Hyruan One Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Hyaluronic acid improves pain in osteoarthritis as intra-articular lubrication and intra-articular viscosity and elasticity are gradually recovered by intra-articular injection of hyaluronic acid, which is the major ingredient constituting synovia and surface of cartilage. This is a treatment method based on the concept of viscosupplementation and the synovia of the patients with arthritis with lower viscoelasticity and elasticity compared to normal people.
Pharmacodynamics of Hyruan One: For the pharmacodynamic study, it is considered that it can be replaced with the clinical study data of Hyruan ONE and other pre-licensed products containing sodium hyaluronate as the active ingredient (such as Hyruan Plus, LG Life Sciences, Ltd.). In addition, neither the general pharmacology nor safety pharmacology study was conducted separately, as there was no special concern in the toxicological study and in the pharmacological study for the intra-articular administration of ¹⁴C-Hyruan ONE in rats, there was insignificant amount of the drug transferred to the systemic circulation or other tissue/organ. The relevant details are described in Pharmacokinetics and Toxicology as follows.
Pharmacokinetics: For the pharmacokinetics of Hyruan ONE, the radiolabelled (¹⁴C)-BDDE, the crosslinking agents of Hyaluronic acid was used to investigate the information on the exposure level in blood, distribution in the tissue/organ, metabolism/degradation products, and excretion etc. of the radioactivity.
Absorption: The pharmacokinetics of ¹⁴C-radiolabelled Hyruan ONE after intra-articular injection was studied in rat. Peak radioactivity concentration in plasma was observed at the first sampling time (1 hr post-dose). Then, plasma radioactivity declined quickly and decreased below the limit of quantification at 72 hr post-dose.
Distribution: Most of administered radioactivity remained at the administration site until 70 days post-dose after intra-articular injection of ¹⁴C-radiolabelled Hyruan ONE to rat. Except for the administration site, relatively higher organ/tissue distribution was observed at liver, spleen, kidney, and mesenteric lymph node, etc. In cerebrum, thyroid gland, adrenal gland, skeletal muscle, and stomach, radioactivity was not detected at any sampling time.
Metabolism: Metabolite profile of ¹⁴C-radiolabelled Hyruan ONE was assessed with plasma and urine samples following intra-articular injection of ¹⁴C-radiolabelled Hyruan ONE to rat. Molecular weight of metabolites was confirmed by comparing HPLC retention time of samples with that of reference marker. In plasma, metabolites below 200,000 Da were detected at 8 hr post-dose. In urine, metabolites below 5,900 Da were detected at 0~24 hr, 144~168 hr, and 240~336 hr post-dose. At the last sampling time (70 days post-dose), 12.9% of administered dose remained at the administration site.
Elimination: Total 82.5% of administered radioactivity was excreted into the urine, feces, and exhaled air while 12.9% of administered radioactivity still remained at the administration site until 70 days post-dose. 72.2% of administered radioactivity was recovered in the urine, indicating that urinary excretion is the major excretion pathway.
Toxicology: Preclinical safety data: The safety of Hyruan ONE was tested by single dose toxicity study in rats and dogs, repeated dose toxicity study in rats and dogs, genotoxicity battery tests, and antigenicity study in guinea pigs.
Based on conventional studies, no special hazard for humans was observed.