WO2006104292A1 - Pharmaceutical composition comprising arsenic acid, meta-arsenite, and pharmaceutically acceptable salts - Google Patents
Pharmaceutical composition comprising arsenic acid, meta-arsenite, and pharmaceutically acceptable salts Download PDFInfo
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- WO2006104292A1 WO2006104292A1 PCT/KR2005/000938 KR2005000938W WO2006104292A1 WO 2006104292 A1 WO2006104292 A1 WO 2006104292A1 KR 2005000938 W KR2005000938 W KR 2005000938W WO 2006104292 A1 WO2006104292 A1 WO 2006104292A1
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- Prior art keywords
- arsenite
- pharmaceutically acceptable
- acceptable salts
- meta
- sodium
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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
Definitions
- This invention relates to a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome comprising arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts. More specifically, this invention identifies that arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts, which are in vivo metabolites of AS2O3, have anti- HIV-I and anti-HIV-2 activities and thereby provides a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome.
- the object of this invention is to provide a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome.
- This invention relates to a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome comprising at least one selected from the group consisting of arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts as active ingredients. This invention is more specifically described hereunder.
- the inventors of this invention have succeeded in identifying the anti-HIV-1 and anti-HIV-2 activities of arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts, which are in vivo metabolites of As 2 O 3 , and therefore this invention relates to a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome comprising arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts.
- Arsenic acid sodium as one of the active ingredients of the pharmaceutical composition of the present invention, is an in vivo metabolite of AS2O3 and can be obtained from blood or living body or synthesized. It has been also known to be effective in curing leukemia or solid cancer.
- Sodium meta-arsenite as another active ingredient of the pharmaceutical composition of the present invention, is also an in vivo metabolite of AS2O3 and can be obtained from blood or living body or synthesized. It has been also known to be effective in curing leukemia or solid cancer.
- the above-mentioned arsenic acid sodium and sodium meta- arsenite can form pharmaceutically acceptable salts by reacting with inorganic acids such as HCl, acetic acid, bromic acid, and the like while they can also form pharmaceutically acceptable salts by reacting with alkali metal ions such as sodium, potassium, and the like. Therefore, the present invention also includes pharmaceutically acceptable salts of both arsenic acid sodium and sodium meta- arsenite.
- arsenic acid sodium and sodium meta-arsenite and their pharmaceutically acceptable salts have anti-HIV-1 and anti-HIV-2 activities, it is apparent that their mixture would also have anti-HIV-1 and anti-HIV-2 activities. Therefore, arsenic acid sodium and sodium meta-arsenite and their pharmaceutically acceptable salts can be used as active ingredients of a pharmaceutical composition for prevention and treatment of AIDS. Further, in manufacturing pharmaceutical drugs containing the above-mentioned active ingredients, they can be prepared in the form of tablets, powder, granules, capsules, suspensions, emulsions, or unit preparations for parenteral administration or other preparations for multiple administrations by containing a pharmaceutically acceptable carriers or excipients.
- the effective amount of active ingredients for the above-mentioned pharmaceutical composition may vary greatly depending on the age, physical condition, body weight of a patient.
- the effective amount is 0.1 - 30 mg/kg/day, more preferably 0.5 - 3 mg/kg/day.
- administration can be done once or a few times daily within the effective range.
- Human T cell transgenic cell line MT-4 was used after culturing in RPMI1640, a medium containing 10% bovine fetal serum. Besides, HIV-I and HIV-2 lines were kindly provided by National Institute for Biological Standards and Control (NIBSC) in United Kingdom. Each virus was allowed to respectively infect H9 cell and subcultured at intervals of about 3 to 4 days. The culture was centrifuged and the resulting supernatant was collected as solution of viral seed solution and stored at - 70 0 C, which was used after thawing at 37 0 C immediately prior to use.
- RPMI1640 a medium containing 10% bovine fetal serum.
- HIV-I and HIV-2 lines were kindly provided by National Institute for Biological Standards and Control (NIBSC) in United Kingdom. Each virus was allowed to respectively infect H9 cell and subcultured at intervals of about 3 to 4 days. The culture was centrifuged and the resulting supernatant was collected as solution of viral seed solution and stored at - 70 0 C,
- CCID50 50% tissue culture infectious dose
- Example 1 Effect of in vitro anti-HIV Activity In vitro experiments were conducted to investigate the anti-HIV effects of sodium arsenate and sodium meta-arsenite.
- sodium arsenic acid and sodium meta-arsenite of the present invention were shown to have superior anti-HIV activities to that of AZT, a currently available AIDS treating agent while having less cytotoxici y at the same concentration.
