ITRM20120077A1 - NEW USE VITAMIN B1. - Google Patents
NEW USE VITAMIN B1. Download PDFInfo
- Publication number
- ITRM20120077A1 ITRM20120077A1 IT000077A ITRM20120077A ITRM20120077A1 IT RM20120077 A1 ITRM20120077 A1 IT RM20120077A1 IT 000077 A IT000077 A IT 000077A IT RM20120077 A ITRM20120077 A IT RM20120077A IT RM20120077 A1 ITRM20120077 A1 IT RM20120077A1
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- Prior art keywords
- vitamin
- pharmaceutical composition
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- hepatitis
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- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 title claims description 14
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
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Description
"NUOVO USO VITAMINA B1 " "NEW USE VITAMIN B1"
DESCRIZIONE DESCRIPTION
La presente invenzione si riferisce all’uso della vitamina B1 e a composizioni farmaceutiche che la comprendono, nel trattamento della deficienza intracellulare di media gravità della vitamina B1 che è presente nella epatite cronica di tipo c e nel gozzo multinodulare. The present invention refers to the use of vitamin B1 and to pharmaceutical compositions that include it, in the treatment of medium severity intracellular deficiency of vitamin B1 which is present in chronic type c hepatitis and in multinodular goiter.
STATO DELLA TECNICA ANTERIORE STATE OF THE PRIOR ART
L’agente causale dell’epatite cronica di tipo c è un virus a RNA, appartenente alla famiglia dei flavivirus. Oltre al danno epatico i pazienti affetti da epatite cronica c spesso (in circa il 60% dei casi) presentano la seguente sintomatologia: stanchezza (postinfective fatigue), disordini del sonno, depressione, ansia, irritabilità, deficit di memoria, attenzione e concentrazione, dolori muscolari e ai polpacci, talvolta tachicardia, intolleranza al freddo, cute secca. Tutti questi sintomi sono stati sempre attribuiti genericamente all’infezione e al danno epatico. La patogenesi non si è mai conosciuta in dettaglio e non è stata mai trovata una terapia efficace. The causative agent of chronic type c hepatitis is an RNA virus, belonging to the flavivirus family. In addition to liver damage, patients with chronic hepatitis c often (in about 60% of cases) have the following symptoms: fatigue (postinfective fatigue), sleep disorders, depression, anxiety, irritability, memory, attention and concentration deficits, muscle and calf pain, sometimes tachycardia, cold intolerance, dry skin. All these symptoms have always been generically attributed to infection and liver damage. The pathogenesis has never been known in detail and an effective therapy has never been found.
Il gozzo multinodulare è una patologia di cui non si conosce l’eziologia. Prevale nel sesso femminile. I pazienti affetti hanno uno o più noduli all’interno della ghiandola tiroide che causano l’aumento di volume dell’organo. Multinodular goiter is a disease whose etiology is unknown. It prevails in the female sex. Affected patients have one or more nodules within the thyroid gland that cause the organ to increase in volume.
Il gozzo multinodulare è spesso associato a normali livelli di ormoni tiroidei nel sangue ma può associarsi a ipo o ipertiroidismo. Questi pazienti una volta diagnosticati (e curati se necessario) possono avere i seguenti stati ormonali: essere in eutiroidismo spontaneo, in eutiroidismo dovuto a somministrazione di inibitori della sintesi della tiroxina (nei casi di gozzo multinodulare tossico), in eutiroidismo dovuto a somministrazione di tiroxina nei casi di ipotiroidismo (ad esempio dopo tiroidectomia). Questi pazienti, anche in fase cronica e con normali livelli di tiroxina nel sangue hanno stanchezza, disturbi del sonno, depressione, ansia, irritabilità, disturbi cognitivi (deficit di memoria, attenzione e concentrazione), dolori muscolari, aritmie cardiache, intolleranza al freddo, pelle secca. Fino a oggi di questi disturbi, che sono presenti in assenza di deficit ormonali dati i loro normali livelli nel sangue, non si conosce la patogenesi né una terapia efficace. Multinodular goiter is often associated with normal levels of thyroid hormones in the blood but can be associated with hypo or hyperthyroidism. These patients once diagnosed (and treated if necessary) may have the following hormonal states: being in spontaneous euthyroidism, in euthyroidism due to administration of inhibitors of thyroxine synthesis (in cases of toxic multinodular goiter), in euthyroidism due to administration of thyroxine in cases of hypothyroidism (for example after thyroidectomy). These patients, even in the chronic phase and with normal levels of thyroxine in the blood, have fatigue, sleep disturbances, depression, anxiety, irritability, cognitive disorders (memory, attention and concentration deficits), muscle pain, cardiac arrhythmias, cold intolerance, dry skin. To date, the pathogenesis and effective therapy of these disorders, which are present in the absence of hormonal deficiencies given their normal levels in the blood, are unknown.
