EP2723352A1

EP2723352A1 - Activated carbon and iodine/iodine salts for treating chronic fatigue syndrome

Info

Publication number: EP2723352A1
Application number: EP12802460.1A
Authority: EP
Inventors: Staffan Skogvall
Original assignee: Pharmalundensis AB
Current assignee: Pharmalundensis AB
Priority date: 2011-06-21
Filing date: 2012-06-14
Publication date: 2014-04-30
Also published as: EP2723352A4; WO2012177211A1

Abstract

The invention provides activated carbon comprising adsorbed iodine and/or an adsorbed iodide salt selected from the group of alkali metal iodides and earth alkali iodides, for use in a method for chronic fatigue syndrom optionally together with a suitable bromide salt. Furthermore, the invention provides a pharmaceutical composition containing such activated carbon as well as methods of using such activated carbon for treating chronic fatigue syndrom.

Description

Activated carbon and iodine/iodine salts for treating chronic fatigue syndrome FIELD OF THE INVENTION

The invention relates to treatment of chronic fatigue syndrome, CFS. More specifically, the invention relates to activated carbon comprising adsorbed iodine and/or an adsorbed iodide salt for use in a method for treating chronic fatigue syndrome, CFS. Furthermore, the invention provides pharmaceutical composition containing such activated carbon as well as methods of using such activated carbon for treating chronic fatigue syndrome, CFS.

BACKGROUND OF THE INVENTION

Chronic Fatigue Syndrome

Chronic fatigue syndrome, or CFS, is a devastating and complex disorder characterized by overwhelming fatigue that is not improved by bed rest and thai may be worsened by physical or mental activity. People with CFS most often function at a significantly tower level of activity than they were capable of before the onset of illness. In addition to these key defining characteristics, patients report various nonspecific symptoms, including weakness, muscle pain, impaired memory and/or mental concentration, insomnia, and post-exertional fatigue lasting more than 24 hours. In some cases, CFS can persist for years. The cause or causes of CFS have not been identified and no specific diagnostic tests are available. Moreover, since many illnesses have incapacitating fatigue as a symptom, care must be taken to exclude other known and often treatable conditions before a diagnosis of cfs is made.

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Activated charcoal is used in medical applications to treat poisoning and oral overdose of various medicaments. Activated charcoal has a very large surface area; 1 gram has a surface area of 300-2000 m² (Greenwood, N. N. and Earnshaw, A. Chemistry of the Elements, page 301 , Pergamon Press, 25 1984).

Prior art

US patents Nos. 5,910,318 and 5,955, 101 disclose starch-iodine

pharmaceutical formulations for the preparation of capsules and tablets. The 30 pharmaceutical formulations are suitable for administration to patients

suffering from iodine deficiency diseases, in particular breast dysplasia, breast cancer, endometriosis, premenstrual syndrome, ovarian cysts and radiation sickness. In the formulation iodine is complexed with starch containing amylase, forming triiodide ions or poiyiodide ions (Ι₅ ^' up to hi ^"). Iodine is released in the upper small bowel after hydrolysis of the starch by a- amylase. Since the triiodide ions cannot exist in non-complexed form S₂ s released,

Iodine toxicity may be a concern when high amounts of iodine are

administered to a human. Iodine toxicity is manifested by, among other symptoms, thyroiditis, goiter, hypothyroidism and hyperthyroidism. It has been suggested that some individuals can tolerate very high levels of iodine with no apparent side effects and that iodine intakes less than or equal to 1 ,000 mg/day are probably safe for the majority of the population, but may cause adverse effects in some individuals (Pennington, J.A., A Review of Iodine Toxicity Reports, journal of the American Dietetic Association 1 S90

90(1 1 ): 1571 -81 ). Administration of a bromide salt, in particular sodium bromide, to animals suffering from the effects of iodine toxicity helps to reverse the symptoms (Baker, D. H., Parr, T. H. and Augspurger, N. R. Oral Iodine Toxicity in Chicks Can Be Reversed by Supplemental Bromine. Journal of Nutrition 2003 133:2309- 2312). Sodium bromide is well tolerated by- humans and it has been found to have a no-effect level of 4 mg/kg body weight (van Gelderen, C. E., Savelkoul, T. J., Blom, J. L, van Dokkum, W. and Kroes, R. The No-effect Level of Sodium Bromide in Healthy Volunteers. Human & Experimental Toxicology 1993 12(1 ):9-14).

