A phase III, randomized, double-blind, matched-pairs, active-controlled clinical trial and preclinical animal study to compare the durability, efficacy and safety between polynucleotide filler and hyaluronic acid filler in the correction of crow's feet: a new concept of regenerative filler.

The Rejuran® is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran® on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire®; and Group 3 were treated with Rejuran®. The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran® treatment for crow's feet on one side and Yvoire-Hydro® on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran® group showed similar durability and inflammatory response to the Yvoire® group. Upon efficacy assessment, the Rejuran® group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran®, as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.

Implantable micro-chip for controlled delivery of diclofenac sodium.

We prepared an implantable micro-chip enabled for controlled delivery of diclofenac sodium (DS). The micro-chip was made of poly(methyl methacrylate), where a pair of micro-channels and micro-wells was embedded to serve as a drug diffusion barrier and a reservoir, respectively. For this purpose, the micro-channel and micro-well were filled with a water-soluble polymer, polyethylene glycol and a fine powder of DS, respectively. To modulate the drug release profile, we varied both the cross-sectional area and length of the micro-channels. Thus, the average rate and onset time of drug release could be varied from 0.32%/day to 3.68%/day and from day 0.5 to day 8, respectively, as the cross-sectional area to length ratio (i.e., A/L) of the micro-channels increased from 0.0026 mm to 0.0280 mm. To achieve both almost immediate onset and zero-order release of DS, we also prepared a micro-chip embedded with multiple pairs of the micro-wells and the micro-channels of different dimensions. In this work, a single micro-chip equipped with the micro-channels with A/Ls of 0.0280 mm, 0.0217 mm and 0.0108 mm exhibited almost zero-order drug release for 31 days (R2>0.996) after the release onset on day 0.5. When the resulting micro-chip was implanted in living rats, the drug concentration in the blood could be maintained at 148 ng/ml-225 ng/ml for the first 23 days while showing good biocompatibility.