WO2012147003A1 - Vitamin b1 for treatment of chronic fatigue - Google Patents

Vitamin b1 for treatment of chronic fatigue Download PDF

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Publication number
WO2012147003A1
WO2012147003A1 PCT/IB2012/051820 IB2012051820W WO2012147003A1 WO 2012147003 A1 WO2012147003 A1 WO 2012147003A1 IB 2012051820 W IB2012051820 W IB 2012051820W WO 2012147003 A1 WO2012147003 A1 WO 2012147003A1
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Prior art keywords
disease
vitamin b1
chronic fatigue
dosage
treatment
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PCT/IB2012/051820
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French (fr)
Inventor
Antonio COSTANTINI
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Costantini Antonio
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Priority to IT000216A priority Critical patent/ITRM20110216A1/en
Priority to ITRM2011A000216 priority
Priority to ITRM2011A000283 priority
Priority to IT000283A priority patent/ITRM20110283A1/en
Priority to ITRM2012A000077 priority
Priority to ITRM20120077 priority patent/ITRM20120077A1/en
Application filed by Costantini Antonio filed Critical Costantini Antonio
Publication of WO2012147003A1 publication Critical patent/WO2012147003A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51Thiamines, e.g. vitamin B1

Abstract

The present invention refers to the use of vitamin B1 and to pharmaceutical compositions comprising it, in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, from multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, Crohn's disease, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis. The present invention also refers to the treatment of chronic fatigue in association with other symptoms, such as depression, sleep disturbances, anxiety, irritability, cognitive impairment, muscle pain, cardiac arrhytmias, cold intolerance, in patients suffering from the aforesaid diseases.

Description

NEW USE OF VITAMIN B1

DESCRIPTION

The present invention refers to the use of vitamin B1 and to pharmaceutical compositions comprising it, in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, from multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis. The present invention also refers to the treatment of chronic fatigue in association with other symptoms such as depression, sleep disturbances, anxiety, irritability, attention, concentration and memory impairment, muscle pain, cardiac arrhytmias, cold intolerance, in patients suffering from said diseases.

STATE OF THE PRIOR ART

Patients suffering from multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, have, with variable percentages ranging from 50 to 95%, a series of symptoms whose pathogenesis is almost unknown. Such symptoms are, e.g., chronic fatigue, sleep disturbances, mood alterations, anxiety, irritability, cognitive disorders, muscle pain, cardiac arrhytmias, cold intolerance. Chronic fatigue is the symptom appearing in a higher percentage in patients suffering from these diseases, and its pathogenesis is unknown. In the state of the art no effective therapy exists for the treatment of chronic fatigue associated with these diseases.

SUMMARY OF THE INVENTION

The present invention is based on the discovery that chronic fatigue associated with multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, can be cured by administering high doses of vitamin B1 (thiamine).

While not wishing to bound the present invention to a specific mechanism, on the basis of the studies reported herein, it can be hypothesized that chronic fatigue, and other disorders associated thereto, such as, e.g., sleep disturbances, depression, anxiety, cognitive impairment, muscle pain, cardiac arrhytmias, cold intolerance, in all of the above-listed pathologies, be due to a dysfunction of active transport of vitamin B1 from blood to mitochondria, or to a structural alteration of the enzymes which have as coenzyme the vitamin B1 and are fundamental for the oxidative metabolism of glucose. It can be hypothesized that the possible dysfunction of active transport of vitamin B1 from blood to mitochondria might lie at the level of high-affinity thiamine carriers, or at the level of the cytoskeleton .

In fact, patients suffering from the above-listed diseases have a normal absorption of vitamin B1 in the small intestine, normal levels of thiamine and thiamine pyrophosphate in blood (i.e., lack of vitamin B1 is not of nutritional origin) and thiamine deficiency in the cells. This entails the onset of all the aforesaid symptomatology, which is the clinical expression of an average deficiency of intracellular vitamin B1. This situation can be corrected by administering high oral or parenteral doses of vitamin B1. In fact, at normal thiamine concentrations in blood , the former is introduced in cells only through a highly specific carrier, carrying the vitamin into the cytoskeleton and then arriving to the mitochondria, where it binds to the enzymatic structures present in these organelles, which are fundamental for oxidative metabolism of glucose. When in these structures there are alterations somehow hindering the normal carrying-metabolism of the vitamin, the deficiency symptomatology onsets with the hereto-described symptoms, of which the most emphasized is chronic fatigue. Instead, when the blood level of the vitamin is high, following administration of high oral or parenteral doses, the vitamin can pass inside cells by passive diffusion, therefore restoring a normal concentration of the vitamin inside the cell and a normal metabolism of glucose. The restoring of mitochondrial enzymes functionality entails a good functional recovery of the energetic processes, a good production of energy deriving from glucose oxidation and a nearly complete regression of symptoms of intracellular lack of thiamine. Regression of symptoms after therapy with high doses of vitamin B1 is the fundamental diagnostic proof for the presence of thiamine deficiency.

