Partial-thickness burn wounds healing by topical treatment: A randomized controlled comparison between silver sulfadiazine and centiderm


Saeidinia, A.; Keihanian, F.; Lashkari, A.Pasdaran.; Lahiji, H.Ghavvami.; Mobayyen, M.; Heidarzade, A.; Golchai, J.

Medicine 96(9): E6168

2017


Burns are common event and associated with a high incidence of death, disability, and high costs. Centella asiatica (L.) is a medicinal herb, commonly growing in humid areas in several tropical countries that improve wound healing. On the basis of previous studies, we compared the efficacy of Centiderm versus silver sulfadiazine (SSD) in partial thickness burning patients. Study population comprised burn victims referred to Velayat Burning Hospital at Rasht, Iran. The intervention group received Centiderm and control group SSD cream. Burn wounds were treated once daily at home. All of the wounds were evaluated till complete healing occurred and at the admission, days 3, 7, 14 objective signs; visual acuity score (VAS) and subjective signs were recorded. Re-epithelialization time and complete healing days were recorded. We used random fixed block for randomization. The randomization sequence was created using the computer. Patients and burning specialist physician were blinded. Seventy-five patients randomized into 2 groups; (40 patients: Centiderm group; 35 patients: SSD group). The mean age of them was 30.67 ± 9.91 years and 19 of them were male (31.7%). Thirty patients in Centiderm and 30 patients in SSD group were analyzed. All of objective and subjective signs and mean of re-epithelialization and complete healing were significantly better in Centiderm group rather than SSD group (P < 0.05). There was no infection in Centiderm group. We showed that use of Centiderm ointment not only improved the objective and subjective signs in less than 3 days, but also the re-epithelialization and complete healing rather than SSD without any infection in the subjects.

I
Clinical
Trial/Experimental
Study
Medicine®
OPEN
Partial-thickness
burn
wounds
healing
by
topical
treatment
A
randomized
controlled
comparison
between
silver
sulfadiazine
and
centiderm
Amin
Saeidinia,
MDa,
Faeze
Keihanian,
MDa.
b
.
*
,
Ardalan
Pasdaran
Lashkari,
PhIr.
*
,
Hossein
Ghawami
Lahiji,
Medical
Student
a
,
Mohammadreza
Mobayyen,
MD
d
,
Abtin
Heidarzade,
MD
e
,
Javad
Golchai,
MD
f
Abstract
Background:
Burns
are
common
event
and
associated
with
a
high
incidence
of
death,
disability,
and
high
costs.
Centella
asiatica
(L)
is
a
medicinal
herb,
commonly
growing
in
humid
areas
in
several
tropical
countries
that
improve
wound
healing.
On
the
basis
of
previous
studies,
we
compared
the
efficacy
of
Centiderm
versus
silver
sulfadiazine
(SSD)
in
partial
thickness
burning
patients.
Methods:
Study
population
comprised
burn
victims
referred
to
Velayat
Burning
Hospital
at
Rasht,
Iran.
The
intervention
group
received
Centiderm
and
control
group
SSD
cream.
Burn
wounds
were
treated
once
daily
at
home.
All
of
the
wounds
were
evaluated
till
complete
healing
occurred
and
at
the
admission,
days
3,
7,
14
objective
signs;
visual
acuity
score
(VAS)
and
subjective
signs
were
recorded.
Re-epithelialization
time
and
complete
healing
days
were
recorded.
We
used
random
fixed
block
for
randomization.
The
randomization
sequence
was
created
using
the
computer.
Patients
and
burning
specialist
physician
were
blinded.
Results:
Seventy-five
patients
randomized
into
2
groups;
(40
patients:
Centiderm
group;
35
patients:
SSD
group).
The
mean
age
of
them
was
30.67±9.91
years
and
19
of
them
were
male
(31.7%).
Thirty
patients
in
Centiderm
and
30
patients
in
SSD
group
were
analyzed.
All
of
objective
and
subjective
signs
and
mean
of
re-epithelialization
and
complete
healing
were
significantly
better
in
Centiderm
group
rather
than
SSD
group
(P
<
0.05).
There
was
no
infection
in
Centiderm
group.
Conclusions:
We
showed
that
use
of
Centiderm
ointment
not
only
improved
the
objective
and
subjective
signs
in
less
than
3
days,
but
also
the
re-epithelialization
and
complete
healing
rather
than
SSD
without
any
infection
in
the
subjects.
Abbreviations:
%WN
=
Percent
Weight/Volume,
pg/mL
=
microgram
per
milliliter,
eNOS
=
Endothelial
nitric
oxide
synthase,
iNOS
=
Inducible
nitric
oxide
synthase,
IRCT
=
Iranian
Clinical
Trial,
MCP-1
=
monocyte
chemoattractant
protein-1,
mRNA
=
messenger
ribonucleic
acid,
SEM
=
standard
error
of
the
mean,
SSD
=
Silver
Sulfadiazine,
TBSA
=
total
body
surface
area,
TECA
=
titrated
extract
of
Centella
asiatica,
TGF-I3
=
Transforming
growth
factor
beta,
TIMP1
=
tissue
inhibitors
of
metalloproteinases-1,
VAS
=
visual
acuity
score,
VEGF
=
Vascular endothelial
growth
factor,
VSS
=
Vancouver
Scar
Scale,
WHO
=
World
Health
Organization.
Keywords:
burning,
Centella
asiatica,
partial
thickness,
silver
sulfadiazine,
wound
Editor:
Thomas
Biederman.
Trial
Registration:
IRCT2013100614915N1
Funding/support:
Funding
for
this
study
was
provided
by
Guilan
University
of
Medical
Sciences.
The
authors
report
no
conflicts
of
interest.
a
Medicinal
Plants
Research
Center
of
Student
Basij,
Guilan
University
of
Medical
Sciences, Rasht,
°
Cardiology
Department
&
Pharmaceutical
Research
Center,
Mashhad
University
of
Medical
Sciences,
Mashhad,
Phamiacognosy
Department
and
Research
and
Development
Center
of
Plants
and
Medicinal
Chemistry,
"Fellowship
of
Bum
Surgery,
Velayat
Hospital,
e
Social
Medicine
Department,
'Dermatology
Department,
Guilan
University
of
Medical
Sciences,
Rasht,
Iran.
*
Correspondence:
Ardalan
Pasdaran
Lashkari,
Department
of
Pharmacognosy,
Faculty
of
Pharmacy,
Guilan
University
of
Medical
Sciences,
Fouman-Saravan
Autobahn,
Lakan
Road,
Rasht
416351655,
Iran
(e-mail:
ardalanpasdar@gmailcom);
Faeze
Keihanian,
MD,
Cardiology
Department
&
Pharmaceutical
Research
Center,
Mashhad
University
of
Medical
Sciences,
Mashhad,
Iran
(e-mail:
faezekeihanian@yahoo.com).
