CA1268714A - Use of an aqueous chlorite matrix solution for the treatment of tumors - Google Patents
Use of an aqueous chlorite matrix solution for the treatment of tumorsInfo
- Publication number
- CA1268714A CA1268714A CA000508249A CA508249A CA1268714A CA 1268714 A CA1268714 A CA 1268714A CA 000508249 A CA000508249 A CA 000508249A CA 508249 A CA508249 A CA 508249A CA 1268714 A CA1268714 A CA 1268714A
- Authority
- CA
- Canada
- Prior art keywords
- tumors
- treatment
- chlorite matrix
- chlorite
- matrix
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- 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
- A61K33/40—Peroxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
USE OF AN AQUEOUS CHLORITE MATRIX SOLUTION
FOR THE TREATMENT OF TUMORS
ABSTRACT OF THE DISCLOSURE
The use of an aqueous solution of a chemically stabilized chlorite matrix for intravenous and/or topical administration in tumor treatments is described.
FOR THE TREATMENT OF TUMORS
ABSTRACT OF THE DISCLOSURE
The use of an aqueous solution of a chemically stabilized chlorite matrix for intravenous and/or topical administration in tumor treatments is described.
Description
Applicant: OXO Chemie GmbH, Maassstrasse 24, 6900 Heidelberg Use of an aqueous chlorite matrix solution for the treatment of tumors The invention relates to the use of a chlorite matrix solution for the treatment of tumors.
In the conventional chemotherapeutic treatment of tumors it has to be accepted that there is a considerable risk of side effects, ~hich impair the quality of life, in order to obtain an objeceively measurable tumor re-gression.
The object of the invention is to diminish this risk of side effects of chemotherapeutic and radio-1~ therapeutic treatments of tumors using a composition with,at the same time, an improvement or at least a mainten-ance of the therapeutic efficacy of the treatments.
This object is achieved by the use of a composi~
tion consisting of an aqueous solution of a chemicaLly stabilized chlorite matrix for intravenous and top;cal administration in tumor treatments.
The use of the composition can be combined with radiotherapy, ~ith chemotherapy~ with radio- and chemo-therapy, and with chemotherapy and hyperthermia.
A chlorite matrix uith activated oxygen is dis-closed in 6erman Offenlegungsschrift 3,213,389 and has already been used successfully as a wound-treatment agent.
It has now been found, surprisingly, that a chemically stabili7ed chlorite matrix can be used with good results for tumor treatments, it being possible for the matrix to be stabilized by oxygen or another element of grpups VI a ~ b oF the periodic table or in another manner. It is kno~n that the oxygen supply to malignant tumors may very greatly influence the efficacy of various therapeutic 3û measures, such as ionizing radiation or particular chemo-therapeutics. Experiments have sho~n that it is possible ~3r~
to obtain a Pasteur effect on intravenous administration of an isotonic solution of the chlorite matrix, the action of the chlorite matrix being direct and/or indirect.
There is a direct and indirect action when the stabilizer S of the chlorite matrix is oxygen. The action is indirect ~hen stabilization is effected by another element of group VI a + b of the periodic table or in another manner, for example a high pH.
It has been found that the chlorite matrix acts in practice as a biochemical even in the micromolar range and below, 2nd thus need not be supplied in excessive concentrations in order to display its action. In this context, it is assumed that an activated, non-toxic oxy-gen species is formed, by which an increase in the blood flow in per;pheral hypoxic areas owing to vasodilatation, and an oxygen-saving measure in the mitochondria is ob-tained. This action probably contributes to an increase in the oxygen levels in the tissue and in the body fluids after administration of the chlorite matrix.
If chemotherapy and radiotherapy are combined ~ith chlorite matrix treatment, it is possible consider-abLy to reduce the doses of chemotherapeutic agents and of the irradiations - and thus the risk of side effects -to achieve the same results.
Experimental results on the antitumor efficacy of stabilized chlorite matrix.
