U.S. patent number RE33,512 [Application Number 07/289,962] was granted by the patent office on 1991-01-01 for novel anti-microbial systems containing the magnesium sulfate adduct of 2,2'-dithiobis-pyridine-1,1'-dioxide and a water soluble zinc salt.
This patent grant is currently assigned to Chesebrough-Pond's, Inc.. Invention is credited to Jose E. Ramirez, William H. Schmitt, Robert J. Tanko, Mohan Vishnupad.
United States Patent |
RE33,512 |
Ramirez , et al. |
January 1, 1991 |
**Please see images for:
( Certificate of Correction ) ** |
Novel anti-microbial systems containing the magnesium sulfate
adduct of 2,2'-dithiobis-pyridine-1,1'-dioxide and a water soluble
zinc salt
Abstract
This invention relates to novel antimicrobial systems containing
a water-soluble, non-ionic pyrethione derivative known chemically
as the magnesium sulfate adduct of
2,2'-dithiobis-pyridine-1,1'-dioxide (referred to hereinafter as
"the magnesium sulfate adduct") and a water soluble zinc salt. The
antimicrobial systems of this invention may be incorporated in
various useful therapeutic and cleansing compositions such, for
example, as surgical scrub compositions, skin disinfectants,
mouthwashes, deodorants, hospital cleaners, etc.
Inventors: |
Ramirez; Jose E. (Trumbull,
CT), Tanko; Robert J. (Cheshire, CT), Vishnupad;
Mohan (Monroe, CT), Schmitt; William H. (Branford,
CT) |
Assignee: |
Chesebrough-Pond's, Inc.
(Greenwich, CT)
|
Family
ID: |
25102079 |
Appl.
No.: |
07/289,962 |
Filed: |
December 23, 1988 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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Reissue of: |
774725 |
Sep 11, 1985 |
04654213 |
Mar 31, 1987 |
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Current U.S.
Class: |
424/641; 424/642;
424/56; 514/188 |
Current CPC
Class: |
A61Q
15/00 (20130101); A61K 8/27 (20130101); C11D
3/48 (20130101); A61K 33/30 (20130101); A61K
31/44 (20130101); A01N 43/40 (20130101); A61K
8/4933 (20130101); A61Q 11/00 (20130101); A61Q
17/005 (20130101); A01N 59/16 (20130101); A01N
43/40 (20130101); A01N 2300/00 (20130101); A01N
59/16 (20130101); A01N 2300/00 (20130101); A61K
33/30 (20130101); A61K 2300/00 (20130101) |
Current International
Class: |
A01N
43/40 (20060101); A01N 43/34 (20060101); A01N
59/16 (20060101); A61K 33/30 (20060101); A61K
31/44 (20060101); A61K 031/555 (); A61K 033/30 ();
A01N 055/02 (); A01N 059/16 () |
Field of
Search: |
;424/145,49,56,641,642,56 ;514/188 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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54-15939 |
|
Feb 1979 |
|
JP |
|
60-16973 |
|
Jan 1985 |
|
JP |
|
Other References
Chemical Abstract 69:343387w (1968); Okomoto, et al. .
Chemical Abstract 80:91617x (1974); Elkhouly, et al. .
Chemical Abstract 87:161376p (1977); Wedig et al. .
Chemical Abstract 88:177003w (1978); Wedig, et al. .
Chemical Abstract 91:32995y (1979); Giloor, et al. .
The Merck Index 9th Ed. (1976)-pp. 1307-1309; Merck &
Co..
|
Primary Examiner: Robinson; Allen J.
Attorney, Agent or Firm: Morgan & Finnegan
Claims
What is claimed is:
1. An antimicrobial composition comprising the magnesium sulfate
adduct of 2,2'-dithiobis-pyridine-1,1'-dioxide and a water soluble
zinc salt, the zinc salt being in an amount from about 1 to 10
parts by weight per part of the antimicrobial adduct.
2. An antimicrobial composition according to claim 1 wherein the
zinc salt is selected from the group consisting of zinc chloride,
zinc acetate, zinc sulfate, zinc nitrate and zinc
phenylsulfonate.
3. An antimicrobial system according to claim 1 wherein the zinc
salt is zinc chloride.
4. An antimicrobial composition according to claim 1, 2 or 3
wherein the zinc salt is in an amount of 1 part by weight per part
of the microbial adduct.
5. An antimicrobial composition according to claims 1, 2 or 3
wherein the magnesium sulfate adduct is in an amount from about 0.1
to 1.5% by weight and the zinc salt is in an amount from about 0.1
to 1% by weight of the total composition.