Objects of the present invention are:

Vitamin B1 for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein vitamin B1 is administered orally with a dosage of at least 600 mg per day.

Vitamin B1 for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, from multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein said vitamin B1 is administered intramuscularly with a dosage of at least 50 mg once every three days or four days.

A pharmaceutical composition comprising vitamin B1 and one or more pharmacologically acceptable excipients for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein vitamin B1 is administered orally with a dosage of at least 600 mg per day.

A pharmaceutical composition comprising vitamin B1 and one or more pharmacologically acceptable excipients for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein vitamin B1 is administered intramuscularly with a dosage of at least 50 mg once every three days or four days.

The advantages, features and the modes of use of the present invention will be made evident in the following detailed description of some embodiments thereof, given by way of example and not for limitative purposes.

DETAILED DESCRIPTION OF THE INVENTION

According to the present invention, vitamin B1 is administered to patients suffering from at least one of the following pathologies: multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, for the treatment of chronic fatigue. Vitamin B1 could be administered orally, with a dosage of at least 600 mg per day, or intramuscularly, with a dosage of at least 50 mg every three or four days.

Chronic fatigue associated with these diseases could appear with other symptoms, such as sleep disturbances, depression, anxiety, irritability, cognitive impairment, muscle pain, cardiac arrhytmias, cold intolerance, dry skin.

In an embodiment, vitamin B1 could be administered orally with a dosage comprised between 600 and 1800 mg per day for female patients and between 1200-2400 mg for male patients, or could be administered intramuscularly with a dosage comprised between 50 and 150 mg every three or four days, preferably 100 mg every five or seven days.

In an embodiment, vitamin B1 could be administered orally with a dosage comprised between 600 and 900 mg per day for patients with a weight lower than 60 Kg, and between 1000 and 2400 mg for patients with a weight higher than 60 Kg.

Vitamin B1 according to the aforesaid dosages could be used for treating chronic fatigue associated with some among chronic inflammatory-autoimmune diseases such as ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, multiple sclerosis.

Inflammatory-autoimmune diseases are pathologies in which the immune system produces autoantibodies directed against an endogenous antigen, with the entailed tissue damage. As a rule, an organ or an apparatus is characteristically affected. Treatment of autoimmune diseases generally envisages immunosuppressive drugs which reduce the immune response. In most cases, however, these treatments are not decisive.

Vitamin B1 according to the above-mentioned dosages could be used for treating chronic fatigue associated with celiac disease. Celiac disease (also known as gluten-sensitive enteropathy) is an affection onsetting in genetically susceptible subjects as a consequence of the ingestion of gluten, which behaves as toxic agent for the intestinal mucosa, causing the specific symptoms of the disease itself. With individuals suffering from celiac disease, very often a chronic fatigue is associated which further complicates the person's pathological state.

Chronic fatigue is also associated with many patients suffering from nervous system diseases, such as Parkinson's disease, and in patients struck by cerebrovascular diseases such as stroke or any other cerebral alteration deriving from a pathological process of the blood vessels of the nervous system.

The causal agent of chronic hepatitis C is an RNA virus, belonging to the flavivirus family. Besides hepatic damage, patients suffering from chronic hepatitis C often (in about 60% of the cases) have the following symptomatology: chronic fatigue (postinfective fatigue), sleep disorders, depression, anxiety, irritability, memory, attention and concentration impairment, muscle pain and calf pain, occasionally tachycardia, cold intolerance, dry skin. All these symptoms have always been generically attributed to infection and hepatic damage. Their pathogenesis has never been known in detail, and an effective therapy has never been found.

Multinodular goiter is a pathology of unknown etiology, prevalent in female sex. Affected patients have one or more nodules inside the thyroid gland, causing an increase in volume of the organ.

