlighted a beneficial effect of magnesium in the case of pre-eclampsia, i.e. a disorder characterized by a significant increase in blood pressure and proteinuria, which appears in 2-8% of pregnancies and in the case of eclampsia, i.e. a generalized seizure during pre-eclampsia, with respiratory depression up to respiratory, cardiac, renal and hepatic insufficiency, cerebral haemorrhage and pulmonary edema. Magnesium has shown a protective effect independent of the severity of the pre-eclamptic state, the gestational age at the time of hospitalization and the number of children delivered (Belfort et Al, The Nimodipine Study Group, NEJM 384: 4, 2003)
Negli ultimi anni si sono avute conferme di quanto il ricorso al magnesio agisca positivamente nel caso di parto pretermine. Questa patologia à ̈ determinata dall’insorgenza di contrazioni uterine ritmiche che ostacolano il normale compimento del periodo di gravidanza. Grazie alla sua azione decontratturante della muscolatura uterina, il magnesio riesce a contrastare tale fenomeno ed à ̈ risultato di estrema utilità nella prevenzione delle nascite di bambini prematuri. A beneficio di quanto esposto, tra i farmaci tocolitici di elezione, che sono stati considerati il pilastro del management farmacologico primario del travaglio pretermine a basso impatto, sia come terapia d’attacco per bloccare l’attività contrattile uterina e sia come mantenimento per prolungare la quiescenza uterina, ritroviamo oltre agli inibitori della sintesi di prostaglandine anche il solfato di magnesio. I sali di magnesio, infatti, proprio per i ridotti effetti collaterali stanno gradualmente soppiantando l’utilizzo nelle patologie predette dei farmaci classici tali come i calcio-antagonisti, i β-agonisti, i donatori di ossido nitrico e gli antagonisti dell’ossitocina (atosiban). Tali farmaci, infatti, sono gravati da molteplici potenziali effetti collaterali materni (tachicardia, nausea, vomito, tremori, vertigini), fetali (tachicardia, bradicardia) e neonatali (morbosità e ricovero presso la terapia intensiva). In recent years there have been confirmations of how much the use of magnesium acts positively in the case of preterm birth. This pathology is determined by the onset of rhythmic uterine contractions which hinder the normal completion of the pregnancy period. Thanks to its decontracting action on the uterine muscles, magnesium is able to counteract this phenomenon and is extremely useful in preventing the birth of premature babies. For the benefit of the above, among the tocolytic drugs of choice, which have been considered the pillar of the primary pharmacological management of low-impact preterm labor, both as attack therapy to block uterine contractile activity and as maintenance for prolong uterine quiescence, we find in addition to inhibitors of prostaglandin synthesis also magnesium sulphate. The magnesium salts, in fact, due to the reduced side effects are gradually supplanting the use in the aforementioned pathologies of classic drugs such as calcium antagonists, β-agonists, nitric oxide donors and oxytocin antagonists (atosiban). These drugs, in fact, are burdened by multiple potential maternal side effects (tachycardia, nausea, vomiting, tremors, dizziness), fetal (tachycardia, bradycardia) and neonatal (morbidity and hospitalization in intensive care).
