WO2006110119A1 - Produit antineoplasique (et variantes) - Google Patents
Produit antineoplasique (et variantes) Download PDFInfo
- Publication number
- WO2006110119A1 WO2006110119A1 PCT/UA2006/000020 UA2006000020W WO2006110119A1 WO 2006110119 A1 WO2006110119 A1 WO 2006110119A1 UA 2006000020 W UA2006000020 W UA 2006000020W WO 2006110119 A1 WO2006110119 A1 WO 2006110119A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- gluconate
- magnesium
- acid
- antineoplastic
- calcium
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 230000000118 anti-neoplastic effect Effects 0.000 title claims abstract description 21
- 229940050410 gluconate Drugs 0.000 claims abstract description 33
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- 239000011777 magnesium Substances 0.000 claims abstract description 23
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 229940091250 magnesium supplement Drugs 0.000 claims abstract description 19
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 18
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000000174 gluconic acid Substances 0.000 claims abstract description 15
- 235000012208 gluconic acid Nutrition 0.000 claims abstract description 15
- 239000001755 magnesium gluconate Substances 0.000 claims abstract description 14
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- IAKLPCRFBAZVRW-XRDLMGPZSA-L magnesium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;hydrate Chemical compound O.[Mg+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O IAKLPCRFBAZVRW-XRDLMGPZSA-L 0.000 claims abstract description 14
- 239000011575 calcium Substances 0.000 claims abstract description 12
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 10
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 8
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- 239000003446 ligand Substances 0.000 claims abstract description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 5
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- HLCFGWHYROZGBI-JJKGCWMISA-M Potassium gluconate Chemical group [K+].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O HLCFGWHYROZGBI-JJKGCWMISA-M 0.000 claims description 3
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- BVXZPASOJPQGKN-UHFFFAOYSA-L calcium;2-hydroxybutanoate Chemical compound [Ca+2].CCC(O)C([O-])=O.CCC(O)C([O-])=O BVXZPASOJPQGKN-UHFFFAOYSA-L 0.000 claims description 2
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- 230000017531 blood circulation Effects 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 229940095625 calcium glucarate Drugs 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- UGZVNIRNPPEDHM-SBBOJQDXSA-L calcium;(2s,3s,4s,5r)-2,3,4,5-tetrahydroxyhexanedioate Chemical compound [Ca+2].[O-]C(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O UGZVNIRNPPEDHM-SBBOJQDXSA-L 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- VUHJZBBCZGVNDZ-TTYLFXKOSA-N chlormadinone Chemical compound C1=C(Cl)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 VUHJZBBCZGVNDZ-TTYLFXKOSA-N 0.000 description 1
- 229960003996 chlormadinone Drugs 0.000 description 1
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- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- PZXJOHSZQAEJFE-UHFFFAOYSA-N dihydrobetulinic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(C)C)C5C4CCC3C21C PZXJOHSZQAEJFE-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
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- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 229960003681 gluconolactone Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940125697 hormonal agent Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000009546 lung large cell carcinoma Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- FRXLRLRBNDGCMF-UHFFFAOYSA-L magnesium;2-hydroxybutanoate Chemical compound [Mg+2].CCC(O)C([O-])=O.CCC(O)C([O-])=O FRXLRLRBNDGCMF-UHFFFAOYSA-L 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- MQYXUWHLBZFQQO-UHFFFAOYSA-N nepehinol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C MQYXUWHLBZFQQO-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the invention relates to the composition of such antineoplastic preparations based on rluconic acid, which exhibit a proapoptotic and antiproliferative effect.
- cytokines The main role in it is played by the immune system. After recognition of foreign (in particular, mutated) cells, its cells produce chemical agents called cytokines, which “shut down” the multi-stage apoptosis process.
- antibiotics of the anthracycline group include (see CD Mosbu's, 2003) antibiotics of the anthracycline group: doxorubicin, otherwise referred to as adriamycin (A. SWadapowski & J. Kopora. Adriatus apditus pogroptochelpocillosophosompochem. 46, 375)), and similar to it bleomycin ⁇ dactinomycin, daunorubicin, idarubicin, etc.
- doxorubicin and its analogues induce apoptosis by inhibiting topoisomerase (the enzyme responsible for malignant cells).
- therapeutic agents of this kind can also induce apoptosis in healthy cells.