Use uas made of an isotonic solution of oxygen-stabilized chlorite matrix ~hich contains 2.8 x 102 oxi-dation units measured by gas chromatographic determination of the ethylene liberated from a suitable indicator mole-cule. Experiments on several transplantation tumor models in mice and rats have sho~n that the chlorite matrix solu-tion slo~s do~n the tumor gro~th as 3 function of the dosage (dosages: 0.17, 0.34 and 0.68 ml of chlorite mat-rix solution per kg of body ueight, administered 1 x a day, parenterally). ~he inhibitory action of metasta-sizing solid tumors relates not only to the primary tumor 7 ~ ~
but also to the secondaries (metastases).
The testing for antitumor efficacy produced posi-tive results with the following transplantation tumors:
Lewis lung, adenocarcinoma of the C 57 91/6 mouse, Harding-Passey sarcoma of the C 57 B1/6 mouse, Friend virus leuk-emia of the NMRI mouse and L 5222 leukemia of the 8D IX
rat. It was noticed with all the tumors mentioned here that although the weight reduction during treatment with the stabilized chlorite matrix was less dramatic than for the positive controls treated with cyclophosphamide, the animals treated with chlorite matrix solution showed a markedly better and more active general condition than the animals treated with the cytotoxic chemotherapeutic.
Stabilized chlorite matrices are activated by complexation with macrocyclic tetrapyrrole-containing biomolecules to give compounds with electron affinity.
It is known of compounds with electron affinity that they act as radiation-sensitizers in the radiotherapeutic treatment of malignant tumors (reference: W. Porschen, K. Gewehr, L.E. Feinendegen, Med. Physik, volume 2, pages 467-479/1976). This pharmacological property has been confirmed by initial positive findings in radiotherapy under previous parenteral treatment with the chlori-te matrix solution of patients with tumors which responded poorly to radiotherapy.
The therapeutic tests on transplantation tumors in animal experiments have shown that the antitumor effi-cacy of stabilized chlorite matrices is not a cytotoxic or cytostatic effect. On the contrary, the stabilized chlorite matrices influence, on the one hand, the body's own defensive system and, on the other hand, the experi-ments carried out with L 5222 and Friend virus leukemia show that the chlorite matrices have a reverting action on the malignant cell phenotyPe of the tumors. These points of attack, which are of an entirely different nature to those of the conventional chemotherapeutics, lead to the conclusion that additional treatment with stabilized chlorite matrices can potentiate the antitumor effect of classical chemotherapeutics.
In the conventional chemotherapeutic treatment of tumors it has to be accepted that there is a considerable risk of side effects, ~hich impair the quality of life, in order to obtain an objeceively measurable tumor re-gression.
The object of the invention is to diminish this risk of side effects of chemotherapeutic and radio-1~ therapeutic treatments of tumors using a composition with,at the same time, an improvement or at least a mainten-ance of the therapeutic efficacy of the treatments.
This object is achieved by the use of a composi~
tion consisting of an aqueous solution of a chemicaLly stabilized chlorite matrix for intravenous and top;cal administration in tumor treatments.
The use of the composition can be combined with radiotherapy, ~ith chemotherapy~ with radio- and chemo-therapy, and with chemotherapy and hyperthermia.
A chlorite matrix uith activated oxygen is dis-closed in 6erman Offenlegungsschrift 3,213,389 and has already been used successfully as a wound-treatment agent.
It has now been found, surprisingly, that a chemically stabili7ed chlorite matrix can be used with good results for tumor treatments, it being possible for the matrix to be stabilized by oxygen or another element of grpups VI a ~ b oF the periodic table or in another manner. It is kno~n that the oxygen supply to malignant tumors may very greatly influence the efficacy of various therapeutic 3û measures, such as ionizing radiation or particular chemo-therapeutics. Experiments have sho~n that it is possible ~3r~
to obtain a Pasteur effect on intravenous administration of an isotonic solution of the chlorite matrix, the action of the chlorite matrix being direct and/or indirect.
There is a direct and indirect action when the stabilizer S of the chlorite matrix is oxygen. The action is indirect ~hen stabilization is effected by another element of group VI a + b of the periodic table or in another manner, for example a high pH.