SOMMARIO DELL’INVENZIONE SUMMARY OF THE INVENTION
La presente invenzione si basa sulla scoperta che i disturbi sopra elencati in entrambe le patologie sono attribuibili a una disfunzione del trasportatore (carrier) che trasporta la vitamina B1 dal sangue all’interno delle cellule di tutti i tessuti. Questi pazienti hanno un normale assorbimento della vitamina B1 nell’intestino tenue, normali livelli di tiamina e tiamina pirofosfato nel sangue e una deficienza di tiamina all’interno delle cellule. Ciò comporta l’insorgenza di tutta la suddetta sintomatologia che è l’espressione clinica di una media deficienza di vitamina B1 intracellulare o, detto in altre parole la manifestazione clinica di un beri beri attenuato. Tale situazione può essere corretta somministrando alte dosi orali o parenterali di vitamina B1. Infatti alle normali concentrazioni di tiamina nel sangue questa viene introdotta nelle cellule solo attraverso un carrier altamente specifico (trasportatore a alta affinità della tiamina). Se questo trasportatore non funziona la vitamina B1 non entra nelle cellule nella quantità necessaria e insorgono i sintomi della carenza. Invece quando il livello ematico della vitamina è alto a seguito della somministrazione di alte dosi orali o parenterali, questa passa per diffusione passiva all’interno delle cellule ripristinando qui una normale concentrazione e un normale metabolismo del glucosio. Il ripristino della funzionalità degli enzimi mitocondriali comporta una buona ripresa funzionale dei processi energetici, una buona produzione di energia derivante dall’ossidazione del glucosio e una pressoché completa regressione dei sintomi della carenza intracellulare della tiamina. La regressione dei sintomi dopo terapia è la prova diagnostica fondamentale per la presenza di una deficienza di tiamina. The present invention is based on the discovery that the disorders listed above in both pathologies are attributable to a dysfunction of the transporter (carrier) that transports vitamin B1 from the blood into the cells of all tissues. These patients have normal absorption of vitamin B1 in the small intestine, normal levels of thiamine and thiamine pyrophosphate in the blood and a deficiency of thiamine within the cells. This involves the onset of all the aforementioned symptoms which are the clinical expression of a medium deficiency of intracellular vitamin B1 or, in other words, the clinical manifestation of an attenuated beriberi. This situation can be corrected by administering high oral or parenteral doses of vitamin B1. In fact, at normal concentrations of thiamine in the blood, this is introduced into the cells only through a highly specific carrier (high affinity transporter of thiamine). If this transporter fails, vitamin B1 does not enter the cells in the necessary quantity and symptoms of deficiency arise. On the other hand, when the blood level of the vitamin is high following the administration of high oral or parenteral doses, it passes by passive diffusion within the cells, restoring normal glucose concentration and metabolism here. Restoring the functionality of mitochondrial enzymes involves a good functional recovery of energy processes, good energy production resulting from the oxidation of glucose and an almost complete regression of the symptoms of intracellular thiamine deficiency. Regression of symptoms after therapy is the fundamental diagnostic test for the presence of a thiamine deficiency.
Per chiarire meglio il concetto di disfunzione del trasporto intracellulare della vitamina B1 è necessario esporre più in dettaglio la patologia da carenza di vitamina B1. To better clarify the concept of dysfunction of the intracellular transport of vitamin B1 it is necessary to expose the pathology of vitamin B1 deficiency in more detail.
