METHOD AND COMPOSITION FOR TREATING MUCO-EPIDERMAL AND EPIDERMAL PAIN, INFLAMMATION AND INFECTION

METHODE ET COMPOSITION POUR LE TRAITEMENT DE LA DOULEUR, DE L'INFLAMMATION ET DES INFECTIONS MUCO-EPIDERMIQUES ET EPIDERMIQUES

English Abstract

A topical pharmaceutical preparation for the treatment of epidermal and muco-epidermal tissue is provided. The composition includes
a therapeutic amount of chlorexidine and at least one non-steroidal anti-inflammatory agent. A method for treating epidermal and muco-
epidermal, pain, inflammation, infection and lesion by applying the topical preparation directly to the affected site is also provided.

French Abstract

L'invention concerne une préparation pharmaceutique à administration locale servant à traiter les tissus épidermiques et muco-épidermiques. La composition comprend une dose thérapeutique de chlorhexidrine et au moins un agent anti-inflammatoire non stéroïdique. L'invention concerne également un procédé de traitement des douleurs, des inflammations, des infections et des lésions épidermiques et muco-épidermiques par application directe de la préparation sur le site atteint.

Claims

I CLAIM:
1. A topical pharmaceutical preparation for the treatment of
epidermal and muco-epidermal tissue comprising a therapeutic amount of
chlorhexidine and a non-toxic amount of at least one non-steroidal anti-
inflammatory agent.
2. The topical preparation of claim 1 wherein the non-steroidal
anti-inflammatory agent is a prostaglandin inhibitor.
3. The topical preparation of claim 1 wherein the non-steroidal
anti-inflammatory agent is a prostaglandin inhibitor selected from the group
consisting of indocin, ibuprofen, ketoprofen, flurbiprofen, naproxen and
mixtures thereof.
4. The topical preparation of claim 1 wherein chlorhexidine is
present in an amount ranging from about 0.1 wt.% to about 1.0 wt.% of the
total preparation.
5. The topical preparation of claim 1 wherein the non-steroidal
anti-inflammatory agent is present in an amount ranging from about 2 wt.%
to about 5 wt.% of the total preparation.
6. The topical preparation of claim 1 wherein the preparation
further comprises a pharmaceutical carrier incorporating the chlorhexidine
and the non-steroidal anti-inflammatory agent.
7. The topical preparation of claim 6 wherein the carrier is selected
from the group consisting of a solution, cream, rinse, lotion and gel.
8. A topical pharmaceutical preparation for the treatment of
epidermal and muco-epidermal tissue comprising a therapeutic amount of
chlorhexidine and at least one non-steroidal anti-inflammatory agent
selected from the group consisting of indocin, ibuprofen, ketoprofen and
mixtures thereof incorporated into a pharmaceutical carrier.

9. The topical preparation of claim 8 wherein the chlorhexidine is
present in an amount ranging from about 0.1 wt.% to about 1.0 wt.% and the
non-steroidal anti-inflammatory agent is present in an amount ranging from
about 2 to about 5 wt.%.
10. The topical pharmaceutical preparation of claim 9 wherein the
carrier is a gel.
11. A method for the treatment of epidermal and muco-epidermal
tissue, said method comprising the steps of:
providing a topical pharmaceutical preparation including a carrier
incorporating a therapeutic amount of chlorhexidine and a non-toxic
amount of at least one non-steroidal anti-inflammatory agent, and
applying the preparation directly to epidermal and muco-epidermal
tissue having pain, inflammation, infection or lesion associated therewith.
12. The method of claim 11 further characterized in that the non-
steroidal anti-inflammatory agent is a prostaglandin inhibitor selected from
the group consisting of indocin, ibuprofen, ketoprofen, flurbiprofen,
naproxen and mixtures thereof.
13. The method of claim 11 further characterized in that the
chlorhexidine is present in an amount ranging from about 0.1 wt.% to about
1.0 wt.% and the non-steroidal anti-inflammatory agent is present in an
amount ranging from about 2 to about 5 wt.%.
14. The method of claim 11 further characterized in that the carrier
is selected from the group consisting of a solution, cream, rinse, lotion and
gel.

