Claims for Patent: 5,854,231

Summary for Patent: 5,854,231

Title:	Pharmaceutical composition for inhibiting the growth of cancers
Abstract:	This invention is a pharmaceutical composition that inhibits the growth of cancers and tumors in mammals, particularly in human and warm blooded animals. The composition contains N-phosphonoglycine derivatives which are systemic herbicides in combination with chemotherapeutic agents for treatment of cancers and tumors. N-phosphonoglycine derivatives can be used to treat viral infections, particularly herpes infections. Optionally potentiators can be included.
Inventor(s):	Camden; James Berger (West Chester, OH)
Assignee:	The Procter & Gamble Company (Cincinnati, OH)
Application Number:	08/680,469
Patent Claims:	1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a safe and effective amount of a chemotherapeutic agent and a safe and effective amount of N-phosphonoglycine of the formula: ##STR5## wherein X is selected from the group consisting of hydroxyl, alkoxy or chloroxyl up to 12 carbon atoms or lower alkenoxy; Y and Z each independently are selected from the group consisting of hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl and acetyl; or pharmaceutically acceptable acid addition salts of said N-phosphonoglycine, which salts are selected from the group consisting of the Group I and II metals having an atomic number of up to 30, hydrochloride, acetate, salicylate, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline. 2. A pharmaceutical composition according to claim 1 comprising a pharmaceutically acceptable carrier and a safe and effective amount of N-(phosphonomethyl)glycine or its isopropyl amine salt. 3. A pharmaceutical composition according to claim 1 wherein said pharmaceutically acceptable acid addition salts are selected from the group consisting of hydrochloride, acetate, salicylate, lower aliphatic amine and mixtures thereof. 4. A pharmaceutical composition according to claim 1 wherein said chemotherapeutic agent is selected from the group consisting of Asparaginase, hydroxyurea, cis-diamminedichloroplatinum (II); 2-[bis(2-chiloroethyl)amino]-tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide; N,N,N',N',N",N"-hexamethyl-1,3,5-triazine-2,4,6-triamine; ##STR6## wherein Thr is the amino acid threonine; D-Val is D-valine; Sar is sarcosine and MeVal is methylvalne; (8S-cis)-10-[(3-Amino-2,3,6-trideoxy-.alpha.-L-lyxohexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-napthace nedione; 9-[(4,6-O-ethylidene-.beta.-D-glucopyranosyl)oxy]-5,8,8a,9-tetra-hydro-5-( 4-hydroxy-3,5-dimethyoxy-phenyl)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6( 5aH)-one; [5R-[5.alpha.,5a.beta.,8a.alpha.:,9.beta.(R*)]]-5,8,8a,9-Tetrahyro-5-(4-hy droxy-3,5-dimethoxyphenyl)-9-[[4,6-O-(2-thienylmethylene)-.beta.-D-glucopyr anosyl]oxy]furo[3',4':6,7]-naphtho[2,3-d]-1,3-dioxol-6(5aH)-one; Bleomycin, and Plicamycin. 5. A pharmaceutical composition according to claim 4 wherein said chemotherapeutic agent is selected from the group consisting of N-[4-[[2,4-diamino-6-pteridinyl)methyl]methyl-amino]benzoyl]-L-glutamic acid; 5-fluoro-2'-deoxy-.beta.-uridinel or 1-(2-deoxy-.beta.-D-ribrofuranosyl)-5-fluorouracil; (2'-dexoy-5-fluorouridine, 4-amino-1-.beta.-arabinofuranosyl-2(1H)-pyrmidinone; purine-6-thiol monohydrate; 2-amino-1,7-dihydro-6H-purine-6-thione, 9-.beta.-D-arabinofuranosyl-2-fluoro 9H-purine-6-amine and (R)-3-(2-deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[ 4,5-d][1,3]diazepin-8-ol. 6. A method of treating cancer in warm blooded mammals comprising administering a safe and effective amount of a pharmaceutical composition comprising a chemotherapeutic agent and N-phosphonoglycine of the formula: ##STR7## wherein X is selected from the group consisting of hydroxyl, alkoxy or chloroxyl up to 12 carbon atoms or lower alkenoxy; Y and Z each independently are selected from the group consisting of hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl and acetyl; or pharmaceutically acceptable acid addition salts of said N-phosphonoglycine, which salts are selected from the group consisting of the Group I and II metals having an atomic number of up to 30, hydrochloride, acetate, salicylate, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline. 7. A method of treating cancer in warm blooded mammals according to claim 6 comprising administering a safe and effective amount of a N-phosphonomethyl) glycine. 8. A method according to claim 7 wherein from about 2 mg/kg body weight to about 400 mg/kg of said N-(phosphonomethyl) glycine is administered. 9. A method according to claim 6 wherein said chemotherapeutic agent is selected from the group consisting of Asparaginase; hydroxyurea; cis-diamminedichloroplatinum (II); 2-[bis(2-chloroethyl)amino]-tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide; N,N,N',N',N",N"-hexamethyl- 1,3,5-triazine-2,4,6-triamine; ##STR8## wherein Thr is the amino acid threonine, D-Val is D-valine, Sar is sarcosine and MeVal is methylvaline; (8S-cis)-10-[(3-Amino-2,3,6-trideoxy-.alpha.-L-lyxohexopyran-osyl)oxy]-7,8 ,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-napthac enedione; 9-[(4,6-O-ethylidene-.beta.-D-glucopyranosyl)oxy]-5,8,8a,9-tetra-hydro-5-( 4-hydroxy-3,5-dimethyoxy-phenyl)furo [3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one; [5R-[5.dbd.,5a.beta.,8a.alpha.,9.beta.