It has been found that the chlorite matrix acts in practice as a biochemical even in the micromolar range and below, 2nd thus need not be supplied in excessive concentrations in order to display its action. In this context, it is assumed that an activated, non-toxic oxy-gen species is formed, by which an increase in the blood flow in per;pheral hypoxic areas owing to vasodilatation, and an oxygen-saving measure in the mitochondria is ob-tained. This action probably contributes to an increase in the oxygen levels in the tissue and in the body fluids after administration of the chlorite matrix.
If chemotherapy and radiotherapy are combined ~ith chlorite matrix treatment, it is possible consider-abLy to reduce the doses of chemotherapeutic agents and of the irradiations - and thus the risk of side effects -to achieve the same results.
Experimental results on the antitumor efficacy of stabilized chlorite matrix.
Use uas made of an isotonic solution of oxygen-stabilized chlorite matrix ~hich contains 2.8 x 102 oxi-dation units measured by gas chromatographic determination of the ethylene liberated from a suitable indicator mole-cule. Experiments on several transplantation tumor models in mice and rats have sho~n that the chlorite matrix solu-tion slo~s do~n the tumor gro~th as 3 function of the dosage (dosages: 0.17, 0.34 and 0.68 ml of chlorite mat-rix solution per kg of body ueight, administered 1 x a day, parenterally). ~he inhibitory action of metasta-sizing solid tumors relates not only to the primary tumor 7 ~ ~
but also to the secondaries (metastases).
The testing for antitumor efficacy produced posi-tive results with the following transplantation tumors:
Lewis lung, adenocarcinoma of the C 57 91/6 mouse, Harding-Passey sarcoma of the C 57 B1/6 mouse, Friend virus leuk-emia of the NMRI mouse and L 5222 leukemia of the 8D IX
rat. It was noticed with all the tumors mentioned here that although the weight reduction during treatment with the stabilized chlorite matrix was less dramatic than for the positive controls treated with cyclophosphamide, the animals treated with chlorite matrix solution showed a markedly better and more active general condition than the animals treated with the cytotoxic chemotherapeutic.
Stabilized chlorite matrices are activated by complexation with macrocyclic tetrapyrrole-containing biomolecules to give compounds with electron affinity.
It is known of compounds with electron affinity that they act as radiation-sensitizers in the radiotherapeutic treatment of malignant tumors (reference: W. Porschen, K. Gewehr, L.E. Feinendegen, Med. Physik, volume 2, pages 467-479/1976). This pharmacological property has been confirmed by initial positive findings in radiotherapy under previous parenteral treatment with the chlori-te matrix solution of patients with tumors which responded poorly to radiotherapy.
The therapeutic tests on transplantation tumors in animal experiments have shown that the antitumor effi-cacy of stabilized chlorite matrices is not a cytotoxic or cytostatic effect. On the contrary, the stabilized chlorite matrices influence, on the one hand, the body's own defensive system and, on the other hand, the experi-ments carried out with L 5222 and Friend virus leukemia show that the chlorite matrices have a reverting action on the malignant cell phenotyPe of the tumors. These points of attack, which are of an entirely different nature to those of the conventional chemotherapeutics, lead to the conclusion that additional treatment with stabilized chlorite matrices can potentiate the antitumor effect of classical chemotherapeutics.
Claims (5)
1. Use of a composition consisting of an aqueous solution of a chemically stabilized chlorite matrix for intravenous and/or topical administration in tumor treat-ments.
