EP1888061A1

EP1888061A1 - Nutrient composition for treating sarcoma and prostate cancer

Info

Publication number: EP1888061A1
Application number: EP05732304A
Authority: EP
Inventors: M. Waheed Roomi; Vadim Ivanov; Aleksandra Niedzwiecki; Matthias Rath
Original assignee: Individual
Current assignee: Individual
Priority date: 2005-04-11
Filing date: 2005-04-11
Publication date: 2008-02-20
Also published as: WO2006108429A1; BRPI0520227A2

Abstract

The present invention relates to the use of a composition comprising an ascorbic acid compound, a L-lysine compound, a L-proline compound, and a polyphenol compound for the preparation of a pharmaceutical composition for treating fibro- or synovial, sarcoma and prostate cancer. Moreover, the invention further relates to a method of treatment wherein said composition is administered to a subject suffering from fibro- or synovial sarcoma or prostate cancer.

Description

00153-05 00008

New PCT application

Rath

Our Ref.: 153-05

Nutrient Composition for treating sarcoma and prostate cancer

The American Cancer Society estimates that approximately 563,700 Americans will die from cancer and approximately 1,368,030 new cancer cases will be reported in 2004 [American Cancer Society (2004)]. Detection tools have improved, leading to early detection of various cancers, and subsequently a broader range of treatment options and a decline in related deaths [Haese et al. (2001)]. Additionally, when diagnosed early, survival rates are favorable; however, in advanced stage cancer and in highly metastatic carcinomas as soft tissue sarcomas, the associated prognoses are generally poor. Approximately 90% of all cancer fatalities occur in patients with metastatic cancer. For example, even when fibrosarcoma is diagnosed and surgically treated early, the probability of the cancer metastasizing to distant parts of the body is greater than 70% [Papagelopoulos et al. (2002)].

While surgery is the treatment of choice for early stage cancer, its use is generally limited to localized tumors and is associated with a number of possible side effects. Patients may suffer from nerve damage, impotence, incontinence or rectal injury as a result of undergoing a prostatectomy [Bishoff et al (1998), Melman et al. (2004), Talcott et al. (2003)]. The second line of defense against cancer includes hormonal therapy, chemotherapy, and radiotherapy. While prostate cancer patients initially benefit from hormonal therapy or androgen ablation therapy, the emergence of androgen-independent or sensitive cancer cells renders this treatment modality ineffective after a maximum of a few years [Isaacs et al. (1999)]. Additionally, patients may experience impotence, hot flashes, nausea, vomiting, diarrhea, liver complications, weakened bones, breast growth, and/or tenderness as a result [National Cancer Institute (2004), Conde et al. (2003)]. Chemotherapy and radiotherapy do not generally benefit patients in advanced stage cancers as they focus on cancer cell destruction, but do not address metastases. These treatment methods have not only been ineffective in providing a cure, but indiscriminately attack all cells—causing cellular damage and destruction of the body's connective tissue, facilitating cancer metastasis. Clearly, current treatment modalities are limited in the treatment and prevention of metastatic cancer, creating a profound need for new safe and effective therapeutic approaches.