Description
SUMMARY OF INVENTION
This invention relates to novel antimicrobial systems containing a
water-soluble, non-ionic pyrethione derivative known chemically as
the magnesium sulfate adduct of
2,2'-dithiobis-pyridine-1,1'-dioxide (referred to hereinafter as
"the magnesium sulfate adduct") and a water soluble zinc salt. More
particularly, it has been found that the presence of a water
soluble zinc salt appears to enhance to an unexpected extent the
antimicrobial activity of the magnesium sulfate adduct against
certain types of microorganisms such, for example, as
.[.Staphylococcus epidermidis, Staphylococcus aureus and.].
Pseudomonas aeruginosa.
The antimicrobial system of this invention may be incorporated in
various useful therapeutic and cleansing compositions such, for
example, as surgical scrub compositions, skin disinfectants,
mouthwashes, deodorants, hospital cleaners, etc.
BACKGROUND OF THE INVENTION
The magnesium sulfate adduct used in accordance with this invention
is a well known broad spectrum antimicrobial agent. For example, a
well known commercially available form is sold by Olin Chemicals of
Stanford, Conn. under the trade name "OMADINE MDS" which is the
trihydrate form.
While the magnesium sulfate adduct used in this 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.
.[.Examples of additional microorganisms against which it would be
desirable to enhance the antimicrobial activity of the pyrithione
derivative used in this invention are Staphylococcus aureus and
Staphylococcus epidermidis..].
OBJECTS OF THE INVENTION
An object of the invention is to provide novel antimicrobial
systems wherein enhanced antimicrobial activity of the magnesium
sulfate adduct is effectuated against certain types of
microorganisms.
Another object of this invention is to provide novel therapeutic
and cleansing compositions having incorporated therein the
antimicrobial system set forth in the foregoing object.
GENERAL DESCRIPTION OF THE INVENTION
It has been found that the objects of this invention may be
realized by forming an antimicrobial system containing the
magnesium sulfate adduct and a water soluble salt.
For example, microbiological testing indicates that the activity of
magnesium sulfate adduct against Ps. aeruginosa is enhanced in the
presence of water soluble zinc salts.
The preferred zinc salt used in accordance with this invention is
zinc chloride (ZnCl.sub.2). Other water soluble zinc salts which
may be used are zinc acetate, zinc sulfate, zinc nitrate, zinc
phenylsulfonate, etc.
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 from about 1
to about 10, and preferably from about 1 to 1 parts by weight per
part of the magnesium sulfate adduct.
In the therapeutic and/or cleansing composition of this invention
the magnesium sulfate adduct in general is in an amount from about
0.1 to 1.5% by weight and the zinc salt from about 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
compositions employing the antimicrobial system of this invention
in an anhydrous foamable base composition. Such surgical scrub
compositions have been found useful in killing .[.both
Staphylococcus aureus and.]. .Iadd.the .Iaddend.Pseudomonas
aeruginosa .[.types of bacteria.]..Iadd.bacterium.Iaddend.. The
anhydrous foamable base composition contains petroleum jelly,
mineral oil and a mild detergent (Sodium cocoyl isethionate).
SPECIFIC DESCRIPTION OF THE PRESENT INVENTION
In order to illustrate the invention by specific examples a number
of compositions containing the magnesium sulfate adduct and zinc
chloride in accordance with the invention were tested for
antimicrobial activity and compared with control compositions
containing either the magnesium sulfate adduct and/or zinc
chloride. These compositions are disclosed in Table I and their
antimicrobial activity determined using the "Zone of Inhibition
Test" determined.
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 I which exemplify of the present
invention are:
TABLE I ______________________________________ SYNERGISTIC EFFECTS
OF ZnCl.sub.2 ON THE ACTIVITY OF THE MAGNESIUM SULFATE ADDUCT .RTM.