(R*)]]-5,8,8a,9-Tetrahyro-5-(4-hydro xy-3,5-dimethoxyphenyl)-9-[[4,6-O-(2-thienylmethylene)-.beta.-D-glucopyrano syl]oxy]furo-[3',4':6,7]-naphtho[2,3-d]-1,3-dioxol-6(5aH)-one; Bleomycin; and Plicamycin. 10. A method according to claim 9 wherein said chemotherapeutic agent is selected from the group consisting of N-[4-[[2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid, 5-fluoro-2'-deoxy-.beta.-uridine or 1-(2-deoxy-.beta.-D-ribofuiranosyl)-5-fluorouracil; (2'-dexoy-5-fluorouridine, 4-amino-1-.beta.-D-arabinofuranosyl-2(1H)-pyrmidinone; purine-6-thiol monohydrate, 2-amino- 1,7-dihydro-6H-purine-6-thione, 9-.beta.-D-arabinofuranosyl-2-fluoro 9H-purine-6-amine and (R)-3-(2-deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[ 4,5-d][1,3]diazepin-8-ol. 11. A method according to claim 10 wherein said chemotherapeutic agent is selected from the group consisting of Methotrexate, Fluorouracil, Fluorodeoxyuridine, CB3717, Azacitidine, Cytarabine, Floxuridine, Mercaptopurine, 6-Thioguanine, Fludarabine, Pentostatin, Cyctrabine, and Fludarabine. 12. A method according to claim 11 wherein said N-phosphonoglycine is N-(phosphonomethyl) glycine isopropyl amine salt. 13. A unit dosage composition comprising a safe and effective amount of a potentiator and N-phosphonoglycine of the formula: ##STR9## wherein X is selected from the group consisting of hydroxyl, alkoxy or chloroxyl up to 12 carbon atoms or lower alkenoxy; Y and Z each independently are selected from the group consisting of hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl and acetyl; or pharmaceutically acceptable acid addition salts of said N-phosphonoglycine, which salts are selected from the group consisting of the Group I and II metals having an atomic number of up to 30, hydrochloride, acetate, salicylate, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline and a pharmaceutically acceptable carrier. 14. A unit dosage composition according to claim 13 wherein said N-phosphonoglycine is N-(phosphonomethyl) glycine or its lower alkyl amine salts. 15. A unit dosage composition according to claim 13 wherein said pharmaceutical acceptable acid addition salts are selected from the group consisting of hydrochlorides, acetates and salicylates. 16. A safe and effective treatment for viral infections comprising administering a safe and effective amount of a pharmaceutical composition comprising N-phosphonoglycine of the formula: ##STR10## wherein X is selected from the group consisting of hydroxyl, alkoxy or chloroxyl up to 12 carbon atoms or lower alkenoxy; Y and Z each independently are selected from the group consisting of hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl and acetyl; or pharmaceutically acceptable acid addition salts of said N-phosphonoglycine, which salts are selected from the group consisting of the Group I and II metals having an atomic number of up to 30, hydrochloride, acetate, salicylate, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline and a safe and effective amount of a potentiator. 17. A treatment according to claim 16 wherein said N-phosphonoglycine is administered orally or enterically or intravenously. 18. A treatment according to claim 16 wherein said N-phosphonoglycine is administered in a solid form. 19. A treatment according to claim 18 wherein said solid form includes a carrier selected from the group consisting of lactose, sucrose, gelatin and agar. 20. A treatment according to claim 19 wherein from about 15 mg/kg to about 150 mg/kg of said N-phosphonoglycine is administered. 21. A safe and effective treatment for viral infections comprising administering from about 15 mg/kg to about 150 mg/kg of a N-phosphonoglycine of the formula: ##STR11## wherein X is selected from the group consisting of hydroxyl, alkoxy or chloroxyl up to 12 carbon atoms or lower alkenoxy; Y and Z each independently are selected from the group consisting of hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl and acetyl; or pharmaceutically acceptable acid addition salts of said N-phosphonoglycine, which salts are selected from the group consisting of the Group I and II metals having an atomic number of up to 30, hydrochloride, acetate, salicylate, pyridine, ammonium, lower aliphatic hydrocarbon amine, lower alkanol amine and aniline said N-phosphonoglycine and a safe and effective amount of a potentiator in a solid form. 22. A treatment according to claim 21 wherein said potentiator is procodazole. 23. A safe and effective treatment for herpes viral infections comprising administering a safe and effective amount of a pharmaceutical composition comprising a N-phosphonoglycine derivatives of the formula: ##STR12## wherein X is selected from the group consisting of hydroxyl, alkoxy or chloroxy up to 12 carbon atoms; lower alkenoxy; Y and Z each independently are selected from the group consisting of hydrogen and lower alkyl; and R is selected from the group consisting of hydrogen, formyl and acetyl and a safe and effective amount of a potentiator. 24. A safe and effective treatment for herpes viral infections comprising administering a safe and effective amount of a pharmaceutical composition comprising N-(phosphonomethyl) glycine or its lower alkyl amine salts and a potentiator.

Details for Patent 5,854,231

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2015-04-12