Several nutrient compounds have been reported to exert anticancer activity. Ascorbic acid has been reported to have cytotoxic and antimetastatic actions on malignant cell lines [Koh, Lee et al. (1998), Roomi, House et al. (1998), Naidu, Karl et al.(2003)]; in addition, low levels of ascorbic acid have been reported in cancer patients [Anthony and Schorah (1982), Nunez, Ortiz de Apodaca et al. (1995), Kurbacher, Wagner et al. (1996)]. ECGC is a potent anticancer agent that has been reported to have a growth inhibitory effect against certain human cancer cell lines [Valcic, Timmerman et. al. (1996), Mukhtar and Ahmed (2000), Yang, Liao et al. (1998)]. The observed effects were, however, rather weak and, thus, not be a suitable basis for a therapeutic approach for a rapid growing and aggressive cancer. Other studies suggested that the synergistic anticancer effect of ascorbic acid and EGCG together with other compounds on several cancer cell lines in tissue culture studies was greater than that of the individual nutrients [Netke, Roomi et al. (2003)]. Cancer cells form tumors and spread by degrading the extracellular matrix (ECM) through various matrix metalloproteinases (MMPs). It has been postulated that nutrients such as lysine and ascorbic acid could act as natural inhibitors of ECM proteolysis and, as such, have the potential to inhibit tumor growth and expansion [Rath and Pauling (1992)]. Additionally, it has been suggested that through the inhibition of hyaluronidase, ascorbic acid can prevent metastases by preventing degradation of the ground substance surrounding the tumor [Cameron et al. (1979)]. Clearly, there is a need for safe and effective therapeutic approaches to control the process of cancer metastasis, in particular for aggressive cancers such as fibro- or synovial sarcoma and prostate cancer.

The technical problem underlying the present invention, thus, must be seen as the provision of means and methods to comply with the aforementioned needs.

This problem is solved by the embodiments characterized in the claims and herein below.

Accordingly, the present invention relates to the use of a composition comprising

(a) an ascorbic acid compound,

(b) a L-lysine compound,

(c) a L-proline compound, and

(d) a polyphenol compound for the preparation of a pharmaceutical composition for treating fibro- or synovial sarcoma or prostate cancer.

The term "composition" encompasses liquid and solid preparations of the nutritional compounds referred to above as well as gels thereof. The solid preparations may be manufactured in a suitable form including tablets, capsules, powders, granules, tea preparations or the like. Its well known in the art how to manufacture said liquid, gel-like and solid preparations referred to herein. The composition referred to herein may be provided in accordance with the uses of the invention as mixture of the compounds or by means of a kit including the ingredients separately. The ingredients may be packaged in said kit in separate vials. The composition is also suitable for human or animal use. Preferably, said animal is mammal, most preferably a dog, cat or horse.

The amino acids "proline" or "lysine" referred to in accordance with the present invention are preferably the L-amino acids. "Proline" or "Lysine" also encompasses its hydroxyl derivatives hydroxyproline and hydroxylysine as well as salts thereof.

The term "ascorbic acid" preferably refers to ascorbate, ascorbic acid and salts thereof. Sometimes ascorbate compounds may be referred to as vitamin C.

The term "polyphenol compound" as used in accordance with the present invention, preferably, refers to a preparation of green tea plants comprising the polyphenols compounds that are present in green tea. Polyphenols compounds may be present as up to 30% dry weight in green tea. They include bioflavinoids such as flavanols, flavandiols, flavonoids, and phenolic acids. Flavanols represent the most abundant polyphenols in green tea and are commonly known as catechins. Most preferably, said catechins are EGCG, EG, ECG or EC. EGCG refers to (-)-epigallocatechin-3-gallate, EC refers to epicatechin which refers to (-)-epicatechin, ECG refers to eipcatechin-3-gallate which refers to (-)-epicatechin-3-gallate, EGC refers to epigallocatechin which refers to (-)-epigallocatechin. It is well known in the art how such preparations may be obtained. Preferably, polyphenols are to be administered in an amount of 200 mg to 5000 mg per day and subject.

The compounds referred to in accordance with the uses of the present invention may be admixed in any suitable ratios or amounts. Whether such a ratio or amount is suitable can be determined by the skilled person by using the assays specified in the accompanied Examples referred to below. Most preferably, the composition referred to in accordance with the present invention provides a daily dosage of vitamin C (as ascorbic acid and as Mg, Ca, and palmitate ascorbate) 700 mg; L-lysine 1000 mg; L-proline 750 mg; L-arginine 500 mg; N-acetyl cysteine 200 mg; standardized green tea extract (80% polyphenol) 1000 mg; selenium 30 mg; copper 2 mg; manganese lmg.

