title: The in vivo effect of esculetin ointment and esculetin-mixed Zyderm for Zyderm.
abstract: BACKGROUND
  Injectable collagen is often used for treatment of wrinkles or scars in cosmetic surgery. However, it is degraded within a short period after subcutaneous injection. The authors aimed to achieve a long-lasting effect of the filler with a new collagenase inhibitor, esculetin (6,7-dihydroxy-2H-chromen-2-one).
  
  
  METHODS
  Nude mice were divided into two study groups and a control group (35 mg cattle collagen): (1) those implanted with Zyderm 0.3 g subcutaneously into the dorsal region followed by daily topical application of 5% esculetin ointment (0.5 g/day) to the skin of the implanted area (the 5% esculetin ointment group), and (2) those implanted with a mixture of Zyderm 0.3 g and esculetin (1 to 4 mM) (the esculetin-mixed Zyderm groups). In each group, Zyderm was removed at different time points to measure the wet weight and hydroxyproline level. Furthermore, each removed Zyderm specimen was sectioned for histologic examination with Azan staining and immunostaining.
  
  
  RESULTS
  In the esculetin ointment group and the 2 mM esculetin-mixed Zyderm group, the hydroxyproline levels at 30, 60, and 90 days were significantly higher than those in the control group, suggesting that esculetin suppresses the biodegradation of Zyderm. There was no significant difference in hydroxyproline level between the esculetin ointment group and the 2 mM esculetin-mixed Zyderm group; biodegradation occurred to a similar extent with either method of application.
  
  
  CONCLUSIONS
  An atelocollagen implant is used as a safe and effective scaffold material for tissue regeneration. Future applications of the present study are expected.
authors.affiliation: Tokyo, Japan From the Department of Plastic, Oral, and Maxillofacial Surgery, Teikyo University School of Medicine; the Departments of Cartilage and Bone Regeneration (Fujisoft) and Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo; the Department of Pharmacy, Teikyo University Hospital; and Teikyo University School of Pharmaceutical Sciences.
authors.forename: Hisayo
authors.initials: H
authors.lastname: Yamaoka
authors.forename: Satoru
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Masateru
authors.initials: M
authors.lastname: Matsui
authors.forename: Koichi
authors.initials: K
authors.lastname: Gonda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirabayashi
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hoshi
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamaoka
mesh_terms: D000818:Animals; D003094:Collagen / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009824:Ointments; D014468:Umbelliferones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D009824:Ointments; D014468:Umbelliferones; D003094:Collagen; C007628:esculetin