WO2007073765A1 - Methylselenol zinc salt and compositions containing it - Google Patents

Methylselenol zinc salt and compositions containing it Download PDF

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Publication number
WO2007073765A1
WO2007073765A1 PCT/EP2005/014094 EP2005014094W WO2007073765A1 WO 2007073765 A1 WO2007073765 A1 WO 2007073765A1 EP 2005014094 W EP2005014094 W EP 2005014094W WO 2007073765 A1 WO2007073765 A1 WO 2007073765A1
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WO
WIPO (PCT)
Prior art keywords
methylselenol
zinc salt
salt
compositions
compositions containing
Prior art date
Application number
PCT/EP2005/014094
Other languages
French (fr)
Inventor
Alessandro Heyda
Original Assignee
Marfarma Holding S.P.A.
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 Marfarma Holding S.P.A. filed Critical Marfarma Holding S.P.A.
Priority to PCT/EP2005/014094 priority Critical patent/WO2007073765A1/en
Publication of WO2007073765A1 publication Critical patent/WO2007073765A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C391/00—Compounds containing selenium

Definitions

  • the present invention relates to the methylselenol zinc salt and compositions containing it.
  • Selenium and particularly some organic compounds thereof, is known to play a fundamental role in a number of biochemical processes.
  • methylselenol (CH 3 SeH), deriving from metabolic transformations of the selenide and selenomethionine, is a remarkably effective compound for the prevention of tumors (Cancer Res. 50: 1206-1211, 1990; ibidem, 51,
  • methylselenol is an extremely volatile liquid, with boiling point of 25°C, and is therefore difficult to use as such in the formulation of pharmaceutical and nutraceutical compositions or dietary supplements.
  • the methylselenol zinc salt that can be represented by the following formula: , (CH 3 Se) 2 Zn can be prepared by reacting methylselenol sodium salt with a zinc salt, preferably with zinc chloride in stoichiometric amounts, in water.
  • Methylselenol sodium salt is conveniently obtained by reduction of the dimethylselenide and subsequent reaction with stoichiometric amounts of sodium hydroxide.
  • the resulting salt can be freeze-dried or precipitated by addition of a non-solvent and/or by concentration and cooling.
  • a dispersion of the salt of the invention in zinc carbonate, having a content in the salt of the invention approximately ranging from 0.1 to 5%, can be prepared.
  • the use of a dispersion of selenol salt in an inert matrix, such as zinc carbonate can be more convenient, in that it can act both as a zinc ions carrier and a pH control agent.
  • the methylselenol zinc salt is a white powder, highly hygroscopic, with characteristic garlic odour.
  • the doses active for the prevention are of the order of the micrograms.
  • the preferred administration route is of course the oral one, considering the characteristics of the product and the use for long-term preventive treatments. However, other administration routes are not excluded. Furthermore, in some cases also a therapeutical treatment, optionally in combination with other chemotherapeutics, can be envisaged.
  • compositions which can be administered through the oral route are soft- or hard- gelatin capsules, tablets, bars, granulates in sachets, syrups, chewing-gums and the like.
  • the compositions of the invention will further contain other compounds known to have chemopreventive and/or antioxidant activity.
  • said compounds comprise vitamin C, vitamin E, lycopene, beta-carotene, lutein, cysteine, resveratrol, sulforafan, ellagic acid, vegetable extracts, such as garlic, broccoli, and other brassicacee extracts, soy and red clover extracts.
  • methylselenol plays an important role in the oxidation of thiol groups such as that of reduced or oxidized glutathione, producing the superoxide anion (Biochem Pharmacol, 2004, Feb l;67(3):547-54; Nutr Cancer,2001;40(l):34-41).A condition of oxidative stress is produced thereby, causing tumor cells apoptosis (MoI. Cancer Therapeutics, 2002; 1 :1059-66).
  • Compositions comprising methylselenol zinc salt and cysteine can accordingly be used as chemopreventive agents.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Methylselenol zinc salt, of formula (CH3Se)2Zn, obtainable by reaction between zinc chloride and methylselenol sodium salt. The novel zinc salt of the invention can be advantageously used as a low-dosage component of pharmaceutical, nutraceutical and dietetic compositions, as an agent able to prevent the onset of neoplasias.