Copyright
CO
2017
the
Author(s).
Published
by
Wolters
Kluwer
Health,
Inc.
This
is
an
open
access
article
distributed
under
the
terms
of
the
Creative
Commons
Attribution-Non
Commercial-No
Derivatives
License
4.0
(CCBY-NC-
ND),
where
it
is
permissible
to
download
and
share
the
work
provided
it
is
properly
cited.
The
work
cannot
be
changed
in
any
way
or
used
commercially
without
permission
from
the
journal.
Medicine
(2017)
96:9(06168)
Received:
28
December
2015
/
Received
in
final
form:
24
January
2017
/
Accepted:
30
January
2017
http://dx.doLorg/10.1097/MD.0000000000006168
1.
Introduction
Burn
is
still
one
of
the
emergency
medicine
affecting
both
genders
and
all
age
groups
in
both
developed
and
developing
countries
leading
to
physical
and
psychological
disabilities
with
an
increasing
trend
in
mortality
and
morbidity
during
pregnan-
cy."
1
Burns
are
a
common
event
and
are
associated
with
a
high
incidence
of
death
and
disability,
several
surgery
operations,
prolonging
of
hospitalization,
rehabilitation,
and
high
health
care
costs.E
31
The
second-degree
burns
are
one
of
the
most
frequent
burning
in
homes
needed
improvement
to
treatment.m
The
incidence
of
burning
in
developing
countries
is
more
than
developed
countries.
Burning
is
a
chief
cause
of
mortality
worldwide.E
51
Healing
is
divided
into
4
main
parts:
formation
of
granulation
tissue,
collagen
deposition,
re-epithelialization,
and
contraction.E
6
'
71
For
many
years,
partial-thickness
burns
have
treated
by
daily
washing
and
cleaning
of
the
wound,
followed
by
a
topical
application
of
the
antimicrobial
cream.
However,
the
pain
suffered
and
damaged
wound
healing
remain
problems
to
be
addressed.
Superficial
partial-thickness
burns
often
heal
in
3
weeks.E
8
'
91
In
topical
burn
therapy,
silver
sulfadiazine
was
introduced
as
the
gold
standard
having
antibacterial
proper-
ties."
However,
it
has
some
disadvantages,
including
retarda-
tion
of
wound
contracture,
delayed
and
incomplete
epithelialization,
generation
of
black
scars,
limited
penetration
1
Saeidinia
et
al.
Medicine
(2017)
96:9
Medicine
the
depth
of
the
wound,
hypersensitivity,
neutropenia,
silver
toxicity,
the
inaccurate
assessment
of
healing
progress
because
of
the
presence
of
a
layer
of
the
slough,
ineffectiveness
against
some
microorganisms,
and
thrombocytopenia.E
111
Other
topical
anti-
biotics
such
as
mafenide
acetate
and
silver
nitrate
are
also
associated
with
side
effects
such
as
pain
and
hypersensitivity
at
the
wound
site,
delayed
wound
healing,
electrolytic
imbalance,
and
hemoglobinemia.E
12431
Currently,
silver-foam
dressings
are
being
the
gold
standard
used
to
manage
the
bio-burden
of
a
wound,
with
or
without
a
silicone
skin
interface
such
as
Acticoat
and
Mepitel.
141
There
are
many
reports
that
have
confirmed
the
use
of
medicinal
plants
for
dressing
wounds
described
by
traditional
medicine.E
151
Centella
asiatica
(L.)
is
a
Stoloniferous
constant
herb,
commonly
growing
in
humid
areas
in
several
tropical
countries.
In
Asia,
it
has
long
been
used
in
traditional
medicine
in
the
treatment
of
different
diseases.
This
plant
is
commonly
found
in
many
parts
of
the
world,
[16-181
including
Asia
and
the
Middle
East.E
191
In
Iran,
it
just
found
in
a
local
wetland
at
Bandar-Anzali
and
it
is
growing
and
blossoms
in
April,
May,
and
June.E
201
Extracts
and
active
constituents
are
found
in
many
herbal
drugs
and
cosmetic
preparations
worldwide,
especially
for
venous
circulation
and
skin
care.
[21,221
The
main
active
principles
of
C.
asiatica
are
triterpene
glycosides
and
their
respective
aglyco-
nes.E
231
C.
asiatica
contains
triterpene
glycosides
such
as
centellasaponin,
alkaloids,
volatile
and
flavonoids
compounds,
steroids,
asiaticoside,
sceffoleoside,
phenolic
acid,
and
made-
cassic
acid.E
24
'
251
Asiaticoside
is
the
most
major
triterpene
glycoside
in
the
water
extract
and
it
is
transformed
in
vivo
by
hydrolysis
into
asiatic
acid,
which
was
shown
to
be
effective
in
induction
of
apoptosis
in
different
types
of
cancer.E
261
The
therapeutic
substances
in
C.
asiatica
are
saponin-containing
triterpene
acids
and
their
sugar
esters,
of
which
asiatic
acid,
madecassic
acid,
and
asiaticosides
are
considered
to
be
the
most
important.E
271
It
has
been
reported
that
1%
C.
asiatica
extract
cream
improves
wound
healing
of
chronic
ulcer
in
width,
length,
and
depth
after
7,14,
and
21
days
of
use
of
the
product.E
281
Phyto-
constituents
present
in
C.
asiatica
have
been
found
to
be
responsible
for
these
wound
healing
properties.
Asiaticoside
isolated
from
C.
asiatica
increased
hydroxyproline
content,
tensile
strength,
collagen
content,
and
epithelialization
in
a
punch
wound
model.
291
Further,
triterpenes
from
C.
asiatica
were
shown
to
increase
remodeling
of
the
collagen
matrix
and
stimulate
glycosaminoglycan
synthesis
in
a
rat
wound
chamber
model.
301
Oral
administration
of
madecassoside
isolated
from
C.
asiatica
herbs
promoted
burn
wound
healing
in
mice
through
its
antioxidative
effect,
collagen
synthesis,
and
angiogenesis.E
311
All
extracts
of
C.
asiatica
promote
the
wound
healing
in
both
incisional
and
burn
wounds.
Asiatic
acid
in
the
ethyl
acetate
extract
is
the
most
active
ingredient
for
healing
the
wound.
The
extracts
of
this
plant
have
antibacterial
effects,
too.E
32-341
The
final
purpose
in
burn
management
is
promotion
of
wound
healing
and
epithelialization
as
soon
as
possible
to
avoid
infection
and
lesser
side
effects.
