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Methods and compositions for ameliorating the undesirable effects of chemotherapy

A composition and chemical technology, applied in the direction of active ingredients of heterocyclic compounds, drug combination, organic chemistry, etc., can solve problems such as neutropenia

Inactive Publication Date: 2005-03-16
SOUND PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, cisplatin can cause a variety of side effects such as seizures, peripheral neuropathy, ototoxicity, hearing loss, deafness, vertigo, dizziness, blurred vision, nausea, vomiting, anorexia, diarrhea, constipation, bone marrow suppression, platelets hypopenias, anemia, neutropenia, and toxic nephropathy

Method used

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  • Methods and compositions for ameliorating the undesirable effects of chemotherapy
  • Methods and compositions for ameliorating the undesirable effects of chemotherapy
  • Methods and compositions for ameliorating the undesirable effects of chemotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] This example shows that N-acetyl cysteine, ebselen and allopurinol alone or in combination do not inhibit the ability of cisplatin to kill cultured NuTu-19 ovarian cancer tumor cells by MTS cell survival assay .

[0061] NuTu-19 cells were placed in 96-well culture dishes at a concentration of 3000 cells per well, and cultured at 37°C for 24 hours, during which 5% carbon dioxide gas was introduced. N-acetylcysteine, ebselen or allopurinol and NuTu-19 cells were incubated for 1 hour or 4 hours, then cisplatin was added and further incubated at 37°C for 24 hours with 5% CO2 gas. NuTu-19 cells were washed again with medium and incubated with cisplatin for an additional 24 hours.

[0062] NuTu-19 cells were washed twice with phosphate buffered saline (PBS), and then the number of surviving cells was determined by MTS assay. MTS is the abbreviation of (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium The MTS assay is a colorimetric...

Embodiment 2

[0070] This example shows that ebselen protects inner ear hair cells from cisplatin in vitro.

[0071] Three cochleae from P3-4 mouse pups per treatment were cultured in 0.4 micron MilliCell-CM supplemented with NeuroBasal A medium and B27 supplement.

[0072] After 24 hours of incubation, ebselen was added to the medium, incubated for 10 minutes, and then cisplatin was added at a final concentration of 43 μM. Another control group was treated with 43 μM cisplatin, and a second control group was treated with 47 μM ebselen without cisplatin. All cultures were incubated at 37°C for 24 hours under 5% carbon dioxide gas.

[0073] Cultured explants were collected, fixed, and stained with calbindin (for detection of hair cells) and DAPI (4',6-Diamindino-2-phenylindole; for detection of nuclear DNA).

[0074] Figure 7 showed that in the presence of 43 μM cisplatin (10), or 43 μM cisplatin and 47 μM ebselen (12), or 47 μM ebselen (14), the inner ear hair cells in the rat cochlea c...

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Abstract

In one aspect, the present invention provides chemoprotectant compositions that each comprise at least two of the chemoprotectants disclosed herein. The chemoprotectant compositions of the invention are useful, for example, for ameliorating at least one adverse effect of chemotherapy. In another aspect, the present invention provides methods of ameliorating at least one adverse effect of chemotherapy, the methods each comprising the step of administering to a subject undergoing chemotherapy an amount of a chemoprotectant composition that is effective to ameliorate at least one adverse effect of the chemotherapy.

Description

Field of invention: [0001] The present invention relates to compositions and methods for alleviating the adverse effects of chemotherapy, such as chemotherapy using cisplatin. Background technique: [0002] One method of treating cancer is chemotherapy, in which one or more chemicals that are toxic or harmful to cancer cells are administered to a cancer patient. Unfortunately, most, though not all, chemotherapeutic agents cause undesired effects that can have a detrimental effect on the patient's health. [0003] For example, the chemotherapeutic agent cisplatin (cis-diaminedichloroplatinum) is a heavy metal complex consisting of two chlorine atoms and two ammonia molecules surrounding a central platinum atom in the cis position. Cisplatin causes intrastrand and interstrand crosslinks in the DNA of rapidly dividing cells, thereby preventing DNA, RNA, and / or protein synthesis. [0004] Cisplatin (usually with other chemotherapeutic agents such as paclitaxel, cyclophosphamid...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D277/20A61K31/145A61K31/197A61K31/198A61K31/41A61K31/426A61K31/519A61K31/7056A61K31/7076A61K31/724A61K33/243A61K38/00A61K38/04A61K45/06A61P35/00A61P39/00C07D277/56C07D293/12C07D487/04C07H19/167C08B37/16
CPCA61K38/04A61K45/06A61K31/519A61K31/7076A61K31/198A61K31/197A61K33/24A61P35/00A61P39/00A61P43/00A61K33/243A61K2300/00A61K31/195A61K38/05
Inventor J·基尔E·D·林奇
Owner SOUND PHARMA
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