WO2006108429A1 - Nutrient composition for treating sarcoma and prostate cancer - Google Patents
Nutrient composition for treating sarcoma and prostate cancer Download PDFInfo
- Publication number
- WO2006108429A1 WO2006108429A1 PCT/EP2005/003766 EP2005003766W WO2006108429A1 WO 2006108429 A1 WO2006108429 A1 WO 2006108429A1 EP 2005003766 W EP2005003766 W EP 2005003766W WO 2006108429 A1 WO2006108429 A1 WO 2006108429A1
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- Prior art keywords
- compound
- composition
- group
- ascorbate
- cancer
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
- A61K31/78—Polymers containing oxygen of acrylic acid or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Definitions
- 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.
- 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.
- the present invention relates to the use of a composition
- a composition comprising
- 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.
- 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.
- ascorbic acid preferably refers to ascorbate, ascorbic acid and salts thereof. Sometimes ascorbate compounds may be referred to as vitamin C.
- polyphenol compound 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.
- polyphenols are to be administered in an amount of 200 mg to 5000 mg per day and subject.
- 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.
- vitamin C as ascorbic acid and as Mg, Ca, and palmitate ascorbate
- 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;
- 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.
- 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.
- 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.
- fibro- or synovial sarcoma refer to cancer types of mesenchymal origin appearing in the connective tissue and synovial membrane.
- 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.
- prevention means said the nutritional composition may also be administered in order to avoid the development of the aforementioned diseases.
- 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.
- NS nutrient mixture
- mice 5-6 week old female mice (Group I) were inoculated with 3x10 6 breast cancer cells MBA-MD-231; male mice were divided into 5 groups and inoculated subcutaneously with 3x10 6 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).
- 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.
- 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.
- 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.
- 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.
- said L-lysine compound is selected from the group consisting of L-lysine hydrochloride, L-lysine, and pharmaceutically acceptable L-lysine salts.
- L-lysine compound preferably, may be also a mixture of at least two of the chemicals of the aforementioned group.
- the L- lysine compound is L-lysine in an amount of 50 mg to 5000 mg per day and subject.
- said L-proline compound is selected from the group consisting of L- proline hydrochloride, L- proline, and pharmaceutically acceptable L- proline salts.
- the L-proline compound preferably, may be also a mixture of at least two of the chemicals of the aforementioned group.
- the L- proline compound is L-proline in an amount of 25 mg to 3000 mg per day and subject.
- composition further comprises a trace element selected from the group consisting of selenium, manganese, magnesium, calcium, and copper.
- the composition preferably, comprises at least two, at least three or more of the trace elements of the aforementioned group.
- the trace elements may be used together, separately or in any comination in the following amounts per day and subject: selenium: 1 ⁇ g to 200 ⁇ g; cooper: 20 ⁇ g to 9000 ⁇ g; manganese: 50 ⁇ g to 10000 ⁇ g; calcium: 300 mg to 600 mg; magnesium: 300 mg to 600 mg.
- 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.
- the L- arginine compound is L-arginine in an amount of 50 mg to 3000 mg per day and subject.
- 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.
- 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.
- 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.
- 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.
- said subject is a human.
- composition is administered orally, par- entarally, subcutaneously, intraarterially, or intravenously.
- 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.
- NS nutrient mixture
- 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).
- NS nutrient formulation
- 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).
- MDA-231 3A - Control, 3B - 0.5% NS
- HCT 116 colon cancer cells
- HCT 116 3C - Control, 3D- 0.5% NS
- melanoma cells A2058 3E - Control, 3F - 0.5% NS
- prostate cancer cells PC-3 (3G - Control, 3H - 0.5% NS).
- 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 ⁇ g/ml streptomycin. The media and sera used were obtained from ATCC, and antibiotics (penicillin and streptomycin) were from Gibco BRL, Long Island, NY.