Given
the
adverse
effects
of
currently
used
topical
drugs,
innovation
of
novel
topical
agents
that
could
effectively
and
safely
promote
wound
healing
and
relieve
the
associated
pain
is
desirable.E
351
On
the
basis
of
the
previously
studies
that
showed
promoting
healing
in
animal
studies
for
burn
and
surgical
wounds
and
antibacterial
effects
of
C.
asiatica,
in
this
study,
we
compared
the
efficacy
of
Centiderm
versus
SSD
in
partial
thickness
burning
patients
referred
to
Velayat
Hospital
_referral
hospital
of
Guilan
province
in
Northern_
Rasht,
Iran.
2.
Methods
2.1.
Participants
Our
study
population
comprised
burn
victims
who
were
treated
in
Velayat
Burning
Hospital
at
Rasht,
Iran.
Period
of
study
was
from
October
2014
to
February
2015.
2.2.
Eligibility
criteria
The
inclusion
criteria
were
partial
thickness,
burning
wound
less
than
10%
of
total
body
surface
area
(TBSA)
and
in
the
limbs,
burning
event
was
fewer
than
48
hours,
no
other
concurrent
injury
except
burning,
general
physical
and
mental
health,
between
14
and
60
years
old.
Exclusion
criteria
were
the
existence
of
any
cerebrovascular
disease,
cardiovascular
disease,
concurrent
endocrine,
hepatic
or
renal
disease,
pregnancy,
history
of
alcohol
or
drug
abuse,
concurrent
use
of
antibiotic.
A
total
of
134
patients
with
second-degree
burn
wounds
on
their
limbs
were
referred
to
Velayat
Hospital
emergency
ward.
Seventy-five
patients
had
the
eligibility
and
entered
the
study,
35
of
them
in
SSD
group
and
40
of
them
in
Centiderm
group.
Fifteen
patients
have
excluded
the
study
because
of
lost
follow-up
and
incomplete
data.
Thirty
patients
in
both
groups
were
evaluated.
One
burning
specialist
physician
evaluated
the
patients
at
admission
and
chose
and
classified
them
on
the
basis
of
inclusion
criteria
and
ruling
out
the
exclusion
criteria
based
on
scientific
definitions
of
partial
thickness
burning
wounds.E
361
Bedside
clinical
evaluation
was
used
to
assess
burn
wound
depth
based
on
the
subjective
assessment
of
visual
and
tactile
characteristics
of
a
burn
wound,
namely
wound
appearance,
capillary
blanching
and
refill,
capillary
staining,
and
burn
wound
sensibility
to
light
touch
and
pinprick.E
371
Lund
and
Browder's
chart
were
used
for
evaluating
TBSA.E
381
If
the
wounds
were
mixed
superficial,
deep
and
full
thickness,
they
were
excluded
from
the
study
because
of
not
confounding
the
results.
2.3.
Interventions
The
intervention
group
subjected
to
use
topical
Centiderm
ointment.
The
control
group
used
silver
sulfadiazine
1%
cream
(routine
treatment)
on
the
area
of
burning
wound.
Burn
wounds
were
treated
once
daily
in
the
home
after
getting
information
about
how
to
use
the
drugs.
Equal
shape
and
boxes
of
ointment
were
used
in
both
groups.
Patient
compliance
was
checked
at
the
first
visit
after
inclusion
on
the
basis
of
jobs
and
ability
to
referring
to
the
hospital
for
follow-up.
After
enrolling
patients
in
the
study,
they
were
given
a
remembering
checklist
for
using
the
drugs
at
home.
They
brought
the
remember
checklist
in
follow-up
sessions.
Also,
for
checking
true
use,
we
called
them
during
the
period
they
used
the
ointment,
and
in
every
visit,
they
showed
the
drug
boxes
to
make
confidence
true
using.
The
herbal
product
was
Centiderm
ointment
that
was
a
derivative
of
C.
asiatica.
This
product
is
cheaper
than
SSD.
The
formulation
of
ointment
was
made
by
pharmacognosist
of
the
pharmacy
faculty
in
Guilan
University
of
Medical
Sciences
and
confirmed
by
the
University
and
registered
and
licensed
as
a
drug
patent
in
Iranian
Intellectual
Property
Office
(Patents)
with
the
registration number
of
86035
and
international
classification
patent
of
A61K3
6/00;
A61
J3/04.E
391
The
fresh
leaves
of
C.
asiatica
were
collected
in
May
2014
from
a
local
wetland
at
Bandar-Anzali,
Iran.
The
accuracy
of
plant
selection
was
proved
and
authenticated
by
Mr.
Asaadi,
a
senior
2
Saeidinia
et
al.
Medicine
(2017)
96:9
www.md-joumal.com
botanist
of
the
Department
of
Botany,
University
of
Guilan,
with
adopting
the
scientific
herbarium
information.
Fresh
leaves
of
the
plant
were
air-dried
at
40°C
and
ground
to
powder
by
mixer.
Then,
they
were
subjected
to
exhaustive
extraction
using
ethanol
(96%)
and
distilled
water
with
the
relation
of
60:40.
The
dark
green
liquid
extract
was
concentrated
under
rotary
evaporator
and
vacuum.
The
resulting
dried
extract
was
partitioned
between
butanol
and
petroleum
ether.
It
made
2
separate
portions
in
which
Butanol
fraction
was
concentrated
under
rotary
evapora-
tor
and
vacuum.
Dried
butanol
fraction
was
mixed
with
Vaseline
and
Glycerin
to
make
the
emulsified
final
based
contained
about
3%
of
the
final
extract
which
named
Centiderm
ointment.
All
chemical
ingredients
were
purchased
from
Merck
Co.,
Germany.
The
last
formulation
was
tested
physically
and
chemically
to
select
the
most
stable
and
desirable
product
thermodynamically
or
physiologically.
Samples
were
sterilized
by
gamma
radiation.
2.4.
Pharmacokinetic
and
safety
C.
asiatica
is
in
World
Health
Organization
(WHO)
medicinal
plants
monographs
and
its
safet
and
pharmacokinetic
is
validated
there.E
461
It
contains
several
active
constituents,
of
which
the
most
important
are
the
triterpenoid
saponins,
including
asiaticoside,
centelloside,
madecassoside,
and
asiatic
acid.
In
addition,
it
contains
other
components,
including
volatile
oils,
flavonoids,
tannins,
phytosterols,
amino
acids,
and
sugars.E
461
A
pharmaco-
kinetic
study
suggests
that
the
active
ingredients
in
total
triterpenoid
fraction
of
C.
asiatica
are
well
absorbed
in
human
volunteers.
