ITMI950773A1 - USE OF S-BENZOYLOXYMETHYLTHIAMINE IN THE TREATMENT OF DIABETES MELLITUS - Google Patents
USE OF S-BENZOYLOXYMETHYLTHIAMINE IN THE TREATMENT OF DIABETES MELLITUS Download PDFInfo
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- ITMI950773A1 ITMI950773A1 IT95MI000773A ITMI950773A ITMI950773A1 IT MI950773 A1 ITMI950773 A1 IT MI950773A1 IT 95MI000773 A IT95MI000773 A IT 95MI000773A IT MI950773 A ITMI950773 A IT MI950773A IT MI950773 A1 ITMI950773 A1 IT MI950773A1
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- insulin
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- diabetes mellitus
- thiamine
- diabetes
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Abstract
Si descrive l'uso della S-benzoilossimetiltiamina nel trattamento del diabete mellito, in particolare in pediatra.The use of S-benzoyloxymethyltiamine in the treatment of diabetes mellitus, particularly in pediatricians, is described.
Description
"USO DELLA S-BENZOILOSSIMETILTIAMINA NEL TRATTAMENTO DEL DIABETE MELLITO" "USE OF S-BENZOYLOXYMETHYLTHIAMINE IN THE TREATMENT OF DIABETES MELLITUS"
Campo dell'invenzione Field of the invention
La presente invenzione si riferisce all'uso della S-benzoilossimetiltiamina nel trattamento del diabete mellito, in particolare in pediatria. The present invention relates to the use of S-benzoyloxymethyllamine in the treatment of diabetes mellitus, in particular in pediatrics.
Sfondo dell'invenzione Background of the invention
Nel diabete mellito di tipo 1 si assiste alla distruzione selettiva delle beta cellule su base autoimmune che porta all'inadeguata sintesi di insulina e alla conseguente iperglicemia. Attualmente la diagnosi clinica avviene quando una grande percentuale delle beta cellule è distrutta. Con l'instaurarsi della terapia insulinica si assiste ad una ripresa spontanea della secrezione di insulina, documentata da una maggiore risposta del peptide C al glueagone e dal miglioramento del controllo metabolico del diabete (normali livelli di HfcAlc). In type 1 diabetes mellitus there is selective destruction of beta cells on an autoimmune basis which leads to inadequate insulin synthesis and consequent hyperglycemia. Clinical diagnosis currently occurs when a large percentage of beta cells are destroyed. With the onset of insulin therapy there is a spontaneous resumption of insulin secretion, documented by a greater response of the C peptide to glueagone and by the improvement of the metabolic control of diabetes (normal levels of HfcAlc).
E* noto che la tiamina svolge un ruolo chiave nel metabolismo glicidioo, essendo un oofattore dell'ossidazione degli alfa chetoacidi (piruvico e alfa chetoglutarico).L'ossidazione dell'acido piruvico infatti è essenziale al metabolismo dei carboidrati, mentre 1'ossidazione dell'acido alfa chetoglutarico è uno step limitante il ciclo di Krebs, via finale comune al metabolismo dei carboidrati, grassi e proteine. Studi biochimici su ratti deficienti di tiamina hanno dimostrato ridotti livelli di insulina sia basali sia dopo stimolo con aminoacidi (leucina, arginina) e tolbutamide ed aumentati livelli di glucagone, che ncn venivano soppressi dagli inadeguati livelli di insulina. Questi studi confermano quindi il ruolo della tiamina nel controllo della funzione beta cellulare insulino-secemente. It is known that thiamine plays a key role in glycide metabolism, being a factor in the oxidation of alpha keto acids (pyruvic and alpha ketoglutaric). Alpha ketoglutaric acid is a limiting step in the Krebs cycle, a common final pathway for the metabolism of carbohydrates, fats and proteins. Biochemical studies on thiamine-deficient rats demonstrated reduced insulin levels both at baseline and after stimulation with amino acids (leucine, arginine) and tolbutamide and increased levels of glucagon, which were also suppressed by inadequate insulin levels. These studies therefore confirm the role of thiamine in the control of insulin-secreting beta cell function.
