OA12802A - Pharmaceutical composition comprising arsenite forthe treatment of malignancy. - Google Patents
Pharmaceutical composition comprising arsenite forthe treatment of malignancy. Download PDFInfo
- Publication number
- OA12802A OA12802A OA1200400272A OA1200400272A OA12802A OA 12802 A OA12802 A OA 12802A OA 1200400272 A OA1200400272 A OA 1200400272A OA 1200400272 A OA1200400272 A OA 1200400272A OA 12802 A OA12802 A OA 12802A
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- OA
- OAPI
- Prior art keywords
- tumour
- sait
- arsenite
- pharmaceutical composition
- malignancy
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/36—Arsenic; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
012802
PHARMACEUTICAL COMPOSITION COMPRISING ARSENITE FOR THE TREATMENT OF MALIGNANCY
The présent invention relates to a pharraaceuticalcomposition containing arsenic for the treatment of a malig-nancy.
Pharmaceutical compositions containing arsenic areknown for cancer therapy. For example, the review by Waxman S. et al (The Oncologist 6(suppl. 2), pp. 3-10 (2001)) de-scribes arsenic disulfide, arsenic trisulfide and arsenictrioxide the use of said composition comprising a sait ofmeta-arsenite (AsC>2~) and a pharmaceutically acceptable auxil-iary.
Due to their inhérent toxicity, and the advent ofgood alternatives, interest in arsenic compounds has remainedlow.
The object of the présent invention is to provide apharmaceutical composition suitable for use in cancer ther-apy, which allows for the treatment of solid tumours. Thepharmaceutical composition may be used for treatment of suchsolid tumours for which currently no treatment exists, or asan alternative or supplementary treatment.for such solid tu-mours .
To this end, the pharmaceutical composition accord-ing to the présent invention is characterized in that it is apharmaceutical composition for the treatment of a solid ma-lignancy chosen from the group consisting of colon tumour,gastric tumour, mammary tumour, ovarian tumour, prostate tu-mour, and rénal tumour, said composition comprising a sait ofmeta-arsenite (AsC>2~) and a pharmaceutically acceptable auxil-iary.
It has been found that the specified types of tumourare surprisingly sensitive to the meta-arsenite sait. In thesait the counter-ion of meta-aresenite may be any pharmaceu-tically acceptable counter-ion.
In the article by Waxman, mention is made of an ar-ticle by Tarnowski G.S. et al (Cancer Research, 26(2), pp.181-206 (1966)) where 8.tumour types were investigated with 012802 2 14 different anti-tumour Chemicals. Potassium arsenite af-fected only the growth of Ehrlich ascites tumour. Regardingthis tumour type it is remarked that it is more sensitive inthe ascites than in the sold form. This emphasizes the sur- 5 prising finding of the présent invention.
According to a preferred embodiment, the sait is an % alkaline or earth alkaline métal sait. According to a morepreferred embodiment, the alkaline métal sait is a potassiumor sodium sait. 10 Such salts are readily soluble and are readily available for exerting their anti-tumour effect.
The' invention also relates to the use of a sait ofmeta-arsenite (AsO2_) for the manufacture of a pharmaceuticalcomposition for the treatment of a solid malignancy chosen 15 from the group consisting of colon tumour, gastric tumour,mammary tumour, ovarian tumour, prostate tumour, and rénaltumour.
It was found that solid malignancy belonging to thegroup consisting of colon tumour, mammary tumour, prostate 20 tumour, and rénal tumour were particularly sensitive.
Finally, the présent invention relates to a method of treating a human individual suffering from a solid malignancychosen from the group consisting of colon tumour, gastric tu-mour, mammary tumour, ovarian tumour, prostate tumour, and 25 rénal tumour, with a pharmaceutically effective dose of asait of meta-arsenite {AsOî') .
The présent invention will now be elucidated withreference to the following non-limiting example.
30 EXÂMPLE
Various human tumor cells were grown at 37°C in ahumidified atmosphère (95% air, 5% CO2) in monolayer culturesin RPMI 1640 medium with phénol red (Life Technologies,Karlsruhe, Germany) supplemented with 10% fêtai calf sérum. 35 Cells were trypsinized and maintained weekly.