After
single
oral
administration
of
30
and
60
mg
of
the
extract,
maximum
plasma
levels
of
asiatic
acid
were
reached
at
4.5
and
4.2
hours,
respectively.
Plasma
half-lives
were
2.2
hours
in
the
30-mg
dose
and
3.4
hours
in
the
60-mg
dose,
with
no
detectable
levels
of
the
saponin
present
24
hours
after
single
dosing.
Seven-day
treatment
with
the
herb
at
the
same
dosing
schedule
resulted
in
higher
peak
plasma
concentrations,
longer
half-lives,
and
greater
area-under-the
curve
values,
[47]
which
ensured
its
external
usage
safety.
Its
external
use
is
validated
by
European
Committee
on
Herbal
Medicinal
Products.
In
this
committee,
reports
about
C.
asiatica
mentioned
that
the
cream
1%
for
cutaneous
use
is
authorized
in
Belgium
since
1969
for
the
treatment
of
moderate
or
benign
problems
in
wound
formation
such
as
atonic
wounds,
hypertrophic
scars,
keloids
in
active
phase,
in
France,
since
1975
to
aid
in
the
local
treatment
for
cutaneous
ulcerations
and
since
2000
to
aid
in
the
local
treatment
for
granulation
phase
of
wounds,
cutaneous
ulcers,
and
cutaneous
gangrene.
The
ointment
1%
is
used
in
Greece
as
a
potent
wound
healing
agent
(induce
collagen
biosynthesis).
[48]
C.
asiatica
is
an
important
medicinal
herb
that
is
widely
used
in
traditional
medicine.
The
safety
of
this
plant
extracts
mentioned
in
many
medical
references
and
clinical
trials.
Therefore,
using
this
product
in
our
research
based
on
such
references
is
safe.
[40-44]
We
carried
out
the
determination
of
total
triterpenoid
content
for
the
product
(Centiderm)
during
the
research
and
findings
showed
that
the
total
triterpenoid
content
of
this
product
is
constant
during
the
trial.
The
content
of
triterpenoids
obtained
by
the
aforementioned
method
was
determined
according
to
the
study
by
Lu
et
al,
[45]
with
a
slight
modification
and
then
expressed
as
milligrams
ursolic
acid
equivalent/gram
dry
weight.
Briefly,
after
a
200-µL
sample
solution
in
a
10-mL
volumetric
flask
was
heated
to
evaporation
in
a
water-bath,
1
mL
new
mixed
5%
(WN)
vanillin-acetic
solution
and
1.8
mL
sulfuric
acid
was
added,
mixed,
and
incubated
at
70°C
for
30
minutes.
Then,
the
mixed
solution
was
cooled
and
diluted
to
10
mL
with
acetic
acid.
The
absorbance
was
measured
at
573
nm
against
blank
using
a
spectrophotometer.
The
blank
consisted
of
all
reagents
and
solvents
without
sample
solution.
The
content
was
determined
using
the
standard
ursolic
acid
calibration
curve.
The
calibration
equation
for
ursolic
acid
was
Y
=
0.0725X
-
0.0207
(R
2=
0.9991),
in
which
Y
was
the
absorbance
value;
X
was
the
concentration
of
ursolic
acid
(
ilg/mL).
The
linear
range
of
ursolic
acid
was
1
to
1014,/mL.
The
patients
were
requested
to
inform
investigators
about
any
adverse
events
or
complaint
during
the
trial.
If
there
were
any
symptoms,
they
were
checked
and
recorded
at
the
beginning
and
at
each
baseline
visit.
Also,
possible
side
effects
were
checked
and
recorded
via
telephone
call
every
day
and
the
physician
was
responsible
for
continuing
or
discontinuing
the
drugs.
The
adverse
effects
check
list
was
completed
by
independent
raters.
2.5.
Objectives
&
outcomes
We
evaluated
the
burn
wounds
based
on
objective
and
subjective
criteria
in
both
groups
and
our
hypothesis
was
that
burning
wound
in
Centiderm
group
cannot
heal
them
better
and
faster
than
the
SSD
group.
All
the
wounds
were
evaluated
at
the
admission
to
the
emergency
ward
of
the
hospital
by
objective
signs,
including
burning
wound
VSS
score
(Pliability,
Pigmenta-
tion,
Height,
Vascularity
of
the
wound),
VAS,
Subjective
criteria
(Itching,
Dryness,
and
Irritation)
and
re-epithelialization,
complete
healing,
and
existence
of
infection
[49]
by
1
burning
specialist
physician.
Re-epithelialization
was
defined
as
noting
the
number
of
days
required
for
the
Escher
to
fall
off
from
the
burn
wound
surface
without
leaving
a
raw
wound
behind
in
examination.E
50,511
The
patients
followed
up
till
complete
healing
daily
with
a
burning
specialist
physician,
and
on
days
3,
7,14,
the
subjective
and
objective
variables
and
VAS
were
recorded.
Also,
the
pathological
changes,
for
example,
granulation
tissue
formation
and
re-epithelialization
in
wounds
and
their
compari-
son
with
the
normal
tissue
part
were
inspected
medically
by
him.
Patients
were
visited
daily
for
compliance
of
drug
consumption
and
evaluation
of
re-epithelialization
and
probable
wound
infection
till
complete
healing
of
wound
reached
and
the
day
of
finishing
re-epithelialization
and
complete
wound
healing
were
recorded
for
each
patient.
We
evaluated
patients
in
all
of
the
days
(even
weekends)
during
the
week
on
the
basis
of
remember
chart.
2.6.
Sample
size
For
the
purpose
of
sample
size
calculation,
the
difference
in
duration
of
treatment
for
complete
wound
healing
was
considered
as
the
primary
outcome
measure.
It
was
calculated
that
30
subjects
would
be
required
per
group
in
order
to
detect
a
difference
of
5
days
in
this
parameter
with
80%
power
and
5%
probability
of
type
I
error.
This
calculation
assumed
a
standard
deviation
of
1.5
days
for
the
complete
wound
healing
feature.
2.7.
Randomization
The
study
was
designed
as
a
prospective,
parallel
group,
randomized
controlled
trial.
We
used
the
foursome
random
fixed
block
for
randomization.
After
allocation
of
patients
into
2
different
groups,
SSD
and
Centiderm
ointment
were
administered
topically
once
a
day.
Seventy-five
subjects
were
randomized
of
whom
data
were
analyzed
for
30
patients
treated
with
1%
SSD
cream
and
30
patients
treated
with
Centiderm.
The
sequence
was
concealed
until
interventions
were
assigned.