Altro argomento caratterizzante la presente invenzione riguarda il fatto che da molti anni si parla anche dei benefici dei grassi polinsaturi della serie omega-3 sull’organismo e più specificatamente degli effetti benefici dell'acido αlinolenico ALA, dell'acido eicosapentaenoico EPA e dell'acido docosaesaenoico DHA. Per quanto riguarda gli aspetti fisiopatologici, vari studi hanno dimostrato che gli acidi grassi polinsaturi della serie omega-3 hanno un effetto antinfiammatorio provocato proprio dal fatto che essi stessi costituiscono i precursori di molecole definite eicosanoidi (prostaglandine, prostacicline, trombossani, leucotrieni e lipoxine) e docosanoidi (decosatrieni e resolvine). La formazione di prostaglandine con effetto antinfiammatorio, si realizza attraverso una competizione tra l’acido arachidonico AA e gli stessi omega-3, a livello degli enzimi ciclossigenasi e lipossigenasi. L’aumento dell'apporto di acidi grassi polinsaturi omega-3, riduce competitivamente l’incorporazione dell’acido arachidonico AA all’interno delle membrane cellulari, inibendo direttamente la sintesi delle PG-2 e quindi promuovendo una netta risposta antinfiammatoria. In generale gli eicosanoidi derivati dall’acido arachidonico AA sono le prostaglandine PG e il trombossano TBX della serie-2 aventi tra i molteplici effetti, quelli infiammatori, di aggregazione piastrinica, di contrazione dell'utero gravidico, di aumento e durata dell'intensità di alcuni tipi di dolore. Gli acidi grassi polinsaturi della serie omega-3 presentano, pertanto, oltre all’effetto antinfiammatorio anche un'azione antitrombotica, antiaritmica, antiaterogenica e di rilassamento uterino analogo a quello osservato con la somministrazione di magnesio. Another argument characterizing the present invention concerns the fact that for many years there has also been talk of the benefits of polyunsaturated fats of the omega-3 series on the body and more specifically of the beneficial effects of Î ± linolenic acid ALA, of eicosapentaenoic acid EPA and of docosahexaenoic acid DHA. As for the pathophysiological aspects, various studies have shown that the polyunsaturated fatty acids of the omega-3 series have an anti-inflammatory effect caused precisely by the fact that they themselves constitute the precursors of molecules defined as eicosanoids (prostaglandins, prostacyclines, thromboxanes, leukotrienes and lipoxins) and docosanoids (decosatrienes and resolvins). The formation of prostaglandins with an anti-inflammatory effect is achieved through a competition between the arachidonic acid AA and the same omega-3s, at the level of the cyclooxygenase and lipoxygenase enzymes. The increase in the intake of omega-3 polyunsaturated fatty acids, competitively reduces the incorporation of arachidonic acid AA inside the cell membranes, directly inhibiting the synthesis of PG-2 and therefore promoting a clear anti-inflammatory response . In general, the eicosanoids derived from arachidonic acid AA are prostaglandins PG and thromboxane TBX of the series-2 having, among the many effects, inflammatory, platelet aggregation, contraction of the pregnancy uterus, increase and duration of intensity some types of pain. The polyunsaturated fatty acids of the omega-3 series therefore have, in addition to the anti-inflammatory effect, also an antithrombotic, antiarrhythmic, antiatherogenic and uterine relaxation action similar to that observed with the administration of magnesium.
Gli acidi grassi polinsaturi della serie omega-3 e prevalentemente il DHA risultano anche abbondantemente presenti nelle strutture del cervello e della retina. Qualsiasi processo che pregiudichi la capacità delle cellule gliali di sintetizzare il DHA, può compromettere la struttura e la funzione delle cellule nervose. Un esempio à ̈ rappresentato da alcune gravi malattie genetiche contrassegnate dalla presenza di scarsi livelli plasmatici di DHA a causa dell'inefficacia della β3-ossidazione che ne termina la sintesi, quali la sindrome di Zellweger e l’adrenoleucodistrofia neonatale. Queste patologie sono caratterizzate da demielinizzazione cerebrale, atrofia surrenalica e accumulo di acidi grassi nella sostanza bianca e nella corteccia surrenale. La loro evoluzione à ̈ un'alterazione del SNC, la cecità e la morte precoce. Polyunsaturated fatty acids of the omega-3 series and mainly DHA are also abundantly present in the structures of the brain and retina. Any process that impairs the ability of glial cells to synthesize DHA can impair the structure and function of nerve cells. An example is represented by some serious genetic diseases marked by the presence of low plasma levels of DHA due to the ineffectiveness of β3-oxidation that terminates its synthesis, such as Zellweger syndrome and neonatal adrenoleukodystrophy. These pathologies are characterized by cerebral demyelination, adrenal atrophy and accumulation of fatty acids in the white matter and adrenal cortex. Their evolution is an alteration of the CNS, blindness and early death.