- Example 2 Test of Subacute Toxicity on Mice Subacute toxicity for oral administration were conducted using 5 week old specific pathogen free (SPF) CD-I mice. Sodium arsenate and sodium meta-arsenite of the present invention were respectively dissolved in 10% glucose solution and orally administered once daily with a concentration of 10, 20, 40 and 80 mg/kg/day, respectively, to 10 mice in each group for 14 days. Then, after 14 days of restoration period, biochemical and hematological tests were conducted on the 29 th day and organ abnormalities were observed by naked eyes after autopsies. Besides, clinical syndromes, change in body weight, and mortality of mice after the administration were observed daily.
- SPPF pathogen free
- mice there were no dead mice or mice with apparent clinical syndromes observed in a group where the above-mentioned two test materials were administered with the concentration of 10, 20 and 40 mg/kg and also no toxicological change was observed in body weight, hematological test, hematobiochemical test, and autopsies. On the contrary, in a group where sodium arsenate was administered with a concentration of 80 mg/kg, one mouse was dead on the 13 th day after the oral administration and two mice showed respiratory problems but no additional death was observed.
- One tablet (200 mg) was mixed with 100 mg of active ingredients (arsenic acid sodium, meta-arsenite or their pharmaceutically acceptable salts), 40 mg of lactose, 51 mg of corn starch and 2 mg of colloidal silicon dioxide.
- active ingredients arsenic acid sodium, meta-arsenite or their pharmaceutically acceptable salts
- lactose lactose
- 51 mg of corn starch 50 mg
- colloidal silicon dioxide colloidal silicon dioxide.
- the mixture was pulverized after adding 3% polyvinylpyrolidone solution and then passed through a size 14 mesh. After drying, the resultant was passed again through the size 14 mesh and added with 1 mg of magnesium stearate to obtain the mixture in the form of a tablet.
- the pharmaceutical composition of the present invention comprising arsenic acid sodium,sodium meta-arsenite or their pharmaceutically acceptable salts as active ingredient have excellent anti-HIV-1 and anti-HIV-2 activities and are thus expected to be very useful for the prevention and treatment of acquired immune deficiency syndrome.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
This invention relates to a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome comprising arsenic acid, meta-arsenite and their pharmaceutically acceptable salts. More specifically, this invention identifies that arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts, which are in vivo metabolites of As203, have anti-HIV-1 and anti-HIV-2 activities and thereby provides a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome.
Description
PHARMACEUTICAL COMPOSITION COMPRISING ARSENIC ACID, META-ARSENITE, AND PHARMACEUTICALLY ACCEPTABLE SALTS
Technical Field This invention relates to a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome comprising arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts. More specifically, this invention identifies that arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts, which are in vivo metabolites of AS2O3, have anti- HIV-I and anti-HIV-2 activities and thereby provides a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome.
Background of Invention
The number of acquired immunodeficiency syndrome (AIDS) patients, since its first report of occurrence in San Francisco (USA) in 1981, increased to 5 mil. in 2002 and about 3 mil. people were known to have died of the disease. The total number of HIV-infected patients as of December 2002 was about 42 mil. people. In Korea, since the first appearance of HIV-infected patients in December 1985, it has drastically increased to 2,405 as of September 2003, thus necessitating the urgent development of appropriate therapeutic treatments. Due to the fast-growing number of AIDS patients worldwide, advanced countries such as USA, Canada, France and Japan have made extreme efforts for early development of therapeutic drugs for AIDS. However, only a few anti-HIV substances have been approved by US FDA such as dideoxyinosine(ddl), dideoxycytidine(ddC), etc. Further, these compounds,
which are currently at use for therapeutic treatment of AIDS, cannot prevent viral replications in the already infected cells but can only prevent further infection of AIDS in most uninfected cells therefore only serving as a life-extending role rather than curing the deadly disease itself. Besides, these compounds have shown other adverse effects such as decrease in thrombocytosis, blood corpuscles in bone marrow and there has been found viruses which have resistant to these compounds thus requiring development of more effective therapeutic drugs.
While performing extensive researches to find drugs to resolve the above problems, the inventors of the present invention, have found that arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts, which are in vivo metabolites of As2O3, have anti-HIV-1 and anti-HIV-2 activities. Therefore, the object of this invention is to provide a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome.
Detailed Description of Invention
This invention relates to a pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome comprising at least one selected from the group consisting of arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts as active ingredients. This invention is more specifically described hereunder.
The inventors of this invention have succeeded in identifying the anti-HIV-1 and anti-HIV-2 activities of arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts, which are in vivo metabolites of As2O3, and therefore this invention relates to a pharmaceutical composition for prevention and
treatment of acquired immune deficiency syndrome comprising arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts.
