Field of the Invention

The present invention relates to cancer therapy by specific dietary compensation. Especially the invention relates to a pharmaceutical composi- tion comprising one or more amino acids, one or more trace elements, and optionally vitamins and neurogenic lipids. The pharmaceutical composition is useful in the treatment or prevention of cancer, especially prostate cancer.

Background

Cancer is a complex multifactorial metabolic deficiency disease. Therefore dietary compensation of the missing functional components can by reception of these vital alimentary components stop the progress or even cure cancer patients. Ingestion of these natural functional components can then be absorbed from the intestine into the blood circulation and reconstitute the internal balance. The longstanding metabolic deficiency causing cancer can thus be compensated and via the regulatory function of organ specific mitochondria malignant cells can be forced to regain a healthy function. Activated mitochondria (electron dense due to the activated metallo-enzymes in their crista) are then seen to surround the nucleus of the cancer cell and some inject their electron dense enzymes into the tumour cell nucleus and the tumour cells be- come normal, but without triggering apoptosis. Genetic weaknesses can also be compensated by administration of missing components; a healthy person gets enough of them from his normal food intake.

This paradigm shift concerning cancer therapies in bioimmunother- apy is based on efforts to reconstruct the physiological metabolic internal bodi- ly balance at variance with the present paradigm based on killing the last tumour cell by cytotoxic agents or radiation. This new paradigm is based on a physiologic truly medical attempt to treat cancer, which has already proved to function in renal cancer and melanoma. It explains the rare events of mysterious cures of cancer, which are based on a complex synergistic signal system spontaneously formed by amino acids, trace element ions, the vast amount of vital central nervous system (CNS) lipids activating organ specific mitochondria to regulate the oncogens to reverse to normal healthy function without apao- tosis. The effect of bioimnnunotherapy on the mitochondria is described in Tallberg, T. et al. Studies on mitochondrial regulation of the genome, Deutsche Zeitschrift fur Onkologie, 2002; 34:128-139. The effect of bioimmunotherapy on malignant and non-malignant diseases is disclosed in Tallberg, T. Devel- opment of a Combined Biological and Immunological Cancer Therapy Modality. A review of Bio-lmmunotherapy. J. Austr. Coll. Nutr. & Env. Med. 2003; 22:3-21 , and in Tallberg, T. Regulation of cancer by therapeutic vaccination and dietary bio-modulation involving organ specific mitochondria. Int. J. Biotechnology 2007; Vol.9, Nos. 3/4, 391 -409.

Amino acids and trace element complexes seem to form the metabolic codes acting on cell receptors to keep specific organ cells in heathy transcription. Seven different chemical groups of amino acids were used as dietary supplements: Ala, lie, Leu, Val | Arg, His, Lys | Thr, Ser | Glu, Asp | Met, Cys I Tyr, Phe | Pro in combinations with trace element ions such as chromi- urn, manganese, molybdenum, selenium, tin, wolfram, titan, ferrous, cobalt, and vanadium. Different combinations of amino acids and trace elements optionally in combinations with vitamins and/or neurogenic lipids were found to be effective on different forms of cancer (Tallberg, T. 2003 and 2007 supra). The effect of strontium and optionally zinc in this kind of treatments is disclo- sed in EP 1 ,523,985.

There are still many gaps in the knowledge and understanding of the complicated connections between the ingredients in dietary supplementation compositions for treating and preventing cancer diseases. The present invention aims to fill in at least some of these gaps. The present invention thus provides an improved pharmaceutical composition for treating or preventing cancer.

Brief Description of the Invention

The present invention provides an inexpensive and safe pharmaceutical composition comprising natural, biological components for treating or compensating the causative metabolic deficeincy associated with cancer. It has now surprisingly been found that the addition of rubidium in a dietary supplement for cancer patients improves the effect of the supplement.

The present invention thus provides a pharmaceutical composition comprising one or more amino acids, one or more trace elements, and option- ally vitamins and neurogenic lipids, characterized in that one trace element is rubidium (Rb). The invention further provides the rubidium containing composition for use as a medicament, and especially for use in the treatment or prevention of cancer, preferably prostate, breast or cervix cancer.