Cytotoxicity assay A modified propidium iodide assay (based on W.A. 012802 3
Dengler et. al, Anti-Cancer Drugs, 6, pp. 522-532 (1995)) wasused to examine the antiproliférative activity of the studycompounds. Briefly, cells will be harvested from exponentialphase cultures growing in RPMI 1640 medium supplemented with10% fêtai calf sérum by trypsination, counted and plated in 96well flat-bottomed microtiter plates (140 μΐ cell suspension, 8 x 104 cells/ml). After a 24h recovery, to allow cells to ré-sumé exponential growth, 10 μΐ culture medium (6 control wellsper plate) or culture medium containing the test drug wereadded to the wells. Each drug concentration was plated intriplicate. After 4 days of incubation culture medium was re-placed by an aqueous propidium iodide solution (6 μg/ml). Mi-crotiter plates were kept at -18°C for 24 h, resulting in atotal cell kill. After thawing of the plates, fluorescence wasmeasured using a Millipore Cytofluor 2350-microplate reader(excitation 530 nm, émission 620 nm) in order to quantify thetotal cell number. The assay included untreated and positiveControls (5-FU and vindesine).
Growth inhibition is expressed as Treated/Control x100 (or T/C%) . IC50 and IC70 values were determined by plottingcompound concentration versus cell number. Mean IC50 and IC70values were calculated according to the formula: n Σ log (ICso,7o)xx—1
Mean ICso,7o = - 10n
With x = spécifie tumor cell line and n = total num-ber of cell Unes studied. If IC50 or IC70 could not be deter-mined within the examined dose range, the lowest or highestconcentration studied was used for the calculation.
Assays were considered valid only if the positivecontrol (5—FU) induced a tumor growth inhibition of T/C <30%and if vehicle treated control cells had a fluorescence in-tensity >500 units.
The results hâve been summarized in Table I, which Résulta 012802 4 shows that in particular tumour cell lines of the type gas-tric tumour, ovarian tumour, and in particular prostate tu-mour, mammary tumour, rénal and colon tumour were sensitiveto the meta-arsenite compound. In comparison, promyelocytic 5 leukaemia, which is known to respond to arsenic trioxide, showed an IC70 value of 6.82 gg/ml. Hence, the tumour cells towhich the présent invention relates are about 2 to 20 timesmore sensitive to the meta-arsenite compound according to theprésent invention. 0
TABLE I
Tumour cell line IC70 (μσ/πιΐ) Colon DLD1 0.48 Gastric GXF251L 3.08 Mammary MXAF401NL 0,32 Ovarian OVCAR3 3.02 Prostate PC 3 0.85 Rénal RXF486L 0.63
Claims (6)
- 012802 CLAIMS1. Pharmaceutical composition for the treatment of asolid malignancy chosen from the group consisting of colontumour, gastric tumour, mammary tumour, ovarian tumour, pros- 5 tate tumour, and rénal tumour, said composition comprising asait of meta-arsenite (AsO2_) and a pharmaceutically accept-able auxiliary.
- 2. Pharmaceutical composition according to claim 1, ► charact-ari in that the sait is an alkaline or earth alka-10 line métal sait.
- 3. Pharmaceutical composition according to claim 2,characterized in that the alkaline métal sait is a potassiumor sodium sait.
- 4. Use of a sait of meta-arsenite (AsOî-) for the 15 manufacture of a pharmaceutical composition for the treatmentof a sclid malignancy chosen from the group consisting of co-lon tumour, gastric tumour, mammary tumour, ovarian tumour,prostate tumour, and rénal tumour.
- 5. Use according to claim 4, characterized in that 20 solid malignancy is chosen from the group consisting of colon tumour, mammary tumour, prostate tumour, and rénal tumour.
- 6. Method of treating a human individual suffering - from a solid malignancy chosen from the group consisting of colon-tumour, gastric tumour, mammary tumour, ovarian tumour, 25 prostate tumour, and rénal tumour, with a pharmaceuticallyeffective dose of a sait of meta-arsenite {AsOî") .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| OA1200400272A OA12802A (en) | 2002-04-10 | 2002-04-10 | Pharmaceutical composition comprising arsenite forthe treatment of malignancy. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| OA1200400272A OA12802A (en) | 2002-04-10 | 2002-04-10 | Pharmaceutical composition comprising arsenite forthe treatment of malignancy. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA12802A true OA12802A (en) | 2006-07-11 |
Family
ID=37023106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200400272A OA12802A (en) | 2002-04-10 | 2002-04-10 | Pharmaceutical composition comprising arsenite forthe treatment of malignancy. |
Country Status (1)
| Country | Link |
|---|---|
| OA (1) | OA12802A (en) |
-
2002
- 2002-04-10 OA OA1200400272A patent/OA12802A/en unknown
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