La carenza di tiamina nella dieta causa una sindrome classica, il beri beri primario. Esiste anche un beri beri, detto secondario, dovuto a malassorbimento (malattie intestinali) e uno dovuto a aumentate richieste da parte dell’organismo (gravidanza, ipertiroidismo). Il beri beri è stato anche classificato a seconda degli organi che di volta in volta sono i più colpiti: umido (cuore), secco (sistema nervoso periferico), e sindrome di Wernicke-Korsakoff (sistema nervoso centrale). Il beri beri franco e la sindrome di Wernicke-Korsakoff mostrano sintomi molto evidenti e subito riferibili a una carenza di vitamina B1 . Le forme più o meno attenuate di beri beri sono meno conosciute e i sintomi sono attribuiti ad altre patologie. Dietary thiamine deficiency causes a classic syndrome, primary beriberi. There is also a beriberi, called secondary, due to malabsorption (intestinal diseases) and one due to increased demands on the part of the body (pregnancy, hyperthyroidism). Beriberi has also been classified according to the organs that are most affected from time to time: wet (heart), dry (peripheral nervous system), and Wernicke-Korsakoff syndrome (central nervous system). Beriberi franco and Wernicke-Korsakoff syndrome show very evident symptoms and immediately referable to a vitamin B1 deficiency. The more or less attenuated forms of beriberi are less well known and the symptoms are attributed to other pathologies.
L’Organizzazione Mondiale della Sanità i sintomi della deficienza di tiamina di media gravità sono vaghi e spesso attribuiti a altri problemi, per cui la diagnosi è difficile. Inoltre anche quando diagnosticata l’Organizzazione Mondiale della Sanità indica che la somministrazione di vitamina B1 , anche a basse dosi, risolve la patologia, Esistono inoltre patologie denominate malattie del trasportatore della tiamina (thiamine transporter diseases, 42 casi circa in letteratura) in cui è presente una mutazione dei geni che codificano la sintesi del carrier (higthy affinity thiamine transporter). Il gene alterato non codifica un trasportatore efficiente e quindi la tiamina non entra facilmente nelle cellule. Si verifica quindi che la tiamina ha normali livelli nel sangue mentre dentro le cellule è mancante dando origine a una sintomatologia da deficienza di tiamina che si può solo curare con alte dosi di vitamina B1 , in quanto non funzionando il trasporto attivo mediante carrier , solo il trasporto passivo dovuto alle alte concentrazioni ematiche può portare la vitamina dentro le cellule. Nel caso dell’epatite c e del gozzo multi nodulare la patogenesi analoga non è dipendente da precise mutazioni genetiche ma verosimilmente da fattori infiammatorio-immunitari. Un primo oggetto della presente invenzione è la Vitamina B1 per uso nel trattamento dei sintomi associati alla disfunzione del trasporto intracellulare della vitamina B1 in pazienti affetti da epatite c o da gozzo multi nodulare. The World Health Organization symptoms of medium-severity thiamine deficiency are vague and often attributed to other problems, making diagnosis difficult. Furthermore, even when diagnosed, the World Health Organization indicates that the administration of vitamin B1, even at low doses, resolves the disease. present a mutation of the genes that encode the synthesis of the carrier (higthy affinity thiamine transporter). The altered gene does not encode an efficient transporter and therefore thiamine does not easily enter cells. It therefore occurs that thiamine has normal levels in the blood while inside the cells it is missing, giving rise to a thiamine deficiency symptomatology that can only be treated with high doses of vitamin B1, as the active transport by carrier does not work, only the passive transport due to high blood concentrations can carry the vitamin into cells. In the case of hepatitis c and multi-nodular goiter, the similar pathogenesis is not dependent on specific genetic mutations but probably on inflammatory-immune factors. A first object of the present invention is Vitamin B1 for use in the treatment of symptoms associated with the dysfunction of the intracellular transport of vitamin B1 in patients with hepatitis C or with multi-nodular goiter.