Lo stato nutrizionale della tiamina è stato studiato nel diabete insùlino-dipendente, ma i risultati sano contrastanti, anche perchè legati a diversi metodi di dosaggio. Seno stati descritti sia bassi sia alti livelli di tiamina, questi ultimi dovuti in realtà ad un difetto endogeno della forma attiva di tiamina (tiamina pirofosfato,TPP). The nutritional status of thiamine has been studied in insulin-dependent diabetes, but the results are conflicting, also because they are linked to different dosage methods. Both low and high levels of thiamine have been described, the latter actually due to an endogenous defect of the active form of thiamine (thiamine pyrophosphate, TPP).
Esiste inoltre una sindrome clinica costituita da anemia megaloblastica tiamino-sensibile, diabete mellito e sordità neurosensoriale. I pazienti trattati con tiamina a dosi farmacologiche mostravano miglioramento della concentrazione di peptide C piasmatico ccn una riduzione del fabbisogno insulinico dopo terapia con tiamina. There is also a clinical syndrome consisting of thiamine-sensitive megaloblastic anemia, diabetes mellitus and sensorineural deafness. Patients treated with thiamine at pharmacological doses showed improvement in piasmatic C-peptide concentration with a reduction in insulin requirements after thiamine therapy.
Tuttavia i risultati ncn seno costantemente confortanti ed è stato verificato che una significativa percentuale di pazienti diabetici affetti da anemia megaloblastica tiamino-sensibile (nota anche cerne TRMA, Thiamine-Responsive Megaloblastic Anemia Syndrane) sviluppava diabete tiamino-resistente quando i livelli plasmatici di insulina e peptide C diventavano non rilevàbili; questi pazienti ora sano insùlino-dipendenti.E1 stato anche verificato che in pazienti ncn insiliino-dipendenti il trattamento con tiamina suscita una normale curva piasmatica del glucosio,ma acccnpagnata da una piatta curva dell'insulina e dalla assenza della risposta insulinica di prima fase. However, the results were consistently comforting and it was found that a significant percentage of diabetic patients with thiamine-sensitive megaloblastic anemia (also known as cerne TRMA, Thiamine-Responsive Megaloblastic Anemia Syndrane) developed thiamine-resistant diabetes when plasma levels of insulin and peptide C became undetectable; These patients are now healthy insulin-dependent. It has also been found that in non-insulin-dependent patients, thiamine treatment elicits a normal piasmatic glucose curve, but accompanied by a flat insulin curve and the absence of the first phase insulin response.
Si pone perciò il problema di fornire un trattamento del diabete mellito ti amino-se risibile che eviti l'insorgere di forme di diabete insuline-resistenti. Un altro problema è il trattamento di diabete non insili ino-dipendente tale per cui si abbia una favorevole curva dell'insulina. The problem therefore arises of providing a laughable treatment of amineous diabetes mellitus which avoids the onset of insulin-resistant forms of diabetes. Another problem is the treatment of ino-dependent non-insile diabetes such that there is a favorable insulin curve.
Sonmario dell'invenzione Sonmario of the invention
Sorprendentemente, è stato ora trevato che la benzoilossimetiltiamina è efficace in pazienti diabetici non insùlino-dipendenti e in pazienti affetti da diabete mellito ncn-TRMA. Surprisingly, it has now been found that benzoyloxymethyliamine is effective in non-insulin-dependent diabetic patients and in patients with ncn-TRMA diabetes mellitus.
Un oggetto della presente invenzione è l'uso di benzoilossimetiltiamina e dei suoi sali farmaceuticamente accettabili nella fabbricazione di un medicamento utile nel trattamento del diabete mellito, in particolare in pediatria. An object of the present invention is the use of benzoyloxymethyllamine and its pharmaceutically acceptable salts in the manufacture of a medicament useful in the treatment of diabetes mellitus, in particular in pediatrics.