- the cytotoxic effect of doxorubicin for the human body as a whole occurs with a cumulative dose of more than 20 mg / kg.
- concomitant organic lesions develop (often with a fatal outcome).
- the main ones are thrombocytopenia, neutropenia, anemia and cardiopathy, leading to the death of 5-20% of patients treated with doxorubicin (CD Mosbu's, 2003) and other well-known drugs of the same class (Ez-assess kur opsologogu. Corea UPHAR PHARM, 2004, p. 107).
- apoptosis is caused by: betulinic acid (Betulipis acid ipodus aortosis ip humapulobell cellulitis: M.L.Schmidt, et al .; Eur. J.
- cytosphatic antineoplastic drugs which slow down, and often completely suppress, the proliferation (growth) of cancerous tumors (or ⁇ z ⁇ z-assess kur opsologogu, p. Z).
- platinum preparations cis-platinum, oxyplatinum, carboplatin
- alkylating agents cyclophosphamide, busulfan, dacarbazine, thiotepa, etc.
- antimetabolites cytarabine, fluorouracil, methotrexate, mercaptopurine, etc.
- herbal preparations docetaxel, paclitaxel, vincristine, vinblastine, etc.
- hormonal agents chlormadinone, diethylstilbestrol, flutamide, etc.
- TNF tumor necrotic factor
- the basis of the invention is the task of changing the composition to create a drug based on gluconic acid, which, when introduced into the human body, would exhibit a pronounced antineoplastic effect against the background of the preservation of healthy cells.
- the antineoplastic preparation based on gluconic acid according to the invention is at least one such salt in which the salt-forming agent is selected from the group consisting of magnesium, sodium, potassium, ⁇ -aminobutyric acid (hereinafter GABA ), ethylenediamine or mixtures thereof.
- GABA ⁇ -aminobutyric acid
- the first and second additional differences, respectively, are that the antineoplastic preparation is magnesium gluconate, or potassium gluconate.
- This drug is preferably used for oncological diseases of arbitrary etiology against a background of deficiency of potassium or magnesium ions in the body.
- the antineoplastic preparation based on gluconic acid according to the invention is a coordination compound based on magnesium gluconate, in which the ligands are selected from the group consisting of GABA, 3-hydroxy-GAMK, ethylene diamine tetraacetic acid (hereinafter EDTA) ) and ethylene glycol tetraacetic acid (hereinafter referred to as EGTA).
- GABA GABA
- 3-hydroxy-GAMK ethylene diamine tetraacetic acid
- EDTA ethylene diamine tetraacetic acid
- EGTA ethylene glycol tetraacetic acid
- antineoplastic preparation is the coordination compound diHAMK-Mg-gluconate. This prep It is preferred to use rats for oncological diseases of the respiratory organs, brain and intestines.
- the antineoplastic preparation is a double salt selected from the group consisting of magnesium butyratogluconate, magnesium hydroxybutyrate gluconate, magnesium glucarate gluconate, calcium butyratogluconate, calcium hydroxybutyrate gluconate, calcium glucarate gluconate and their combination. These drugs are preferably used for neoplasty.
- antineoplastic drug is magnesium glucaratogluconate, which is preferable for cancer of arbitrary etiology against the background of a deficiency of magnesium ions in the body.
- Gluconic acid empirical formula C 6 H 12 O 7
- magnesium gluconate empirical formula dihydrate C 12 H 22 MgO 11 ⁇ H 2 O
- GABA empirical formula C 4 H 9 NO 2
- 3-hydroxy-GAMK empirical formula C 4 H 9 NO 3
- EDTA empirical formula C 10 H 2 o0 10 N 2
- EGTA empirical formula Ci 4 H 24 N 2 Oi 0
- glu- carboxylic acid empirical formula C 6 H 8 O 8
- chemical reagents which for the implementation of the invention must have a quality of at least “xh” (chemically pure).
- magnesium gluconate can be obtained by neutralizing gluconic acid (usually taken as an aqueous solution of the easily hydrolyzable d-gluconolactone) with an almost equimolar amount of magnesium oxide (or hydroxide).
- Normal gluconic acid salts are prepared by a neutralization reaction, in particular by adding a calculated amount of a base (or amphoteric compound) to a (usually aqueous) acid solution.
