Cancer therapy system for effecting oncolysis of malignant neoplasms
AssigneeTherapeutical Systems Corp.
InventorClarence D. Cone, Jr.
Life of this patent
Estimating the term…
Abstract
A method for effecting oncolysis, regression, and control of malignant neoplasms in humans and other mammals without adverse effects on normal body cells is described. An ATP-availability depressor may be combined with a defined nutritional regimen, a fatty acid blocker, an amino acid blocker, a lactate export blocker, or any combination thereof.
Claims172
A method for effecting in a human or other mammal oncolysis of a malignant neoplasm wherein the malignant cells of said neoplasm are characterized by an in vivo metabolism in which said cells are substantially incapable of utilizing glucose-derived energy for the production of adenosine triphosphate (ATP) by the Citric Acid Cycle-Respiratory Chain oxidative pathway, which method comprises administering an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells.
A method for effecting in a human or other mammal oncolysis of a malignant neoplasm wherein the malignant cells of said neoplasm are characterized by an in vivo metabolism in which said cells are substantially incapable of utilizing glucose-derived energy for the production of ATP by the Citric Acid Cycle-Respiratory Chain oxidative pathway, which method comprises the concurrent administration of
- (a) an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells;
- and
- (b) an effective amount of a lactate export blocking agent for limiting the rate at which lactic acid is exported from the malignant cells.
A method for effecting in a human or other mammal oncolysis of a malignant neoplasm wherein the malignant cells of said neoplasm are characterized by an in vivo metabolism in which said cells are substantially incapable of utilizing glucose-derived energy for the production of ATP by the Citric Acid Cycle-Respiratory Chain oxidative pathway, which method comprises the concurrent administration of
- (a) an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells;
- (b) an effective amount of a lactate export blocking agent for limiting the rate at which lactic acid is exported from the malignant cells;
- and
- (c) one or more metabolic effectors selected from the group consisting of:
- (1) an effective amount of a defined nutritional regimen for limiting the amount of exogenously derived free fatty acids and amino acids available to the malignant cells while providing calorically adequate glucose for normal cell metabolism;
- (2) an effective amount of a fatty acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived free fatty acids;
- and
- (3) an effective amount of an amino acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived amino acids.
The method of claim a defined nutritional regimen is administered and wherein the ATP-availability depressor agent and the amino acid blocking agent are both thyroid hormone, the fatty acid blocking agent is lente insulin, and the lactate export blocking agent is quercetin.
The method of claim wherein the thyroid hormone is administered orally daily in an amount physiologically equivalent to 0.5 to 5.0 grains of pharmacologically standard desiccated thyroid gland, the lente insulin is of substantially 16- to 20-hour active duration and is administered by intramuscular injection daily in an amount of 5.0 to 50.0 I.U., and the pure quercetin is administered orally at twelve hour intervals in the amount of 1.5 to 8.0 milligrams per kilogram of body weight per administration.
A method for effecting in a human or other mammal oncolysis of a malignant neoplasm wherein the malignant cells of said neoplasm are characterized by an in vivo metabolism in which said cells are substantially incapable of utilizing glucose-derived energy for the production of ATP by the Citric Acid Cycle-Respiratory Chain oxidative pathway, which method comprises the concurrent administration of
- (a) an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells;
- (b) an effective amount of a defined nutritional regimen for limiting the amount of exogenously derived free fatty acids and amino acids available to the malignant cells while providing calorically adequate glucose for normal cell metabolism;
- (c) an effective amount of a fatty acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived free fatty acids;
- (d) an effective amount of an amino acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived amino acids;
- and
- (e) an effective amount of a lactate export blocking agent for limiting the rate at which lactic acid is exported from the malignant cells.
The method of claim the ATP-availability depressor agent is selected from the group consisting of 4-nitrophenol, 4-chlorophenol, phenylhydrazonocyanoacetic acid methyl ester, (3-chlorophenylhydrazono)cyanoacetic acid methyl ester, 5-chlorotrifluoromethyl benzimidazole, and combinations thereof.
A method for effecting in a human or other mammal oncolysis of a malignant neoplasm wherein the malignant cells of said neoplasm are characterized by an in vivo metabolism in which said cells are substantially incapable of utilizing glucose-derived energy for the production of ATP by the Citric Acid Cycle-Respiratory Chain oxidative pathway, which method comprises the concurrent administration of
- (a) an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells, wherein said ATP-availability depressor agent is selected from the group consisting of that
- (1) which inhibits the rate of ATP production;
- (2) which wastefully hydrolyzes ATP;
- (3) which inhibits participation of ATP in cellular energy metabolism;
- and
- (4) combinations thereof;
- and
- (b) one or more metabolic effectors selected from the group consisting of:
- (1) an effective amount of a defined nutritional regimen for limiting the amount of exogenously derived free fatty acids and amino acids available to the malignant cells while providing calorically adequate glucose for normal cell metabolism;
- (2) an effective amount of a fatty acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived free fatty acids, wherein said fatty acid blocking agent is selected from the group consisting of that
- (i) which inhibits fatty acid mobilization;
- (ii) which inhibits fatty acid transport;
- (iii) which inhibits fatty acid metabolism, and
- (iv) combinations thereof;
- (3) an effective amount of an amino acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived amino acids;
- and
- (4) an effective amount of a lactate export blocking agent for limiting the rate at which lactic acid is exported from the malignant cells,
- with the proviso that (A) when the defined nutritional regimen is utilized as the only metabolic effector, then the ATP-availability depressor agent is not a substance which inhibits the rate of ATP production, and (B) when the defined nutritional regimen and an agent which inhibits either fatty acid metabolism or fatty acid transport are utilized as the only metabolic effectors, then the ATP-availability depressor agent is not a substance which inhibits the rate of ATP production.
The method of claim 68 wherein the ATP-availability depressor agent is one whose intracellular concentration and intensity of action are substantially unaltered by changes in the intracellular pH within the range of about pH 5.0 to about pH 7.5.
The method of claim wherein the fatty acid blocking agent is selected from the group consisting of insulin, 2-tetradecylglycidic acid, methyl 2-tetradecylglycidate, and mixtures thereof.
The method of 76 wherein the insulin is lente insulin with an active duration of 18 hours or greater.
A method for effecting in a human or other mammal oncolysis of a carcinoma of the tongue, throat, stomach, cecum, colon, rectum, breast, ovary, uterus, lung, kidney, prostate, pancreas, a melanoma, a basal cell carcinoma of the skin, a leukemia, a lymphoma, or an osteosarcoma, which method comprises administering an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells.
A method for effecting in a human or other mammal oncolysis of a carcinoma of the tongue, throat, stomach, cecum, colon, rectum, breast, ovary, uterus, lung, kidney, prostate, pancreas, a melanoma, a basal cell carcinoma of the skin, a leukemia, a lymphoma, or an osteosarcoma, which method comprises the concurrent administration of
- (a) an effective amount of an ATP-availability depressor agent for limiting the overall rated of ATP energy availability for supporting the metabolism of the malignant cells;
- and
- (b) an effective amount of a lactate export blocking agent for limiting the rate at which lactic acid is exported from the malignant cells.
The method or claim the lactate export blocking agent is one or more or the natural plant bioflavonoids, selected from one group consisting of 5,7,4'-trihydroxyflavone, 3,7,3',4'-quadrahydroxyflavone, 3,5,7,2'4'-pentahydroxyflavone, 5,7,4'-trihydroxy-3,6-OCH.sub.3 -flavone, 5,7,3'-trihydroxy-3,6,4'-OCH-flavone and 3,5,7,3',4'-pentahydroxyflavone.
The method of claim wherein the intracellular concentration and intensity of action of said ATP-availability depressor agent are substantially unaltered by changes in the intracellular pH within the range of about pH 5.0 to about pH 7.5 and wherein the ATP-availability depressor agent is selected from the group consisting of that
- (a) which inhibits the rate of ATP production;
- (b) which wastefully hydrolyzes ATP;
- (c) which inhibits participation of ATP in cellular energy metabolism;
- and
- (d) combinations thereof.
A method for effecting in a human or other mammal oncolysis of a carcinoma of the tongue, throat, stomach, cecum, colon, rectum, breast, ovary, uterus, lung, kidney, prostate, pancreas, a melanoma, a basal cell carcinoma of the skin, a leukemia, a lymphoma, or an osteosarcoma, which method comprises the concurrent administration of
- (a) an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells;
- (b) an effective amount of a lactate export blocking agent for limiting the rate at which lactic acid is exported from the malignant cells;
- and
- (c) one or more metabolic effectors selected from the group consisting of:
- (1) an effective amount of defined nutritional regimen for limiting the amount of exogenously derived free fatty acids and amino acids available to the malignant cells while providing calorically adequate glucose for normal cell metabolism;
- (2) an effective amount of a fatty acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived free fatty acids;
- and
- (3) an effective amount of an amino acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived amino acids.
The method of claim wherein the ATP-availability depressor agent is selected from the group consisting of 4-nitrophenol, 4-chlorophenol, phenylhydrazonocyanoacetic acid methyl ester, (3-chlorophenylhydrazono)cyanoacetic acid methyl ester, 5-chlorotrifluoromethyl benzimidazole, and combinations thereof.
A method for effecting in a human or other mammal oncolysis of a carcinoma of the tongue, throat, stomach, cecum, colon, rectum, breast, ovary, uterus, lung, kidney, prostate, pancreas, a melanoma, a basal cell carcinoma of the skin, a leukemia, a lymphoma, or an osteosarcoma, which method comprises the concurrent administration of
- (a) an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells;
- (b) an effective amount of a defined nutritional regimen for limiting the amount of exogenously derived free fatty acids and amino acids available to the malignant cells while providing calorically adequate glucose for normal cell metabolism;
- (c) an effective amount of a fatty acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived free fatty acids;
- (d) an effective amount of an amino acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived amino acids;
- and
- (e) an effective amount of a lactate export blocking agent for limiting the rate at which lactic acid is exported from the malignant cells.
The method of claim wherein the agent which inhibits ATP production is an oxidative phosphorylation uncoupling agent having a pK.sub.a greater than or equal to about 7.0.
A method for effecting in a human or other mammal oncolysis of a carcinoma of the tongue, throat, stomach, cecum, colon, rectum, breast, ovary, uterus, lung, kidney, prostate, pancreas, a melanoma, a basal cell carcinoma of the skin, a leukemia, a lymphoma, or an osteosarcoma, which method comprises the concurrent administration of
- (a) an effective amount of an ATP-availability depressor agent for limiting the overall rate of ATP energy availability for supporting the metabolism of the malignant cells, wherein said ATP-availability depressor agent is selected from the group consisting of that
- (1) which inhibits the rate of ATP production;
- (2) which wastefully hydrolyzes ATP;
- (3) which inhibits participation of ATP in cellular energy metabolism;
- and
- (4) combinations thereof;
- and
- (b) one or more metabolic effectors selected from the group consisting of:
- (1) an effective amount of a defined nutritional regimen for limiting the amount of exogenously derived free fatty acids and amino acids available to the malignant cells while providing calorically adequate glucose for normal cell metabolism;
- (2) an effective amount of a fatty acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived free fatty acids, wherein said fatty acid blocking agent is selected from the group consisting of that
- (i) which inhibits fatty acid mobilization;
- (ii) which inhibits fatty acid transport;
- (iii) which inhibits fatty acid metabolism, and
- (iv) combinations thereof;
- (3) an effective amount of an amino acid blocking agent for limiting the rate of availability of energy to the malignant cells from endogenously derived amino acids;
- and
- (4) an effective amount of a lactate export blocking agent for limiting the rate at which lactic acid is exported from the malignant cells,
- with the proviso that (A) when the defined nutritional regimen is utilized as the only metabolic effector, then the ATP-availability depressor agent is not a substance which inhibits the rate of ATP production, and (B) when the defined nutritional regimen and an agent which inhibits either fatty acid metabolism or fatty acid transport are utilized as the only metabolic effectors, then the ATP-availability depressor agent is not a substance which inhibits the rate of ATP production.
The method of wherein the amino acid blocking agent is thyroid hormone, aminoglutethimide or both.
Dependencies are inferred from the claim text.