MXPA97007810A - A pharmaceutical composition containing n-phosphonoglycine derivatives to inhibit the growth of viruses and cance - Google Patents

Abstract

The invention relates to a pharmaceutical composition that inhibits the growth of cancers and tumors in mammals, in particular in humans and in warm-blooded animals. The composition is also effective against viruses. The composition contains N-phosphonoglycine derivatives which are systematic herbicides. The composition may contain N-phosphonoglycine derivatives in combination with chemotherapeutic agents for the treatment of cancers and tumors. The enhancers may also be optionally included. N-phosphonoglycine derivatives with an enhancer can also be used to treat viral infections

Description

A PHARMACEUTICAL COMPOSITION CONTAINING N-PHOSPHONOGLYCINE DERIVATIVES TO INHIBIT THE GROWTH OF VIRUSES AND CANCERS FIELD OF THE INVENTION The invention relates to a pharmaceutical composition that inhibits the growth of cancers and tumors in mammals, particularly in humans and warm-blooded animals. The composition is also effective against viruses. The composition contains N-phosphonoglycine derivatives which are systemic herbicides.

BACKGROUND OF THE INVENTION Cancers are the leading cause of death in animals and humans. The exact cause of cancer is unknown but it is linked to certain activities such as smoking or exposure to carcinogens, and the incidence of certain types of cancers and tumors has been shown by several researchers. Many types of chemotherapeutic agents have been shown to be effective against cancers and tumor cells, but all types of cancers and tumors respond to these agents. Unfortunately, many of these agents also destroy normal cells. The exact mechanism for the action of these agents M'H Chemotherapy is also unknown. Despite advances in the field of cancer treatment, the main therapies to date are surgery, radiation and chemotherapy. Chemotherapeutic approaches are said to fight cancers that are metastasized or those that are particularly aggressive. These cytocidal or cytostatic agents work best in cancers with large growth factors, ie those whose cells divide rapidly. To date, hormones, and in particular estrogen, progesterone and testosterone, and some antibiotics produced by a variety of microbes, alkylating agents and antimetabolites form the bulk of the therapies available to oncologists. The ideal cytotoxic agents would be those that present specificity for cancer and tumor cells while not affecting normal cells. Unfortunately, no one has found these types of agents and, on the contrary, agents that specifically target fast dividing cells (both tumor and normal type) have been used. Obviously, the development of materials that target tumor cells due to a certain specificity unique to these would represent an extraordinary advance. Alternatively, it would also be desirable to have materials that they were cytotoxic to the tumor cells and at the same time exerted mild effects on normal cells. Therefore, it is an object of this invention to provide a pharmaceutical composition that is effective to inhibit the growth of tumors and cancers in mammals, while having mild effects or having no effects on normal cells. More specifically, it is an object of the invention to provide an anti-cancer composition comprising a pharmaceutical carrier and an N-phosphonoglycine derivative as defined herein, as well as a method of treating that type of cancer. It is believed that the phosphonoglycine derivatives in combination with chemotherapeutic agents can suppress and reduce the growth of cancer cells, including leukemia. Therefore, an object of this invention is to provide a pharmaceutical composition that is effective both for suppressing and inhibiting the growth of cancers in mammals. It has been found that N-phosphonoglycine are especially effective in suppressing the growth of cancer, tumors, viruses or bacteria. The use of these N-phosphonoglycine in combination with other chemotherapeutic agents that are effective in destroying the tumor is a novel method of treatment.

I 1) i More specifically, it is an object of the invention to provide an anti-cancer composition comprising a pharmaceutical carrier and an N-phosphonoglycine derivative and a chemotherapeutic agent as defined herein, together with a method for the treatment of these cancers. These phosphonoglycine compositions with enhancers are also effective against viruses. The specifications of phosphonoglycine can be used to treat viral infections. Therefore, a further objective of the invention is to provide a method for treating viral infections such as HIV, influenza and rhinovirus. These and other objects will become apparent from the following detailed description of this invention.