- the target products are isolated, as a rule, by evaporation of the solvent and drying the residue to constant weight (and, optionally, additional recrystallization).
- Magnesium gluconate coordination compounds are prepared from magnesium gluconate and a source of selected ligand as follows. First in distilled When stirring and heating in a water bath, a certain amount (for example, 0.1 mole) of magnesium gluconate is slowly dissolved. The solution is cooled to. temperature 35-4O 0 C and gradually, with stirring, the calculated amount of the ligand is introduced in a molar ratio to magnesium r-jonate 2: 1. The finished product is isolated from the solution by spray drying.
- DiHAMK-Mg-gluconate (empirical formula of dihydrate C 20 H 38 MgN 2 O 18 ⁇ H 2 O) is obtained by dissolving magnesium gluconate in water when heated in a water bath. After cooling the solution to 35-4O 0 C, the calculated amount of GABA in molar ratio to magnesium gluconate 2: 1 is added with stirring. The desired product is isolated by spray drying.
- Coordination compounds of calcium gluconate are obtained from calcium gluconate and the corresponding ligand according to a scheme that is similar to the above.
- Double magnesium salts are obtained in this way. Initially, an almost 50% aqueous solution of an equimolar (calculated as a cation) mixture of gluconic and one of the above (butyric, or hydroxybutyric, or glucaric) acids is prepared. Then, an equimolar amount of magnesium oxide (or hydroxide) is gradually introduced into such a solution with vigorous stirring. After assimilation of the magnesium source, the reaction mixture is cooled in an ice bath, the remaining water is separated on a Shot filter, and the precipitate dried to constant weight.
- an equimolar (calculated as a cation) mixture of gluconic and one of the above (butyric, or hydroxybutyric, or glucaric) acids is prepared. Then, an equimolar amount of magnesium oxide (or hydroxide) is gradually introduced into such a solution with vigorous stirring. After assimilation of the magnesium source, the reaction mixture is cooled in an ice bath, the remaining water is
- Double calcium gluconate salts are prepared in a similar manner.
- Experimental dosage forms are prepared by dissolving said compounds in an isotonic aqueous solution of sodium chloride or glucose. 2) Experiments on laboratory models of cancer cultures.
- A-549 cells obtained by biopsy of a large cell lung cancer of a person
- A-549-R cells of the same type, resistant to interferon at a concentration of 10,000 IU / ml
- U-937 cells sensitive to known apoptosis inducers.
- the control was healthy cells of the same tissues, not exposed to antineoplastic drugs.
- Cells of each indicated line and corresponding healthy cells were cultured at 37 ° C in complete nutrient medium RPMM 640 (SIGMA, USA) with the addition of 2 mM L-glutamine, 10% fetal serum, and 40 ⁇ g / ml gentamicin in a humidified atmosphere with volumetric concentration of CO 2 5%. The indicated medium was replaced every 2-3 days. After the formation of a dense monolayer of cells on a substrate (4-5 days of growth), cell suspensions were prepared and 24-well plates were seeded at a concentration of 3 * 10 4 cells per well.
- control drug doxorubicin and preparations according to the invention were used as additives to liquid nutrient media at the same concentration of 10 "3 mM / L. During the experiments, the nutrient medium was replaced daily.
- part of the preparations according to the invention exhibits either predominantly antiproliferative activity or predominantly proapoptotic activity and that the cumulative antineoplastic effect depends both on the type of tumor and on the composition and structure of the preparation and on its concentration and / or duration of action on tumor cells.
- Example 1 Cell suspensions based on the A-549 line were obtained and seeded in four 24-well plates at a concentration of 3 ⁇ 10 4 cells per well, as described above. DiHAMK-Mg-gluconate was added to the culture media in dilutions of 10 ⁇ 1 , 10 "2 , 10 ⁇ , and 10 ⁇ mmol / L.
- Example 2 Cell suspensions based on the line U-937 were obtained and seeded in four 24-well plates at a concentration of 3-10 4 cells per well, as described above. DiHAMK-Mg-gluconate was added to the culture media in dilutions from 10 ⁇ 1 to 10 "4 mM / L.
- the antineoplastic preparations according to the invention can be easily manufactured industrially and used for the prevention and outpatient or clinical treatment of cancer. They are easily absorbed and practically harmless to the human body, even in such single doses, which significantly exceed the therapeutically necessary doses.