Un ulteriore oggetto della presente invenzione è una composizione farmaceutica comprendente vitamina B1 e uno o più eccipienti farmacologicamente accettabili per uso nel trattamento dei sintomi associati alla disfunzione del trasporto intracellulare della vitamina B1 in pazienti affetti da epatite c o da gozzo multinodulare. A further object of the present invention is a pharmaceutical composition comprising vitamin B1 and one or more pharmacologically acceptable excipients for use in the treatment of symptoms associated with the dysfunction of the intracellular transport of vitamin B1 in patients suffering from hepatitis C or from multinodular goiter.
I vantaggi, caratteristiche e le modalità di impiego della presente invenzione risulteranno evidenti dalla seguente descrizione dettagliata di alcune forme di realizzazione, presentate a scopo esemplificativo e non limitativo. The advantages, characteristics and methods of use of the present invention will become evident from the following detailed description of some embodiments, presented by way of example and not of limitation.
DESCRIZIONE DETTAGLIATA DELL'INVENZIONE DETAILED DESCRIPTION OF THE INVENTION
Secondo la presente invenzione la vitamina B1 è somministrata a pazienti affetti da epatite c o da gozzo multinodulare per il trattamento di uno o più dei seguenti sintomi stanchezza cronica, disturbi del sonno, depressione, ansia, irritabilità, deficit cognitivi, dolori muscolari, aritmie cardiache, intolleranza al freddo, cute secca. According to the present invention, vitamin B1 is administered to patients suffering from hepatitis C or multinodular goiter for the treatment of one or more of the following symptoms of chronic fatigue, sleep disturbances, depression, anxiety, irritability, cognitive deficits, muscle pain, cardiac arrhythmias, cold intolerance, dry skin.
I pazienti affetti da gozzo multinodulare da trattare potranno essere ad esempio pazienti affetti da gozzo multinodulare da eutiroidismo spontaneo o farmacologico che presentano una sintomatologia quale stanchezza, disturbi del sonno, depressione, ansia, irritabilità, deficit di memoria, di attenzione e concentrazione, dolori muscolari, aritmie cardiache, intolleranza al freddo, cute secca. Patients with multinodular goiter to be treated may be, for example, patients with multinodular goiter from spontaneous or pharmacological euthyroidism who present symptoms such as fatigue, sleep disturbances, depression, anxiety, irritability, memory, attention and concentration deficits, muscle pain , cardiac arrhythmias, cold intolerance, dry skin.
Nella presente descrizione con l’espressione “pazienti affetti da epatite c” s’intendono tutti i pazienti infettati dal virus dell'epatite C, in particolare i pazienti in cui l’epatite si cronicizza. Pazienti con epatite cronica mostrano uno o più dei seguenti sintomi stanchezza cronica, disturbi del sonno, depressione, ansia, irritabilità, deficit cognitivi, dolori muscolari, aritmie cardiache, intolleranza al freddo, cute secca. In this description, the expression "patients with hepatitis C" means all patients infected with the hepatitis C virus, in particular patients in whom hepatitis becomes chronic. Chronic hepatitis patients show one or more of the following symptoms chronic fatigue, sleep disturbance, depression, anxiety, irritability, cognitive impairment, muscle aches, cardiac arrhythmias, cold intolerance, dry skin.
La vitamina B1 potrà essere somministrata in funzione dell’età e delle condizioni generali del paziente, della natura e della gravità della patologia o disturbo e della via e tipo di somministrazione. Il dosaggio dovrà quindi tener conto, della particolare condizione da trattare, della severità della condizione da trattare, dell’età, del peso e delle condizioni fisiche generali del particolare paziente. Inoltre, è evidente che le quantità efficaci possono essere all’occorrenza abbassate o aumentate secondo le risposte del paziente trattato e/o secondo la valutazione del medico. Vitamin B1 can be administered according to the age and general condition of the patient, the nature and severity of the disease or disorder and the route and type of administration. The dosage must therefore take into account the particular condition to be treated, the severity of the condition to be treated, the age, weight and general physical condition of the particular patient. Furthermore, it is clear that the effective quantities can be lowered or increased if necessary according to the responses of the patient being treated and / or according to the doctor's evaluation.