The pharmaceutical composition to be administered in accordance with the present invention may include a pharmaceutically acceptable carrier, diluent, or excipient. The composition to be used in accordance with the present invention can be prepared by procedures known in the art. Respective ingredients may be formulated with common excipients, diluents, or carriers, and formed into tablets, capsules, suspensions, powders, and the like, xamples of excipients, diluents, and carriers include: i) fillers and extenders such as starch, sugars, mannitol, and silicic derivatives; ii) binding agents such as carboxymethyl cellulose and other cellulose derivatives, alginates, gelatin, and polyvinyl-pyrrolidone; iii) moisturizing agents such as glycerol; disintegrating agents such as calcium carbonate and sodium bicarbonate; agents for retarding dissolution such as paraffin; iv) resorption accelerators such as quaternary ammonium compounds; v) surface active agents such as acetyl alcohol, and glycerol monostearate; v) adsorptive carriers such as kaolin and bentonite; and vi) lubricants such as talc, calcium and magnesium stearate, and solid polyethyl glycols. The compositions may also be formulated as elixirs or solutions for convenient oral administration or as solutions appropriate for parenteral administration, for example, by intramuscular, subcutaneous or intravenous routes. Ideally the formulation is in the form of a pill, tablet, capsule, lozenge, liquid or similar dosage form as referred to aove. The compositions may well be suited to formulation as sustained release dosage forms and the like.

As used herein, the term "treating" is used to mean reducing, inhibiting, attenuating or treating the syndromes accompanied with the pathological conditions referred to in accordance with the present invention. Treating becomes apparent for the clinician by monitoring the symptoms accompanied with the said pathological conditions. The symptoms are described in detail in standard text books such as Stedman or Pschyrembel. Treatment preferably refers to significant reduction, inhibition, attenuation or treatment. The significance can be determined by standard methods of statistics, e.g., Student's t-test, chi square test an others. The terms "fibro- or synovial sarcoma" refer to cancer types of mesenchymal origin appearing in the connective tissue and synovial membrane. "The term "prostate cancer" relates to all cancer types derived from the prostate. Preferaly, the term relates to prostate carcinoma. The symptoms accompanied with said diseases or disorders are well known in the art and described in detail in medical text books such as Stedman or Pschyrembel. Accordingly, the clinician can determine without further ado whether a patient suffers thereforom. The term "prevention" means said the nutritional composition may also be administered in order to avoid the development of the aforementioned diseases.

In the study underlying the present invention, the inhibitory effect of a composition, sometimes also referred to as nutrient mixture (NS), containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate, on the growth of human cancer xenografts in athymic nude mice was investigated. After one-week of isolation, 5-6 week old female mice (Group I) were inoculated with 3x10⁶ breast cancer cells MBA-MD-231; male mice were divided into 5 groups and inoculated subcutaneously with 3x10⁶ cancer cells: Group II, prostate cancer cells PC-3; Group III colon cancer cells HCT 1 16; Group IV, melanoma cells A2058; Group V, fibrosarcoma HT 1080; Group VI, synovial sarcoma Hs 701. T After injection, each group was randomly divided into two subgroups; groups IA-VIA were fed a regular diet and groups IB-VIB were fed a regular diet with 0.5% of the nutrient mixture. (Each subgroup consisted of 6 mice). Four weeks later, the mice were sacrificed, and their tumors were excised, weighed, and processed for histology. Results surprisingly showed that nutrient synergy inhibited the growth and reduced the size of tumors in nude mice: prostate cancer by 53%, fibrosarcoma by 59%, and synovial sarcoma by 44% were particularly strong reduced, while breast cancer was less strong reduced (27%, data not shown). Additionally, histological examination revealed that the nutrient mixture decreased the mitotic index. The nutrient mixture strongly suppressed the growth of tumors without any adverse effects in nude mice, suggesting it as a promising anticancer agent.

Thanks to the present invention sarcoma such as fibrosarcoma and synovial sarcoma and prostate cancer can be treated without harmful side effects of the conventional therapies such as surgery and/or radiation therapy.