- Control 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100
- GABA-gluconate 50 50 60 50 50 60 50 50 60
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Le produit antinéoplasique à base d'acide gluconique est capable d'avoir un effet apoptosique et antiprolifératif sur un fond de préservation des cellules saines. Dans une première variante, il se présente comme au moins un gluconate dans lequel l'agent de formation de sel est sélectionné dans un groupe constitué de sodium, de potassium, de magnésium, d'acide aminogammabutyrique (GABA), d'éthylènediamine ou de leurs mélanges. Dans une deuxième variante, il se présente comme une composition coordonnée sur la base de gluconate de magnésium dans laquelle les ligands ont été sélectionnés dans un groupe constitué de GABA, de 3-hydroxy-GABA, d'acide éthylène-diamine-tétra-acétique et d'acide éthylène-glycol-tétra-acétique. Dans une troisième variante, il se présente comme un sel double sélectionné dans un groupe constitué de butyrate-gluconate de magnésium, d'oxybutyrate-gluconate de magnésium, de glucarate-gluconate de magnésium, d'oxybutyrate-gluconate de calcium, de glucarate-gluconate de calcium et de leurs combinaisons.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
UAA200503576 | 2005-04-15 | ||
UA200503576 | 2005-04-15 |
Publications (1)
Publication Number | Publication Date |
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WO2006110119A1 true WO2006110119A1 (fr) | 2006-10-19 |
Family
ID=37087313
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/UA2006/000020 WO2006110119A1 (fr) | 2005-04-15 | 2006-04-12 | Produit antineoplasique (et variantes) |
Country Status (2)
Country | Link |
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RU (1) | RU2358721C1 (fr) |
WO (1) | WO2006110119A1 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MD4132C1 (ro) * | 2010-12-13 | 2012-05-31 | Государственный Университет Молд0 | Di(µ-S)-bis{cloro-[fenil(piridin-2-il)metanon-tiosemicarbazonato(1-)]cupru} care manifestă proprietatea de inhibare a proliferării celulelor T-47D ale cancerului mamar |
CN111281968A (zh) * | 2020-02-14 | 2020-06-16 | 杭州憶盛医疗科技有限公司 | 一种抗神经组织肿瘤药及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2356347A (en) * | 1999-10-04 | 2001-05-23 | John Carter | Pharmaceutical compositions for treating neoplastic disease |
WO2001087265A2 (fr) * | 2000-05-18 | 2001-11-22 | Zentaris Ag | Forme d'administration pharmaceutique pour des peptides, son procede de production et son utilisation |
RU2223759C1 (ru) * | 2002-09-18 | 2004-02-20 | Виктор Павлович Кутняк | Антиаритмический препарат |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2223756C1 (ru) * | 2002-05-23 | 2004-02-20 | Сотникова Лариса Федоровна | Способ лечения рецидивирующего иридоциклохориоидита лошадей |
-
2006
- 2006-04-12 WO PCT/UA2006/000020 patent/WO2006110119A1/fr active Application Filing
- 2006-04-12 RU RU2007141831/15A patent/RU2358721C1/ru not_active IP Right Cessation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2356347A (en) * | 1999-10-04 | 2001-05-23 | John Carter | Pharmaceutical compositions for treating neoplastic disease |
WO2001087265A2 (fr) * | 2000-05-18 | 2001-11-22 | Zentaris Ag | Forme d'administration pharmaceutique pour des peptides, son procede de production et son utilisation |
RU2223759C1 (ru) * | 2002-09-18 | 2004-02-20 | Виктор Павлович Кутняк | Антиаритмический препарат |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MD4132C1 (ro) * | 2010-12-13 | 2012-05-31 | Государственный Университет Молд0 | Di(µ-S)-bis{cloro-[fenil(piridin-2-il)metanon-tiosemicarbazonato(1-)]cupru} care manifestă proprietatea de inhibare a proliferării celulelor T-47D ale cancerului mamar |
CN111281968A (zh) * | 2020-02-14 | 2020-06-16 | 杭州憶盛医疗科技有限公司 | 一种抗神经组织肿瘤药及其制备方法 |
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RU2358721C1 (ru) | 2009-06-20 |
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