The
randomization
3
Assessed
for
eligibility
and
burns
(n=134)
Excluded
(n=59)
-
Not
meeting
inclusion
criteria
(n=49)
-
Declined
informed
consent
(n=10)
Randomized
n=75)
V
Analyzed
(n=30)
Allocated
to
Centiderm
treatment
(n=40)
-
Received
treatment
(n=40)
-
Not
received
treatment
(n=0)
Lost
to
follow-up
(n=2)
Discontinued
participation
(n=8)
-
Declined
participation
(n=2)
-
Incomplete
treatment
(n=6)
Saeidinia
et
al.
Medicine
(2017)
96:9
Medicine
Allocated
to
SSD
treatment
(n=35)
-
Received
treatment
(n=35)
-
Not
received
treatment
(n=0)
Lost
to
follow-up
(n=2)
Discontinued
participation
(n=3)
-
Declined
participation
(n=1)
-
Incomplete
treatment
(n=2)
Analyzed
(1=30)
Figure
1.
Study
flow
chart.
sequence
was
created
using
Excel
2010
(Microsoft,
Redmond,
WA)
with
a
1:1
allocation
using
random
block
sizes
of
2
and
4
by
an
independent
doctor.
Patients
and
burning
specialist,
and
physician
were
blinded.
2.8.
Statistical
analysis
Analysis
was
performed
per
protocol.
The
data
statistically
were
analyzed
using
SPSS
18.0
for
Windows
(SPSS
Inc.,
Chicago,
IL).
The
means
of
the
experimental
groups
were
compared
with
the
control
group
using
the
repeated-measure
General
Linear
Model
test
and
Student
t
and
independent
t
tests.
Data
were
expressed
as
mean
+SEM
and
P
<
0.05
was
considered
as
a
significant
difference.
2.9.
Ethics
statement
The
study
design
protocol
and
ethical
issues
were
reviewed
and
approved
by
Guilan
University
of
Medical
Sciences
(2013.12.
7)
with
ethical
code
of
1920341317.
Ethical
issues
were
considered
throughout
the
experiment.
The
patient
followed
the
approval
of
the
ethics
committee
of
the
Guilan
University
of
Medical
Sciences
and
Velayat
Hospital.
We
described
the
risks
and
benefits
of
the
treatment.
Then,
written
informed
consent
was
obtained
from
each
participant.
The
IRCT
(Iranian
Clinical
Trial)
code
was
registered
at
2013.10.06,
which
is
IRCT2013100614915N1.
3.
Results
3.1.
Demographic
data
A
total
of
134
participants
were
recruited,
and
75
patients
met
the
inclusion
criteria.
Of
these,
40
patients
were
placed
in
the
Centiderm
group
and
35
patients
placed
in
the
SSD
group.
During
the
study,
10
participants
in
the
Centiderm
group
and
5
participants
in
the
control
group
dropped
out
(Fig.
1)
due
to
incomplete
participation
and
declining
participation
during
the
clinical
trial.
The
mean
age
of
the
participants
was
30.67±9.91
years
and
19
of
them
were
male
(31.7%)
and
41
of
them
were
female
(68.3%).
Other
demographic
data
are
summarized
in
Table
1.
3.2.
Objective
indexes
All
of
the
objective
indexes,
that
is,
pliability,
vascularity,
pigmentation,
height,
and
VAS,
significantly
led
to
better
healing
of
the
burning
wound
in
Centiderm
group
rather
than
SSD
group
(P
<
0.05).
Although
the
mean
of
pigmentation
score
was
better
in
Centiderm
group
rather
than
the
SSD
group,
it
was
not
significant
on
day
7
(P
=0.52).
One
of
the
characteristics
of
Centiderm
was
this
pigmentation
on
day
7
(Table
2).
The
mean
of
VSS
score
in
Centiderm
group
in
days
0,
3,
7,
14
was
7.2
+
1.9,
2.5
+
1.6,
1.4
+
1.2,
and
0.23
+
0.43,
respectively.
The
mean
of
VSS
score
in
SSD
group
in
days
0,
3,
7,14
was
7.1
±
1.3,
5.8+
1.7,
4.9
+
1.3,
and
2.86±1.19,
respectively.
There
was
a
significant
4
Saeidinia
et
al.
Medicine
(2017)
96:9
www.md-joumal.com
Demographic
data
in
the
Centiderm
and
Silver
sulfadiazine
groups.
Characteristics
Centidenn
SSD
*
Age,
y
29.5+9.7
31.8±10
0.36
Sex
M/F
9/21
10/20
0.78
Cause
of
burning
Hot
water
8
(26.7%)
16
(53.3%)
0.001
Heater
4
(13.3%)
7
(23.3%)
Hot
oil
3
(10%)
6
(20%)
Fire
2
(6.7%)
1
(3.3%)
Water
steam
13
(43.3%)
0
Site
of
burning
wound
Right
upper
limb
18
(60%0
13
(43.3%)
0.46
1
,
Left
upper
limb
12
(40%)
10
(33.3%)
Left
lower
limb
0
6
(20%)
Right
lower
limb
0
1
(3.3%)
*
Silver
sulfadiazine.
difference
between
VSS
score
in
all
days
between
2
groups
(P
=
0.0001).
63
-
0
2
-
0
0-
10
1
20
Time
(days)
Group
--r
,
Cenuriern
-
-
SSD
3.3.
Subjective
indexes
All
of
the
subjective
indexes,
that
is,
dryness,
itching,
and
irritation,
significantly
led
to
better
healing
of
the
burning
wound
both
in
time
and
efficacy
in
Centiderm
group
rather
than
SSD
group
(P
<
0.05)
(Table
2).
3.4.
Re-epithelialization
Mean
of
re-epithelialization
in
burning
wounds
was
13.7
±
1.48
days
in
Centiderm
versus
20.67
±
2.02
days
in
SSD
group.
Starting
time
of
re-epithelialization
in
Centiderm
group
patients
was
on
the
10th
day,
which
was
the
16th
day
in
SSD
group.
It
means
that
the
first
patient
in
Centiderm
group
reached
faster
to
re-epithelializa-
tion
than
the
SSD
group.
Finishing
time
of
re-epithelialization
was
Figure
2.
Re-epithelialization
in
Centiderm
versus
SSD
groups.
the
17th
day,
whereas
it
was
finished
on
23rd
day
in
SSD
group
patients.
It
means
that
the
last
patient
in
Centiderm
group
reached
faster
to
re-epithelialization
than
the
SSD
group.
The
average
time
of
re-epithelialization
was
6.9
days
sooner
in
Centiderm
group
versus
SSD
group
patients.
Multivariate
analysis
showed
a
significant
difference
in
re-epithelialization
between
Centiderm
and
SSD
groups
(P
=
0
.001)
(Fig.
2).
3.5.
Complete
healing
The
mean
of
complete
healing
in
burning
wounds
was
14.67±
1.78
days
in
Centiderm
versus
21.53
±
1.65
days
in
SSD
group.