L’accumulo di DHA avviene in massimo grado durante l’ultimo trimestre di vita intrauterina ed à ̈ quindi il prematuro a essere più esposto alla carenza di questo fondamentale componente nutrizionale. Tuttavia, anche dopo la nascita si registra una notevole deposizione di DHA a livello delle strutture nervose, dai primi 2-3 mesi di vita fino a tutto il secondo anno. L’immaturità e l’incapacità del sistema enzimatico fetale preposto a questi meccanismi non consentono di soddisfare le elevate richieste neonatali di DHA fino a 16 settimane dopo la nascita. Per tali motivi sia il feto e sia il neonato nei primi mesi di vita extrauterina sono totalmente dipendenti dal trasferimento materno di DHA mediato prima dalla placenta e poi dall’allattamento. Di conseguenza si può affermare con assoluta certezza che il DHA, derivante dal metabolismo materno degli acidi grassi polinsaturi della serie omega-3 assunti dalla dieta o mediante idoneo integratore, à ̈ indispensabile per una corretta crescita fetale e per l'accumulo nel cervello in via di sviluppo. The accumulation of DHA occurs to the highest degree during the last trimester of intrauterine life and it is therefore the premature baby who is most exposed to the deficiency of this fundamental nutritional component. However, even after birth there is a significant deposition of DHA in the nervous structures, from the first 2-3 months of life up to the entire second year. The immaturity and inability of the fetal enzymatic system responsible for these mechanisms do not allow to meet the high neonatal DHA requirements up to 16 weeks after birth. For these reasons both the fetus and the newborn in the first months of extrauterine life are totally dependent on the maternal transfer of DHA mediated first by the placenta and then by breastfeeding. Consequently, it can be affirmed with absolute certainty that DHA, deriving from the maternal metabolism of polyunsaturated fatty acids of the omega-3 series taken from the diet or through a suitable supplement, is essential for correct fetal growth and for accumulation in the brain on the way. of development.
Come per gli studi sui composti del magnesio anche gli studi sugli effetti dell'integrazione della dieta con gli omega 3 in gravidanza hanno dimostrato un promettente prolungamento della gestazione e la prevenzione del parto pretermine. Sebbene non siano ancora perfettamente compresi i meccanismi che legano gli omega 3 con il prolungamento della gestazione, devono essere considerate attentamente le interazioni di tali acidi grassi nei confronti degli enzimi della sintesi degli eicosanoidi e degli eicosanoidi stessi. Uno studio rilevante di Sadovsky et al. ha rivelato che la sintesi di PGE2 aumenta di 2-5 volte nelle donne in prossimità del parto rispetto ai controlli e che sia le PGE2 e sia le PGF2 aumentano nel fluido amniotico durante il parto. Altre evidenze sperimentali hanno indicato che le PG prevalentemente della serie-2 sono implicate nel rilascio del calcio intracellulare a livello del miometrio, evento questo cruciale affinché si verifichi un rapido ed efficiente rilascio dei potenziali di azione cellulare e la generazione sincrona delle contrazioni dello stesso miometrio. Da quanto riferito risulta perciò evidente, come la caratteristica competitiva nei confronti delle PG2 operata dai grassi polinsaturi della serie omega-3 nell’organismo, esplichi efficacemente anche l’effetto di rilassamento uterino che costituisce uno dei principali scopi della presente trovato. As with the studies on magnesium compounds, studies on the effects of dietary supplementation with omega 3s in pregnancy have also shown promising prolongation of gestation and the prevention of preterm birth. Although the mechanisms that bind omega 3 with the prolongation of gestation are not yet fully understood, the interactions of these fatty acids with the enzymes of the synthesis of eicosanoids and of the eicosanoids themselves must be carefully considered. A relevant study by Sadovsky et al. revealed that PGE2 synthesis increases 2-5 times in women near delivery compared to controls and that both PGE2 and PGF2 increase in amniotic fluid during delivery. Other experimental evidences have indicated that PGs predominantly of the series-2 are involved in the release of intracellular calcium at the level of the myometrium, an event that is crucial for a rapid and efficient release of cellular action potentials and the synchronous generation of the contractions of the same. myometrium. From what has been reported it is therefore evident that the competitive characteristic towards PG2 operated by the polyunsaturated fats of the omega-3 series in the organism also effectively exerts the effect of uterine relaxation which constitutes one of the main purposes of the present invention.