SUMMARY OF THE INVENTION A pharmaceutical composition for the treatment of mammals and, in particular, in warm-blooded and human animals, comprising a pharmaceutical carrier and an effective amount of an anti-cancer compound selected from the group consisting of N-derivatives. phosphonoglycine of the formula: GOLD II I II X-C-CH2-N-CH2-P-OY OZ wherein X is selected from the group consisting of hydroxy, alkoxy and chloroxy up to 12 carbon atoms; lower alkenoxy, cyclohexyloxy, morpholino, pyrrolidinyl, piperidino and NHR '; Y and Z are each independently selected from hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl, acetyl, benzoyl, nitrobenzoyl and chlorobenzoyl; and R1 is selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, cyclohexyl, phenalkyl of up to 8 carbon atoms, phenyl, chlorinated phenyl and anisyl, and certain salts of these compounds, the salts are selected from the group that you of Group I and II of the metals that have an atomic number of up to 30; hydrochloride, acetate, salicylate, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline. A pharmaceutical composition for the treatment of mammals and, in particular, warm-blooded and human animals, comprising a pharmaceutical carrier and an effective amount of a chemotherapeutic agent and an anti-cancer compound selected from the group consisting of N-phosphonoglycine derivatives as defined above. The enhancers can also be employed in these compositions. These compositions can be used to inhibit the growth of cancers and other tumors in humans or animals, by administration of an effective amount of the N-phosphonoglycine derivative either orally, rectally, topically, parenterally, intravenously or by direct injection near or to the tumor. These compositions are effective in killing or slowing the growth of tumors, but still safer than adriamycin in relation to normal healthy cells.

DETAILED DESCRIPTION OF THE INVENTION A. DEFINITIONS In the sense used herein the term "comprising" refers to various components that can be used together in the pharmaceutical composition of the invention, consequently, the term "consisting essentially of" and "consisting of" are included in the term "comprising". In the sense used herein the term "pharmaceutically acceptable" in terms of a component refers to that component is suitable for use in humans and / or animals without undue adverse side effects (such as toxicity, irritation and allergic response) in commensurate form to a reasonable benefit / risk ratio.

In the sense used herein the term "safe and effective amount" refers to the amount of a component that is sufficient to give a desired therapeutic response without undue adverse side effects (such as toxicity, irritation or allergic response) commensurate with a reasonable ratio of benefit / risk when used in the form of this invention. The specific term "safe and effective amount" will obviously vary with factors such as the particular condition being treated, the physical condition of the patient, the type of mammal being treated, the duration of treatment, the nature of the concurrent therapy (in its case) and the specific formulations used and the structure of the compounds or their derivatives. In the sense used herein a "pharmaceutical addition salt" includes a pharmaceutically acceptable salt of the anti-cancer compound with an organic or inorganic acid and the amine salts of the acid. In the sense used herein a "pharmaceutical carrier" refers to a pharmaceutically acceptable solvent, a suspending agent or a vehicle for administering the anti-cancer agent to the animal or human. The carrier may be liquid or solid and is selected in the planned manner of administration that is kept in mind. In the sense used here the term "cancer" refers to all types of cancers or neoplasms or tumors that are found in mammals, including leukemia. In the sense in which the term "anti-cancer compounds" is used herein refers to the N-phosphonoglycines and their salts. The exact N-phosphonoglycins are described in detail below. The preferred material are the products sold under the name (H) 'V glyphosate or Roundup of Monsato. It is a N- (phosphonomethyl) glycine. In the sense used here, the term "virus" includes viruses that can cause diseases in warm-blooded animals, including HIV, influenza, rhinovirus, herpes and the like. In the sense used herein, the term "chemotherapeutic agents" includes DNA-interactive agents, antimetabolites, tubulo-interactive agents, hormonal agents and others, such as, for example, asparaginase or hydroxyurea. In the sense used herein, the word "enhancers" refers to materials such as triprolidine and its cis-isomers and procodazole which are used in combination with chemotherapeutic agents and phosphonoglycins.