Impregnated activated charcoals are carbonaceous adsorbents which have chemicals finely distributed on their internal surface (Henning and Schaefer Gas Separation & Purification 1993 Vol 7 No 4 235-240). The impregnation optimizes the existing properties of the activated charcoal giving a synergism between the chemicals and the charcoal. WO2009067067 A1 and WO2009078782 A1 describe methods for producing bronchorelaxation in a human or an animal affected by airway obstruction comprising administration of a pharmacologically effective amount of elemental iodine on activated charcoal (iodinated activated charcoal) to the intestine of said human or animal. A pharmaceutical composition comprising elemental iodine on activated charcoal and uses thereof is also disclosed.

Accordingly, there is a need for new methods for treating chronic fatigue syndrome, CFC.

OBJECTS OF THE INVENTION

An object of the present invention is to provide a method and a means of the aforementioned kind, which is efficient, easy to apply, and acceptable to most persons.

In particular, an object of the present invention is to provide such a method and means by which chronic fatigue syndrome, CFC, could be treated.

Further objects of the present invention will become obvious from the following summary of the invention, detailed description and preferred embodiments thereof, and the appended claims. SUMMARY OF THE INVENTION

In a first embodiment, the invention provides activated carbon comprising iodine and/or an adsorbed iodide salt selected from the group of alkali metal iodides and earth alkali iodides, for use in a method for treating symptoms caused by chronic fatigue syndrome.

As disclosed herein, the term "activated carbon" also comprises what is meant by the term "activated charcoal". Typical examples of such iodides that could be used in the present invention are Nal, Kl, Mgl₂, and Cal₂. Preferably, potassium iodide, Kl, is included as adsorbed such iodide. Preferably, the amount of adsorbed iodine and/or iodide salt is within the range of 0.25 - 20 % (wt.), and more preferably within the range of 0.5 - 10 % (wt.). Preferably the amount of adsorbed iodine is within the range of 1 - 20 % (wt.) and the amount of adsorbed iodide salt within the range of 0.5 - 10 5 (wt.).

Preferably, the activated carbon also comprises an adsorbed,

pharmaceutically acceptable bromide salt, such as sodium bromide, potassium bromide, magnesium bromide, lithium bromide, ammonium bromide and/or calcium bromide. The amount of bromide salt may be within the range of 1 - 1000 % (wt.) calculated on the weight of the adsorbed iodide salt.

In a second embodiment, the present invention provides use of activated carbon comprising an adsorbed iodide salt according to the first embodiment, in a method for treating chronic fatigue syndrome.

In a third embodiment, the present invention provides a pharmaceutical composition comprising activated carbon comprising an adsorbed iodide salt according to the first embodiment, together with a pharmaceutically

acceptable excipient. The selection of excipient is not critical and most commonly used pharmaceutically acceptable excipients could be included in the pharmaceutical composition according to the present invention. Preferably, the pharmaceutical composition is selected from the group of an aqueous suspension, a capsule, a powder for preparing an oral suspension or a tablet. For instance, when the activated carbon comprising adsorbed iodide salt is administrated in the form of a tablet or capsule, said activated carbon comprising adsorbed iodide salt can be combined with an oral, non-toxic pharmaceutical acceptable inert carrier such as ethanol, glycerol, water and the like. Moreover, when desired or necessary, suitable binders, lubricants, disintegrating agents and coloring agents can also be incorporated into the mixture. Suitable binders include, without limitation, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum and the like.

In a fourth embodiment, the present invention provides use of a

pharmaceutical composition according to the third embodiment, in a method for treating depression.

DETAILED DESCRIPTION OF THE INVENTION

It turns out that chronic fatigue syndrome could be treated by administration of activated carbon onto which iodine and/or an alkali metal iodide or an alkaline earth metat iodide has been adsorbed.

