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WO2006104292A1 - Composition pharmaceutique qui comprend de l’acide arsénique, du meta-arsénite et des sels pharmaceutiquement acceptables - Google Patents

Composition pharmaceutique qui comprend de l’acide arsénique, du meta-arsénite et des sels pharmaceutiquement acceptables Download PDF

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Publication number
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
Authority
WO
WIPO (PCT)
Prior art keywords
arsenite
pharmaceutically acceptable
acceptable salts
meta
sodium
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.)
Ceased
Application number
PCT/KR2005/000938
Other languages
English (en)
Inventor
Yong Jin Yang
Sang Bong Lee
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Komipharm International Co Ltd
Original Assignee
Komipharm International Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Komipharm International Co Ltd filed Critical Komipharm International Co Ltd
Priority to PCT/KR2005/000938 priority Critical patent/WO2006104292A1/fr
Publication of WO2006104292A1 publication Critical patent/WO2006104292A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K33/24—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.

Landscapes

  • 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)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention concerne une composition pharmaceutique pour la prévention et le traitement du syndrome d’immunodéficience acquise comprenant de l’acide arsénique, du meta-arsénite et leurs sels pharmaceutiquement acceptables. Plus spécifiquement, cette invention détermine que l’acide arsénique sodique, le méta-arsénite sodique et leur sels pharmaceutiquement acceptables, qui sont des métabolites du As203 in vivo, ont des activités anti-VIH 1 et anti-VIH 2 et fournissent ainsi une composition pharmaceutique pour la prévention et le traitement du syndrome d’immunodéficience acquise.
PCT/KR2005/000938 2005-03-31 2005-03-31 Composition pharmaceutique qui comprend de l’acide arsénique, du meta-arsénite et des sels pharmaceutiquement acceptables Ceased WO2006104292A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/KR2005/000938 WO2006104292A1 (fr) 2005-03-31 2005-03-31 Composition pharmaceutique qui comprend de l’acide arsénique, du meta-arsénite et des sels pharmaceutiquement acceptables

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2005/000938 WO2006104292A1 (fr) 2005-03-31 2005-03-31 Composition pharmaceutique qui comprend de l’acide arsénique, du meta-arsénite et des sels pharmaceutiquement acceptables

Publications (1)

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WO2006104292A1 true WO2006104292A1 (fr) 2006-10-05

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PCT/KR2005/000938 Ceased WO2006104292A1 (fr) 2005-03-31 2005-03-31 Composition pharmaceutique qui comprend de l’acide arsénique, du meta-arsénite et des sels pharmaceutiquement acceptables

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WO (1) WO2006104292A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009072779A1 (fr) * 2007-12-04 2009-06-11 Sang Bong Lee Composition contenant du méta-arsénite de sodium pour le traitement de l'hépatite c
WO2011031890A3 (fr) * 2009-09-10 2011-08-25 Kominox, Inc. Thérapie ciblée sur des cellules souches cancéreuses et contre un cancer pharmacorésistant
WO2011034775A3 (fr) * 2009-09-18 2011-10-06 Kominox, Inc. Méthodes de traitement de tumeurs cérébrales
TWI404538B (zh) * 2007-02-02 2013-08-11 Panaphix Inc 砷化合物用於治療疼痛及發炎之用途
WO2019178643A1 (fr) * 2018-03-22 2019-09-26 Komipharm International Australia Pty Ltd Composition pharmaceutique comprenant du méta-arsénite et procédé de fabrication
WO2021159187A1 (fr) * 2020-02-16 2021-08-19 Komipharm International Australia Pty Ltd Méthode de traitement à l'aide de méta-arsénite

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20020083458A (ko) * 2001-04-28 2002-11-02 주식회사 한국미생물연구소 아르세닉산나트륨 염, 메타아르세나이트 염 또는 이의혼합물을 함유한 항암제 조성물

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20020083458A (ko) * 2001-04-28 2002-11-02 주식회사 한국미생물연구소 아르세닉산나트륨 염, 메타아르세나이트 염 또는 이의혼합물을 함유한 항암제 조성물
KR20020083678A (ko) * 2001-04-28 2002-11-04 주식회사 한국미생물연구소 아르세닉산나트륨 염, 소디움 메타아르세나이트 또는 이의혼합물을 함유한 항암제 조성물

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI404538B (zh) * 2007-02-02 2013-08-11 Panaphix Inc 砷化合物用於治療疼痛及發炎之用途
US10058570B2 (en) 2007-02-02 2018-08-28 Panaphix Inc. Use of arsenic compounds for treatment of pain and inflammation
RU2665362C2 (ru) * 2007-02-02 2018-08-29 Панафикс Инк. Применение соединений мышьяка для лечения отторжения ткани или органа
WO2009072779A1 (fr) * 2007-12-04 2009-06-11 Sang Bong Lee Composition contenant du méta-arsénite de sodium pour le traitement de l'hépatite c
WO2011031890A3 (fr) * 2009-09-10 2011-08-25 Kominox, Inc. Thérapie ciblée sur des cellules souches cancéreuses et contre un cancer pharmacorésistant
RU2568834C2 (ru) * 2009-09-10 2015-11-20 Коминокс, Инк. Противораковая терапия, направленная против раковых стволовых клеток и форм рака, устойчивых к лечению лекарственными препаратами
WO2011034775A3 (fr) * 2009-09-18 2011-10-06 Kominox, Inc. Méthodes de traitement de tumeurs cérébrales
JP2021518434A (ja) * 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 メタ亜ヒ酸塩を含む医薬組成物および製造方法
WO2019178643A1 (fr) * 2018-03-22 2019-09-26 Komipharm International Australia Pty Ltd Composition pharmaceutique comprenant du méta-arsénite et procédé de fabrication
JP7419333B2 (ja) 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 メタ亜ヒ酸塩を含む医薬組成物および製造方法
IL277456B1 (en) * 2018-03-22 2024-07-01 Komipharm Int Australia Pty Ltd Medicinal composition containing meta arsenite and production method
IL277456B2 (en) * 2018-03-22 2024-11-01 Komipharm Int Australia Pty Ltd Pharmaceutical composition comprising meta arsenite and method of manufacture
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 (fr) * 2020-02-16 2021-08-19 Komipharm International Australia Pty Ltd Méthode de traitement à l'aide de méta-arsénite
CN115243692A (zh) * 2020-02-16 2022-10-25 科微范国际澳大利亚私人有限公司 使用偏亚砷酸盐的治疗方法

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