Table
Objective
and
subjective
information
in
patients
with
partial
thickness
burning
wound.
Day
characteristics
Groups
0 3
7
14
Pliability
Centiderm
2.37+0.85
1.10+0.60
0.53+0.57
0.23+0.43
SSD
2.30+0.53
1.90+0.48 1.63±0.55
1.00+0.37
P
0.718
0.001 0.001
0.001
Height
Centiderm
1.63+0.49
0.27+0.45 0.07±0.25
0.00+0.00
SSD
1.77+0.43
1.63+0.49
1.47±0.50
0.70+0.46
P
0.267 0.001 0.001
0.001
Vascularity
Centiderm
1.77+0.50
0.73+0.52
0.23±0.43
0.00+0.00
SSD
1.63+0.49
1.47+0.50
1.07±0.25
0.70+0.53
P
0.303
0.001
0.002
0.001
Pigmentation
Centiderm
1.47+0.68
0.47+0.57
0.63±0.80 0.00+0.00
SSD
1.40+0.49
0.87+0.62
0.77±0.43
0.47+0.50
P
0.667
0.012
0.52
0.001
VAS
Centiderm
8.10+1.51
1.70+2.46
0.17±0.64
0.07+0.35
SSD
8.43+1.04
5.60+1.63
3.27±
1.70
1.17
+
0.95
P
0.335
0.001 0.001
0.001
Dryness
Centiderm
0.80+0.40
0.17±0.37
0.27±0.45 0.07+0.25
SSD
0.83+0.37
0.70+0.46
0.60±0.49 0.40+0.49
P
0.744
0.001
0.009
0.002
Itching
Centiderm
0.93+0.25 0.27+0.45
0.37±0.49
0.20+0.40
SSD
0.97±0.18 0.97±0.18 0.73±0.45 0.70+0.46
P
0.561 0.001 0.004
0.001
Irritation
Centiderm
0.93+0.25 0.30+0.46
0.20±0.40
0.03±0.18
SSD
0.97±0.18
1.00+0.00
0.77±0.43
0.43+0.50
P
0.561 0.001 0.001
0.001
5
0—
O
B
C
0
6
ao
E
a-
or
0
0
Saeidinia
et
al.
Medicine
(2017)
96:9
Medicine
10
15
20
25
Time
(Days)
Figure
3.
Complete
healing
in
Centiderm
versus
SSD
groups.
Starting
time
of
complete
healing
in
Centiderm
group
patients
was
on
the
10th
day,
which
was
the
18th
day
in
SSD
group.
It
means
that
the
first
patient
in
Centiderm
group
reached
faster
to
complete
healing
than
the
SSD
group.
Finishing
time
of
complete
healing
was
20th
day,
whereas
it
was
finished
on
27rd
day
in
SSD
group
patients.
It
means
that
the
last
patient
in
Centiderm
group
reached
faster
to
complete
healing
than
the
SSD
group.
The
average
time
of
re-epithelialization
was
6.8
days
sooner
in
Centiderm
group
versus
SSD
group
patients.
Multivariate
analysis
showed
a
significant
difference
in
complete
healing
between
Centiderm
and
SSD
groups
(P=
0.001)
(Fig.
3).
Figure
4
shows
the
pre
and
post
treatment
with
Centiderm
in
1
of
4
patients.
3.6.
Adverse
events
There
was
no
adverse
reaction
such
as
severe
itching,
hypersensitivity,
systemic
symptoms
in
the
Centiderm
group
during
the
trial,
while
in
the
SSD
group,
4
patients
were
infected
and
received
antibiotic
therapy
and
conservative
treatment.
4.
Discussion
C.
asiatica
has
a
powerful
history
in
traditional
medicine
in
many
diseases.
Its
effects
on
healing
surgical
and
burning
wound
have
mentioned
and
evaluated
in
many
documents.
[23,29-32]
Antioxi-
dant
[34]
and
antibacterial
35]
effects
of
this
medicinal
plant
had
proved
previously.
These
properties
are
based
on
this
plant
constitutes
as
seen
in
previous
studies.
[22-25]
Burns
are
the
most
common
forms
of
trauma.
They
are
physical
and
chemical
phenomena
and
cause
many
morbidities
and
mortalities
in
the
world.
The
best
goal
of
all
the
current
burn
treatments
is
to
speed
up
skin
healing
and
prevent
wound
infection.
[15]
One
standard
antimicrobial
topical
ointment
is
silver
sulfadiazine
with
advantages
such
as
easy
and
convenient
use.
It
is
not
causing
pain
during
administration,
yielding
low
toxicity
and
sensitivity,
and
having
antibacterial
effects.
These
properties
have
made
it
known
as
the
gold
standard
among
antimicrobial
topical
drugs
for
the
patients
with
burns
and
turned
it
to
the
main
consumed
drug
in
treating
burn
wounds
around
the
world.
[9]
Investigation
of
our
results
showed
that
indexes
of
the
burning
wound
healing
with
Centiderm
after
3
days
of
treatment
healed
better
than
routine
treatment
of
1%
silver
sulfadiazine
(P
<
0.001)
that
was
surprising
in
the
few
first
days
of
the
burn
and
its
maximum
effects
seen
in
the
first
3
days.
The
range
of
re-
epithelialization
was
between
10
and
16
days
after
administrat-
ing
the
Centiderm
ointment
that
was
significantly
better
than
the
SSD
(P
<
0.001).
Also,
because
of
good
antioxidant
and
antibacterial
activity
of
Centiderm,
patients
showed
no
adverse
reaction
and
infection
in
comparison
with
SSD.
Some
clinical
studies
about
external
use
of
C.
asiatica
will
be
mentioned.
Basset
[52]
assessed
the
effects
of
impregnated
dressing
of
Madecassol
derivate
from
C.
asiatica
on
ulcer
cicatrization
and
burns
recovery
were
investigated
and
Madecassol
individual
gauze
(10
x
10
cm)
impregnated
with
a
mixture
of
titrated
extract
of
C.
asiatica
(TECA)
was
used
on
76
patients
who
had
experienced
previous
allergic
dermatitis
or
were
affected
by
dermatosis
of
different
kinds.
The
results
were
favorable
after
a
treatment
period
of
8
to
10
days.
[52]
Haftek
et
al
53]
performed
a
randomized,
double-blind
study
on
photo-aged
skin
of
20
female
volunteers
with
actinically
aged
facial,
neck,
and
forearm
skin
to
investigate
the
effects
of
topically
applied
5%
vitamin
C
and
0.1%
madecassoside
on
the
clinical,
biophysical,
and
structural
skin
properties,
and
their
results
indicated
a
functional
and
structural
remodeling
of
chronically
sun-damaged
skin.