The definitions and explanations of the terms made hereinabove apply mutatis mutandis for the other embodiments of the present invention disclosed hereinafter.

In a preferred embodiment of the use of the present invention said ascorbic acid compound is selected from the group consisting of ascorbic acid, a pharmaceutically acceptable ascorbate salt, an ascorbate ester, more preferably ascorbyl palmitate, and/or mixtures of the aforementioned compounds. More preferably, said pharmaceutical acceptable ascorbate salt is selected from the group consisting of calcium ascorbate salts and magnesium ascorbate salts. Suitable amounts of the compounds to be used for the preparation of the composition referred to in accordance with the present invention are disclosed in WO 03/057201 A2, which is hereby incorporated by reference, in detail. Preferably, the ascorbic acid compound is ascorbic acid in an amount of 25 mg to 5000 mg and/or calcium ascorbate and/or magnesium ascorbate and/or ascorbyl palmitate in the same amounts. All amounts are calculated per day and subject.

In a further preferred embodiment of the use of the present invention said L-lysine compound is selected from the group consisting of L-lysine hydrochloride, L-lysine, and pharmaceutically acceptable L-lysine salts.

Suitable amounts of the compounds to be used for the preparation of the composition referred to in accordance with the present invention are disclosed in WO 03/057201 A2, which is hereby incorporated by reference, in detail. The L-lysine compound, preferably, may be also a mixture of at least two of the chemicals of the aforementioned group. Preferably, the L- lysine compound is L-lysine in an amount of 50 mg to 5000 mg per day and subject. In another preferred embodiment of the use of the present invention said L-proline compound is selected from the group consisting of L- proline hydrochloride, L- proline, and pharmaceutically acceptable L- proline salts.

Suitable amounts of the compounds to be used for the preparation of the composition referred to in accordance with the present invention are disclosed in WO 03/057201 A2, which is hereby incorporated by reference, in detail. The L-proline compound, preferably, may be also a mixture of at least two of the chemicals of the aforementioned group. Preferably, the L- proline compound is L-proline in an amount of 25 mg to 3000 mg per day and subject.

In yet another preferred embodiment of the use of the present invention said composition further comprises a trace element selected from the group consisting of selenium, manganese, magnesium, calcium, and copper.

Suitable amounts of the compounds to be used for the preparation of the composition referred to in accordance with the present invention are disclosed in WO 03/057201 A2, which is hereby incorporated by reference, in detail. The composition, preferably, comprises at least two, at least three or more of the trace elements of the aforementioned group. Preferably, the trace elements may be used together, separately or in any comination in the following amounts per day and subject: selenium: 1 μg to 200 μg; cooper: 20 μg to 9000 μg; manganese: 50 μg to 10000 μg; calcium: 300 mg to 600 mg; magnesium: 300 mg to 600 mg.

In a further preferred embodiment of the use of the present invention said composition further comprises an L-arginine compound. More preferably, said L-arginine compound is selected from the group consisting of L- arginine hydrochloride, L- arginine, and pharmaceutically acceptable L- arginine salts.

Suitable amounts of the compounds to be used for the preparation of the composition referred to in accordance with the present invention are disclosed in WO 03/057201 A2, which is hereby incorporated by reference, in detail. The L-arginine compound, preferably, may be also a mixture of at least two of the chemicals of the aforementioned group. Preferably, the L- arginine compound is L-arginine in an amount of 50 mg to 3000 mg per day and subject. In another preferred embodiment of the use of the invention, the composition may further comprise N-acetyl cysteine.

"N-acetyl-cysteine" as used herein comprises cysteine or cystine (dimer of cysteine) and cysteine salts thereof. Suitable amounts of the compounds to be used for the preparation of the composition referred to in accordance with the present invention are disclosed in WO 03/057201 A2, which is hereby incorporated by reference, in detail. Preferably, the N-acetyl cystein is administered in an amount of 10 mg to 1500 mg per day and subject.