Arsenic acid sodium, as one of the active ingredients of the pharmaceutical composition of the present invention, is an in vivo metabolite of AS2O3 and can be obtained from blood or living body or synthesized. It has been also known to be effective in curing leukemia or solid cancer.
Sodium meta-arsenite, as another active ingredient of the pharmaceutical composition of the present invention, is also an in vivo metabolite of AS2O3 and can be obtained from blood or living body or synthesized. It has been also known to be effective in curing leukemia or solid cancer.
Meanwhile, the above-mentioned arsenic acid sodium and sodium meta- arsenite can form pharmaceutically acceptable salts by reacting with inorganic acids such as HCl, acetic acid, bromic acid, and the like while they can also form pharmaceutically acceptable salts by reacting with alkali metal ions such as sodium, potassium, and the like. Therefore, the present invention also includes pharmaceutically acceptable salts of both arsenic acid sodium and sodium meta- arsenite.
When the above-mentioned pharmaceutically acceptable salts of both arsenic acid sodium and sodium meta-arsenite were tested by Microculture Tetrazolium (MTT) method of their inhibitory activities of cytopathic effect (CPE) on MT-4 cells infected with HIV-I and HIV-2, respectively, it was shown that the pharmaceutically acceptable salts of both arsenic acid sodium and sodium meta-arsenite had antiviral activities superior to that of AZT, a commercially available therapeutic agent of AIDS, and also had less cytotoxicity.
Besides, since arsenic acid sodium and sodium meta-arsenite and their pharmaceutically acceptable salts have anti-HIV-1 and anti-HIV-2 activities, it is apparent that their mixture would also have anti-HIV-1 and anti-HIV-2 activities. Therefore, arsenic acid sodium and sodium meta-arsenite and their pharmaceutically acceptable salts can be used as active ingredients of a pharmaceutical composition for prevention and treatment of AIDS. Further, in manufacturing pharmaceutical drugs containing the above-mentioned active ingredients, they can be prepared in the form of tablets, powder, granules, capsules, suspensions, emulsions, or unit preparations for parenteral administration or other preparations for multiple administrations by containing a pharmaceutically acceptable carriers or excipients.
The effective amount of active ingredients for the above-mentioned pharmaceutical composition may vary greatly depending on the age, physical condition, body weight of a patient. Preferably, the effective amount is 0.1 - 30 mg/kg/day, more preferably 0.5 - 3 mg/kg/day. In addition, administration can be done once or a few times daily within the effective range.
Examples
The present invention is described further in detail with reference to the following examples, however, they should not be construed as limiting the scope of the invention.
Reference Example
(1) Cells and Viral Lines
Human T cell transgenic cell line MT-4 was used after culturing in RPMI1640, a medium containing 10% bovine fetal serum. Besides, HIV-I and HIV-2 lines were kindly provided by National Institute for Biological Standards and Control (NIBSC) in United Kingdom. Each virus was allowed to respectively infect H9 cell and subcultured at intervals of about 3 to 4 days. The culture was centrifuged and the resulting supernatant was collected as solution of viral seed solution and stored at - 70 0C, which was used after thawing at 37 0C immediately prior to use.
(2) Specimen Sodium arsenate and sodium meta-arsenite were kindly provided by
Rephartox Co., Ltd. and they were stored at below 4 0C. For in vitro study, sodium arsenate and sodium meta-arsenite were dissolved in DMSO to a concentration of 0.3% or less. AZT was used as a standard drug.
(3) Viral Titration The viral titer of a viral solution used in the experiment was indicated via
50% tissue culture infectious dose (CCID50) by performing titration according to using a less volume of culture medium in MT-4 cell.
Example 1 : Effect of in vitro anti-HIV Activity In vitro experiments were conducted to investigate the anti-HIV effects of sodium arsenate and sodium meta-arsenite.
One hundred microliters of sodium arsenate and sodium meta-arsenite, respectively, which were diluted twice in each well, and 100 μL each of 1.0 XlO4MT- 4 cells infected with HIV-I and HIV-2, respectively, to have the inoculation of 100
CCIU50 were added into 96-well plates. The mixture was cultured at 37 0C in CO2 incubator for 5 days and antiviral effects and cytotoxicity of sodium arsenate and sodium meta-arsenite were observed by comparing the number of cells survived counted by using a microscope via MTT inspection method with that of cell count (CC).