In una forma di realizzazione la vitamina B1 potrà essere somministrata per via orale con un dosaggio unitario di vitamina B1 di almeno 600 mg, preferibilmente compreso tra 600 e 1800 mg al giorno per pazienti donna e tra 1200-2400 mg per pazienti uomini, oppure con una somministrazione intramuscolare di almeno 100 mg. Il regime di dosaggio potrà essere ad esempio per una somministrazione orale di almeno 600 mg al giorno per almeno una settimana o oppure con una somministrazione intramuscolare di almeno 100 mg una volta a settimana. In one embodiment, vitamin B1 can be administered orally with a unit dosage of vitamin B1 of at least 600 mg, preferably between 600 and 1800 mg per day for female patients and between 1200-2400 mg for male patients, or with an intramuscular administration of at least 100 mg. The dosage regimen may be for example for an oral administration of at least 600 mg per day for at least a week or or with an intramuscular administration of at least 100 mg once a week.
La sperimentazione clinica riportata negli esempi ha evidenziato che la forte riduzione o totale eliminazione dei sintomi associati alla disfunzione del trasporto intracellulare della vitamina B1 in pazienti affetti da epatite c o da gozzo multinodulare è ottenuta con i regimi di dosaggio sopra descritti. The clinical trial reported in the examples showed that the strong reduction or total elimination of symptoms associated with the dysfunction of the intracellular transport of vitamin B1 in patients with hepatitis c or with multinodular goiter is obtained with the dosage regimens described above.
Sono oggetto della presente invenzione anche composizione farmaceutiche e uno o più eccipienti farmacologicamente accettabili dei sintomi associati alla disfunzione del trasporto intracellulare della vitamina B1 in pazienti affetti da epatite c o da gozzo multi nodulare. Also object of the present invention are pharmaceutical compositions and one or more pharmacologically acceptable excipients of the symptoms associated with the dysfunction of the intracellular transport of vitamin B1 in patients suffering from hepatitis C or from multi-nodular goiter.
Tipicamente dette composizioni possono contenere una quantità di vitamina B1 compresa 100 e 150 mg per unità di dosaggio o in forma solida per somministrazione orale e detta vitamina B1 è in una quantità compresa tra 600 e 1800 mg per unità di dosaggio. Typically, said compositions can contain an amount of vitamin B1 ranging from 100 to 150 mg per dosage unit or in solid form for oral administration and said vitamin B1 is in an amount ranging from 600 to 1800 mg per dosage unit.
Con il termine unità di dosaggio s’intende nella presente descrizione la formulazione unitaria per una singola somministrazione, ad esempio una compressa, capsula, una fiala per iniezione, ecc. In this description, the term dosage unit refers to the unit formulation for a single administration, for example a tablet, capsule, vial for injection, etc.
Per dosaggio unitario s’intende nella presente descrizione la quantità di principio attivo per una singola somministrazione. By unit dosage we mean in this description the amount of active ingredient for a single administration.