Ryu
et
al
[54]
performed
a
study
to
evaluate
the
efficacy
of
wrinkle
improving
lipstick
containing
asiaticoside
(0.2%
concentration)
and
showed
that
by
using
the
lipstick
containing
asiaticoside
for
8
weeks,
the
change
of
visual
grading
scores
and
replica
analysis
indicated
the
wrinkle-improving
effect.
The
results
of
our
study
were
better
than
other
natural
products
used
for
burning
wound.
Panahi
[33]
evaluated
the
herbal
cream
consisting
of
Aloe
vera,
Lavandula
stoechas,
and
Pelargonium
roseum
as
an
alternative
for
silver
sulfadiazine
in
burn
management.
They
showed
that
Group
—r
1
Centiderm
D
Figure
4.
Patient
pictures
before
and
after
treatment
with
Centiderm.
(A)
Patient
with
partial
thickness
burning
wound;
(B)
3
days
after
treatment
with
Centiderm;
(C)
7
days
after
treatment
with
Centiderm;
(D)
10
days
after
treatment
with
Centiderm
showed
complete
healing.
6
Saeidinia
et
al.
Medicine
(2017)
96:9
www.md-joumal.com
both
herbal
and
SSD
groups
experienced
a
significant
reduction
in
the
pain
severity
at
day
14
compared
with
baseline
(P
<
0.001)
and
there
was
a
significantly
greater
reduction
from
baseline
to
the
7
(P
=
0.014)
and
14
(P
=
0.05)
day
in
the
herbal
cream
compared
with
control
group.
However,
the
frequency
of
skin
dryness
was
not
significantly
different
between
the
groups
at
any
of
the
assessed
time
points
(P
>
0.05)
and
there
was
a
single
case
of
infection
in
the
herbal
cream
group.E
331
Akbari
et
al
15
showed
that
use
of
nettle
extract
treatment
led
to
shorter
wound
healing
time,
fewer
dressing
changes,
and
shorter
hospital
stay,
than
silver
sulfadiazine
treatment.
But
no
difference
in
the
incidence
of
wound
infection
or
grafting
was
found.E
151
Malik
et
ar
s]
compared
honey
with
SSD
in
the
treatment
of
superficial
partial-
thickness
burns.
They
showed
that
the
rate
of
re-epithelialization
and
healing
of
superficial
and
partial-thickness
burns
was
significantly
faster
in
the
sites
treated
with
honey
than
in
the
sites
treated
with
SSD
(13.47
vs
15.62
days,
respectively:
P<
0.0001)
and
the
site
treated
with
honey
healed
completely
in
less
than
21
versus
24
days
for
the
site
treated
with
SSD.
Six
patients
had
positive
culture
for
Pseudomonas
aeruginosa
in
honey-
treated
site.E
551
Khorasani
et
al
[561
evaluated
Aloe
versus
SSD
creams
for
second-degree
burns
on
30
patients
with
similar
types
of
second-degree
burns
at
2
sites
on
different
parts
of
the
body.
They
showed
that
the
rate
of
re-epithelialization
and
healing
of
the
partial
thickness
burns
was
significantly
faster
in
the
site
treated
with
aloe
than
SSD
(15.9
vs
18.73
days,
respectively;
P
<
0.0001).
[56]
There
was
no
clinical
trial
similar
to
our
work.
However,
animal
and
in
vitro
studies
were
performed
on
this
subject
that
are
in
line
with
our
results.
Somboonwong
et
al
321
investigated
wound
healing
activities
of
different
extracts
of
C.
asiatica
in
incision
and
burn
wound
models.
They
showed
that
similar
to
our
study,
the
degrees
of
healing
in
the
burn
wound
with
the
4
extracts
were
significantly
higher
than
that
of
the
control
on
Days
3,
10,
and
14.
Also,
histopathological
findings
on
Day
14
after
burn
injury
revealed
prominent
fibrinoid
necrosis
and
incomplete
epithelialization
in
the
control
and
untreated
groups,
whereas
fully
developed
epithelialization
and
keratiniza-
tion
were
observed.
They
referred
these
effects
to
the
phyto-
constituents
B-sitosterol,
asiatic
acid,
and
asiaticoside
and
madecassocide.E
321
Shukla
et
al
[291
showed
that
asiaticoside
in
streptozotocin
diabetic
rats,
where
healing
is
delayed,
improved
by
topical
application
of
0.4%
solution
of
asiaticoside.
They
indicated
that
asiaticoside
exhibits
significant
wound
healing
activity
in
normal
as
well
as
delayed
healing
models
and
is
the
main
active
constituent
of
C.
asiatica.
Lu
et
al
571
explained
the
mechanism
of
asiaticoside
by
using
cDNA
microarray
technology
and
showed
that
alternation
of
genes
expression
profiles
was
determined
in
a
human
dermal
fibroblast
in
vitro
in
the
presence
of
30
ilg/mL
asiaticoside,
and
54
genes,
with
known
functions
for
cell
proliferation,
cell-cycle
progression,
and
synthesis
of
the
extracellular
matrix,
were
significantly
upregulated.
They
showed
that
there
is
a
close
correlation
among
the
gene
profile,
mRNA,
and
protein
production
in
the
cells
response
to
asiaticoside
stimulation.E
571
Ermertcan
et
al
[581
compared
the
effects
of
collagenase
and
C.
asiatica
in
the
rat
model.
Their
immunohistochemical
examinations
showed
strong
inducible
nitric
oxide
synthase
(iNOS)
and
transforming
growth
factor-
beta
(TGF-0)
immunoreactivities
in
C.
asiatica
group.
Endothe-
lial
nitric
oxide
synthase
(eNOS)
immunoreactivity
was
moderate
in
this
group.E
581
Zhang
et
al
591
indicated
that
asiaticoside
can
downregulate
TGF-01
mRNA
and
tissue
inhibitors
of
metal-
loproteinases-1
(TIMP1)
expressions
and
upregulate
TGF-03
mRNA
expression
in
postburn
hypertrophic
scars
capable
of
decomposing
the
products
of
type
I
collagen,
contributing
to
the
reduction
of
hypertrophic
scars.
Kimura
et
al
601
suggested
that
the
enhancement
of
burn
wound
healing
by
asiaticoside
might
be
due
to
the
promotion
of
angiogenesis
during
skin
wound
repair
as
a
result
of
the
stimulation
of
vascular
endothelial
growth
factor
(VEGF)
production
caused
by
the
increase
in
monocyte
chemo-
attractant
protein-1
(MCP-1)
expression
in
keratinocytes
and
the
increase
in
IL-1
R
expression
in
macrophages
induced
coopera-
tively
by
asiaticoside
along
with
MCP-1.