Multinodular goiter is often associated with normal levels of thyroid hormones in blood, but can be associated with hypo- or hyperthyroidism. These patients, once diagnosed (and cured if necessary) can have the following hormonal states: be in spontaneous euthyroidism, in euthyroidism due to administration of thyroxine synthesis inhibitors (in cases of toxic multinodular goiter), in euthyroidism due to thyroxine administration in hypothyroidism cases (e.g., after thyroidectomy). In all thyroid pathologies, the patients we treated were all in spontaneous or pharmacological euthyroidism.

Fibromyalgia, or fibromyalgia syndrome or Atlas syndrome, is a syndrome characterized by chronic diffused muscle pain associated with fatigue, sleep disturbances, depression, cognitive impairment, and by the presence of points painful at palpation, called "tender points".

Object of the present invention are pharmaceutical compositions comprising vitamin B1 and one or more pharmacologically acceptable excipients for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein vitamin B1 is administered orally with a dosage of at least 600 mg per day or is administered intramuscularly with a dosage unit of at least 50 mg once every three or four days.

Said compositions could, e.g., contain an amount of vitamin B1 comprised between 600 and 1800 mg per dosage unit when formulated for oral administration, or an amount of vitamin B1 comprised between 50 and 150 mg when formulated for intramuscular administration.

By the term "dosage unit" in the present description it is meant the unitary formulation for a single administration, e.g. a tablet, capsule, an injection phial, etc. The pharmaceutical compositions according to the present invention can be formulated in a variety of ways depending on the selected 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 and pharmaceutically acceptable excipients. Such excipients may be selected among 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, derivatives of starch, of cellulose and of polyvinylpirrolidone, silicates and sodium carbonate e) binders, such as carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, cellulose polymer derivatives, 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 bentonite clays and kaolin, k) lubricants, such as talc, calcium stearate, magnesium stearate, polyethylene glycol, sodium lauryl sulphate, sodium stearyl fumarate j) glidants, such as talc, colloidal silica.

Solid dosage forms, such as tablets, capsules, pills and granules, may be coated with enteric, gastric coatings, or with coatings of other type well-known in the state of the art. Said forms may contain matting agents and may be of a type allowing release of active ingredients only or preferably in a certain tract of the intestine, optionally in a delayed manner. Substances that can allow such a delayed use include, but are not limited to polymers and waxes.

Liquid forms suitable for oral administration are emulsions, solutions, prepared or extemporary suspensions, syrups and elixirs. Excipients suitable to the formulations according to the present invention in liquid forms for oral use include, but are not limited to diluents commonly used in the art, such as water or other solvents, solubilizing and emulsifying agents selected from ethyl alcohol, polyalcohols, propylene glycol, glycerol, polyethylene glycol and sorbitan esters. These formulations can also contain sweeteners and aromas selected from those well- known in the state of the art.

Compositions suitable for pharmaceutically acceptable parenteral (preferably intramuscular) injections may comprise sterile aqueous solutions, sterile dispersions, suspensions or emulsions or powders for a reconstitution in injectable solutions or dispersions; examples of excipients suitable therefor include, but are not limited to aqueous or non-aqueous carriers, diluents, solvents or vehicles selected from: water, ethanol, polyoils (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 (in particular of olive, cotton, peanut, corn, wheat germ, olive, castor, sesame), organic esters such as ethyl oleate or the like.

These compositions may also contain preservatives of antibacterial or antifungal type, selected, yet not exclusively, from: paraben, chlorbutanol, phenol, ascorbic acid and the like. It may also be useful to include an isotonic agent, e.g., a sugar, sodium chloride or the like. Moreover, pharmaceutical forms with a delayed absorption may be obtained with agents such as, for instance, yet not exclusively, aluminium monostearate and gelatin.

Also slow-release formulations can be prepared, by the techniques and products well-known in the state of the art.

The present description provides also a method for the treatment of chronic fatigue associated with multiple sclerosis, hepatitis C, from multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis comprising the administration by oral route of at least 600 mg per day of vitamin B1 or the administration by intramuscular route of at least 50 mg every three or four days, to patients in need thereof.

Hereinafter experiments and examples are reported, aimed at better illustrating what has been reported in the present description; such examples are in no way to be considered as a limitation of the present description and of the claims hereinafter.

EXAMPLES

Testing

Hereinafter, it is reported the clinical testing demonstrating the therapeutic activity of vitamin B1 according to the invention.