B. ANTI-CANCER COMPOUNDS Anti-cancer compounds are N-phosphonoglycine derivatives that are known for their herbicidal activities. They are systemic herbicides that are used to prevent and eradicate certain plants or weeds. Systemic herbicides differ from other herbicides in their ability to move through the plant. In this invention it is not required that the anti-cancer compounds have this capacity. The compounds have the following structure: GOLD X-C-CH2-N-CH2-P-OY OZ wherein X is selected from the group consisting of hydroxy, thioyl, alkoxy and chloroxy of up to 12 carbon atoms; lower alkenoxy, cyclohexyloxy, morpholino, pyrrolidinyl, piperidino and NHR '; Y and Z are each independently selected from hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl, acetyl, benzoyl, nitrobenzoyl and chlorobenzoyl; and R 'is selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, cyclohexyl, phenalkyl of up to 8 carbon atoms, phenyl, chlorinated phenyl and anisyl; and certain salts of these compounds, the salts are selected from the group consisting of Group I and Group II of the metals with an atomic number of up to 30; hydrochloride, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline. The most preferred compounds are those with the following structure: HO-C-CH2-N-CH2-P- (OH) 2 Alkylamine salts, in particular isopropyl amine salts, are preferred. These compounds are prepared according to the method described in U.S. Pat. 3,794,758 issued to Franz on December 10, 1974.

CL \ OUIMIOTERAPÉUTICOS AGENTS The chemotherapeutic agents in general are grouped as DNA-interactive agents, antimetabolites, tubulo-interactive agents, hormonal agents and others such as asparaginase or hydroxyurea. Each of the groups of chemotherapeutic agents can be further divided by the type of activity or compound. The agents Chemotherapeutics used in combination with the fo.s fonogl i c i ns of the pw ont invontion include members of all these groups. For a detailed analysis of the chemotherapeutic agents and their methods of administration, refer to Dorr, et al. Cancer Chemo therapy Handbook, 2d edition, pages 15-34, Appleton & Lange (Connecticut, 1994) which is incorporated herein by reference. DNA-interacting agents include alkylating agents, for example cisplatin, cyclophosphamide, altretamine, - DNA chain-breaking agents, for example bleomycin, the intercalating topoisomerase II inhibitors for example dactinomycin and doxirubicin; the non-intercalating inhibitors of topoisomerase II such as etoposide and teniposide; and minor groove binders of DNA plicamidin. Alkylating agents form covalent chemical adducts with DNA, RNA and protein molecules and with small amino acids, glutathione and similar chemical agents. In general, these alkylating agents react with a nucleophilic atom in a cellular constituent, for example an amino, carboxyl, phosphate, sulfhydryl group in nucleic acids, proteins, amino acids or glutathione. The mechanism and role of these alkylating agents in cancer therapy is not well understood. The agents Typical alkylating agents include: Nitrogen mustards, such as, for example, chlora busil, cyclophosphamide, isofamide, mechlorethamine, melphalan, uracil mustard; Aziridine as thiotepa methanesulfonate esters such as bisulfan; nitrous ureas such as carotin, lomustine, is reptozocin; platinum complexes such as cisplatin, carboplatin; biorreductive alkylator such as mitomycin and procarbazine, dacarbazine and altetramine; DNA chain breaking agents that include bleomycin; DNA topoisomerase II inhibitors that include the following: intercalators such as amsacrine, dactinomycin, daunorubicin, doxorubicin, idarubicin and mitoxantrone, - non-intercalators such as etoposide and teniposide. The minor groove binders of DNA such as plicamicin. Antimetabolites interfere with the production of nucleic acids by any of two main mechanisms. Some of the drugs inhibit the production of deoxyribonucleoside triphosphates, which are the immediate precursors for DNA synthesis, inhibiting I l'i thus DNA replication. Some of the compounds are sufficiently similar to the pupils or pyrimidmas to be able to substitute them in the anabolic routes of the nucleotide. These analogs can then be substituted in the DNA and RNA instead of their normal counterparts. Useful antimetabolites include: folate antagonists such as methotrexate and trimetrexate pyrimidine antagonists such as fluorouracil, fluorodeoxyuridine, CB3717, azacitidine, cytarabine and floxuridine purine antagonists include mercaptopurine, 6-thioguanine, fludarabine, pentostatin; analogs modified with sugars including cyclabin, fludarabine; ribonucleotide reductase inhibitors including hydroxyurea. Tumor-interactive agents that act by binding to specific sites in tubilin, a protein that polymerizes to form cellular microtubules. Microtubules are critical cellular structural units. When the interactive agents bind to the protein, the cell can not form microtubules. The tubulo-interactive agents include vincristine and vinblastine, both are alkaloids, and paclitaxel.