In comparison with CC, the concentration of a drug with antiviral activity for the survival of 50% of infected cells was indicated as EC50 (50% effective concentration), while the concentration of a drug with cytotoxicity for killing 50% of mocked infected cells was indicated as CC50 (50% cytotoxic concentration). Table 1 Comparison of Cytotoxicity of Specimens
Specimen CC50(μg/mL)
AZT 2.9 sodium arsenate 6.0 sodium meta-arsenite 4.6
Table 2. Comparison of Anti-HIV Activities
As shown in the above Tables 1 and 2, sodium arsenic acid and sodium meta-arsenite of the present invention were shown to have superior anti-HIV
activities to that of AZT, a currently available AIDS treating agent while having less cytotoxici y at the same concentration.
Example 2: Test of Subacute Toxicity on Mice Subacute toxicity for oral administration were conducted using 5 week old specific pathogen free (SPF) CD-I mice. Sodium arsenate and sodium meta-arsenite of the present invention were respectively dissolved in 10% glucose solution and orally administered once daily with a concentration of 10, 20, 40 and 80 mg/kg/day, respectively, to 10 mice in each group for 14 days. Then, after 14 days of restoration period, biochemical and hematological tests were conducted on the 29th day and organ abnormalities were observed by naked eyes after autopsies. Besides, clinical syndromes, change in body weight, and mortality of mice after the administration were observed daily. The results showed that there were no dead mice or mice with apparent clinical syndromes observed in a group where the above-mentioned two test materials were administered with the concentration of 10, 20 and 40 mg/kg and also no toxicological change was observed in body weight, hematological test, hematobiochemical test, and autopsies. On the contrary, in a group where sodium arsenate was administered with a concentration of 80 mg/kg, one mouse was dead on the 13th day after the oral administration and two mice showed respiratory problems but no additional death was observed. Further, in a group where sodium meta-arsenite was administered with a concentration of 80 mg/kg, three mice were dead on the 4th day after the oral administration, one mouse was dead on the 7* day and four mice showed respiratory problems but no additional death was observed.
The result of subacute toxicity test of the present invention using CD-I mice, where both sodium arsenate and sodium meta-arsenite were orally administered, there was no toxical change observed until the concentration reached 40 mg/kg and thus 40 mg/kg was determined as safe dose for oral administration.
Preparation Example 1: Preparation of Tablets
One tablet (200 mg) was mixed with 100 mg of active ingredients (arsenic acid sodium, meta-arsenite or their pharmaceutically acceptable salts), 40 mg of lactose, 51 mg of corn starch and 2 mg of colloidal silicon dioxide. The mixture was pulverized after adding 3% polyvinylpyrolidone solution and then passed through a size 14 mesh. After drying, the resultant was passed again through the size 14 mesh and added with 1 mg of magnesium stearate to obtain the mixture in the form of a tablet.
Preparation Example 2: Preparation of Injections
Of 10 mL ampoule, 10 mg of active ingredients (arsenic acid, meta-arsenite or their pharmaceutically acceptable salts) was dissolved in 200 mg of polyoxyethylenehydrogenated castor oil and then added with injectional distilled water to a final volume of 10 mL and prepared an injection with a concentration of 1 mg/mL.
Industrial Applicability
As stated above, the pharmaceutical composition of the present invention comprising arsenic acid sodium,sodium meta-arsenite or their pharmaceutically
acceptable salts as active ingredient have excellent anti-HIV-1 and anti-HIV-2 activities and are thus expected to be very useful for the prevention and treatment of acquired immune deficiency syndrome.