In a preferred embodiment of the use of the present invention said composition is to be administered in oral, parenteral, subcutaneous, intraarterial, or intravenous form.

The invention also relates to a method for treating fibro- or synovial sarcoma or prostate cancer in a subject comprising the step of administering to a subject suffering from fibro- or synovial sarcoma or prostate cancer a composition as defined hereinabove in a therapeutically efficient amount.

It is well known for the person skilled in the art how such compositions can be administered to a subject. Particularly preferred techniques are describe in detail in WO 03/057201 A2 which is hereby incorporated by reference. Moreover, all embodiments of the use of the present invention apply mutatis mutandis for the aforementioned method for treating fibro- or synovial sarcoma or prostate cancer.

In a preferred embodiment of the method said subject is a human.

In a further preferred embodiment of the method the composition is administered orally, par- entarally, subcutaneously, intraarterially, or intravenously.

Full bibliographic information on the references cited above and below will be found below. The disclosure content of these references is hereby incorporated by reference. References

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2. N. Jaffe, H. Carrasco, K. Raymond, A. Ayala, F. Eftekhari (2002). Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery? Cancer. 10: 2202-10.

3. W.S. Koh, S. J. Lee, H. Lee, C. Park, M.H. Park, W.S. Kim, S.S. Yoon, K. Park, S.I. Hong, M.H. Chung, CH. Park (1998). Differential effects and transport kinetics of ascorbate derivatives in leukemic cell lines. Anticancer Res 8: 2487-2493.

4. CM. Kurbacher, U. Wagner, B. Kolster, P.E. Andreotti, D. Krebs, H.W. Bruckner (1996). Ascorbic acid (vitamin C) improves the antineoplastic activity doxorubicin, cisplatin and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett. 103(2): 183-189.

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6. R. Miller, S. Dowshen, and M. Trigg, Childhood Cancer: Osteosarcoma (May 2002) The Nemours Foundation: Kids Health http://kidshealth.org/parent/medical/cancer/cancer osteosarcoma pl-3.html

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9. S. P. Netke, M. W. Roomi, V. Ivanov, A. Niedzwiecki, and M. Rath. A specific combination of ascorbic acid, lysine, proline and epigallocatechin gallate inhibits prolif- eration and extracellular matrix invasion of various human cancer cell lines. Research Communications in Pharmacology and Toxicology: Emerging Drugs. 2, 37-50.

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14. S. Valcic, B.N. Timmerman, D.S. Alberts, G.A. Wachter, M. Krutzch, J. Wymer, J.M. Guillen (1996). Inhibitory effects of six green tea catechins and caffeine on the growth of four selected human tumor cell lines. Anticancer Drugs. 7: 461-468.

15. G.Y. Yang, J. Liao, K. Kim, E.J. Yurkow, CS. Yang (1998). Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 19:61 1-616.

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17. Haese A, Partin AW. New serum tests for the diagnosis of prostate cancer. Drugs Today 2001 ; 37(9): 607-616.

18. Papagelopoulos PJ, Galanis EC, Trantafyllidis P, Boscainos PJ, Sim FH, Unni KK. (2002). Clinicopathologic features, diagnosis, and treatment of fibrosarcoma of bone. Am J Orthop. 31(5):253-7.

19. Bishoff JT, Motley G, Optenberg SA, et al. Incidence of fecal and urinary incontinence following radical perineal and retropubic prostatectomy in a national population. J Urol 1998; 160(2): 454-8. 20. Melman A, Boczko J, Figueroa J, Leung AC. Critical Surgical Techniques for Radical Perineal Prostatectomy. J Urol 2004; 171(2): 786-790.

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24. Conde FA, Aronson WJ. Risk factors for male osteoporosis. Urol Oncol 2003; 21(5): 380-3.