Hormonal agents are also useful in the treatment of cancers and tumors. They are used in your oi is susceptible to hormones and are usually derived from natural sources. These include: estrogens, conjugated estrogens and ethinylestradiol and diethylstilbesterol, clortrianicen and idenestol; progestins such as hydroxyprogesterone caproate, medroxyprogesterone and megestrol; androgens such as testosterone, testosterone propionate; Fluoxymesterone, methyltestosterone. Adrenal corticosteroids are derived from cortisol or natural adrenal hydrocortisone. They are used due to their anti-inflammatory benefits as well as the ability of some to inhibit mitotic division and to interrupt DNA synthesis. These compounds include: prednisone, dexamethasone, methylprednisolone and prednisolone. Hormone agents that release leutinizing hormones or gonadotropin-releasing hormone antagonists are used primarily in the treatment of prostate cancer. These include leuprolide acetate and goserelin acetate. They avoid the biosynthesis of spheroids in the testicles. Antihormonal antigens include: antiestrogenic agents such as tamosifen antiandrogenic agents such as flutamide; and anti-adrenal agents such as mitotane and aminoglutethimide. Hydroxyurea appears to act primarily through the inhibition of the enzyme ribonucleotide reductase. Asparaginase is an enzyme that converts asparagine into non-functional aspartic acid and thus blocks the synthesis of protein in the tumor.

D. POTENTIATORS "Enhancers" can be any material that improves or increases the efficacy of the pharmaceutical composition or is an immunosuppressant. One of these enhancers is triprolidine and its cis-isomer which are used in combination with the chemotherapeutic agents and the N-phosphonoglycine derivative. Triprolidine is described in US Pat. No. 5,114,951 (1992). Another enhancer is procodazole, 1H-benzimidazole-2-propanoic acid, [β- (2-benzimidazole) propionic acid, 2- (2-carboxyethyl) benzimidazole; propazole]. Procodazole is a non-specific active immunoprotective agent against bacterial and viral infections and can be used with the compositions claimed in C-1 '• i I presented. It is effective with N-phosphonoglycine alone in the treatment of cancers, tumors, leukemia and viral infections or in combination with N-phosphonoglycine derivatives and chemotherapeutic agents. The propionic acid and its salts and esters can also be used in combination with the pharmaceutical compositions claimed herein. Antioxidant vitamins such as vitamins A, C and E and beta-carotene can be added to these compositions.

E ^. DOSAGE Any suitable dose can be administered in the method of the invention. The type of compound and carrier and the amount will vary widely depending on the species of warm or human blood animals, body weight and tumor being treated. For chemotherapeutic agents a lower dose of between 5 mg / kg of body weight to about 400 mg / kg of body weight is acceptable. In general, the dose will be between about 2 milligrams (mg) per kilogram (kg) of body weight to about 400 mg per kg of body weight. Preferably from 15 mg to about 150 mg / kg of body weight is what will be used. In general, the dose in man is less than that used in mammals My small warm-blooded ones like the mouse. A unit dose may comprise a single compound or mixture thereof with other compounds or other cancer inhibiting agents. The exact range and proportion of the chemotherapeutic agent relative to N-phosphonoglycine will depend on the type of chemotherapeutic agent or cancer being treated. The unit dose may also comprise diluents, extenders, carriers and the like. The unit may be in the form of a solid or gel, for example: pills, tablets, capsules and the like in liquid form suitable for oral, rectal, topical or parenteral administration or intravenous administration or by injection to the tumor site or close to East.