Altri vantaggi dell’invenzione risulteranno dalla descrizione particolareggiata di una sua forma di esecuzione esemplificativa e non limitativa, illustrata di seguito. Other advantages of the invention will result from the detailed description of an exemplary and non-limiting embodiment thereof, illustrated below.
Descrizione dell’invenzione Description of the invention
Si vuole sottolineare come nel seguito saranno illustrate, a titolo esemplificativo ma non limitativo, soltanto alcune delle possibili forme di realizzazione della presente invenzione, essendo possibile descriverne molte altre sulla base delle particolari soluzioni individuate. It should be emphasized that in the following, only some of the possible embodiments of the present invention will be illustrated, by way of non-limiting example, since it is possible to describe many others on the basis of the particular solutions identified.
L'applicabilità della formulazione di un innovativo prodotto contenente gli acidi grassi polinsaturi della specie omega-3 in associazione con i composti del magnesio, si riferisce alla somministrazione in una serie di patologie e sindromi riguardanti l’ostetricia e la ginecologia. The applicability of the formulation of an innovative product containing polyunsaturated fatty acids of the omega-3 species in association with magnesium compounds, refers to the administration in a series of pathologies and syndromes concerning obstetrics and gynecology.
In particolare detta formulazione di un innovativo prodotto comprende l'acido eicosapentaenoico EPA, l'acido docosaesaenoico DHA e l'acido α-linolenico ALA singolarmente oppure in combinazione tra loro e in associazione con almeno un composto del magnesio sottoforma di sale e/o di chelato. Una realizzazione particolarmente preferita della presente invenzione comprende specificatamente l’associazione dell'acido docosaesaenoico DHA con il magnesio orotato diidrato. In particular, said formulation of an innovative product comprises eicosapentaenoic acid EPA, docosahexaenoic acid DHA and Î ± -linolenic acid ALA individually or in combination with each other and in association with at least one compound of magnesium in the form of salt and / or of chelate. A particularly preferred embodiment of the present invention specifically comprises the association of docosahexaenoic acid DHA with magnesium orotate dihydrate.
Le caratteristiche farmacologiche dei predetti componenti di detta innovativa formulazione, che come riferito precedentemente e seppur con meccanismi di azione differenti, riguardano la cura e la profilassi di una serie di condizioni fisiologiche e patologiche, ne consentono in sinergia un’eccellente applicabilità nei confronti del parto pretermine, laddove per aborto abituale o ricorrente si intende la condizione in cui una donna va incontro a seguito di due o più aborti consecutivi e quindi non ascrivibili a un evento casuale. The pharmacological characteristics of the aforementioned components of said innovative formulation, which as previously reported and albeit with different mechanisms of action, concern the treatment and prophylaxis of a series of physiological and pathological conditions, allow in synergy an excellent applicability towards the preterm birth, where by habitual or recurrent abortion we mean the condition in which a woman undergoes following two or more consecutive abortions and therefore not attributable to a random event.
