ANTI-MICROBIAL SYSTEMS CONTAINING THE MAGNESIUM SULFATE ADDUCT OF 2,2'-DITHIOBIS-PYRIDINE-1,1'-DIOXIDE AND A WATER-SOLUBLE ZINC SALT

Abstract: An antimicrobial system characterised in that it comprises the magnesium sulfate adduct of 2,2'-dithiobis-­ pyridine-1,1'-dioxide and a water-soluble zinc salt is disclosed. The present antimicrobial systems may be incorporated in various useful therapeutic and cleansing compositions, such as surgical scrub compositions, skin disinfectants, mouthwashes, deodorants and hospital cleaners.

Description: This invention relates to antimicrobial compositions containing the magnesium sulfate adduct of 2,2'-dithiobis-pyridine-1,1'-dioxide and a water-soluble zinc salt; more particularly, it relates to antimicrobial compositions containing a water-soluble, non-ionic pyrithione derivative known chemically as the magnesium sulfate adduct of 2,2'-dithiobis-pyridine-1,1'-dioxide (referred to herein as "the magnesium sulfate adduct") and a water-soluble zinc salt. More specifically, it has been found that the presence of a water-soluble zinc salt appears to enhance to an unexpected extent the anti-microbial activity of the magnesium sulfate adduct against certain types of micro-organisms, such as Pseudomonas aeruginosa . US-A-4,161,526 discloses the prevention or removal of discoloration in pyrithione, pyrithione salt or dipyrithione compositions using a zinc salt. From US-A-3,890,434 are known hair shampoo compositions containing adducts of bis-(-2-pyridyl-1-oxide) disulfide which exhibit antimicrobial effects. The antimicrobial compositions in accordance with the present invention may be incorporated in various useful therapeutic and cleansing compositions, such as surgical scrub compositions, skin disinfectants, mouthwashes, deodorants and hospital cleaners. The magnesium sulfate adduct used in accordance with the present invention is a well known broad spectrum anti-microbial agent. For example, a well known commercially available form is sold by Olin Chemicals of Stanford, Conn., USA, under the trade name "OMADINE MDS", which is the trihydrate form. While the magnesium sulfate adduct used in accordance with the present invention has broad spectrum antimicrobial activity, it lacks the desired activity against Pseudomonas aeruginosa , the microorganism associated with infection that often follows severe burning of the skin. An object of the present invention is to provide antimicrobial composition wherein enhanced antimicrobial activity of the magnesium sulfate adduct is effectuated against certain types of microorganisms. Another object of the present invention is to provide therapeutic and cleansing compositions having incorporated therein such an antimicrobial composition. The present invention provides an antimicrobial composition characterised in that it comprises the magnesium sulfate adduct of 2,2'-dithiobis-pyridine-1,1'-dioxide and a water-soluble zinc salt in an amount having a synergistic effect against Pseudomonas areuginosa . The preferred zinc salt used in accordance with the present invention is zinc chloride (ZnCl₂). Other water-soluble zinc salts which may be used include zinc acetate, zinc sulfate, zinc nitrate and zinc phenylsulfonate. In general, it has been found that in order to obtain the desired enhancement of antimicrobial activity in accordance with the present invention the zinc salt should be in an amount of from 1 to 10 parts, by weight, per part of the magnesium sulfate adduct, preferably 1 part, by weight, per part of the magnesium sulfate adduct. When the present composition is applied to a therapeutic and/or cleansing composition, the magnesium sulfate adduct in general is in an amount of from 0.1 to 1.5%, by weight, and the zinc salt from 0.1 to 1%, by weight, of the total composition. It has been found that a most useful antimicrobial composition that may be obtained utilizing the present invention is a surgical scrub composition employing the present antimicrobial composition in an anhydrous foamable base composition. Such surgical scrub compositions have been found useful in killing the Pseudomonas aeruginosa bacterium. The anhydrous foamable base composition thereof contains petroleum jelly, mineral oil and a mild detergent (sodium cocoyl isethionate). In order to illustrate the present invention by specific examples, a number of compositions containing the magnesium sulfate adduct and zinc chloride in accordance with the present invention were tested for antimicrobial activity and compared with control compositions containing either the magnesium sulfate adduct and/or zinc chloride. These compositions are reported in Table 1 with the antimicrobial activity thereof determined using the "Zone of inhibition test". "Zone of inhibition test" is the relationship between a standard application of a test formulation on a solid agar surface and the resulting zone of inhibited growth of a test organism applied to the agar surface. The larger the zone of growth inhibition, the greater the antimicrobial activity. This test method is used to determine antimicrobial activity in both liquids and solids. The compositions of Table 1 which exemplify of the present invention are: SYNERGISTIC EFFECTS OF ZnCl₂ ON THE ACTIVITY OF THE MAGNESIUM SULFATE ADDUCT vs. PSEUDOMONAS ACTIVE INGREDIENTS AND PERCENTAGE PHYSICAL FORM ZONES (mm) vs . PSEUDOMONAS Example A Omadine MDS @ 0.135% Solution 0 Example B Aluminum chlorohydrate (ACH) @ 17.5% Solution 0 Example C Omadine MDS @ 0.135% ACH @ 17.5% Solution 0 Example 1 Omadine MDS @ 0.135% (ACH) @ 17.5% ZnCl₂ @ 0.1% Solution 7.6 Example D ZnCl₂ @ 0.1% Lotion 0 Example E Omadine MDS @ 0.135% ACH @ 17.5% Solution 0 Example 2 Omadine MDS @ 0.135% ACH @ 17.5% ZnCl₂ @ 0.1% Solution 8.6 Example F Omadine MDS @ 0.135% Solution 0 Example 3 Omadine MDS @ 0.135% ZnCl₂ @ 0.10% Solution 5.6 Example G ZnCl₂ @ 0.10% Solution 0 Example H Omadine MDS @ 0.135% Solution 0 Example I Omadine MDS @ 0.135% ACH @ 17.5% Solution 0 Example 4 Omadine MDS @ 0.135% ACH @ 17.5% ZnCl₂ @ 0.10% Solution 8.3 Example J Base Formula Only Lotion 0 Example K ZnCl₂ 1.0% Lotion 2.9 Example L Omadine MDS 0.225% Lotion 1.9 Example 5 Omadine MDS 0.225% ZnCl₂ 1.0% Lotion 11.9 Example M ZnCl₂ 2.0% Solution 1 Example N Omadine MDS 0.225 Solution 0.5 Example 6 Omadine MDs @ 0.5% ZnCl₂ 2.0% Powder 11.3 Another useful determination for evaluating antimicrobial activity is to the minimal inhibitory concentration (M.I.C.) amount. The minimal inhibitory concentration is a serial two-fold dilution of the test formulation in a broth culture medium which is inoculated with a standardized culture of microorganisms. The amount of test agent that will inhibit visible microbial growth is termed the minimal inhibitory concentration (MIC) level. The lower the amount of test agent, the greater the antimicrobial activity. The results of experimental analyses indicated an eight-fold increase in activity against Pseudomonas aeruginosa for the combination of ZnCl₂ with Omadine MDS compared to the activity of ZnCl₂ alone or Omadine MDS alone. In still further comparison study, compositions were prepared and evaluated both by the minimum inhibitory concentration method and the zone of inhibition. The results were similar for all salts tested at 1% concentration with Omadine MDS at 0.5%. Again, the zone of inhibition was almost non-existent for controls 0-2 mm and 10-14 mm for the combination of the magnesium sulfate adduct and ZnCl₂ combination employed in accordance with the present invention. In Table 2 there is reported a surgical scrub composition, Composition I, employing the above-mentioned anhydrous foaming base composition containing petroleum jelly, mineral oil, glycerine, TiO₂ and sodium cocoyl isethionate and the magnesium sulfate adduct and ZnCl₂ combination in accordance with the present invention and the control base Composition II. Formula Composition I Composition II Petroleum jelly 31.00 31.00 Mineral oil 19.50 19.50 Glycerine 5.00 5.00 TiO₂ 0.50 0.50 Na cocoyl isethionate 40.00 42.00 Omadine MDS 2.00 2.00 ZnCl₂ (50% Solution) 2.00 - When tested for antimicrobial activity, the minimum inhibitory concentration activity was enhanced for the Omadine MDS 2%, ZnCl₂ 1% in Composition I, providing a substantial increase in activity compared to Composition II.