Methods of treating or preventing cancer are disclosed comprising administering an effective amount of the pharmaceutical composition to a person in need thereof. Prevention as used herein includes the prevention of precancerous states.

Specific embodiments of the invention are set forth in the dependent claims. Detailed Description of the Invention

The treatment successfully used in the present investigation is based on administration of rubidium in combination with amino acids and other trace elements, neurogenic lipids and optionally vitamins. Preferably the pharmaceutical compositions contain the indicated ingredients as sole pharmaceu- tically active components.

Amino acids

The amino acids included in the pharmaceutical compositions are natural amino acids i.e. L-amino acids, preferably selected from the group consisting of alanine (Ala), arginine (Arg), aspartic acid (Asp), glutamine (Gin), glu- tamic acid (Glu), glycine (Gly), isoleucine (lie), leucine (Leu), lysine (Lys), serine (Ser), threonine (Thr) and valine (Val). They may be used in free form or e.g. as hydrochlorides for better taste, especially Lys and Arg. Ser is essential in the treatment of prostate and breast cancer.

Trace elements

In addition to the essential trace element rubidium (Rb) the composition preferably also comprises at least one further trace element selected from the group consisting of chromium (Cr), molybdenium (Mo), selenium (Se), tin (Sn), strontium (Sr), vanadium (V), and wolfram (W). Optionally the trace elements also include e.g. manganese (Mn) and zinc (Zn). To be biologically active the trace elements should be in ionic form, wherefore in practice they are administered as salts. A trace element salt having a neutral taste is preferred, and salts having a strong or bad taste should be avoided. Both rubidium and strontium are used in non-radioactive form. Rubidium is conveniently in the form of rubidium chloride, and strontium as strontium chloride or oxide. Neurogenic lipids

"Neurogenic lipids" as used herein refers to lipids included in the central nerve system (CNS), also called CNS-lipids. The central nerve system mainly consists of the brain, but also includes the brain stem and spinal cord (marrow). The neurogenic lipids are required for normal mammalian lymphopoiesis. In practice the neurogenic lipids are cooked tissue of the CNS, optionally further purified. The neurogenic lipids are preferably obtained from the brain of a mammal, e.g. from porcine brain, especially piglet brain, which is rinsed, boiled, and homogenized, after which it may be canned. It may be pur- chased from Neurofood Ltd. In a preferred embodiment, the boiled and homogenized brain is lyophilzed and then further purified by extracting the lyophi- lisate with ether/alcohol (10/90% to 90/10%, preferably 20/80% to 80/20%, most preferably about 30/70%) followed by distillation to obtain a prion-free, biologically active purified fraction of CNS lipids. The purification may be up to 200 times.

The brain, brain stem and spinal cord substance as used in the present invention contains a number of various components including the whole neurogenic lipids, which are in collaboration with each other and which in balanced ratios have the desired immunostimulating effect. The exact composi- tion of this fraction is not known, but in addition to the neurogenic lipids it contains e.g. titan, chromium and manganese, and has a lymphopoietic effect seen as 5-nucleotidase ectoenzyme activity, measured as disclosed in Uu- sitalo R.J., Uusitalo H., Palkama A. Ecto-5'-nucleotidase activity in lymphocytes in cases of uveitis. Acta Ophthalmol 1983;61 :362-372.

Other components

The pharmaceutical compositions may further contain physiological amounts of vitamins A, B, C, D, K and E, folic acid and lycopene.

Doses and administration

The composition used comprises the components in biologically and pharmaceutically active amounts, that is amounts sufficient to achieve the desired health promoting effect. As will be readily understood by a physician, the amounts will vary depending on the individual and his or her health status as well as on other factors such as weight, age, nutrition, stress, environmental factors, etc. Examples of suitable amounts include, but are not limited to about 1-10 g of each amino acid, 0.1-60 mg of each trace element, and neurogenic lipids in an amount corresponding to 10-100 g brain. Normally 2-5 g/day of each amino acid is suitable. Rubidium is preferably used in amounts of 1-10 mg/day, more preferably 2-8 mg/day, e.g. 3-7 mg/day. The other trace elements are usually used in amounts of 0.1 - 10 mg/day, preferably 0.5-9 mg/day, more preferably 2 to 4 mg/day of Sr, and 1-3 mg/day of each of the trace elements Cr, Mo, Se, Sn, V and W. Manganese (Mn) and zinc (Zn) may be administered in doses of about 30-60 mg/day preferably 40-50 mg/day. All the amounts indicated refer to the metal ion part of the trace element salt.