Claims
1. A pharmaceutical composition for prevention and treatment of acquired immune deficiency syndrome comprising at least one selected from the group consisting of arsenic acid sodium, sodium meta-arsenite and their pharmaceutically acceptable salts as active ingredients.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR2005/000938 WO2006104292A1 (en) | 2005-03-31 | 2005-03-31 | Pharmaceutical composition comprising arsenic acid, meta-arsenite, and pharmaceutically acceptable salts |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR2005/000938 WO2006104292A1 (en) | 2005-03-31 | 2005-03-31 | Pharmaceutical composition comprising arsenic acid, meta-arsenite, and pharmaceutically acceptable salts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2006104292A1 true WO2006104292A1 (en) | 2006-10-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2005/000938 Ceased WO2006104292A1 (en) | 2005-03-31 | 2005-03-31 | Pharmaceutical composition comprising arsenic acid, meta-arsenite, and pharmaceutically acceptable salts |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2006104292A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009072779A1 (en) * | 2007-12-04 | 2009-06-11 | Sang Bong Lee | Composition comprising sodium meta-arsenite for treatment of hepatitis c |
| WO2011031890A3 (en) * | 2009-09-10 | 2011-08-25 | Kominox, Inc. | Cancer stem cell-targeted and drug resistant cancer therapy |
| WO2011034775A3 (en) * | 2009-09-18 | 2011-10-06 | Kominox, Inc. | Methods for treating brain tumors |
| TWI404538B (en) * | 2007-02-02 | 2013-08-11 | Panaphix Inc | Use of arsenic compounds for treatment of pain and inflammation |
| WO2019178643A1 (en) * | 2018-03-22 | 2019-09-26 | Komipharm International Australia Pty Ltd | Pharmaceutical composition comprising meta arsenite and method of manufacture |
| WO2021159187A1 (en) * | 2020-02-16 | 2021-08-19 | Komipharm International Australia Pty Ltd | Method of treatment using meta-arsenite |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20020083458A (en) * | 2001-04-28 | 2002-11-02 | 주식회사 한국미생물연구소 | Anticancer drug composition containing arsenic acid sodium salt, salt of meta-arsenite or their mixture |
-
2005
- 2005-03-31 WO PCT/KR2005/000938 patent/WO2006104292A1/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20020083458A (en) * | 2001-04-28 | 2002-11-02 | 주식회사 한국미생물연구소 | Anticancer drug composition containing arsenic acid sodium salt, salt of meta-arsenite or their mixture |
| KR20020083678A (en) * | 2001-04-28 | 2002-11-04 | 주식회사 한국미생물연구소 | Anticancer drug composition containing arsenic acid sodium salt, sodium meta arsenite or their mixture |
Non-Patent Citations (1)
| Title |
|---|
| WANG Z.Y.: "Arsenic compounds as anticancer agents", CANCER CHEMOTHER. PHARMACOL., vol. 48, no. SUPPL. 1, August 2001 (2001-08-01), pages S72 - S76 * |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI404538B (en) * | 2007-02-02 | 2013-08-11 | Panaphix Inc | Use of arsenic compounds for treatment of pain and inflammation |
| US10058570B2 (en) | 2007-02-02 | 2018-08-28 | Panaphix Inc. | Use of arsenic compounds for treatment of pain and inflammation |
| RU2665362C2 (en) * | 2007-02-02 | 2018-08-29 | Панафикс Инк. | Use of arsenic compounds to treat tissue or organ rejection |
| WO2009072779A1 (en) * | 2007-12-04 | 2009-06-11 | Sang Bong Lee | Composition comprising sodium meta-arsenite for treatment of hepatitis c |
| WO2011031890A3 (en) * | 2009-09-10 | 2011-08-25 | Kominox, Inc. | Cancer stem cell-targeted and drug resistant cancer therapy |
| RU2568834C2 (en) * | 2009-09-10 | 2015-11-20 | Коминокс, Инк. | Anti-cancer therapy, directed against cancer stem cells and forms of cancer, resistant to treatment by medications |
| WO2011034775A3 (en) * | 2009-09-18 | 2011-10-06 | Kominox, Inc. | Methods for treating brain tumors |
| JP2021518434A (en) * | 2018-03-22 | 2021-08-02 | コミファーム インターナショナル オーストラリア ピーティーワイ リミテッド | Pharmaceutical composition containing meta-arsenate and method for producing |
| WO2019178643A1 (en) * | 2018-03-22 | 2019-09-26 | Komipharm International Australia Pty Ltd | Pharmaceutical composition comprising meta arsenite and method of manufacture |
| JP7419333B2 (en) | 2018-03-22 | 2024-01-22 | コミファーム インターナショナル オーストラリア ピーティーワイ リミテッド | Pharmaceutical composition containing metaarsenite and manufacturing method |
| IL277456B1 (en) * | 2018-03-22 | 2024-07-01 | Komipharm Int Australia Pty Ltd | Pharmaceutical composition comprising meta arsenite and method of manufacture |
| IL277456B2 (en) * | 2018-03-22 | 2024-11-01 | Komipharm Int Australia Pty Ltd | Medicinal composition containing meta arsenite and production method |
| AU2019239671B2 (en) * | 2018-03-22 | 2025-02-27 | Komipharm International Australia Pty Ltd | Pharmaceutical composition comprising meta arsenite and method of manufacture |
| US12257347B2 (en) | 2018-03-22 | 2025-03-25 | Komipharm International Australia Pty Ltd | Pharmaceutical composition comprising meta arsenite and method of manufacture |
| WO2021159187A1 (en) * | 2020-02-16 | 2021-08-19 | Komipharm International Australia Pty Ltd | Method of treatment using meta-arsenite |
| CN115243692A (en) * | 2020-02-16 | 2022-10-25 | 科微范国际澳大利亚私人有限公司 | Treatment using metaarsenite |
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