All patients subjected to therapy reported chronic fatigue, often associated with other symptoms such as sleep disturbances, depression, anxiety, irritability, cognitive impairment, muscle pain, cardiac arrhytmias, cold intolerance.

Therapeutic effect obtained with administration of vitamin B1 was assessed by FSS (Fatigue Severity Scale) standard test.

Discontinuance of vitamin B1 -based therapy causes again the onset of chronic fatigue and other associated symptoms.

Determination of vitamin B1 concentration in patients' plasma

Before treatment all patients exhibited vitamin B1 values in the plasma well within average, suggesting that an administration of vitamin B1 would not have been necessary.

Clinical studies concerning patients with ulcerative colitis (UQ)

Eight patients (6 women and 2 men) suffering from ulcerative colitis (UC) were recruited for the study. Average duration of disease was of 15.1 years. Two patients were not under any medical treatment. The other patients used mesalazine or salazopyrin, or mesalazine and azathioprine together.

The clinical protocol provided:

1 ) History and objective examination of each patient;

2) Evaluation of fatigue using the CFS scale (Reference - NEUROLOGIA - Scale e Punteggi di Harald Masur, 1999 Edi.Ermes s.r.l. - Milan);

3) Blood dosage of thiamine and thiamine pyrophosphate (TPP);

4) Oral administration of 600 mg/day of thiamine.

Dosage was empirically defined for this study as follows: first administration of 600 mg/day for each patient. Every two days, progress of therapy was assessed via consultation with a physician. In those cases in which fatigue regression was not satisfactory, an increment of 300 mg/day of thiamine was prescribed in addition to the 600 mg/day. Patients weighing < 60 Kg responded to therapy at doses of 600 mg/day. Patients responded to therapy at higher doses (up to 1.500 mg/day for patients above 90 kg).

CFS scale score was considered as follows:

Zero points→ no fatigue;

Up to 13 points→ medium-low fatigue (five UC cases)

13 to 26 points→ severe fatigue (three UC cases)

Total sum of points before therapy was of 1 1 1.0. Average was of 13.8.

Evaluation of fatigue using the CFS scale and thiamine dosage in blood were repeated after 20 days of therapy. Table 1 shows Thiamine, TPP values, and CFS scores before therapy for the 8 patients with UC.

Table 1. Thiamine, TPP and CFS scores before therapy

UC Thiamine, n.v. 2.1^1.3 ^g/L TPP, n.v. >49 glL CFS scores

Patient

1 12.6 77.1 26

2 8.6 76 9

3 6.6 92 14

4 10.5 140 10

5 3.9 74 17

6 7.8 95.4 13

7 12.8 78.5 9

8 12.05 91.7 13

Table 2. Thiamine, TPP and CFS scores before therapy

Ulcerative C. Thiamine, n.v. 2.1-4.3 ^g/L TPP, n.v. >49 glL CFS scores

Patient

1 20.64 137.6 0

2 69.0 1 18.0 0

3 34.4 1 15.5 0

4 177.1 180.1 5

5 23.2 122.9 0

6 56.7 141 .0 0

7 71 .8 156.4 3

8 181.7 161 .58 0 Clinical studies concerning patients with multiple sclerosis (MS)

15 patients (9 women and 6 men) suffering exclusively from multiple sclerosis (MS) were recruited for the testing. Average duration of disease was of 14.1 years.

The clinical protocol provided:

1 ) History and objective examination of each patient;

2) Evaluation of fatigue using FSS (fatigue severity scale), a scale by which fatigue is evaluated in neurology.

3) Blood levels of thiamine and thiamine pyrophosphate (TPP);

4) Oral administration of 600 mg/day of thiamine or 100 mg every three days, intramuscularly.

FSS score was considered as follows:

0 points→ no fatigue;

Up to 36 points→ medium-low fatigue (2 cases)

36 to 63 points→ severe fatigue (13 cases)

Table 1 . Subjects and main data before therapy

Patient Thiamine TPP Duration Barthel Index FSS

n.v 2.1 -4.3 n.v.>49 of disease scores

L μ g /L

1 7.0 91 .0 25 100 38

2 6.6 86.2 25 100 37

3 6.3 50.8 21 100 30

4 4.1 38.8 10 52 51

5 1 1 .4 89.5 1 1 19 61

6 8.2 72.9 4 100 49

7 9.2 45.2 13 100 55

8 8.4 105.4 18 100 38

9 7.3 73.1 10 100 42

10 10.8 86.4 13 69 21

1 1 5.9 96.2 19 52 61

12 8.0 122.2 3 100 40

13 9.4 106.5 1 1 100 55

14 6.1 73.1 24 100 64

15 21 .5 128.1 5 52 39 Total sum of points before therapy was of 681.0. Average was of 45.4

Evaluation of fatigue using the FSS scale and blood levels of thiamine were repeated after 20 days of therapy.