25. Cameron E, Pauling L, Leibovitz, B. Ascorbic acid and cancer; a review. Cancer Res. 1979;39:663-681.

The figure show:

Figure 1: Tumor size and weight was measured in nude mice after four weeks of treatment with the nutrient mixture (NS): human breast cancer cells MDA-231(1A), prostate PC-3 (IB), colon cancer cells HCT 116 (1C), melanoma cells A2058 (ID), fibrosarcoma HT 1080 (IE), and synovial sarcoma Hs 701. T (F). Results were expressed as means + SE for the groups.

Figure 2: Effect of nutrient synergy on tumor burden in male nude mice on colon cancer cells HCT 116, melanoma cells A2058 and prostate cancer cells PC-3 (2A) and effect of 0.5% of the nutrient formulation (NS) on tumor growth (tumor value) in prostate cancer cells PC-3 in nude mice (2B).

Figure 3: Histological examination following four weeks of administration of 0.5% of the nutrient mixture (NS) revealed a decreased the mitotic index in human breast cancer cells MDA-231 (3A - Control, 3B - 0.5% NS), colon cancer cells HCT 116 (3C - Control, 3D- 0.5% NS), melanoma cells A2058 (3E - Control, 3F - 0.5% NS), and prostate cancer cells PC-3 (3G - Control, 3H - 0.5% NS).

The invention will be illustrated by the following Examples. However, the Examples shall not be used to limit the scope of the invention.

Example: Treatment of different cancer types in nude mice

All cancer lines used in the present investigation were obtained from the American Type Culture Collection (Rockville, MD). These included: breast cancer (MDA-MB-231), prostate cancer (PC-3), colon cancer (HCT 116), melanoma (A2058), fibrosarcoma (HT-1080) and synovial sarcoma (HTB-93).

Melanoma and synovial sarcoma cultures were maintained in Dulbecco's modified Eagle medium, PC-3 in Ham's F12 medium (F12K), colon cancer in McCoy's medium, HT-1080 in MEM, and MBA-MD-231 in Leibovitz medium. All media were supplemented with 10% fetal bovine serum, 100 U/ml penicillin and 100 μg/ml streptomycin. The media and sera used were obtained from ATCC, and antibiotics (penicillin and streptomycin) were from Gibco BRL, Long Island, NY. At near confluence, the cultured cells were detached by trypsinizing, washed with PBS, and diluted and emulsified to a concentration of 3x10⁶ cells in 0.2 ml PBS and 0.1 ml Matrigel (BD Bioscience, Bedford, MA) for inoculation. Male and female athymic nude mice (NCr-nu/nu), approximately 6 weeks of age on arrival, were purchased from Simonsen Laboratories, Gilroy, CA and maintained in microinsulator cages under pathogen-free conditions on a 12-hour light/ 12-hour dark schedule for a week. All animals were cared for in accordance with institutional guidelines for the care and use of experimental animals.

After housing for a week, the mice were divided into groups: female nude mice were placed in Group I and male nude mice were divided into five groups, Groups H-VI with each group consisting of 6 mice. The site of injection, the right flank was cleaned with ethanol and inoculated with 3x10⁶ cancer cells in 0.2 ml of PBS and 0.1 ml of Matrigel: Group II prostate cancer cells PC-3; Group III colon cancer cells HCT 116; Group IV, melanoma cells A2058; Group V, fibrosarcoma HT 1080; Group VI, synovial sarcoma Hs 701. T. Female mice (Group I) were inoculated with breast cancer cells MBA-MD-231. After injection, each group was randomly divided into two subgroups, A and B. Six mice were allocated to each subgroup. From day one, Groups IA-VIA were fed a regular diet and Groups IB-VIB were fed a regular diet supplemented with 0.5% of the nutrient formulation (NS). The growth of tumors was monitored, by measuring the length and width of the tumors with a caliper every three days. Tumor volume was calculated using the following equation: Volume (mm3)= Length x Width² x ¹A. After four weeks, mice were sacrificed, tumors were excised, weighed, fixed in 10% (v/v) buffered formalin and processed for histology.