Le composizioni farmaceutiche secondo la presente invenzione possono essere formulate in una varietà di modi che dipendono dalla via di somministrazione prescelta. Secondo una specifica forma di realizzazione dell’invenzione, la composizione farmaceutica è idonea alla somministrazione orale di forme solide e può includere forme quali capsule, compresse, pillole, polveri e granuli. In queste forme solide la vitamina B1 può essere miscelata con uno o più eccipienti inerti, farmaceuticamente accettabili. Tali eccipienti possono essere scelti fra quelli normalmente noti nello stato dell’arte e includono, ma non sono ad essi limitati : a) carrier, quali citrato di sodio e calcio fosfato, b) filler quali amido, lattosio, cellulosa microcristallina, saccarosio, glucosio, mannitolo e silice colloidale, c) umettanti, quali il glicerolo, d) agenti disintegranti, quali alginati, carbonato di calcio, amidi, derivati dell’amido, della cellulosa e del polivinilpirrolidone, silicati e carbonato di sodio e) leganti quali carbossimetilcellulosa, alginati, gelatina, polivinilpirrolidone, saccarosio, derivati polimerici della cellulosa, derivati dell’amido f) agenti ritardanti quali paraffina, polimeri della cellulosa, esteri degli acidi grassi g) accelleratori dell’assorbimento, quali composti di ammonio quaternario, h) agenti bagnanti e tensioattivi quali alcool cetilico e glicerolo monostearato, i) adsorbenti, quali argille bentoniche e caolino, k) lubrificanti quali talco, stearato di calcio, stearato di magnesio, glicol polietilenico, sodio lauril solfato, sodio stearilfumarato j) glidanti quali talco, silice colloidale. The pharmaceutical compositions according to the present invention can be formulated in a variety of ways which depend on the chosen route of administration. According to a specific embodiment of the invention, the pharmaceutical composition is suitable for oral administration of solid forms and can include forms such as capsules, tablets, pills, powders and granules. In these solid forms, vitamin B1 can be mixed with one or more inert, pharmaceutically acceptable excipients. These excipients can be selected from those normally known in the state of the art and include, but are not limited to: a) carriers, such as sodium citrate and calcium phosphate, b) fillers such as starch, lactose, microcrystalline cellulose, sucrose, glucose , mannitol and colloidal silica, c) humectants, such as glycerol, d) disintegrating agents, such as alginates, calcium carbonate, starches, starch, cellulose and polyvinylpyrrolidone derivatives, silicates and sodium carbonate e) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, polymeric derivatives of cellulose, starch derivatives f) retardants such as paraffin, cellulose polymers, fatty acid esters g) absorption accelerators, such as quaternary ammonium compounds, h) wetting agents and surfactants such as cetyl alcohol and glycerol monostearate, i) adsorbents, such as benthic clays and kaolin, k) lubricants such as talc, calcium stearate, stea magnesium rate, polyethylene glycol, sodium lauryl sulfate, sodium stearyl fumarate j) glidants such as talc, colloidal silica.
Le forme di dosaggio solido, quali compresse, capsule, pillole e granuli, possono essere rivestite con rivestimenti enterici, gastrici o di altro tipo ben noto nello stato dell’arte. Esse possono contenere agenti opacizzanti e possono essere del tipo da permettere il rilascio degli ingredienti attivi soltanto o preferibilmente in un certo tratto dell’intestino, eventualmente, in modo ritardato. Sostanze che possono permettere tale uso ritardato includono, ma non sono ad esse limitate, polimeri e cere. The solid dosage forms, such as tablets, capsules, pills and granules, can be coated with enteric, gastric or other coatings well known in the state of the art. They may contain opacifying agents and may be of the type to allow the release of the active ingredients only or preferably in a certain tract of the intestine, possibly in a delayed manner. Substances which may permit such delayed use include, but are not limited to, polymers and waxes.
Forme liquide adatte ad una somministrazione orale sono emulsioni, soluzioni, sospensioni preparate o estemporanee, sciroppi e elisir. Eccipienti adatti alle formulazioni secondo la presente invenzione in forme liquide ad uso orale includono, ma non sono ad essi limitati, diluenti comunemente usati nell’arte, quali acqua o altri solventi, agenti solubilizzanti e emulsificanti scelti fra alcool etilico, polialcoli, glicol propilenico, glicerolo, polietilenglicol e sorbitan esteri. Queste formulazioni possono anche contenere dolcificanti e aromi scelti fra quelli ben noti nello stato dell’arte. Liquid forms suitable for oral administration are emulsions, solutions, prepared or extemporaneous suspensions, syrups and elixirs. Excipients suitable for the formulations according to the present invention in liquid forms for oral use include, but are not limited to them, diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers selected from ethyl alcohol, polyalcohols, propylene glycol, glycerol, polyethylene glycol and sorbitan esters. These formulations may also contain sweeteners and flavors selected from those well known in the state of the art.