Altra effettiva applicabilità della formulazione inventiva oggetto della presente invenzione, che associa l’attività anticontratturante del magnesio a quella PG2-antagonista degli omega 3, si riferisce a tutte quelle condizioni in cui risulta utile mantenere la muscolatura uterina in uno stato di riposo, ovvero utilizzabile nella prevenzione dell’attività contrattile in ostetricia e ginecologia durante le indagini diagnostiche invasive (amniocentesi, villocentesi, ecc.) e dopo l'introduzione del dispositivo intrauterino (IUD). Another effective applicability of the inventive formulation object of the present invention, which associates the anticontracting activity of magnesium with the PG2-antagonist of omega 3, refers to all those conditions in which it is useful to keep the uterine muscles in a state of rest, that is it can be used in the prevention of contractile activity in obstetrics and gynecology during invasive diagnostic investigations (amniocentesis, CVS, etc.) and after the introduction of the intrauterine device (IUD).
Ulteriore effettiva applicabilità della formulazione inventiva, consiste nel trattamento e prevenzione di patologie quali la dismenorrea. In particolare il sinergismo degli acidi grassi con il composto del magnesio à ̈ da raccomandare in quelle patologie caratterizzate da danni vascolari primitivi e/o secondari della microcircolazione uterina (come nel caso dell'abortività ricorrente), o di quella uteroplacentare (come nel caso delle pazienti con precedente anamnestico di preeclampsia ed eclampsia), associati a formazione di microtrombi e/o aggregati anticorpali, ecc. Further effective applicability of the inventive formulation consists in the treatment and prevention of pathologies such as dysmenorrhea. In particular, the synergism of fatty acids with the magnesium compound is to be recommended in those pathologies characterized by primary and / or secondary vascular damage of uterine microcirculation (as in the case of recurrent abortion), or of uteroplacental abortion (as in the case of patients with a previous history of preeclampsia and eclampsia), associated with formation of microthrombi and / or antibody aggregates, etc.
Ulteriore applicabilità di detta formulazione dell'innovativo prodotto si riferisce alla somministrazione a tutte le donne che si trovano nella fase di allattamento al seno. Tale efficace somministrazione risulta dal fatto, come à ̈ stato ampiamente riferito in precedenza, che l’alimentazione materna così come lo sviluppo fetale e prenatale implica un aumentato fabbisogno di tutti i principi nutritivi tra cui il magnesio e gli acidi grassi polinsaturi della serie omega-3. Altresì, un adeguato apporto di detti acidi grassi polinsaturi durante la gravidanza e nei primi mesi di vita à ̈ stato associato a un migliore sviluppo sia morfologico che funzionale e, secondo alcuni Autori, addirittura ad un più alto coefficiente intellettivo nella vita adulta. Considerata la scarsa rappresentazione degli acidi grassi polinsaturi della serie omega-3 nella dieta tipica dei paesi occidentali e dell’insufficiente apporto di magnesio con l’alimentazione, un’integrazione con prodotti tali come la formulazione oggetto della presente invenzione à ̈ pertanto consigliabile a tutte le donne in gravidanza o comunque in tutte coloro che si trovano nella fase di allattamento al seno. Further applicability of said formulation of the innovative product refers to the administration to all women who are in the breastfeeding phase. This effective administration results from the fact, as has been widely reported previously, that maternal nutrition as well as fetal and prenatal development implies an increased need for all nutrients including magnesium and polyunsaturated fatty acids of the series Omega 3. Furthermore, an adequate intake of these polyunsaturated fatty acids during pregnancy and in the first months of life has been associated with a better morphological and functional development and, according to some authors, even with a higher intellectual coefficient in adult life. Considering the scarce representation of polyunsaturated fatty acids of the omega-3 series in the typical diet of Western countries and the insufficient intake of magnesium with the diet, an integration with products such as the formulation object of the present invention is therefore recommended for all pregnant women or in any case in all those who are in the breastfeeding phase.
Altra caratteristica del tutto innovativa della presente invenzione riguarda la via di somministrazione di detto prodotto, contenente in associazione gli acidi grassi polinsaturi della serie omega-3 e i composti di magnesio, caratterizzata per via vaginale ovvero preferibilmente da ovuli vaginali. Another completely innovative feature of the present invention relates to the route of administration of said product, containing in association the polyunsaturated fatty acids of the omega-3 series and the magnesium compounds, characterized by the vaginal route or preferably by vaginal ovules.
