Db. Johns et al., REDUCTION OF ADHESION FORMATION BY POSTOPERATIVE ADMINISTRATION OF IONICALLY CROSS-LINKED HYALURONIC-ACID, Fertility and sterility, 68(1), 1997, pp. 37-42
Objective: To examine the efficacy of various formulations of hyaluron
ic acid (HA), including HA ionically cross-linked with trivalent iron,
in animal models of adhesion formation. Design: Hyaluronic acid formu
lations of varying concentrations and cross-linked densities were prep
ared and evaluated in a rabbit uterine horn model and a rabbit sidewal
l model. Setting: ETHICON, Inc., Somerville, New Jersey. Subject(s): N
ew Zealand White rabbits. Intervention(s): Test formulations were appl
ied as intraperitoneal instillates after surgery. Main Outcome Measure
(s): Adhesion formation was assessed at 7 and 14 days (sidewall and ut
erine horn model, respectively). Result(s): Hyaluronic acid that was n
ot ionically cross-linked was ineffective in reducing adhesions in the
se models even at high viscosity, whereas the ionically cross-linked f
ormulations of HA with trivalent iron were highly effective. Efficacy
improved with increased levels of ionic cross-linking. Flowable gels,
which could be delivered readily by syringe and cannula, also were eff
ective when administered at a site remote from injury and with saline
present. Conclusion(s): Whereas previous studies showed that HA was ef
fective in reducing adhesions peripheral to the site of injury, HA ion
ically cross-linked with trivalent iron was effective in reducing adhe
sions at all sites. From these studies, a formulation of HA. ionically
cross-linked with trivalent iron, 0.5% Ferric Hyaluronate Gel (LUBRIC
OAT; ETHICON, Inc., Somerville, NJ), was identified for subsequent cli
nical evaluations. (C) 1997 by American Society for Reproductive Medic
ine.