2. Use of the composition as claimed in claim 1, combined with radiotherapy.
3. Use of the composition as claimed in claim 1, combined with chemotherapy.
4. Use of the composition as claimed in claim 1, combined with radiotherapy and chemotherapy.
5. Use of the composition as claimed in claim 1, combined with chemotherapy and hyperthermia.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853515748 DE3515748A1 (en) | 1985-05-02 | 1985-05-02 | USE OF ISOTON CHLORITE MATRIX SOLUTION IN TUMOR TREATMENT |
| DEP3515748.8 | 1985-05-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1268714A true CA1268714A (en) | 1990-05-08 |
Family
ID=6269617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000508249A Expired - Fee Related CA1268714A (en) | 1985-05-02 | 1986-05-02 | Use of an aqueous chlorite matrix solution for the treatment of tumors |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0200156B1 (en) |
| JP (1) | JPS6230715A (en) |
| AT (1) | ATE75144T1 (en) |
| AU (1) | AU595514B2 (en) |
| CA (1) | CA1268714A (en) |
| DE (2) | DE3515748A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7252772B2 (en) | 2001-06-07 | 2007-08-07 | P&W Invest Vermogensverwaltungsgesellschaft Mbh | Method for producing an essentially chlorite-free, stable aqueous chlorine-oxygen solution, the chlorine-oxygen solution obtained by means of said method, and the use of the same |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3515745A1 (en) * | 1985-05-02 | 1986-11-06 | Oxo Chemie GmbH, 6900 Heidelberg | AQUEOUS CHLORITE MATRIX SOLUTION |
| DE3515749A1 (en) * | 1985-05-02 | 1986-11-06 | Oxo Chemie GmbH, 6900 Heidelberg | USE OF A STABILIZED CHLORITE MATRIX SOLUTION IN INFECTIOUS CONDITIONS |
| DE3600931A1 (en) * | 1986-01-15 | 1987-07-16 | Oxo Chemie Gmbh | Formulation of chlorite matrices in solution |
| US4851222A (en) * | 1988-01-27 | 1989-07-25 | Oxo Chemie Gmbh | Method of promoting regeneration of bone marrow |
| DE4208828A1 (en) * | 1992-03-19 | 1993-09-23 | Oxo Chemie Gmbh | USE OF A CHEMICALLY STABILIZED CHLORITE MATRIX FOR THE PRODUCTION OF MEDICINAL PRODUCTS FOR THE TREATMENT OF HIV INFECTIONS |
| EP1408994A2 (en) * | 1999-08-18 | 2004-04-21 | OXO Chemie AG | Chemically-stabilized chlorite solutions for treating cancer |
| US20080292729A1 (en) * | 2005-07-21 | 2008-11-27 | Nuvo Research Inc. | Stabilized Chlorite Solutions in Combination with Fluoropyrimidines for Cancer Treatment |
| US8067035B2 (en) * | 2005-12-22 | 2011-11-29 | Neuraltus Pharmaceuticals, Inc. | Chlorite formulations, and methods of preparation and use thereof |
| WO2008145376A1 (en) | 2007-06-01 | 2008-12-04 | Dimethaid Ag | Use of wf10 for treating allergic asthma, allergic rhinitis and atopic dermatitis |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU68443A1 (en) * | 1946-07-09 | 1977-02-25 | Method of treating skin cancers | |
| US4296103A (en) * | 1980-08-08 | 1981-10-20 | Felipe Laso | Stabilized solution of chlorine oxides |
| DE3213389A1 (en) * | 1982-04-10 | 1983-10-20 | Friedrich-Wilhelm Dr. 7107 Neckarsulm Kühne | STABILIZED ACTIVATED OXYGEN AND MEDICINAL PRODUCTS CONTAINING THIS STABILIZED ACTIVATED OXYGEN |
| BR8405351A (en) * | 1983-02-25 | 1985-02-12 | Peter Berger | PROCESS FOR THE PREPARATION OF A WATER CHLORITIC SOLUTION AND THE CLORITIC SOLUTION OBTAINED |
| DE3515745A1 (en) * | 1985-05-02 | 1986-11-06 | Oxo Chemie GmbH, 6900 Heidelberg | AQUEOUS CHLORITE MATRIX SOLUTION |
-
1985
- 1985-05-02 DE DE19853515748 patent/DE3515748A1/en not_active Withdrawn
-
1986
- 1986-04-24 EP EP86105647A patent/EP0200156B1/en not_active Expired - Lifetime
- 1986-04-24 AT AT86105647T patent/ATE75144T1/en not_active IP Right Cessation
- 1986-04-24 DE DE8686105647T patent/DE3684953D1/en not_active Expired - Lifetime
- 1986-04-30 AU AU56840/86A patent/AU595514B2/en not_active Ceased
- 1986-05-02 JP JP61101259A patent/JPS6230715A/en active Granted