The A, B, C, D, K and E vitamins are used in small, well-established physiological amounts, and folic acid and lycopene e.g. in a dose of 1-2 mg/day, and 2 mg/day, respectively.

Neurogenic lipids should be administered in an amount capable of inducing a lymphopoietic response in the patient. A suitable daily or twice a week intake of neurogenic lipids may correspond to about 20-60 g, preferably 30-50 g of cooked brain. If an ether/alcohol lipid fraction of the brain is used, a dose corresponding to 2-8 g purified lipids/day is suitable.

All the components are administered orally, preferably in connection with meals as a dietary supplementation composition. They may be administered separately, or in variable combinations. They may be purchased e.g. in powder form separately, or as ready made powders containing all ingredients. Such a powder mixture may be pre-packed and used as such or as a supplement to conventional food items e.g. in a dairy product such as yoghurt or icecream. Of course the pharmaceutical composition may also be processed into granulates, capsules or tablets, which may comprise pharmaceutically ac- ceptable carriers. Conveniently it is in the form of microcapsules. The neurogenic lipid product can be administered either simultaneously with the other ingredients or separately at a different time. According to one embodiment cancer is prevented or treated by a method comprising administering separately: i) an effective amount of a pharmaceutical composition comprising one or more amino acids, one or more trace elements, and optionally vitamins, wherein one trace element is rubidium (Rb), and ii) an effective amount of a purified prion- free fraction of the central nerve system (CNS) obtained by extraction with a solvent mixture of ether and alcohol, to a person in need thereof, after distillation.

Specific Embodiments

The invention relates to the dietary treatment and prophylaxis of cancer. In particular the invention relates to several metabolic agents acting in synergy as a signal system regulating the genome. These spontaneous complexes of strontium Sr, rubidium Rb, tin Sn, vanadium V, and wolfram W ions, coupled to L-amino acids; alanine, arginine, glutamine, glycine, leucine, iso- leucine, serine, threonine, valine have a therapeutic effect. They have been successfully used for the treatment and prophylaxis of cancer. Promising results have been achieved in treating breast cancer and cervix cancer, and especially prostate cancer (pCA). Main components were Ser, Arg, Sr, V, Mo and Rb together with neurogenic lipids. Good prognostic traits to specific dietary treatment display increased FSH, prolactin PRL and SHBG levels, while DHEAS and PSA decline.

According to one preferred embodiment the composition comprises the following amounts of the following trace elements: 1 -3 parts by weight of Cr, 1 -3 parts by weight of Mo, 1 -3 parts by weight of Sn, 3-5 parts by weight of Rb, 3-5 parts by weight of Sr, 2-4 parts by weight of V, 2-4 parts by weight of W and 40-50 parts by weight of Zn. Preferably the composition further comprises the amino acids Arg, Asp, Glu, Gly, Lys and Ser in approximately the same proportions to each other. This composition is especially suitable for treating prostate cancer.

According to another preferred embodiment the composition com- prises the following amounts of the following trace elements: 1 -3 parts by weight of Cr, 1 -3 parts by weight of Se, 1 -3 parts by weight of Sn, 1 -3 parts by weight of Rb, 2-4 parts by weight of Sr, 2-4 parts by weight of V, 2-4 parts by weight of W and 40-50 parts by weight of Mn. Preferably the composition further comprises the amino acids Ala, Glu, Gly, lie, Leu, Lys, Ser, Thr and Val in approximately the same proportions to each other. This composition is especially suitable for treating breast cancer.

According to still another preferred embodiment the composition comprises the following amounts of the following trace elements: 1 -3 parts by weight of Cr, 1 -3 parts by weight of Mo, 0.1 -0.3 parts by weight of Se, 1 -3 parts by weight of Sn, 3-5 parts by weight of Rb, 2-4 parts by weight of V, 2-4 parts by weight of W, and 40-50 parts by weight of Mn. Preferably the composition further comprises the amino acids Arg, Asp, Gin, Gly, lie, Leu, Lys and Thr in approximately the same proportions to each other. This composition is especially suitable for treating cervix cancer. Example 1. Preparation of CNS lipid fraction

After slaughter of healthy young pigs, the brain including part of the brainstem was cut off, rinsed in cold tap water, and purified from bone pieces, and boiled for 20 minutes. 4 kg of the cooked mass was homogenized, spread in thin layers of about 0.5 cm on trays and lyophilized to for about 2-3 days depending on the apparatus to give about 800 g of lyophilized brain mass containing the lipids from the central nerve system. Specific lipids from the dried material are then extracted with a diethyl ether/ethanol solution (30/70%) for three days at room temperature in a shaker. The extract was then filtered through a filter paper or cloth, and the filtrate was distilled to remove the solvents. A fraction of about 80 g purified lipids was obtained. The purified lipids were either dissolved in sterile ionic free water in bottles containing 2 g/100 ml and preserved deep-frozen until use, or microcapsulated.

Example 2. Improved dietary bio-modulation schedule for treatment of prostate cancer patients (Table I)

Supportive dietary measures

1 . Oral administration of each (2-5 g/day) of respective L-amino acids; Arg, Asp, Glu, Gly, Lys, & Ser, in connection with meals.

2. Essential trace-element salts prescribed orally as biologically active ions, at dose levels of some milligrams (1 -3 mg/day); Chromium (CrCI ₃ .6H ₂ O) 6 mg

(* 1 .17 mg Cr), Molybdenum (Na ₂ MoO ₄ .2H ₂ O) 4 mg ( ^« 2 mg Mo), Rubidium (RbCI ₂ .5H ₂ O) 7 mg ( ^« 4 mg Rb), Tinn (SnCI ₄ .5H ₂ O) 4 mg (~ 1 .35 mg Sn), Strontium (SrCI ₂ ) 1 -7 mg (~ 4 mg Sr), Vanadine (Na ₂ VO ₄ .4H ₂ O), 6 mg (* 2.5 mg V), Wolfram (Na ₂ WO ₄ .2H ₂ O), 4 mg (* 2.3 mg W), Zinc oxide ( * 45 mg Zn)/day.

3. Small physiologic amounts of vitamins A, B, C, D, E, K, folic acid & lyco- pene [Powder 1 = 1 + 2 + 3].

4. To improve lymphopoiesis and the immune defence of patients a diet containing prionfree central nervous system lipid molecules (equivalent to ap- prox. 50 g of brain) plus its vitamin-like titanium (Ti) containing lipids activating white cells, and improving immunity was recommended, (purchased and canned by Neurofood Ltd. Finland mixed with fruits or dry in a microcapsulated form).

To remove eventual prion-peptides a purified fraction of CNS-lipids can be used. This is extracted for days from lyophylized mammalian brain by ether/alcohol (30/70%). The soluble lipids are filtered, distilled free of the solvent mixture and the thousands of lipid molecules suspended in sterile water stored deep-frozen until used. These purified CNS lipids may also be micro-capsulated in preformed powders to improve patient compliance [Powder II].

5. All these dietary ingredients can be mixed together in yoghurt, forming a daily ration, using pre-packed powders.

6. Dose-levels are adjusted based on clinical response as measured, and correlated to the patients body weight. Clinical curative effects from the specific dietary supplementation shown in Table I was demonstrated in prostate cancer patients suffering from multiple hurting bone metastases.

Example 3. Dietary bio-modulation schedule for treatment of breast cancer patients (Table II)

Supportive dietary measures for breast cancer patients

1 . Oral administration of each (2-5 g/day) of respective L-amino acids; Ala, Glu, Gly, lie, Leu, Lys, Ser, Thr & Val in connection with meals.