- the cultured cells were detached by trypsinizing, washed with PBS, and diluted and emulsified to a concentration of 3x10 6 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.
- mice 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 3x10 6 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.
- NS nutrient formulation
- 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).
- 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.
- Vitamin C ascorbic acid and as Mg, Ca, and palmitate ascorbate
- L-arginine 500 mg N-acetyl cysteine 200 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.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNA2005800498406A CN101180049A (en) | 2005-04-11 | 2005-04-11 | Nutritive composition for treating sarcoma and prostate cancer |
BRPI0520227-2A BRPI0520227A2 (en) | 2005-04-11 | 2005-04-11 | Use of a Nutrient Composition for the Treatment of Sarcoma and Prostate Cancer |
EP05732304A EP1888061A1 (en) | 2005-04-11 | 2005-04-11 | Nutrient composition for treating sarcoma and prostate cancer |
PCT/EP2005/003766 WO2006108429A1 (en) | 2005-04-11 | 2005-04-11 | Nutrient composition for treating sarcoma and prostate cancer |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/EP2005/003766 WO2006108429A1 (en) | 2005-04-11 | 2005-04-11 | Nutrient composition for treating sarcoma and prostate cancer |
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WO2006108429A1 true WO2006108429A1 (en) | 2006-10-19 |
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PCT/EP2005/003766 WO2006108429A1 (en) | 2005-04-11 | 2005-04-11 | Nutrient composition for treating sarcoma and prostate cancer |
Country Status (3)
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EP (1) | EP1888061A1 (en) |
BR (1) | BRPI0520227A2 (en) |
WO (1) | WO2006108429A1 (en) |
Cited By (1)
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US20110300227A1 (en) * | 2010-05-21 | 2011-12-08 | North Texas Medical Associates | Malignant neoplasm treatment protocol |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003057201A2 (en) * | 2002-01-11 | 2003-07-17 | Matthias Rath | A nutrient pharmaceutical formulation comprising polyphenols and use in treatment of cancer |
-
2005
- 2005-04-11 EP EP05732304A patent/EP1888061A1/en not_active Withdrawn
- 2005-04-11 BR BRPI0520227-2A patent/BRPI0520227A2/en not_active IP Right Cessation
- 2005-04-11 WO PCT/EP2005/003766 patent/WO2006108429A1/en active Application Filing
Patent Citations (1)
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WO2003057201A2 (en) * | 2002-01-11 | 2003-07-17 | Matthias Rath | A nutrient pharmaceutical formulation comprising polyphenols and use in treatment of cancer |
Non-Patent Citations (3)
Title |
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ROOMI M WAHEED ET AL: "Antitumor effect of nutrient synergy on human osteosarcoma cells U-20S, MNNG-HOS and Ewing's sarcoma SK-ES.1", ONCOLOGY REPORTS, vol. 13, no. 2, February 2005 (2005-02-01), pages 253 - 257, XP009055466, ISSN: 1021-335X * |
ROOMI M WAHEED ET AL: "In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human prostate cancer PC-3 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry.", IN VIVO (ATHENS, GREECE) 2005 JAN-FEB, vol. 19, no. 1, January 2005 (2005-01-01), pages 179 - 183, XP009055464, ISSN: 0258-851X * |
ROOMI M WAHEED ET AL: "Inhibitory effect of Epican Forte: a specific formulation of nutrients containing lysine, proline, ascorbic acid and epigallocatechin gallate on the matrix metalloproteinases activities and invasion of human fibrosarcoma HT-1080 cells.", FASEB JOURNAL, vol. 17, no. 4-5, March 2003 (2003-03-01), & FASEB MEETING ON EXPERIMENTAL BIOLOGY: TRANSLATING THE GENOME; SAN DIEGO, CA, USA; APRIL 11-15, 2003, pages Abstract No. 867.1 URL - http://ww, XP002350469, ISSN: 0892-6638 * |
Cited By (1)
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