Oral doses of 600 to 1 .500 mg per day, or of 100 mg every 7-12 days were administered to the patients.

Results of testing on patients with multiple sclerosis

The results concerning fatigue levels in 14 patients out of 15 (93.3% of the cases) showed a partial regression of fatigue. Only 1 patient out of 15 exhibited no sign of fatigue regression.

Table 2. FSS scores after 20 days of therapy

Figure imgf000012_0001

The total sum of FSS points before therapy was of 681 (Table 1 ), whereas the sum of FSS points after therapy was of 403. Overall fatigue regression in the sample was equal to 40.8%. Results of testing on patients suffering from multinodular goiter and on patients with hepatitis C

All patients subjected to therapy (both those suffering from multinodular goiter and those suffering from hepatitis C) reported the aforedescribed symptoms of a lack of vitamin B1 from onset of the disease, at various intensities. The therapeutic effect obtained with administration of vitamin B1 was evaluated by FSS standard test, as fatigue is the guiding symptom of lack of thiamine. Before therapy, scale scores yielded as result a severe-grade fatigue in 45% of the cases, and a medium-grade one in the remaining 55%. With a detailed medical history, also results obtained for the other symptoms were collected.

Patients suffering from multinodular goiter recruited in the testing were all women (12), those with chronic hepatitis C were a woman and two men. They took an oral therapy, ranging from 600 to 1550 mg/day for 20 days, with complete regression of symptomatology in a mere 3-4 days in the patients with multinodular goiter. The three patients with hepatitis C (one of which treated with one 100-mg phial per week, intramuscularly) showed an evident improvement after one/two weeks or after two months of therapy. In all patients, all symptoms ascribable to lack of vitamin B1 were almost completely regressed.

Results of testing on patients suffering from celiac disease, Parkinson's and cerebrovascular disease

All patients subjected to therapy reported chronic fatigue from onset of the disease, at various intensities. The therapeutic effect obtained with administration of vitamin B1 was evaluated by CFS (Chronic Fatigue Syndrome) scale and FSS (Fatigue Severity Scale) standard tests. Before therapy, scale scores yielded as result a severe-grade fatigue in 30% of the cases, and a medium-grade one in the remaining 70%.

All patients suffering from celiac disease took an oral therapy, ranging from 600 to 900 mg per day for 20 days, with recovery from fatigue in about 5 days, followed by a maintenance therapy with 300-600 mg per day which they took also in the maintenance therapy.

3 patients suffering from Parkinson's disease and chronic fatigue were treated with the same therapy.

Administration of oral vitamin B1 with doses of from 600 to 2400 mg led to complete recovery from fatigue in about 3-5 days of all patients with Parkinson's disease.

4 male patients suffering from hemiplegia as a consequence of cerebrovascular disease were treated. Treatment was performed orally with a dosage comprised between 600 and 1800, or parenterally with 100 mg intramuscular (im) per week. Fatigue regressed completely over 3-5 days

Results of testing on patients with fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, thyroidites, Basedow's disease.

Groups of patients suffering from fibromyalgia (5 patients), psoriasis (5 patients), psoriatic arthritis (5 patients), rheumatoid arthritis (10 patients), thyroidites (30 patients), or Basedow's disease (5 patients) and with evident symptoms of chronic fatigue, were treated with high doses of vitamin B1 as described for the other pathologies reported above. Treated patients had a >50% improvement (on the basis of FSS scores before and after treatment with vitamin B1 ).

All patients with thyroid pathologies at the time of the study were in spontaneous or pharmacological euthyroidism.

Clinical observations

None of the patients recruited for the various clinical studies and subjected to the therapy showed relevant side effects.

Discontinuance of vitamin B1 -based therapy causes again the onset of chronic fatigue and other associated symptoms in patients subjected to clinical testing.