P DOSAGE ADMINISTRATION FORMS The anti-cancer compounds and, optionally, the chemotherapeutic agent and / or the enhancer are typically mixed with pharmaceutically acceptable carriers. This carrier can be a solid or a liquid and is of the type that is generally selected based on the type of administration being used. The active agent can be co-administered in the form of a tablet or capsule, as an agglomerated powder or as a liquid. Examples of the solid carriers include lactose, sucrose, gelatin and agar. Capsules or tablets may easily formulated and can be made to be easy to swallow or chew, - other solid forms include granules and bulk powders. The tablets may contain binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents and fusion agents. Examples of liquid dosage forms include solutions or suspensions in water, pharmaceutically acceptable oils or fats, alcohols or other pharmaceutically acceptable organic solvents, including esters, emulsions, elixirs, syrups, solutions and / or reconstituted suepensiones from non-effervescent granules and effervescent preparations reconstituted from effervescent granules. These liquid dosage forms may contain, for example: suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, thickeners and melting agents. The oral dosage forms may contain flavors and coloring agents. Parenteral and intravenous forms also include minerals and other materials to make them compatible with the type of injection or delivery system chosen. Specific examples of pharmaceutically acceptable carriers and excipients that can be used to formulate the oral dosage forms of this invention are described in United States Patent no. 3,903,297 by Robert, issued September 2, 1975. The techniques and compositions for making dosage forms useful in the present invention are described in the following references: 7 Modern Pharmaceutics, Chapters 9 and 10 (Banker &Rhodes, Editore, 1979); Lieberman et al., Pharmaceutical Dosage Forms, • Tablets (1981); and Ansel, Introduction to Pharmaceutical Dosage Forms 2nd Edition (1976).

G. METHODS OF TREATMENT The treatment method can be any suitable method that is effective in the treatment of the type of tumor or virus in particular that is being treated. Treatment can be oral, rectal, topical, parenteral, intravenous administration or injection to the tumor site directly or close to it, or the like. The method for applying an effective amount also varies depending on the tumor being treated. It is believed that parenteral treatment by intravenous, subcutaneous or intramuscular application formulated with a suitable carrier, an additional cancer inhibitor compound or diluent (s) to facilitate application, will be the preferred method for administering the compounds in warm-blooded animals.

It is believed that many herbicides alone or in combination with other herbicides and / or fungicides will exhibit this beneficial anti-tumor effect. Preferred fungicides include benzimidazole such as carbendazin, thiabendazole, benomyl. Other agents that can be used include griseofulvin, fluconazole and propiconazole. The N-phosphonoglycine derivatives are also effective against viruses and include rhinoviruses, HIV, herpes and influenza. The combination of the N-fosfonoglicinas with enhancers is especially effective against viruses. The dosage form and the treatment method is the same for tumors or cancers. The following examples are illustrative and should not be construed as limiting to the invention.

