COMPOSES POUR TRAITER LES BRULURES INFECTEES

COMPOSITIONS FOR TREATING INFECTED BURN WOUNDS

Abrégé anglais

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Abstract
Improved compositions for treating infected burn wounds
A pharmaceutical composition comprises in admixture with a
pharmaceutically acceptable vehicle or carrier, a thera-
peutically effective amount of a silver compound suitable
for treating burns, preferably silver sulphadiazine, and
a synergistic amount of dibromopropamidine or pharmaceutically
acceptable salts thereof, preferably the isethionate or
pamoate.

Revendications

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The embodiments of the invention in which an exclusive
property or privilege is claimed are defined as follows.
1. A pharmaceutical composition comprising in admixture with
a pharmaceutically acceptable vehicle or carrier, a thera-
peutically effective amount of a silver compound suitable
for treating burns and a synergistic amount of dibromo-
propamidine or pharmaceutically acceptable salts thereof.
2. A composition according to claim 1 which contains silver
sulphadiazine and one of dibromopropamidine, dibromo-
propamidine isethionate B.P. 1980 or dibromopropamidine
pamoate.
3. A composition according to claim 2 wherein the dibromo-
propamidine or salts thereof are present in concentrations
of from 0.00015 to 0.30 per cent w/w in pharmaceutical
formulations of silver sulphadiazine at 0.01 to 2.0 per cent
w/w .
4. A composition according to claim 1 which contains 0.15%
dibromopropamidine isethionate and 1% silver sulphadiazine.
5. A composition according to claim 1 wherein the vehicle
is an aqueous carbomer dispersion gel.

Description

"Improved Compositions for Treating Infected Burn Wound~"
This invention relateæ to lpharmaceutical
compoæitions containing silver compounds. More particularly
it relates to silver compounds ~uitable for use in the treatment
of burn wound infection.
Silver sulphadiazine is the most commonly used
compound in pharmaceutical compositions for treating patients
having burn wounds infected by Pseudomonas aeru~ nosa,
Enterobacter cloacae and Staphylococcus aureus. However the
. ~ .
activity of silver sulphadiazine in controlling these infections
is less than optimum.
Gayle et al, 1978 (Journal of Trauma, 18, 317-323)
_ _ _
reported 15 cases of silver sulphadiazine resistant Enterobacter
cloacae in one burn~ unit and 13 of the lG patients died. Of these
deaths 7 were directly caused by, and 2 others significantly
related to E cloacae ~epticaemia.
An object of the present invention is to enhance the
antimicrobial activity of silver compounds suitable for use in
the treatment of burn wound infection.
According to the present invention there is provided a
pharmaceutical composition cormprising in admix-ture with a
pharmaceutically acceptable vehicle or carrier, a therapeutically
effective amount of a ~ilver compound ~uitable for treating burns
and a synergistic amount of dibromopropamidine or
pharmaceutically acceptable salts thereof.
Preferably the pharmaceutical composition contains
silver sulphadiazine and one of dibromopropamidine, dibromo-
propamidine isethionate B. P. 1980 or dibromopropamidine
pamoate. The dibromopropamidine or salts thereof may be
present in concentrations of 0. 00015 to 0. 30 per cent w/w in
~"~ ~

pharmaceutical formulations OI silver ~ulphadiazine at 0. al to
2, 0 per cent w/w.
Sirnilar concentrations with preparations containing
other silver salts are found to enhance the activity of these
preparations which may infect the burn wound.
The dibromopropamidine salts have been proposed
for use as topical antibacterials (BPC 1980 and Martindale, The
Extra Pharmacopoeia, 1977, 27th Edition, Pharmaceutical
Pre~s, Lontlon p. 517) but the synergistic effect exhibited in
combination with sil~er salts is wholly unexpected. Thus
greater antibacterial activity i~ obtained against all organisms
tested than is observed with silver salts used alone at equivalent
concentrations. The combination of dibromopropamidine
isethionate 0.15% with silver sulphadiazine 1. 0% also possesses
activity against the silver re~istant Pseudomonas aeru~inosa
R 351 against which silver sulphadiazine 1. O~o alone has no
activity, The Minimum Inhibitory Concentration of ~Ag+~alone
against this strain of Pseudomonas aeruginosa is 12B pg ml 1
Exampleæ are given in Table 1 of the in vitro
enhancement of activity when cream formulations were tested
in duplicate by the agar diffusion method against an inoculum
of approximately 5 x 10 organisms ml of test organism. The
test organisms used were Pseudomonas aeruginosa NCTC 6750,
Staph~ococcus aureus NCTC 6751, Enterobacter cloacae NCTC
_, _
939~ and NCTC 10005.
Typically the compositions of this inventlon are prepared
as topical antibiotic preparations in for example a water-miscible
cream such as Cetomacrogol cream BPC 1968, or modifications
of such a cream, or into a gel such as can be prepared from a
dispersion of carbomer tCarbopal*940, Honeywell and Stein
Ltd. ) by neutralising with dilute ammonia solution. Gel
*Trade Mark
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formulations show a greater aetivity than equivalent cream
formulations when tested by the agar diffusion method. This
activity is shown by larger zones of inhibition of the order
of 2-4 mm with the gel formulations. The gel also has the
advantage that it can be st~rilised by heating in an autoclave
at 115 C for 30 minutes.
The preparation is applied to the cleansed and
debrided burn wound to give a layer approximately 2 to 4
mm thick. If left exposed the cream gel is applied twice
daily but when used under an occlusive dressing then it may
be applied at daily or longer intervals, according to the
condition of the wound, until satisfactory healing has
occured or the burn site is ready for grafting.