Claims

1 . Vitamin B1 for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein vitamin B1 is administered orally with a dosage of at least 600 mg per day.
2. Vitamin B1 for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, hepatitis C, from multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein said vitamin B1 is administered intramuscularly with a dosage of at least 50 mg once every three or four days.
3. Vitamin B1 according to claim 1 or 2, wherein chronic fatigue is associated with sleep disturbances, depression, cognitive impairment, muscle pain, cardiac arrhytmias and/or cold intolerance.
4. Vitamin B1 according to claim 1 or 3, wherein said Vitamin B1 is administered orally to a female patient with a dosage comprised between 600 and 1800 mg per day.
5. Vitamin B1 according to claim 1 or 3, wherein said Vitamin B1 is administered orally to a male patient with a dosage comprised between 1200 and 2400 mg per day.
6. Vitamin B1 according to claim 2 or 3, wherein said Vitamin B1 is administered intramuscularly with a dosage comprised between 50 and 150 mg every three days or four days.
7. A pharmaceutical composition comprising vitamin B1 and one or more pharmacologically acceptable excipients for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, chronic hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein vitamin B1 is administered orally with a dosage of at least 600 mg per day.
8. The pharmaceutical composition according to claim 7, wherein chronic fatigue is associated with sleep disturbances, depression, anxiety, cognitive impairment muscle pain, cardiac arrhytmias and/or cold intolerance.
9. The pharmaceutical composition according to claim 7 or 8, wherein said composition is in the form of granulate, powder, solution, capsule, tablet, pill, lyophilized product, pill for oral administration.
10. The pharmaceutical composition according to claim 9, wherein said vitamin B1 is in an amount comprised between 600 and 2400 mg per dosage unit.
1 1. The pharmaceutical composition comprising vitamin B1 and one or more pharmacologically acceptable excipients for use in the treatment of chronic fatigue in patients suffering from multiple sclerosis, hepatitis C, multinodular goiter, celiac disease, Parkinson's disease, cerebrovascular disease, ulcerative colitis, thyroidites, Basedow's disease, fibromyalgia, psoriasis and psoriatic arthritis, rheumatoid arthritis, wherein vitamin B1 is administered intramuscularly with a dosage unit of at least 50 mg once every three or four days.
12. The pharmaceutical composition according to claim 1 1 , wherein chronic fatigue is associated with sleep disturbances, muscle pain, cardiac arrhytmias and/or cold intolerance.
13. The pharmaceutical composition according to claim 12, in the form of injectable solution.
14. The pharmaceutical composition according to claim 13, wherein said vitamin B1 is in an amount comprised between 50 and 150 mg per dosage unit.
PCT/IB2012/051820 2011-04-27 2012-04-13 Vitamin b1 for treatment of chronic fatigue WO2012147003A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
IT000216A ITRM20110216A1 (en) 2011-04-27 2011-04-27 Vitamin B1 for use in the treatment of inflammatory diseases - autoimmune.
ITRM2011A000216 2011-04-27
ITRM2011A000283 2011-06-08
IT000283A ITRM20110283A1 (en) 2011-06-08 2011-06-08 Vitamin B1 for use in the treatment of celiac disease and nervous system diseases.
ITRM20120077 ITRM20120077A1 (en) 2012-03-01 2012-03-01 New use of vitamin b1.
ITRM2012A000077 2012-03-01

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DR ANTONIO COSTANTINI: "Mi è stata diagnosticata la celiachia tramite gastroscopia con biopsie duodenali e esami del sangue", INTERNET CITATION, 11 January 2011 (2011-01-11), pages 1 - 2, XP007919628, Retrieved from the Internet <URL:http://www.medicitalia.it/consulti/Medicina-interna/169391/Mi-e-stata-diagnosticata-la-celiachia-tramite-gastroscopia-con-biopsie-duodenali-e-esami-del-sangue> [retrieved on 20111025] *
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] *
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None
TORRINOMEDICA: "Benerva", INTERNET CITATION, 1 July 2010 (2010-07-01), pages 1 - 6, XP007919626, Retrieved from the Internet <URL:http://www.torrinomedica.it/farmaci/schedetecniche/BENERVA.asp#P2> [retrieved on 20111025] *
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT201700059814A1 (en) * 2017-05-31 2018-12-01 Antonio Costantini Vitamin b1 in high doses for use in the medical treatment of some sporadic neurodegenerative diseases of genetic origin and primary headaches
WO2018220457A1 (en) * 2017-05-31 2018-12-06 COLANGELI, Marco Vitamin b1 in high doses for use in the medical treatment of motor symptoms of some sporadic neurodegenerative diseases, of genetic origin, and of cluster headache and of migraine headache

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