Un altro oggetto della presente invenzione è l'uso di benzoilossimetiltiamina e dei suoi sali farmaceuticamente accettabili nella fabbricazione di un medicamento utile nel trattamento del diabete noi insùlino-dipendente. Another object of the present invention is the use of benzoyloxymethyllamine and its pharmaceutically acceptable salts in the manufacture of a medicament useful in the treatment of insulin-dependent diabetes.
Descrizione dettagliata dell'invenzione Detailed description of the invention
La presente invenzione ha per oggetto l'uso di benzoilossimetiltiamina o dei suoi sali farmaceuticamente accettabili per la fabbricazione di un medicamento utile per il trattamento del diabete mellito, in particolare in pediatria, sia nella sua forma insulino-dipendente, eventualmente in presenza di gravi sindromi, quali anemia megaloblastica tiamino-sensibile, sindrome DIDMQAD, sordità neurosensoriale, sia nella sua forma non insulino-dipendente. The present invention relates to the use of benzoyloxymethylthiamine or its pharmaceutically acceptable salts for the manufacture of a medicament useful for the treatment of diabetes mellitus, in particular in pediatrics, and in its insulin-dependent form, possibly in the presence of severe syndromes , such as thiamine-sensitive megaloblastic anemia, DIDMQAD syndrome, sensorineural deafness, both in its non-insulin-dependent form.
La benzoi lo ss imet il t iantina, avente la seguente formula Benzoi lo ss imet il tiantina, having the following formula
è utilizzata, da sola o in associazione, cane derivato della vitamina Bl. E' noto il suo utilizzo, ad esempio in associazione con vitamina B6 e/o vitamina B12, in medicamenti utili nella terapia delle nevriti, polinevriti di natura metabolica e tossica, sciatalgie, osteartrosi, periartriti. it is used, alone or in combination, as a derivative of vitamin Bl. Its use is known, for example in association with vitamin B6 and / or vitamin B12, in medicaments useful in the therapy of neuritis, metabolic and toxic polyneuritis, sciatica, osteoarthritis, periarthritis.
La sua preparazione è descritta nella letteratura brevettuale e scientifica; si veda ad esempio il brevetto italiano n. 1,044,232, a nome della richiedente,e i riferimenti ivi citati. Its preparation is described in the patent and scientific literature; see for example the Italian patent n. 1,044,232, in the name of the applicant, and the references cited therein.
Secondo l'invenzione, la benzoilossimetiltiantina può essere utilizzata cane base libera o sotto forma di un suo sale farmaceuticamente accettabile, quale cloridrato, hromidrato, solfato, fosfato, acetato,propicnato, succinato,tartrato,citrato,e così via. According to the invention, benzoyloxymethylthiantine can be used as a free base or in the form of a pharmaceutically acceptable salt thereof, such as hydrochloride, hromhydrate, sulfate, phosphate, acetate, propychnate, succinate, tartrate, citrate, and so on.
In una prima realizzazione della presente invenzione, il medicamento contenente benzoilossimetiltiantina, o un suo sale, come principio attivo, si presenta sotto forma di preparazione orale, quindi capsule, conpresse,soluzioni e sospensioni bevibili, incluse le forme a cessione controllata. In a first embodiment of the present invention, the medicament containing benzoyloxymethylthiantine, or a salt thereof, as an active principle, is in the form of an oral preparation, i.e. capsules, tablets, solutions and drinkable suspensions, including the controlled release forms.
Sono previste anche altre forme di scnministrazione, ad esempio iniettabili oppure forme a cessione progrannata, quali cerotti transdermici o forme inpiantabili sottocute. Other forms of administration are also envisaged, for example injectable or forms with progressive release, such as transdermal patches or subcutaneous implantable forms.
I medicamenti seno preparati secondo tecniche convenzionali note all'esperto del settore,come ad esenpio descritto in "Remingtcn1s Pharmaceutical Sciences Handbook MXVII ed.;Mack Pub. Ine.,N.Y.,U.S.A.. The medicaments prepared according to conventional techniques known to the skilled in the art, as for example described in "Remingtcn1s Pharmaceutical Sciences Handbook MXVII ed.; Mack Pub. Ine., N.Y., U.S.A ..