Description

WO 95/04s20 2 14 ~ ~ 7 PCT/uss4lo8944
~THOD ~ND COMPOSmON FOR TREATING MUCO-FPIDFRMAL AND
nFRl~AL PAIN, INFLAMMATION AND INFECTION
BACKGROUND OF I~F. INVENIION
The present invention relates generally to pharmaceutical
preparations for the treatment of muco-epidermal and epidermal tissue.
More particularly, the present invention relates to gels, creams, solutions
and other topical preparations including a mixture of chlorhexidine and at
least one non-steroidal anti-iIlflAmmAtory agent. The invention further
provides a method for the treatment of muco-epidermal and epitlermAl
tissue using such preparations.
The antimicrobial effects of chlorhexidine are well-documented.
Chlorhexidine gels, rinses and creams are routinely used to control bacterial
infections on mucosal epi-l~rmAl and epic~rmAl tissue. For example,
chlorhexidine gels and rinses are widely used in dentistry for the treatment
of periodontal disease. Non-steroidal anti-ir fl~mmAtory agents such as
ibuprofen, ketoprofen and indomethacin have applicAtion in the treatment
of, for example, inflAmmAtory diseases such as arthritis, general muscle,
skeletal and joint pain and menstrual cramps.
While these compounds have been widely used individually by
physicians and dentists in the above-described manner for many years, the
effectiveness of a combination of chlorhexidine and a non-steroidal anti-
i~flAmmAtory agent has not been appreciated.
Accordingly, it is the object of the present invention to provide a
pharmaceutical preparation including a combination of chlorhexidine and at
least one anti-i~flAmmAtory agent which together show a synergistic effect in
the treatment of muco-epi~lermAl and epidermal irlflAmmAtion and
infection.
It is a further object of the invention to provide a method for treating
muco-epidermal and epidermal tissue using such preparations.
SUMMARY OF THE INVENTION
The present invention meets the above-stated objects and others that
will become readily apparent by providing topical pharmaceutical
preparations which include chlorhexidine and at least one non-steroidal
anti-irflAmmAtory agent. These active ingredients are incorporated into a
gel, cream, solution, rinse or other pharmaceutically acceptable carrier and
are applied topically to sites of epi~1ermAl and muco-epidermal
inflammation, infection or lesion.

wo 95/04520 æ~465 4~ PCT/US94/08944
The preparations which are the subject of the present invention
include a non-toxic amount of chlorhexidine and preferably include, as the
non-steroidal anti-inflammatory agent, indomethacin, ibuprofen, ketoprofen
or other prostaglandin inhibitors.
As demonstrated below by the various examples provided, the
combination of chlorhexidine and a non-steroidal anti-inflAmm~tory agent
unexpectedly show a synergistic effect in the treatment of a number of
conditions including, periodontal disease, acne, post-r~iAtion therapy, post-
chemotherapy therapy, post-surgical therapy, burns and non-specific
epidermal and muco-epidermal infections.
The present invention is also directed to a method for treating
epi~rm~l and muco-epidermal tissue employing the above-described topical
preparations. The course of therapy with such preparations generally
requires one to three applications per day or is applied on an as needed basis,
depending on the severity of the ronr~ition. Treatment includes directly
applying the topical preparations to the affected site.
DRT~ D DF~ lONOF TH~ TION
As noted above, the-topical pharmaceutical preparations of the present
invention include chlorhexidine in a therapeutically effective amount. For
most therapies, from about 0.1 wt.% to about 1.0 wt.%, preferably about 0.2
wt.% of chlorhexidine, has been found to be effective. The preparations
further include a non-toxic amount of at least one non-steroidal anti-
inflammatory agent, most preferably indocin, ibuprofen and/or ketoprofen,
in an amount ranging from about 2 wt.% to about 5 wt.% of the total
preparation.
The active ingredients are incorporated into a solution, cream, rinse,
lotion, gel or other acceptable carrier. In some instances, depending upon the
particular carrier, the active ingredients are first solubilized and then
incorporated into the carrier. The addition of a suspending agent to the
carrier such as, for example, acacia powder, xanthan gum, methylcellulose,
hydroxymethylcellulose or hydroxypropylcellulose, has been found to be
particularly useful when compounding the carrier. In this regard,
hydroxymethylcellulose gel is the ~reL~led carrier where
treatment requires manual application of the preparation to affected
epidermal or muco-epidermal tissue.
Fxample I
Ten patients exhibiting advanced periodontal disease were treated with
a preparation of 0.2% chlorhexidine and 2% ketoprofen incorporated into a

WO 95/04520 2 ~ PCT/US94/08944
hydroxymethylcellulose gel. The patients were each instructed to apply one
of the preparations to the affected gums with a tooth brush twice a day for a
week. All of these patients experienced relief from pain, infection and
inflammation after the prescribed course of therapy.
Fxample II
Two surgical patients were instructed to apply the preparation
described in Example I to post surgical sites twice a day for seven days. In
both cases pain, inflammation and infection at the affected sites were
relieved.
Example m
Three patients exhibiting acne sores were instructed to apply the
preparation described in Example I to the affected sites twice a day for seven
days. In all cases, treatment with the preparations provided a reduction in
the pain and inflammation associated with the sores.
Rxample IV
One patient undergoing radiation therapy and two patients
undergoing chemotherapy were each instructed to apply the preparation
described in Example I twice daily for one week. All three patients received
relief from pain and showed faster healing rates of intraoral tissues following
treatment with the prescribed preparations.
While ~rererred embodiments have been shown and described,
various modifications and substitutions may be made without departing
from the spirit and scope of the invention. For example, those skilled in the
art will recognize that related derivatives of the active ingredients, such as
pharmaceutically acceptable salts of chlorhexidine, and other prostaglandin
inhibitors, such as flurbiprofen and naproxen, are useful in practicing the
present invention