Composizioni adatte per iniezioni parenterali (preferibilmente intramuscolari) farmaceuticamente accettabili possono comprendere soluzioni acquose sterili, dispersioni, sospensioni o emulsioni o polveri sterili per una ricostituzione in soluzioni o dispersioni iniettabili; esempi di eccipienti adatti a queste includono, ma non sono ad essi limitati, carrier acquosi o non acquosi, diluenti, solventi o veicoli scelti fra: acqua, etanolo, polioli (glicol propilenico o polietilenico, glicerolo e simili), polialcoli, alcool isopropilico, etil acetato, benzil alcool, benzoato di benzile, glicol propilenico, glicol 1 .3-butilenico, dimetilformammide, olii vegetali (in particolare di oliva, cotone, arachide, mais, germe di grano, oliva, ricino, sesamo), esteri organici quali etile oleato o simili. Queste composizioni possono anche contenere dei conservanti del tipo antibatterico o antifungino, scelti, ma non esclusivamente, tra: parabenzoato, clorbutanolo, fenolo, acido ascorbico e simili. Può essere anche utile includere un agente isotonico, per esempio, uno zucchero, cloruro di sodio o simili. Inoltre si possono ottenere delle forme farmaceutiche ad assorbimento ritardato con agenti quali, per esempio, ma non esclusivamente, alluminio monostearato e gelatina. Compositions suitable for pharmaceutically acceptable parenteral (preferably intramuscular) injections may comprise sterile aqueous solutions, dispersions, suspensions or emulsions or sterile powders for reconstitution into injectable solutions or dispersions; Examples of excipients suitable for these include, but are not limited to, aqueous or non-aqueous carriers, diluents, solvents or vehicles selected from: water, ethanol, polyols (propylene or polyethylene glycol, glycerol and the like), polyalcohols, isopropyl alcohol, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 .3-butylene glycol, dimethylformamide, vegetable oils (especially olive, cotton, peanut, corn, wheat germ, olive, castor, sesame), organic esters such as ethyl oleate or the like. These compositions can also contain preservatives of the antibacterial or antifungal type, selected, but not exclusively, from: parabenzoate, chlorbutanol, phenol, ascorbic acid and the like. It may also be useful to include an isotonic agent, for example, a sugar, sodium chloride or the like. Furthermore, it is possible to obtain pharmaceutical forms with delayed absorption with agents such as, for example, but not exclusively, aluminum monostearate and gelatin.
Si possono anche preparare formulazioni a lento rilascio mediante le tecniche ed i prodotti ben noti nello stato dell’arte. It is also possible to prepare slow-release formulations using techniques and products well known in the state of the art.
Sono di seguito riportati esperimenti ed esempi che hanno lo scopo di illustrare meglio quanto riportato nella presente descrizione, tali esempi non sono in alcun modo da considerare come una limitazione della precedente descrizione e delle successive rivendicazioni. Experiments and examples are reported below which have the purpose of better illustrating what is reported in the present description, these examples are in no way to be considered as a limitation of the previous description and subsequent claims.
ESEMPI EXAMPLES
Sperimentazione Experimentation
Di seguito è riportata la sperimentazione clinica che dimostra l'attività della vitamina B1 secondo l'invenzione. The clinical trial demonstrating the activity of vitamin B1 according to the invention is reported below.
Tutti i pazienti sottoposti alla terapia (sia quelli affetti da gozzo multinodulare che quelli afffetti da epatite C) accusavano i sintomi descritti precedentemente di una carenza di vitamina B1 fin dall’inizio della malattia, a varia intensità. L’effetto terapeutico ottenuto con la somministrazione della vitamina B1 è stato valutato mediante il test standard della scala FSS (fatigue severità scale) in quanto la stanchezza è il sintomo guida della carenza di tiamina. Prima della terapia i punteggi delle scala davano come risultato una stanchezza di grado severo nel 45% dei casi, di grado medio nel restante 55%. Con una dettagliata anamnesi si sono raccolti anche i risultati ottenuti per gli altri sintomi. All patients undergoing therapy (both those suffering from multinodular goiter and those suffering from hepatitis C) accused the symptoms described above of a vitamin B1 deficiency from the onset of the disease, to varying degrees. The therapeutic effect obtained with the administration of vitamin B1 was evaluated using the standard test of the FSS scale (fatigue severity scale) as fatigue is the guiding symptom of thiamine deficiency. Before therapy, the scores on the scale resulted in severe fatigue in 45% of cases, and moderate in the remaining 55%. The results obtained for the other symptoms were also collected with a detailed anamnesis.