- 1986-05-02 CA CA000508249A patent/CA1268714A/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7252772B2 (en) | 2001-06-07 | 2007-08-07 | P&W Invest Vermogensverwaltungsgesellschaft Mbh | Method for producing an essentially chlorite-free, stable aqueous chlorine-oxygen solution, the chlorine-oxygen solution obtained by means of said method, and the use of the same |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3684953D1 (en) | 1992-05-27 |
| AU5684086A (en) | 1986-11-06 |
| EP0200156A2 (en) | 1986-11-05 |
| EP0200156B1 (en) | 1992-04-22 |
| JPS6230715A (en) | 1987-02-09 |
| ATE75144T1 (en) | 1992-05-15 |
| AU595514B2 (en) | 1990-04-05 |
| EP0200156A3 (en) | 1989-05-10 |
| JPH026740B2 (en) | 1990-02-13 |
| DE3515748A1 (en) | 1986-11-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1268714A (en) | Use of an aqueous chlorite matrix solution for the treatment of tumors | |
| Rivera et al. | Response of L1210 to combinations of cytosine arabinoside and VM-26 or VP16-213 | |
| Kim et al. | Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice | |
| US20070149476A1 (en) | Combination Comprising Combretastatin and Anticancer Agents | |
| Kano et al. | Effect of nitrous oxide on human bone marrow cells and its synergistic effect with methionine and methotrexate on functional folate deficiency | |
| Woodman et al. | Enhancement of the effectiveness of daunorubicin (NSC-82151) or adriamycin (NSC-123127) against early mouse L1210 leukemia with ICRF-159 (NSC-129943) | |
| Sherman et al. | The effect of dose rate and adriamycin on the tolerance of thoracic radiation in mice | |
| Wilkie | Antimitochondrial drugs in cancer chemotherapy: preliminary communication | |
| Bersani et al. | Involvement of tumour necrosis factor in monocyte-mediated rapid killing of actinomycin D-pretreated WEHI 164 sarcoma cells. | |
| Ebadi et al. | Metallothionein, neurotrophins and selegiline in providing neuroprotection in Parkinson's disease | |
| NO891122L (en) | PLATINO COORDINATION COMPOUNDS AND USING THE COMPOUNDS IN CHEMICAL THERAPY. | |
| Esposito et al. | Improved therapeutic index of cisplatin by procaine hydrochloride | |
| Burchenal | The newer nitrogen mustards in the treatment of leukemia | |
| Clapp et al. | Diethylnitrosamine oncogenesis in RF mice as influenced by variations in cumulative dose | |
| Gold | Enhancement by Hyrazine Sulfate of Antitumor Effectiveness of Cytoxan, Mitomycin C, Methotrexate and Bleomycin, in Walker 256 Carcinosarcoma in Rats | |
| Shtalrid et al. | Review of clinical and haematological response to low‐dose cytosine arabinoside in acute myeloid leukaemia | |
| AU605494B2 (en) | The use of 15-deoxyspergualine as a pharmaceutical | |
| Teicher et al. | Enhancement of fractionated radiation therapy by an experimental concentrated perflubron emulsion (Oxygent®) in the Lewis lung carcinoma | |
| TEICHER et al. | Decreased tumor oxygenation after cyclophosphamide, reoxygenation and therapeutic enhancement with a perflubron emulsion carbogen breathing | |
| Kroes et al. | Synergistic growth inhibiting effect of nitrous oxide and cycloleucine in experimental rat leukaemia | |
| Benchekroun et al. | Inhibition of DNA repair and sensitization of cisplatin in human ovarian carcinoma cells by interleukin-1α | |
| Kobayashi et al. | Systemic chemotherapy in tumor‐bearing rats using high‐dose cis‐diamminedichloroplatinum (II) with low nephrotoxicity in combination with angiotensin II and sodium thiosulfate | |
| Kessinger et al. | Mini-dose weekly Adriamycin therapy for patients with advanced malignant disease at increased risk for adriamycin toxicity | |
| Shaeffer et al. | Route dependence of adriamycin effectiveness in murine osteosarcoma | |
| Kamradt et al. | The effect of hydrazine sulfate on prostate cancer growth. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |