Methods and compositions for reducing toxicity of a pharmaceutical compound
First Claim
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1. A method of ameliorating or eliminating a p53-mediated toxic effect of a pharmaceutical compound in a subject comprising:
- administering to a subject a clear aqueous solution comprising;
(a) a first material selected from the group consisting of a bile acid, a bile acid salt, and a bile acid conjugated with an amine by an amide linkage;
(b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product or an aqueous soluble non-starch polysaccharide;
(c) water, wherein the first material and the carbohydrate both remain in solution for all pH values attainable in an aqueous solution; and
administering a pharmaceutical compound that has a toxic effect in the subject, wherein the pharmaceutical compound is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, suramin, bleomycin sulfate, mitomycin, epothitone, sulfasalazine, disulfiram, vincristine, vidarabine, leflunomide, and bortezomib.
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Abstract
The present disclosure is related to clear aqueous solutions of one or more bile acids and either an aqueous soluble starch conversion product or a non-starch polysaccharide. Solutions of the disclosure may be administered to a subject in conjunction with a pharmaceutical compound having one or more toxic effects. In some embodiments, solutions of the disclosure are administered to a mammal in conjunction with a pharmaceutical compound associated with a peripherial neurotoxicity (e.g., cisplatin and/or suramin) to reduce or eliminate the neuropathic effect(s).
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Citations
24 Claims
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1. A method of ameliorating or eliminating a p53-mediated toxic effect of a pharmaceutical compound in a subject comprising:
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administering to a subject a clear aqueous solution comprising; (a) a first material selected from the group consisting of a bile acid, a bile acid salt, and a bile acid conjugated with an amine by an amide linkage; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product or an aqueous soluble non-starch polysaccharide; (c) water, wherein the first material and the carbohydrate both remain in solution for all pH values attainable in an aqueous solution; and administering a pharmaceutical compound that has a toxic effect in the subject, wherein the pharmaceutical compound is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, suramin, bleomycin sulfate, mitomycin, epothitone, sulfasalazine, disulfiram, vincristine, vidarabine, leflunomide, and bortezomib. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 21)
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17. A method of reducing or eliminating a p53-mediated neuropathic effect of a pharmaceutical compound in a human subject that receives a pharmaceutical compound, said method comprising:
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administering to the human subject the pharmaceutical compound that has a p53-mediated neuropathic effect, wherein the pharmaceutical compound is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, suramin, bleomycin sulfate, mitomycin, epothitone, sulfasalazine, disulfiram, vincristine, vidarabine, leflunomide, and bortezomib, administering to the human subject a clear aqueous solution comprising; (a) a first material selected from the group consisting of a bile acid, a bile acid salt, and a bile acid conjugated with an amine by an amide linkage; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product or an aqueous soluble non-starch polysaccharide;
(c) water, wherein the first material and the carbohydrate both remain in solution for all pH values attainable in an aqueous solution. - View Dependent Claims (18)
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19. A clear aqueous solution comprising:
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(a) a first material selected from the group consisting of an aqueous soluble bile acid, a bile acid salt, and a bile acid conjugated with an amine by an amide linkage; (b) an aqueous soluble hydrolytic product of starch; (c) a pharmaceutically effective amount of a chemotherapeutic compound selected from the group consisting of cisplatin and suramin; and (d) water, wherein the first material and the aqueous soluble hydrolytic product of starch both remain in solution at all pH values from about pH 1 to about pH 14.
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22. A method of ameliorating or eliminating a toxic effect of a pharmaceutical composition comprising axonal degeneration in a subject comprising:
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administering to a subject a clear aqueous solution comprising; (a) a first material selected from the group consisting of a bile acid, a bile acid salt, and a bile acid conjugated with an amine by an amide linkage; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product or an aqueous soluble non-starch polysaccharide; (c) water, wherein the first material and the carbohydrate both remain in solution for all pH values attainable in an aqueous solution; and administering a pharmaceutical composition that has a toxic effect in the subject, wherein the pharmaceutical compound is selected from the group consisting of cisplatin, oxaliplatin, bleomycin sulfate, bortezomib, vincristine, isoniazid, vincaalkaloids, disulfram, sulfasalazine, and dapsone. - View Dependent Claims (23, 24)
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Specification