Results showed that nutrient synergy inhibited the growth and reduced the size of the tumors in groups IB-VIB (nude mice supplemented with 0.5% nutrient mixture). Nutrient synergy effected a significant reduction in tumor size in all cancer lines studied: breast cancer cells MBA-MD-231 by 27% (p=. 0082), prostate cancer cells PC-3 by 53% (p=. 0001), colon cancer cells HCT 116 by 63% (p=. 0002), melanoma cells A2058 by 57% (p=. 0001), fibrosarcoma HT 1080 by 59% (p=. 0001), and synovial sarcoma Hs 701. T. by 44% (p=. 0099) (See figures IA- IE). Histological examination revealed that treatment with the nutrient mixture resulted in a decreased mitotic index. Treatment with the nutrient formulation resulted in significantly decreased mean tumor burden in nude mice with human cancer cell xenografts (prostate, melanoma, and colon) studied over the 4-week treatment period: colon by 46% (p=. 0005); melanoma by 32% (p=. 0015); prostate by 47% (p=. 0001). See Figure 2 A. Prostate tumor growth over the 4-week treatment period in nude mice supplemented with the nutrient formulation demonstrated 36% (p= .002) reduced growth compared to the control group at 4.5 weeks. (See Figure 2B.)

All chemicals used were purchased from Sigma (St.Louis, Mo) and were of high quality. Stock solution of the nutrient mixture (total weight 4.4 Gm) is composed of the following: Vitamin C (as ascorbic acid and as Mg, Ca, and palmitate ascorbate) 700 mg; L-lysine 1000 mg; L-proline 750 mg; L-arginine 500 mg; N-acetyl cysteine 200 mg; standardized green tea extract (80% polyphenol) 1000 mg; selenium 30 mg; copper 2 mg; manganese lmg. The statistical results were expressed as means + SE for the groups. Data was analyzed by independent sample "t" test.

Claims

1. Use of a composition comprising

(a) an ascorbic acid compound,

(b) a L-lysine compound,

(c) a L-proline compound, and

2. The use of claim 1, wherein said ascorbic acid compound is selected from the group consisting of ascorbic acid, a pharmaceutically acceptable ascorbate salt, an ascorbate ester and/or mixtures of the aforementioned compounds.

3. The use of claim 2, wherein said pharmaceutical acceptable ascorbate salt is selected from the group consisting of calcium ascorbate salts and magnesium ascorbate salts.

4. The use of claim 1, wherein said ascorbate compound is an ascorbate ester.

5. The use of claim 4, wherein said ascorbate ester is ascorbyl palmitate.

6. The use of any one of claims 1 to 5, wherein said L-lysine compound is selected from the group consisting of L-lysine hydrochloride, L-lysine, and pharmaceutically acceptable L-lysine salts.

7. The use of any one of claims 1 to 6, wherein said L-proline compound is selected from the group consisting of L- proline hydrochloride, L- proline, and pharmaceutically acceptable L- proline salts.

8. The use of any one of claims 1 to 7, wherein said composition further comprises a trace element selected from the group consisting of selenium, manganese, magnesium, calcium, and copper.

9. The use of any one of claims 1 to 8, wherein said composition further comprises an L- arginine compound.

10. The use of claim 9, wherein said L-arginine compound is selected from the group consisting of L- arginine hydrochloride, L- arginine, and pharmaceutically acceptable L- arginine salts.

11. The use of any one of claims 1 to 10, wherein said composition further comprises N- acetyl cysteine.

12. The use of any one of claims 1 to 11, wherein said composition is to be administered in oral, parenteral, subcutaneous, intraarterial, or intravenous form.

13. A method for treating fibro- or synovial sarcoma or prostate cancer in a subject comprising the step of administering to a subject suffering from fibro- or synovial sarcoma or prostate cancer a composition as defined in any one of claims 1 to 12 in a therapeutically efficient amount.

14. The method of claim 13, wherein said subject is a human.

15. The method of claim 13 or 14, wherein the composition is administered orally, paren- tarally, subcutaneously, intraarterially, or intravenously.