On
the
basis
of
clinical
and
experimental
findings,
our
ointment
originated
from
C.
asiatica
can
promote
the
wound
healing
in
burn
wounds.
The
use
of
C.
asiatica
is
safe
and
some
clinical
trials
in
other
topics
were
done.
It
was
used
clinically
for
periodontal
treatment
that
showed
adjunctive
local
delivery
of
extracts
from
C.
asiatica
in
combination
with
significantly
improved
clinical
signs
of
chronic
periodontitis
and
IL-1beta
level
in
maintenance
patients.E
611
It
was
used
for
minor
oral
aphthous
ulcers
by
Ruengprasertkit
et
al
621
and
they
demonstrated
that
its
oral
paste
was
safe
and
effective
in
reducing
pain,
ulcer
size,
and
erythema.
Kuo
et
al
631
evaluated
the
effects
of
a
topical
cream
containing
P.
amboinicus
(Lour.)
Spreng.
(Lamiaceae)
and
C.
asiatica
(L.)
for
diabetic
foot
ulcers
and
showed
that
treating
diabetic
foot
ulcers
with
them
is
a
safe
alternative
to
hydrocolloid
fiber
dressing
without
a
significant
difference
in
effectiveness.
The
pharmacological
activity
of
C.
asiatica
is
thought
to
be
due
to
several
saponin
constituents,
including
asiaticoside,
asiatic
acid,
and
madecassic
acid.E
641
In
vitro,
each
of
these
compounds
stimulated
the
production
of
human
collagen
I,
a
protein
involved
in
wound
healing.E
651
Stimulation
of
collagen
synthesis
in
foreskin
fibroblast
monolayer
cultures
by
an
extract from
Herba
Centellae
has
also
been
reported.E
301
Asiaticoside
quickened
the
healing
of
superficial
postsurgical
wounds
and
ulcers
by
speeding
up
cicatricial
action.E
661
Asiaticoside
stimulates
the
epidermis
by
activating
t28he
cells
of
the
malpighian
layer
in
porcine
skin,
and
by
keratinization
in
vitro.E
671
Topical
application
of
asiaticoside
promoted
wound
healing
in
rats
and
significantly
increased
the
tensile
strength
of
newly
formed
skin.
[66,68]
Extracts
of
C.
asiatica,
and,
in
particular,
its
major
triterpene
ester
glycoside,
asiaticoside,
are
valuable
in
treating
hypertrophic
scars
and
keloids.E
661
Asiaticoside
has
been
reported
to
decrease
fibrosis
in
wounds,
thus
preventing
new
scar
formation.E
661
The
mechanism
of
action
appears
to
be
2-fold:
by
increasing
the
synthesis
of
collagen
and
acidic
mucopolysaccharides
and
by
inhibiting
the
inflammatory
phase
of
hypertrophic
scars
and
keloids.
It
has
further
been
proposed
that
asiaticoside
interferes
with
scar
formation
by
increasing
the
activity
of
myofibroblasts
and
immature
collagen.
[66]
In
clinical
trials,
an
extract
of
C.
asiatica
in
a
1%
salve
or
2%
powder
accelerated
healing
of
wounds.E
691
A
formulation
containing
asiaticoside
as
the
main
ingredient
healed
64%
of
soiled
wounds
and
chronic
or
recurrent
atony
that
was
resistant
to
usual
treatment.E
661
In
an
open
clinical
study,
the
treatment
of
20
patients
with
soiled
wounds
and
chronic
or
recurrent
atony
with
a
galenical
formula
containing
89.5%
C.
asiatica
healed
64%
and
produced
improvement
in
another
16%
of
the
lesions
studied.
Local
application
of
an
extract
of
the
drug
to
second-
and
third-degree
burns
speeded
up
healing,
prevented
the
shrinking
and
swelling
caused
by
infection,
and
further
inhibited
hypertrophic
scar
formation.E
661
Previous
studies
have
focused
on
the
effects
of
Centella
ointment
on
the
process
of
healing
burn
wounds
or
surgical
in
the
laboratory
and
in
vivo
conditions.
In
this
study,
we
showed
that
healing
effects
of
Centiderm
were
significantly
better
than
the
routine
drug
_SSD_
7
Saeidinia
et
al.
Medicine
(2017)
96:9
Medicine
for
treating
partial
thickness
burning
wounds
such
as
pain,
objective
and
subjective
signs,
and
also
re-epithelialization
and
complete
healing
time.
None
of
subjected
patients
had
infection
rather
than
SSD.
Previous
studies
displayed
the
positive
antibacterial,
anti-
inflammatory
effects,
and
positive
results
on
in
vitro
and
in
vivo
experiments
of
the
drug
on
the
wound
healing
and
its
useful
and
effective
features.
Our
results
showed
that
consumption
of
Centiderm
ointment
not
only
improved
the
objective
and
subjective
signs
but
also
improved
the
re-epithelialization
and
complete
healing
rather
than
SSD
without
any
infection
in
the
subjects
with
burning
event.
In
our
evaluation,
patients
who
underwent
Centiderm
treatment
showed
their
optimal
effects
in
first
3
days
that
is
clear
in
figures
and
detailed
results.
Centiderm
is
cheaper
than
SSD
and
it
can
be
a
suitable
choice
for
treating
partial
thickness
burning
wounds.
Performing
a
clinical
trial
for
deeper
thickness
burning
wounds
for
Centiderm
is
recom-
mended.
We
also
suggested
using
Centiderm
in
dressing
form
and
comparing
it
with
other
dressing
methods
and
also
with
other
antiseptic
and
burn
wound
healer
drugs.
Acknowledgements
We
wish
to
thank
Shahid
Ali
Es'hagh
Moafi
for
moral
support.
We
also
thank
Medicinal
Plants
research
center
of
student
Basij
for
scientific
support
and
Dr.
Morteza
Fallah
Karkan
for
helping
in
all
of
steps
of
the
research.
We
thank
Mr.
Mandi
Nabaei
and
Mr.
Mostafa
Hasanpour
for
helping
in
formulation
step,
Mrs
Fateme
Keihanian
and
Mrs
Motlagh,
and
other
nurses
of
emergency
ward
of
Velayat
Hospital
for
helping
us
in
patient
gathering
step.
We
also
thank
Mr.
Asaadi
for
helping
in
identification
and
confirming
herb,
Mr.
Mohammad
Bagher
Gholami
for
collecting
herb
from
its
ecology,
Mr
Hamid
Morovati
in
extraction
steps,
and
all
other
persons
who
helped
us
during
this
clinical
trial.
We
also
thank
Guilan
University
of
Medical
Sciences
for
financial
support.
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