As disclosed herein, the term "treatment of chronic fatigue syndrom" relates to treatment of symptoms fulfilling the following two criteria;

1 . Unexplained, persistent fatigue that is not due to ongoing exertion, is not substantially relieved by rest, is of new onset and results in a significant reduction in previous levels of activity,

2. Four or more of the following symptoms are persistent for six months or more:

i) Impaired memory or concentration;

ii) Extreme, prolonged exhaustion and sickness following physical or mental activity (postexertional malaise);

iii) Unrefreshing sleep;

iv) Muscle pain;

v) ultijoint pain without swelling or redness;

vi) Headaches of a new type or seventy;

vii) Sore throat that is frequent or recurring; and

viii) Tender cervical or axillary lymph nodes. In addition to these key defining characteristics, patients report various symptoms, including weakness and insomnia.

A person in need of treatment for chronic fatigue syndrome would receive an efficient amount of activated carbon impregnated with iodine and/or an iodide salt after oral administration of such impregnated activated carbon.

The activated carbon loaded with an alkali metal or earth alkali metal iodide should preferably be administered in the interval between two meals, such as one or two or three or more hours after a meal and one or two or three or more hours prior to the next meal. A preferred form of administration comprises per-oral ingestion of an aqueous suspension of particulate activated carbon loaded with an alkali metal or earth alkali metal iodide. The aqueous media can be water but also mineral water, fruit juice or a soft drink.

Instead of an aqueous suspension particulate activated charcoal loaded with alkali metal or earth alkali metal iodide can be administered filled in soft or hard gelatin capsules, vegetable or pullulan capsules, or in form of a tablet formed from particulate activated charcoal loaded with alkali metal or earth alkali metal iodide and a suitable pharmaceutically acceptable binder. The binder should be of a kind allowing the tablet to disintegrate in gastrointestinal fluid. Suitable binders comprise chemically modified cellulose such as carboxymethyl cellulose and polyvinylpyrrolidone. Because of the fragile nature of the carbon only slight compression should be used when forming the tablets so as not to crush the carbon particles.

A suitable dosage regime for treating chronic fatigue syndrom comprises administration of a pharmacologically effective amount of activated charcoal loaded with an alkali metal or earth alkali metal iodide over an extended period of time, such as one or several months and even one or several years. Preferably administration of the pharmacologically effective amount of activated carbon loaded with an alkali metal or earth alkali metal iodide is daily and even twice or trice daily but can also be intermittent, such as every second or third day or once or several times per week.

DESCRIPTION OF EXPERIMENTAL WORK

EXAMPLE 1 . Preparation of activated carbon samples loaded with alkali metal iodide or earth alkali metal iodide

Materials. Activated carbon (Sigma C7606), Potassium iodide (Sigma P7744), de-ionized water.

Equipment. Magnetic stirrer IKA RTC basic, oil bath, reflux condenser, balance XP-300 Denver Instruments, Pyrex glass flask 2 L, polymer-enclosed magnetic bar, vacuum filter flask 2 L, OOH filter paper (Whatman), laboratory drying oven TS80000, Termaks.

Method. 8.0 g Kl is dissolved in 1 L of water. Activated carbon (92 g) is added. The suspension is stirred for 12 hours at room temperature (21 -23 °C). The activated carbon product is separated from the Kl solution by filtration under reduced pressure and dried for 12 h in 75 °C. This resulted in a sample consisting of activated carbon impregnated with ~1.6 % (wt.) Kl.

EXAMPLE 2: Preparation of activated iodinated carbon product of the invention Capsules comprising iodine on activated charcoal and sodium bromide

Materials: Activated carbon from Sigma C7606; meets USP testing

specification. Elemental Iodine from Sigma-Aldrich 03002; meets USP testing. Undenaturated ethanol from Kemetyl; meets USP and EP testing

specification with < 0.5 % water content.

Equipment: Mixing cylinder 500 ml, measuring cylinder 500 ml, E-flask 50 ml, Buchner funnel Duran diameter 105 mm and stirrer motor with blade, RZR 1 from Heidolph. Filterpaper grade 00H from Munktell. Evaporation dish made from borosilicate glass.

Method: Depending on the batch size the amount of activated carbon, elemental iodine and ethanol is calculated. For a batch size of 50 g iodinated carbon, 4.5 g of iodine, 45.5 g of activated carbon and 450 ml ethanol is used. The activated carbon is suspended in the measuring cylinder with 410 ml ethanol and the elemental iodine is solved in the E-flask with 40 ml ethanol. The iodine is added, stirred for 2 min and allowed to impregnate the carbon for 1 h. Thereafter, the iodinated activated carbon is separated from the ethanol solution by filtration under reduced pressure and dried for 5 hrs. at 150 C. This results in iodinated activated charcoal impregnated with 9 % I2.