Tumor Cell Tests in Colon, Mama and_ Lung The following cell culture tests were performed to test the toxicity of N-phosphonoglycine compounds in human tumor cells of the colon, breast and lung. The availability of the cells was tested by observing the MTT reduction (3 - [4,5-dimethiazol-2-yl] -2,5-diphenyltetrazolium bromide). The MTT assay is well known for measuring cell viability. Colon tumor cells (HT29 from the American Type Culture Collection (ATCC)) and cells P'l'l -, of breast (MXl of the ATCC cell line)) were cultured in an Eagle minimal essential medium with 10% fetal bovine serum. Lung tumor cells (A549 from the ATCC cell lines) were cultured in Ham's F12 medium with 10% fetal bovine serum. The tumor cells were passed and seeded in culture flasks up to the desired cell densities. The culture medium was decanted and the cell lamellae were washed twice-with phosphate buffer saline (PBS). The cells were triptinized and ground before the flasks were seeded. Unless otherwise indicated, the cultures were incubated at 37 + 1 ° C in a humidified atmosphere of 5 ± 1% carbon dioxide in air. The cultures were incubated until they were 50 to 80% confluent. The cells were subcultured when the flasks were subconfluent. The medium was aspirated from the flasks and the cell leaves or lamellae were washed twice with PBS. Subsequently, the trypsin solution was added to each flask to cover the cell lamellae. The trypsin solution was removed after 30 to 60 seconds and the flasks were incubated at room temperature for 2 to 6 minutes. When 90% of the cells were dislodged, the growth medium was added. The cells were removed by trituration and transferred to I 'l ( a sterile centrifuge tube. The concentration of the cells in the euepension was determined and an adequate dilution was made to obtain a density of 5000 cells / ml. The cells were subcultured in the cells destined for 96-well bioassay plates (200 microliters of cell suspension per well). The PBS was added to all remaining cavities to maintain moisture. Subsequently the plates were covered for the entire night before the treatment of the test article. Each dose of the test article was tested by treating the cavities in quadruplicate with 100 microliters of each dilution. Those cavities designated as solvent controls received 100 microliters of methanol control; the negative control cavities received 100 microliters more of the treatment medium. The PBS was added to the remaining cavities not treated with the medium or test article. Subsequently the plates were incubated for approximately 5 days. At the end of the fifth day of incubation each group of doeis was examined microscopically to determine toxicity. A 0.5 mg / ml dilution of MTT was made in the treatment medium and the dilution was filtered through a 0.45 micron filter to remove the undissolved crystals. The medium was decanted from the cavities of the bioassay plates. Immediately afterwards, 2000 microliters of the filtered MTT solution was added to all the test cavities, except for the two untreated blank test cavities. The two white cavities received 200 microliters of the treatment medium. The plates were returned to the incubator for approximately 3 hours. After incubation, the medium containing MTT was decanted. The excess medium was added to each well and the plates were shaken at room temperature for about 2 hours. The absorbance at 550 nm (OD550) of each cavity was measured with a molecular diepoeitive (Menlo Park, CA) Vmax plate reader. The average OD550 of the solvent control wells and those of each test item dilution and those of the white wells and those of the positive control were calculated. The average OD550 of the white cavities was subtracted from the mean of the solvent control cavities and the test article cavities respectively to give the corresponding average OD55o. OD550 corrected average of the Dilution of the Test Article Control% = X 100 corrected average of OD550 Solvent Control The dose response curves were prepared as semi-logarithmic graphs with percent control I '.] 1' t in the ordinates (linear scale) and the concentration of the test article in the abscissa (logarithmic scale). The EC5Q was interpolated from the graphs of each test item. For the test articles administered in methanol, separate responses were prepared to correct the methanol data. Adriamycin was used as a positive control. In all cases, it did not result in greater toxicity to any of the test materials in more than one or two logarithmic units. Adriamycin is one of the most potent agents that is currently available and one that has significant natural effects. The peak plasma concentration of other highly effective chemotherapeutic agents may be 10 to 50 times higher than that of adriamycin. The EC-50 is the concentration at which half of the cells are killed.

TABLE 1 Test Material Result EC-50 (ppm 0 microgram / ml) HT29 HR29 MXl MXl A549 A549 Adriamycin 0.003 0.006 0.02 0.001 0.03 0.009 glyphosate 5.41 3.73 36.5 14.6 25.9 22.3 1 •: "< In normal healthy cells the following results were obtained: TABLE 2 EC-50 Material Test glyphosate adriamycin These experiments show that these compositions are effective in killing tumor cells without significantly affecting healthy cells.