2. Essential trace-element salts prescribed orally as biologically active ions, at dose levels of some milligrams (1 -4 mg/day); Chromium (CrCl3.6H ₂ O) 6 mg (= 1 .17 mg Cr), Rubidium (RbCI ₂ 2H ₂ O) 4 mg (= 2.5 mg Rb), Selenium (Na ₂ SeO ₃ .5H ₂ O) 2 mg (~ 1 .2 mg Se), Tinn (SnCI ₄ .5H ₂ O) 4 mg (* 1 .35 mg Sn), Strontium (SrCI ₂ .H ₂ O) 1 -7 mg (~ 3 mg Sr), Vanadine (Na ₂ VO ₄ .4H ₂ O), 6 mg (* 2.5 mg V), Wolfram (Na ₂ WO ₄ .2H ₂ O), 4 mg (* 2.3 mg W), + Manganese sulphate ( ^« 45 mg Mn)/day.

3. Small physiologic amounts of vitamins A, B, C, D, E, K [Powder I, containing 1 , 2 & 3].

4. To improve lymphopoiesis and the immune defence of patients a diet containing prionfree central nervous system lipids (equivalent to approx. 50 g of brain) plus its vitamin-like titanium containing lipids activating white cells, and improving immunity was recommended, (purchased and canned by Neurofood Ltd. Finland mixed with fruits or dry in a micro-capsulated form). To remove any prion peptides a purified fraction of CNS-lipids can be used. Lyophylized brain is extracted by ether/alcohol (30/70%) for days. The soluble lipids are filtered, destilled free of solvent mixture and the thousands of lipid molecules dissolved in sterile water stored deep-frozen until used. These purified CNS lipids can also be microcapsulated, as pre formed powders to improve patient compliance [Powder II].

5. All these dietary ingredients can be mixed together in yoghurt, forming a daily ration, using pre-packed powders (e.g. I & II).

6. Dose-levels are adjusted based on clinical response as measured, and cor- related to the patients' body weight and laboratory results.

In breast cancer patients the formulae presented in Table II has caused regression of multiple liver metastases and rapid improvement of general health condition. Patients have also been able to stop the use of analget- ics since ingestion of CNS-lipids are in many cases more effective than morphin.

Example 4. Dietary bio-modulation schedule for treatment of epidermoid, e.g. cervix cancer patients (Table III)

Supportive dietary measures

1 . Oral administration of each (2-5 g/day) of respective L-amino acids; Arg ar- ginine hydrochloride, Asp asparaginic acid, Gin glutamin, glysine, Gly, leucine, Leu, lysine hydrochloride Lys, isoleusine lie, threonine Thr, in connection with meals.

2. Essential trace-element salts prescribed orally as biologically active ions, at dose levels of some milligrams/day (1 -7 mg/day); Chromium (CrCl3.6H ₂ O)

6 mg ( ^« 1 .2 mg Cr), Molybdenium (Na ₂ MoO ₄ .2H ₂ O) 4 mg ( ^« 1 .59 mg Mo), Rubidium (RbCI ₂ .5H ₂ O) 7 mg (z 4 mg Rb), Tin (Sn CI ₂ .2H ₂ O) 2.56 mg ( ^« 1 .35 mg Sn), Selenium (Na ₂ .SeO ₄ ) 0.438 pg (* 200 pg Se), Manganese sulphate (« 45 mg Mn), Vanadium (Na ₃ .VO ₄ ) 9.027 mg (« V 2.5 mg V), Wolfram (Na ₂ WO ₄ .2H ₂ O) 4.126 mg (* 2.3 mg W).

3. Small physiologic amounts of vitamins; A, B, C, D, K, E, and 4 mg folic acid 25% (* 1 mg).

4. To improve lymphopoiesis and the immunedefence of patients a diet containing priofree neurogenic lipids (equivalent to approx. 50 g of brain) is recommended, purchased and canned by Neurofood Ltd. Finland. It is also available in dry microcapsulated from, as ready-made powders.

