Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 23, 246–250 (2009)
DOI: 10.1002/ptr
246 A. A. MOGHADAMNIA ET AL.
Copyright © 2008 John Wiley & Sons, Ltd.
PHYTOTHERAPY RESEARCH
Phytother. Res. 23, 246–250 (2009)
Published online 13 October 2008 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/ptr.2601
The Efficacy of the Bioadhesive Patches
Containing Licorice Extract in the Management
of Recurrent Aphthous Stomatitis
A. A. Moghadamnia
1
*, M. Motallebnejad
2
and M. Khanian
3
1
Department of Pharmacology, Babol University of Medical Sciences, Babol, Iran
2
Department of Oral Medicine, Babol University of Medical Sciences, Babol, Iran
3
Faculty of Dentistry, Babol University of Medical Sciences, Babol, Iran
This study evaluated the efficacy of licorice bioadhesive hydrogel patches to control the pain and reduce the
healing time of recurrent aphthous ulcer.
This study was carried out in three episodes of ulcers: in the first episode of ulcer, all 15 patients were asked to
record their baseline individual pain level by a visual analog scale. In the second and third episodes, comparative
and consecutive subjective and objective evaluations of the bioadhesive were done. The effects of the following
variables were investigated: (1) VAS pain score for 5 consecutive days, (2) profile of aphthous ulcers on days 3
and 5, (3) time to complete relief of pain and healing of the ulcers, (4) diameter of the lesions and necrotic zone.
A significant reduction in VAS was recorded following application of the licorice patches on days 2, 3, 4 and
5 compared with the no-treatment group ( p < 0.001). Licorice patches caused a significant reduction in the
diameter of the inflammatory halo and necrotic center compared with the placebo group ( p = 0.03).
According to the results of this study, licorice bioadhesive can be effective in the reduction of pain and of
the inflammatory halo and necrotic center of aphthous ulcers. Copyright © 2008 John Wiley & Sons, Ltd.
Keywords: recurrent aphthous stomatitis; licorice; mucoadhesive; biopatch; topical therapy.
Received 5 May 2007
Revised 26 April 2008
Accepted 14 May 2008
* Correspondence to: A. A. Moghadamnia, Department of Pharmacology,
Babol University of Medical Sciences, post code 4717641367, Babol, Iran.
E-mail: moghadamnia@yahoo.com
INTRODUCTION
Recurrent aphthous stomatitis (RAS) is a common
condition in which recurring ovoid or round ulcers
affect the oral mucosa. It is one of the most painful
oral inflammatory ulcerative conditions which cause pain
during eating, swallowing and speaking (Miller and Ship,
1977; Sircus et al., 1967). Recurrent aphthous stomatitis
is the most common oral condition diagnosed by dentists
and physicians (Rogers, III, 1977; Woo and Sonis, 1996).
The prevalence of the disease varies in different stud-
ies according to the investigated populations (Harries
et al., 1987; Scully et al., 2003). An overall prevalence
of 10–20% has been reported for the general popula-
tion (Rennie et al., 1985; Scully et al., 2003), with a
higher prevalence of RAS (56%) in selected groups,
such as university students (Donatsky, 1973). Although
hereditary (Ship, 1965; Shohat-Zabarski et al., 1992),
dietary (Eversole, 1994), hematologic (Burgan et al.,
2006), infectious (Barile et al., 1963; Sun et al., 1996),
allergic (Boulinguez et al., 2003) and immunologic (Natah
et al., 2000) factors have been implicated, their role as
the main etiological factors in the pathogenesis remains
to be elucidated. Furthermore, with the dramatic world-
wide increase in patients with immuno-suppression
caused by medical treatments, systemic diseases, or both,
the prevalence of these conditions may be increasing.
Pain is a common symptom of RAS (Mahdi et al., 1996).
There is no specific management for RAS, and there-
fore analgesic, antimicrobial and immuno-modulatory
drugs have been used individually or simultaneously
(Porter et al., 1998). Topical treatment is used to pro-
mote healing and pain relief (Scully et al., 2003) mean-
while, systemic treatment is reserved for severe cases
and is not applicable in most situations (Katz et al.,
1994). Antiinflammatory, antibiotic and some immuno-
modulatory agents have been used as topical and
systemic treatments in RAS (Jurge et al., 2006) so far
topical medications with mucosal adherence properties
have been used with some success, including Orabase
(Scully et al., 2003), Zirlactin (Rodu and Russell, 1988)
and Cianoacrylate (Jasmin et al., 1993). In Chinese
traditional medicine, licorice remains one of the most
commonly prescribed herbs and has been used in the
treatment of various ailments ranging from tuberculosis
to peptic ulcers (Huang, 1993). Since licorice has been
shown to have antiinflammatory properties in herbal
medicine (Shibata, 2000), the present study undertook
to assess the efficacy of the application of licorice
bioadhesive hydrogel patches formulated from tragacant
gum in the pain control of RAS. As dental practitioners
and researchers become better trained in oral medi-
cine, it is anticipated that the physiopathology, preven-
tion and treatment of RAS will improve in the future.
MATERIAL AND METHODS
Patients. A total of 15 patients, 5 women and 10 men
(age 22–35 years, mean ± SD, 26.27 ± 4.28 years) with