Come à ̈ ampiamente noto a coloro che sono esperti della tecnica, detta forma farmaceutica à ̈ destinata a svolgere quasi esclusivamente un'azione locale a livello della mucosa vaginale e dell'utero, comportando degli indiscutibili vantaggi rispetto la via orale, che sono così rappresentati: As is widely known to those skilled in the art, said pharmaceutical form is intended to perform almost exclusively a local action at the level of the vaginal mucosa and uterus, resulting in indisputable advantages over the oral route, which are thus represented:
- possibilità di utilizzare formulazioni a rilascio controllato, che consentono di raggiungere concentrazioni sieriche costanti, evitando le fluttuazioni ormonali giornaliere, - possibility of using controlled release formulations, which allow to reach constant serum concentrations, avoiding daily hormonal fluctuations,
- possibilità di evitare interferenze nel tratto gastrointestinale, - possibility to avoid interference in the gastrointestinal tract,
- possibilità di evitare il fenomeno del primo passaggio epatico e quindi di somministrare il composto a dosi più basse di quelle normalmente richieste per la somministrazione orale, - possibility of avoiding the phenomenon of the first hepatic passage and therefore of administering the compound at doses lower than those normally required for oral administration,
- possibilità di avvantaggiarsi del primo passaggio uterino e quindi di una biodisponibilità migliore. - possibility of taking advantage of the first uterine passage and therefore of a better bioavailability.
Inoltre, un ulteriore vantaggio di detta via di somministrazione vaginale rispetto alle altre consiste nel fatto che i principi attivi raggiungono direttamente l'organo bersaglio anche in caso di vomito e diarrea, condizioni queste frequenti nello stato fisiologico dei soggetti in gravidanza e che vanno a costituire un problema rilevante nel caso di assunzione per via orale a causa dell’assorbimento modificato. Furthermore, a further advantage of said vaginal administration route compared to the others consists in the fact that the active ingredients reach the target organ directly even in case of vomiting and diarrhea, conditions which are frequent in the physiological state of pregnant subjects and which constitute a significant problem in the case of oral intake due to the modified absorption.
Per quanto riguarda la composizione quantitativa di predetta formulazione inventiva somministrata per via vaginale, deve riferirsi che gli intervalli di riferimento delle rispettive concentrazioni per singolo ovulo vaginale sono abbastanza ampi e corrispondenti per quanto riguarda gli acidi grassi polinsaturi della serie omega-3 in un intervallo tra 2,5 g e 0,1 g, più preferibile in un intervallo tra 2,0 g e 0,5 e ancora più preferibilmente tra 1 g e 1,5 g mentre per quanto riguarda i composti del magnesio in un intervallo tra 100 mg e 600 mg, più preferibile in un intervallo tra 200 mg e 500 mg e ancora più preferibilmente tra 300 mg e 400 mg. As regards the quantitative composition of the aforementioned inventive formulation administered vaginally, it should be noted that the reference ranges of the respective concentrations for each single vaginal ovum are quite wide and corresponding as regards the polyunsaturated fatty acids of the omega-3 series in an interval between 2.5 g and 0.1 g, more preferably in a range between 2.0 g and 0.5 and even more preferably between 1 g and 1.5 g while for magnesium compounds in a range between 100 mg and 600 mg , more preferably in a range between 200 mg and 500 mg and even more preferably between 300 mg and 400 mg.
Sebbene questa invenzione sia stata descritta in riferimento alla specifica e concreta realizzazione mostrata nel presente documento, non deve essere considerata limitata ai dettagli indicati e il brevetto deve considerarsi comprensivo delle modifiche e dei cambiamenti che possono derivare dalle seguenti rivendicazioni. Although this invention has been described with reference to the specific and concrete embodiment shown herein, it is not to be considered limited to the details indicated and the patent is to be considered inclusive of the modifications and changes that may arise from the following claims.
Claims (10)
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