Claims (15)

1. EIV INDICATIONS: 1. A pharmaceutical composition for treating cancers, tumors or viral infections, comprising a safe and effective amount of N-foephonoglycine derivatives of the formula: GOLD X-C-CH2-N-CH2-P-OY OZ wherein X is selected from the group consisting of hydroxyl, alkoxy and chloroxyl of up to 12 carbon atoms; lower alkenoxy, cyclohexyloxy, morpholino, pyrrolidinyl, piperidino and NHR '; Y and Z are independently selected from hydrogen and lower alkyl, and R is selected from the group consisting of hydrogen, formyl, acetyl, benzoyl, nitrobenzoyl and chlorobenzoyl, and R 'is selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, cyclohexyl, phenalkyl of up to 8 carbon atoms, phenyl, chlorinated phenyl and anisyl, and certain salts of these compounds, which are selected from the group consisting of groups I and II of metals with an atomic number of up to 30; hydrochloride, acetate, salicylate, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline.
2. 2. A pharmaceutical composition according to claim 1, further comprising an enhancer.
3. 3. A pharmaceutical composition according to claim 1 or 2, further comprising a chemotherapeutic agent.
4. 4. A pharmaceutical composition according to claim 1, 2 or 3, comprising a pharmaceutically acceptable carrier and a safe and effective amount of N- (phosphonomethyl) glycine and / or one of its isopropyl amine salt and wherein the addition salts of pharmaceutically acceptable acids are selected from the group consisting of hydrochloride, acetate, salicylate, lower alkyl amine and mixtures thereof.
5. 5. A pharmaceutical composition according to claims 1, 2, 3 or 4, wherein the chemotherapeutic agent is selected from the group consisting of DNA-interacting agent, antimetabolitoe, tubulo-interactive agent, hormone agent, aeparaginase or hydroxyurea, asparagine, hydroxyurea , ciplatin, cyclophosphamide, altretamine, bleomycin, dactin icin, doxorubicin, etoposide, teniposide, and plicamidin, methotrexate, fluorouracil, fluorodeoxyuridine, CB3717, azacitidine, cytarabine, and floxuridine, mercaptopurine, 6-thioguanine, fludarabine, pentoetatin, cictrabine, and fludarabine.
6. 6. A method for treating viral cancer and infections in warm-blooded animals, comprising administering a safe and effective amount and a pharmaceutical composition according to claims 1, 2, 3, 4 or 5.
7. 7. A unit dose composition for treating tumors or viralee infections comprising N-phosphonoglycine derivatives of the formula: 0 R 0 X-C-CH2-N-CH2-P-OY OZ wherein X is selected from the group that connects hydroxyl, alkoxy and chloroxyl of up to 12 carbon atoms; lower alkenoxy, cyclohexyloxy, morpholino, pyrrolidinyl, piperidino and NHR '; Y and Z are independently selected from hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl, acetyl, benzoyl, nitrobenzoyl and chlorobenzoyl; and R1 is selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, cyclohexyl, phenalkyl of up to 8 carbon atoms, phenyl, chlorinated phenyl and anisyl, and certain salts of these compounds, the salts are select from the group you have found in Groups I and II of the metals with an atomic number of up to 30; hydrochloride, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline.
8. 8. A unit dose composition according to claim 7, wherein the N-phosphonoglycine is N- (phosphonomethyl) glycine and its lower alkyl amine salts.
9. 9. A unitary doe composition according to claim 6, 7 or 8, wherein the pharmaceutically acceptable acid addition salts are selected from the group consisting of mixtures thereof and hydrochlorides, acetates and salicylates, wherein about 2 mg / kg of body weight to approximately 400 mg / kg of N-phosphonoglycine.
10. 10. A unit dose composition according to claim 9, comprising a safe and effective amount of a chemotherapeutic agent.
11. 11. A unit dose composition according to claim 10, wherein the N-phosphonoglycine is N- (phosphonomethyl) glycine and its lower alkyl amine saltse, and wherein the pharmaceutically acceptable acid addition salts are selected from the group consisting of hydrochlorides, acetates, salicylate and mixtures thereof. f'-l "1
12. 12. A method for inhibiting tumor growth comprising administering a safe and effective amount of a systemic herbicide.
13. 13. A unit dose composition for inhibiting tumor growth comprising a safe and effective amount of a systemic herbicide.
14. 14. A unit dose composition for inhibiting tumor growth comprising a safe and effective amount of a systemic herbicide, a fungicide and a chemotherapeutic agent.
15. 15. A unit dose composition according to claims 10, 11, 12, 13 or 14, further comprising an enhancer.