vs. PSEUDOMONAS PHYSI- ZONES (mm) ACTIVE ING.'S CAL vs. PSEUDO- AND
PERCENTAGE FORM MONAS ______________________________________
Example Omadine MDS @ 0.135% Solution 0 Example Aluminum
Chlorohydrate Solution 0 B (ACH) @ 17.5% Example Omadine MDS @
0.135% Solution 0 C ACH @ 17.5% Example Omadine MDS @ 0.135%
Solution 7.6 1 (ACH) @ 17.5% ZnCl.sub.2 @ 0.1% Example ZnCl.sub.2 @
0.1% Lotion 0 D Example Omadine MDS @ 0.135% Solution 0 E ACH @
17.5% Example Omadine MDS @ 0.135% Solution 8.6 2 ACH @ 17.5%
ZnCl.sub.2 @ 0.1% Example Omadine MDS @ 0.135% Solution 0 F Example
Omadine MDS @ 0.135% Solution 5.6 3 ZnCl.sub.2 @ 0.10% Example
ZnCl.sub.2 @ 0.10% Solution 0 G Example Omadine MDS @ 0.135%
Solution 0 H Example Omadine MDS @ 0.135% Solution 0 I ACH @ 17.5%
Example Omadine MDS @ 0.135% Solution 8.3 4 ACH @ 17.5% ZnCl.sub.2
@ 0.10% Example Base Formula Only Lotion 0 J Example ZnCl.sub.2
1.0% Lotion 2.9 K Example Omadine MDS 0.225% Lotion 1.9 L Example
Omadine MDS 0.225% Lotion 11.9 5 ZnCl.sub.2 1.0% Example ZnCl.sub.2
2.0% Solution 1 M Example Omadine MDS 0.225 Solution 0.5 N Example
Omadine MD @ 0.5% Powder 11.3 6 ZnCl.sub.2 2.0%
______________________________________ *The magnesium sulfate
adduct is sold by Olin Chemicals under the trade name OMADINE
MDS.
Another useful determination for evaluating antimicrobial activity
is to the minimal inhibitory concentration (M.I.C.) amount. The
minimal inhibitory concentration is a serial twofold dilution of
the test formulation in a broth culture medium which is innoculated
with a standardized culture of microorganisms. The amount of test
agent that will inhibit visible microbial growth is termed the
minimal inhibitory concentration (M.I.C.) level. The lower the
amount of test agent, the gretaer the antimicrobial activity.
.[.In Table 2 there is reported minimal inhibitory concentration
values for Example 7 formed in accordance with the present
invention and controls containing only the magnesium sulfate adduct
and/or zinc chloride..].
TABLE 2
__________________________________________________________________________
FORMULA ACTIVE ING.'S PHYSICAL MIMINUM INHIBITORY CONCENTRATION
NOS. AND PERCENTAGE FORM (PPM) vs. PSEUDOMONAS
__________________________________________________________________________
Example O ZnCl.sub.2 0.1% Solution No Activity Example P Omadine
MDS Solution 250 0.135% Example 7 Omadine MDS Solution 30 0.135%
ZnCl.sub.2 0.1%
__________________________________________________________________________
The results .[.reported in Table 2.]. .Iadd.of experimental
analyses .Iaddend.indicated .[.no activity for ZnCl.sub.2, activity
of 250 ppm for Omadine MDS alone and 30 ppm for the combination of
ZnCl.sub.2 with Omadine MDS. This indicates.]. an eightfold
increase in activity against Pseudomonas aeruginosa for the
combination of ZnCl.sub.2 with omadine MDS compared to the activity
of ZnCl.sub.2 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%. .[.The
activities for all the controls were from 125 to 550 ppm using the
M.I.C. method and from 4 to 8 ppm for the combination of zinc salt
with Omadine MDS..]. 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 ZnCl.sub.2 combination employed
in the present invention.
In Table 3 there is disclosed a surgical scrub composition
Composition I employing the anhydrous foaming base composition of
pending application Ser. No. .Iadd.028,072 .Iaddend.containing
petroleum jelly, mineral oil, glycerine, TiO.sub.2 and sodium
cocoyl isethionate and the magnesium sulfate adduct and ZnCl.sub.2
combination of the present invention and the control base
Composition II.
TABLE 3 ______________________________________ Formula Composition
I Composition II ______________________________________ Petroleum
Jelly 31.00 31.00 Mineral Oil 19.50 19.50 Glycerin 5.00 5.00
TiO.sub.2 0.50 0.50 Na Cocoyl Isethionate 40.00 42.00 Omadine MDS
2.00 2.00 ZnCl.sub.2 (50% Solution) 2.00
______________________________________
When tested for antimicrobial activity, the minimum inhibitory
concentration activity was enhanced .[.from 125 ppm for the 2%
Omadine MDS control Composition II to 2.0 ppm.]. for the Omadine
MDS 2%, ZnCl.sub.2 1% in Composition I.[.. This is over.]..Iadd.,
providing .Iaddend.a .[.sixtyfold.]. .Iadd.substantial
.Iaddend.increase in activity .Iadd.against Pseudomonas aeruginosa
compared to Composition II.Iaddend...[.Evidence for synergism was
also observed against Staphylococcus aureus, for Composition I
activity is 0.003 ppm, while the control Composition II with 2%
Omadine is 0.1 ppm. This is a thirty-threefold increase in
activity. For Staphylococcus epidermidis, once again the synergism
was confirmed, with 0.0007 ppm activity for the 2% Omadine MDS 1%
ZnCl.sub.2 combination, while the Composition II control is 0.006
ppm. This is an elevenfold increase in activity..].
* * * * *