EXAMPLE 3. Treament of patient having chronic fatigue syndrome with impregnated activated carbons.

The patient is a 46-year old woman who used to be in good health and who performed well both at work and at home. However, some years ago she started to experience severe and chronic fatigue of unclear origin, which was not relieved by rest. This led to a significant reduction of her level of activity at work, and to problems with her social life. The symptoms have gradually worsened, and she was recently forced to reduce her working hours to only a few days per week. There have been talks about her retiring from work completely.

In addition to the above symptoms, she has also experienced severely impaired concentration, unclear pain in muscle and joints, postexertional malaise, insomnia and, occasionally, tender axillary lymph nodes. After excluding several other diseases, she was diagnosed with Chronic Fatigue Syndrome (CFS) about a year ago. Since then, the symptoms have persisted, and no drugs or other treatments have improved the symptoms significantly. Some time ago she tested activated charcoal impregnated with 9 % \₂ (custom made at PharmaLundensis A8 according to Example 2). She took 2 g impregnated carbon per day for two weeks, and recorded her symptoms daily.

After 2 weeks of treatment her fatigue was clearly reduced, she slept better and felt rested and sharp after sleep, her concentration improved, the pain in muscle and joints were better and the postexertional malaise was reduced.

After this, she changed to activated charcoal impregnated with 1 .6 % potassium iodide (impregnated carbon) prepared in accordance with what is stated in example 1 , She took 2 g carbon impregnated with 1 ,6 % potassium iodide per day for two weeks, and recorded her symptoms daily. The improvements that she had felt when taking activated charcoal impregnated with 9 % \₂ remained, and even improved slightly.

Thereafter, she wanted to clarify if the clear improvement in health was caused by the treatment with impregnated carbon. Therefore, she stopped taking all types of impregnated carbon for two weeks, which resulted in a return of ail of the previous symptoms. To clarify if it was the elemental iodine in the impregnated carbon which caused the improvement of her health, she took daily in a capsule in the same amount that was present in the daily intake of the impregnated carbon (180 mg) for two weeks. This did not improve her health at all.

To clarify if it was the potassium iodide in the impregnated carbon which caused the improvement of her health, she took Kl daily in a capsule in the same amount that was present in the daily intake of the impregnated carbon (32 mg). After 2 weeks of intake of potassium iodide capsules, her health had not improved. To clarify if the health improvement was caused by the activated charcoal, she took, for two weeks, non-impregnated activated charcoal in the amount of 2 g/day. This did not improve her health at all. After these tests, where the two components of the two different impregnated carbon samples had been tested separately and found to lack effect, the combination (carbon impregnated with i₂) was taken in the amount of 2 g per day. This once again improved ail her symptoms, and this improvement persisted when, after 2 weeks, the substance was changed to carbon impregnated with Kl in the amount of 2 g/day.

Claims

1 . Activated carbon comprising adsorbed iodine and/or an adsorbed iodide salt selected from the group of alkali metal iodides and earth alkali iodides, for use in a method for treating chronic fatigue syndrom.

2. Activated carbon according to claim 1 , characterized in that the amount of adsorbed iodine and/or iodide salt is within the range of 0.25 - 20 % (wt.), and preferably within the range of 0.5 - 10% (wt.).

3. Activated carbon according to any of claims 1 and 2, characterized in that the adsorbed iodide is potassium iodide.

4. Activated carbon according to any of claims 1 - 3, characterized in that the activated carbon also comprises an adsorbed pharmaceutically acceptable bromide salt, such as sodium bromide, potassium bromide, magnesium bromide, lithium bromide, ammonium bromide and/or calcium bromide.

5. Use of activated carbon comprising an adsorbed iodide salt according to any of claims 1 - 4, in a method for treating chronic fatigue syndrom.

6. A pharmaceutical composition comprising activated carbon comprising adsorbed iodine and/or an adsorbed iodide salt according to any of claims 1 - 4, together with a pharmaceutically acceptable excipient.

7. A pharmaceutical composition according to claim 6, which is selected from the group of an aqueous suspension, a capsule, a powder for preparation of an oral suspension, or a tablet.

8. Use of a pharmaceutical composition according to any of claims 6 - 7, in a method for treating chronic fatigue syndrom.