Claims: An antimicrobial composition characterised in that it comprises the magnesium sulfate adduct of 2,2'-dithiobis-pyridine-1,1'-dioxide and a water-soluble zinc salt in an amount having a synergistic effect against Pseudomonas areuginosa . A composition as claimed in claim 1 wherein the zinc salt is selected from zinc chloride, zinc acetate, zinc sulfate, zinc nitrate and zinc phenylsulfonate. A composition as claimed in claim 1 or claim 2 wherein the zinc salt is zinc chloride. A composition as claimed in any of claims 1 to 3 wherein the zinc salt is in an amount of from 1 to 10 parts, by weight, per part of the antimicrobial adduct. A composition as claimed in any of claims 1 to 4 wherein the magnesium sulfate adduct is in an amount of from 0.1 to 1.5%, by weight, and the zinc salt is in an amount of from 0.1 to 1%, by weight, of the total composition.

Inventors: RAMIREZ, JOSE E., SCHMITT, WILLIAM H., TANKO, ROBERT J., VISHNUPAD, MOHAN
Applicants: CHESEBROUGH-POND'S INC.
Application year: 1986
Main classification: A61K33
IPC codes: A61K31, A01N55, A01N59, A61Q15, C11D3, A61K33, A61K8, A01N43, A61Q11, A61Q17