I pazienti affetti da gozzo multi nodulare reclutati nella sperimentazione erano tutte donne (12), quelli con epatite cronica c una donna e due uomini. Hanno assunto una terapia per bocca variabile da 600 a 1550 mg al giorno per 20 giorni, con completa regressione della sintomatologia in soli tre quattro giorni nelle pazienti con gozzo multinodulare. Nei tre pazienti con epatite c (uno dei quali trattato con 1 fiala da 100 mg intramuscolo a settimana hanno mostrato un miglioramento evidente dopo una/due settimane o dopo due mesi di terapia. In tutti i pazienti sono pressoché completamente regrediti tutti i sintomi riferibili alla carenza di vitamina B1. The patients with multi-nodular goiter recruited in the trial were all women (12), those with chronic hepatitis c one woman and two men. They took oral therapy ranging from 600 to 1550 mg per day for 20 days, with complete regression of symptoms in just three to four days in patients with multinodular goiter. In the three patients with hepatitis c (one of whom treated with 1 vial of 100 mg intramuscularly per week, they showed an evident improvement after one / two weeks or after two months of therapy. vitamin B1 deficiency.
Determinazione della concentrazione di vitamina B1 nel plasma Determination of the concentration of vitamin B1 in plasma
Tutti i pazienti prima del trattamento mostravano valori di vitamina B1 nel plasma ampiamente nella norma suggerendo che non fosse necessario una somministrazione di vitamina B1. All patients prior to treatment showed plasma vitamin B1 values well within normal range suggesting that no vitamin B1 administration was necessary.
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| IT000077A ITRM20120077A1 (en) | 2012-03-01 | 2012-03-01 | NEW USE VITAMIN B1. |
| PCT/IB2012/051820 WO2012147003A1 (en) | 2011-04-27 | 2012-04-13 | Vitamin b1 for treatment of chronic fatigue |
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| IT000077A ITRM20120077A1 (en) | 2012-03-01 | 2012-03-01 | NEW USE VITAMIN B1. |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2189160A1 (en) * | 2007-09-19 | 2010-05-26 | Suntory Holdings Limited | Composition comprising sesamin component and vitamin b1 component |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2189160A1 (en) * | 2007-09-19 | 2010-05-26 | Suntory Holdings Limited | Composition comprising sesamin component and vitamin b1 component |
Non-Patent Citations (5)
| Title |
|---|
| ANONYMOUS: "Benerva", 1 July 2010 (2010-07-01), pages 1 - 6, XP007919626, Retrieved from the Internet <URL:http://www.torrinomedica.it/farmaci/schedetecniche/benerva.asp> [retrieved on 20111025] * |
| ANONYMOUS: "Betabion Ampullen", February 2010 (2010-02-01), XP002682635, Retrieved from the Internet <URL:http://www.fachinfo.de/data/fi/jsearch?wirkstoff> [retrieved on 20120830] * |
| ANONYMOUS: "Vitamine del gruppo B", 29 December 2010 (2010-12-29), pages 1 - 9, XP002682633, Retrieved from the Internet <URL:http://www.medicinaecologica.it/Vitamina%20B.htm> [retrieved on 20120830] * |
| DR ANTONIO COSTANTINI: "Stanchezza Generale", INTERNET CITATION, 4 January 2011 (2011-01-04), pages 1 - 2, XP007919625, Retrieved from the Internet <URL:http://www.medicitalia.it/consulti/Medicina-generale/189285/Stanchezza-generale> [retrieved on 20111025] * |
| MERCK & CO.: "The Merck Manual of Diagnosis and Therapy", 2006, MERCK RESEARCH LABORATORIES, USA, article "Thiamin", XP002682634 * |
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