Description

METHYLSELENOL ZINC SALT AND COMPOSITIONS CONTAINING IT
DISCLOSURE
The present invention relates to the methylselenol zinc salt and compositions containing it.
Selenium, and particularly some organic compounds thereof, is known to play a fundamental role in a number of biochemical processes.
In addition to a general antioxidizing activity, selenium compounds have recently been investigated for their chemopreventive activity against neoplasias.
By way of example, Ip et al, in Cancer Res. 60, 2882-2886, 2000, have investigated the in vitro and in vivo activity of methylseleninic acid and proved that a monomethylated metabolite of selenium is an important chemoprotective factor.
According to the extensive studies carried out by the same researchers, methylselenol (CH3SeH), deriving from metabolic transformations of the selenide and selenomethionine, is a remarkably effective compound for the prevention of tumors (Cancer Res. 50: 1206-1211, 1990; ibidem, 51,
595-600,1991).
On the other hand, methylselenol is an extremely volatile liquid, with boiling point of 25°C, and is therefore difficult to use as such in the formulation of pharmaceutical and nutraceutical compositions or dietary supplements.
It has now been found that the methylselenol zinc salt, besides being an easy-to-handle solid, has improved functional characteristics which make it particularly suitable for the preparation of the above cited pharmaceutical and nutraceutical compositions or dietary supplements, in combination with suitable carriers and excipients and optionally with other active ingredients. Said compositions are a further object of the invention. The methylselenol zinc salt, that can be represented by the following formula: , (CH3Se)2Zn can be prepared by reacting methylselenol sodium salt with a zinc salt, preferably with zinc chloride in stoichiometric amounts, in water. Methylselenol sodium salt is conveniently obtained by reduction of the dimethylselenide and subsequent reaction with stoichiometric amounts of sodium hydroxide. The resulting salt can be freeze-dried or precipitated by addition of a non-solvent and/or by concentration and cooling. Alternatively, a dispersion of the salt of the invention in zinc carbonate, having a content in the salt of the invention approximately ranging from 0.1 to 5%, can be prepared. In fact, in view of the very low dosages necessary for the compositions containing the methylselenol zinc salt, the use of a dispersion of selenol salt in an inert matrix, such as zinc carbonate, can be more convenient, in that it can act both as a zinc ions carrier and a pH control agent.
The methylselenol zinc salt is a white powder, highly hygroscopic, with characteristic garlic odour. The doses active for the prevention are of the order of the micrograms.
The preferred administration route is of course the oral one, considering the characteristics of the product and the use for long-term preventive treatments. However, other administration routes are not excluded. Furthermore, in some cases also a therapeutical treatment, optionally in combination with other chemotherapeutics, can be envisaged.
Examples of suitable compositions which can be administered through the oral route are soft- or hard- gelatin capsules, tablets, bars, granulates in sachets, syrups, chewing-gums and the like. The compositions of the invention will further contain other compounds known to have chemopreventive and/or antioxidant activity. Examples of said compounds comprise vitamin C, vitamin E, lycopene, beta-carotene, lutein, cysteine, resveratrol, sulforafan, ellagic acid, vegetable extracts, such as garlic, broccoli, and other brassicacee extracts, soy and red clover extracts.
The combination with cysteine is particularly preferred since it is known that methylselenol plays an important role in the oxidation of thiol groups such as that of reduced or oxidized glutathione, producing the superoxide anion (Biochem Pharmacol, 2004, Feb l;67(3):547-54; Nutr Cancer,2001;40(l):34-41).A condition of oxidative stress is produced thereby, causing tumor cells apoptosis (MoI. Cancer Therapeutics, 2002; 1 :1059-66). Compositions comprising methylselenol zinc salt and cysteine can accordingly be used as chemopreventive agents.

Claims

1. Methylselenol zinc salt, of formula:
(CH3Se)2Zn.
2. Compositions containing the salt of claim 1 in admixture with suitable carriers.
3. Compositions according to claim 2 further comprising comprising vitamin C, vitamin E, lycopene, beta-carotene, lutein, cysteine, resveratrol, sulforafan, ellagic acid, garlic extract, broccoli extract or other brassicacee extracts, soy and red clover extracts.
4. Compositions according to claim 3 comprising cysteine.
5. The use of the methylselenol zinc salt for the preparation of compositions with chemopreventive and chemotherapeutic activity.
PCT/EP2005/014094 2005-12-28 2005-12-28 Methylselenol zinc salt and compositions containing it WO2007073765A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/EP2005/014094 WO2007073765A1 (en) 2005-12-28 2005-12-28 Methylselenol zinc salt and compositions containing it

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2005/014094 WO2007073765A1 (en) 2005-12-28 2005-12-28 Methylselenol zinc salt and compositions containing it

Publications (1)

Publication Number Publication Date
WO2007073765A1 true WO2007073765A1 (en) 2007-07-05

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9586192B2 (en) 2012-07-20 2017-03-07 Brown University Functionalized media and methods of making and using therefor
US10406091B2 (en) 2011-12-06 2019-09-10 Conopco, Inc. Skin anti-ageing composition

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3678067A (en) * 1969-10-01 1972-07-18 Mallinckrodt Chemical Works Method for preparing seleno-derivatives of {65 -amino acids
US4601860A (en) * 1982-09-23 1986-07-22 Ppg Industries, Inc. Method for producing selenoethers from selenoalcohols or their salts, and carbonates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3678067A (en) * 1969-10-01 1972-07-18 Mallinckrodt Chemical Works Method for preparing seleno-derivatives of {65 -amino acids
US4601860A (en) * 1982-09-23 1986-07-22 Ppg Industries, Inc. Method for producing selenoethers from selenoalcohols or their salts, and carbonates

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GANTHER H E ET AL: "Chemical Transformations of Selenium in Living Organisms. Improved Forms of Selenium for Cancer Prevention", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 53, no. 36, 8 September 1997 (1997-09-08), pages 12299 - 12310, XP004106083, ISSN: 0040-4020 *
VOSTOKOV, I.A.; BYCHKOV, V.T.;, J.GEN.CHEM.USSR (ENGL. TRANSL), vol. 41, 1971, pages 845 - 849, XP009056826 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10406091B2 (en) 2011-12-06 2019-09-10 Conopco, Inc. Skin anti-ageing composition
US9586192B2 (en) 2012-07-20 2017-03-07 Brown University Functionalized media and methods of making and using therefor

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