5. All these dietary ingredients can be mixed together in yogurt, forming a daily ration, using pre-packed powders (2-3 /day).

6. Dose-levels are adjusted based on clinical response as measured (in papa tests) and correlated to the patients body weight. In epidermoid cancer patients the malignant cervix cells have regressed, and papa tests have shown more benign features caused by ingestion of these natural non-toxic alimentary components, listed in Table III.

Example 5. Case studies

In prostate cancer (pCA) patients diagnosed by screening dietary compensation of their etiologic metabolic deficiency has stopped the progress of the disease. The clinical effect of this specific non-toxic natural dietary supplementation is furthermore linked to a dose response, but not on a homeopathic level. Screening for pCA got a new incentive as progression could be arrested by dietary means without side-effects.

Case 1

A 54 year old man was in 1996 found to have pCA. His PSA had increased from 4.7 ng/ml to 6.7 ng/ml in 3 months, with a Gleason score of 6-7. He was scheduled for prostatectomy but opted to try only our biological dietary treatment, as presented in Table 1 , except that zinc was replaced by 45 mg manganese. He started to ingest a high dose of serine, 10 g every day, plus all other natural supportive ingredients as listed. In six month his PSA had decreased to 3.1 . ng/ml. He was then allowed to decrease the intake of Ser to only 5 g per day. In 6 months his PSA started again to rise to 3.6 ng/ml. He was then reallocated to the higher intake of Ser (10 g/d), He responded well and his PSA fell to 2.9 ng/ml. This positive dose-response kept his disease stable for six years on continuous supplementation. Administration of arginine was then temporarily stopped for only three months. During this short selective depletion his PSA increased from, 6.6 to 7.7 ng/ml. This led to prostatectomy, in July 2002. The extirpated prostate gland revealed that the Gleason score had decreased to 4, (from 6-7 previously) and that the tumour volume had diminished. His pCA had been arrested for seven years without side-effects, and economically. Based on this clinical result pCA patients diagnosed by screening should primarily be offered dietary supplementary treatment controlled by all our regular laboratory tests to monitor the effect.

Case 2

Multiple bone metastases may be cured by specific dietary supplementation, following castration. A prostate cancer (pCA) patient with elevated PSA, 30.0 ng/ml, was diagnosed with aggressive prostate cancer with multiple bone metastases in 1992. Orchiectomy was performed but he had still hurting metastases when a dietary supplementary treatment according to Example 2 started 1993. The intensive pain was alleviated in six months from the dietary supplementation including intake of strontium, rubidium (7 mg/day each) and zinc (40 mg/ day). His general condition improved markedly. All bone metastases disappeared after four years of dietary treatment, in 1996. There has not been any recurrent disease during the follow-up, now for over 18 years. He is living at home in excellent clinical condition.

FSH LH PRL DHEA DHEAS Testost Inhibin Activin S-Ferrit SHBG PSA

IU/L IU/L mU/L nmol/L μηιοΙ/L nmol/L pg/ml pg/ml μglL· nmol/L ng/ml 1-7#9 2.5-12 50-300 3.0-17.0 0.5-8.0 9-38 -60 -500 16-253 15-50 <4.0

30-67 16-37 95-159 < 2.0 < 0.8 1.0 < 7.8 330 99-109 58-61 <0.1

The patient's blood analysis results are shown above. The first row shows the normal levels and the second row the patient's levels. His elevated FSH-levels have been a constant finding, though levels have fluctuated for 19 years (the range is indicated). LH-levels are also elevated after castration in all pCA patients who respond, evidenced as declining PSA-levels. Extremely low levels for DHEA and DHEAS (<2.0% <0.8) are also seen, indicating a good prognosis effected by the dietary supplementation. All our other castrated pCA patients have died, if not placed on our specific dietary support.

Abbreviations: FSH = follicle-stimulating hormone, LH = luteinizing hormone, PRL = prolactin, DHEA = dehydroepiandrosterone, DHEAS = dehy- droepiandrosterone sulphate, SHBG = sex hormone-binding globulin, PSA = prostate-specific antigen, pCA = prostate cancer.