Le forme di dosaggio saranno meglio determinate dal clinico esperto. A titolo di esenpio, seno previste unità di dosaggio in grado di fornire da 10 a 300 mg/die di principio attivo, in forma divisa o indivisa. Dosage forms will best be determined by the experienced clinician. By way of example, there are dosage units capable of supplying from 10 to 300 mg / day of active principle, in divided or undivided form.
Pazienti diabetici ncn insulino-dipendenti (non TRMA) sono stati trattati con un medicamento secondo l'invenzione e hanno mostrato un netto miglioramento nei livelli di glucosio e della curva di tolleranza del glucosio. Insulin-dependent (non-TRMA) diabetic patients were treated with a medicament according to the invention and showed a marked improvement in the glucose levels and in the glucose tolerance curve.
20 Pazienti di età conpresa tra 0,5 e 18 anni affetti da diabete mellito di tipo 1, con diagnosi di malattia effettuata entro le prime 4 settimane e in terapia con insulina, furono trattati, a partire dal 28® giorno dall'inizio della terapia insulinica, con 50 mg/die di benzoliossimetiltiamina. 20 Patients aged between 0.5 and 18 years with type 1 diabetes mellitus, diagnosed with the disease within the first 4 weeks and on insulin therapy, were treated, starting from day 28 after the start of therapy insulin, with 50 mg / day of benzolyloxymethyliamine.
I pazienti furono amnessi alla prova con il criterio che non dovevano avere assunto alcun preparato vitaminico nei tre mesi precedenti l'esordio del diabete e dovevano essere esenti da qualunque altra malattia cronica.Al tempo 0 furono valutati i parametri classici della patologia,ovvero peso corporeo, fabbisogno giornaliero di insulina, livelli di HhAlc, test di riserva pancreatica beta cellulare (livelli di peptide C). Dopo 6 mesi di terapia una quota significativa di pazienti mostrò un decisivo miglioramento del quadro patologico, in particolare si era ridotto in maniera costante il fabbisogno di insulina. Patients were admitted to the test with the criterion that they must not have taken any vitamin preparations in the three months prior to the onset of diabetes and must be free from any other chronic disease. At time 0, the classical parameters of the disease, i.e. body weight, were evaluated , daily insulin requirement, HhAlc levels, beta cell pancreatic reserve test (C peptide levels). After 6 months of therapy, a significant number of patients showed a decisive improvement in the pathological picture, in particular the need for insulin was constantly reduced.
50 Pazienti in età pediatrica, affetti da diabete non insulino-dipendente, furerò trattati ccn benzoilossimetiltiantina sotto forma di capsule per un dosaggio di 100 mg/die per un periodo di 6 mesi. Alla fine del trattamento,una quota significativa di pazienti risultò nonnoglicemica. 50 Pediatric patients, suffering from non-insulin-dependent diabetes, will be treated with benzoyloxymethylthiantine in the form of capsules for a dosage of 100 mg / day for a period of 6 months. At the end of treatment, a significant proportion of patients were found to be nonnoglycemic.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI950773A IT1273565B (en) | 1995-04-14 | 1995-04-14 | Use of S-benzoyloxymethylthiamine in the treatment of diabetes mellitus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI950773A IT1273565B (en) | 1995-04-14 | 1995-04-14 | Use of S-benzoyloxymethylthiamine in the treatment of diabetes mellitus |
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| Publication Number | Publication Date |
|---|---|
| ITMI950773A0 ITMI950773A0 (en) | 1995-04-14 |
| ITMI950773A1 true ITMI950773A1 (en) | 1996-10-14 |
| IT1273565B IT1273565B (en) | 1997-07-08 |
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| Application Number | Title | Priority Date | Filing Date |
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| ITMI950773A IT1273565B (en) | 1995-04-14 | 1995-04-14 | Use of S-benzoyloxymethylthiamine in the treatment of diabetes mellitus |
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1995
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| IT1273565B (en) | 1997-07-08 |
| ITMI950773A0 (en) | 1995-04-14 |
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