Comparison of the Effects of Contractubex® Gel in an Experimental Model of Scar Formation in Rats: An Immunohistochemical and Ultrastructural Study

January 2012 | Volume 11 | Issue 1 | Original Article | 74 | Copyright © January 2012

Mustafa T. Sahin MD,a Sevinc Inan MD,b Serap Ozturkcan MD,a Elif Guzel MDc Cemal Bilac MD,a Gülsen Giray MD,b Sevda Muftuoglu MDd

aDepartment of Dermatology, Celal Bayar University Medical Faculty, Manisa, Turkey bDepartment of Histology and Embryology, Celal Bayar University Medical Faculty, Manisa, Turkey cDepartment of Histology and Embryology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey dDepartment of Histology and Embryology, Hacettepe University Medical Faculty, Ankara, Turkey


Background: Contractubex® gel, a commercial treatment for scars, consists of a mixture of onion extract (cepea extract), heparin sodium, and allantoin. It exerts a softening and smoothing effect on indurated, hypertrophic, painful, and cosmetically-disfiguring scar tissue.
Aim: To compare and discuss the immunohistochemical and ultrastructural effects of treatment of an experimental scar in a rat model with Contractubex gel.
Methods: Thirty-two Sprague-Dawley rats were divided into four groups. Skin biopsies were taken to develop full thickness wounds. After 10 days, Contractubex gel, heparin, and allantoin were topically applied daily to groups 2, 3, and 4, respectively. Group 1 was the control group. On the 30th day, scar tissues were excised to investigate the immunohistochemical and ultrastructural effects of these agents. For this purpose we used TGF-beta, laminin, and fibronectin primary antibodies.
Results: Increased immunoreactivities of laminin, fibronectin, and TGF-beta in control group, moderate immunoreactivities in heparin and allantoin groups, and mild immunoreactivities in the Contractubex gel group were observed. In semi-thin sections, Group 2 showed the thinnest epidermis of the four groups. In electron micrographs of Group 2, completely keratinized and normally appearing cells could be seen.
Conclusions: Immunohistochemical and ultrastructural observations demonstrated that the Contractubex gel significantly improved the quality of wound healing and reduction of scar formation. Also, it was a more appropriate treatment choice than heparin monotherapy and allantoin monotherapy in keloidal and hypertrophic scars.

J Drugs Dermatol. 2012;11(1):74-81.


There are two kinds of abnormal scar formation in the skin: keloid and hypertrophic scars. The causative mechanism of such scars is not fully understood, but local histological factors in connection with a hereditary component are thought to be involved in most cases. In genetically predisposed individuals, traumatic factors including burns, incisional wounds, infections, acne, and other inflammatory disorders may trigger keloid formation. Keloid and hypertrophic scars, which result from excessive collagen deposition may lead to significant morbidity as well as pruritus, pain, restriction of motion, or cosmetic disfigurement.1,2
There is no universally accepted treatment protocol in the management of keloid and hypertrophic scars. Hypertrophic scars, which are often resistant to treatment and have a higher rate of recurrence, may be more responsive to treatment than keloids.1,3 Laser surgery, surgical removal, radiotherapy, silicone gel sheeting and other dressings, cryotherapy, interferon, bleomicin, 5-fluorouracil, and intralesional corticosteroids have all been used alone or in various combinations, with variable but largely transient success.3,4
Clinical studies demonstrated that the gel-based mixture of extractum cepae-heparin sodium-allantoin (Contractubex® gel, Merz Pharma, Frankfurt, Germany) [components: 10% aqueous onion extract (extractum cepae), 50 U heparin per gram of gel, 1% allantoin] was effective in the treatment, reduction, and prevention of hypertrophic scars and keloids.5-8 These agents exert a softening and smoothing effect that visually and functionally improves scar tissue.5,9 However, there has been little research on how these agents influence scar formation processes and key wound-healing components such as transforming growth factor-beta (TGF-β)