A randomized, double-blind, placebo-controlled, parallel study to evaluate theefficacy and safety of YH23537 on the improvement of gum (gingival) health

Periodontal diseases are diseases of the periodontium comprised of alveolar bone, the gingiva, periodontal ligament, and cement. Periodontal diseases are divided into gingivitis, which is localized to the gingiva, and periodontitis, which results from periodontal inflammation damaging periodontal ligaments and alveolar bone.

Bacteria are the main cause of periodontal diseases among many known causes. Hydrogen sulfide produced by anaerobic gram-negative bacteria around periodontal pockets and cytotoxins such as ammonia and amines directly damage periodontal tissues. LPS present on the cell walls of anaerobic gram-negative bacteria activate immune reactions, triggering the release of reactive oxygen species, and various cytokines such as prostaglandin, leukotriene, histamine, and interleukin that destroy periodontal tissues and induce inflammation. Enzymes from bacteria and white blood cells such as collagenase degrade collagen in periodontal tissues, causing a gingival recession that can lead to periodontal disease if left untreated. As such, antimicrobial and bacteriostatic actions, toxin removal, anti-inflammatory actions, and periodontal tissue restoration are the key to the prevention and treatment of periodontal diseases.

Surgical (scaling, root planning, subgingival curettage, and periodontal tissue regeneration) and non-surgical methods (pharmacotherapy) are used to treat periodontal diseases. While surgical methods are the most effective, they require patients visit to a clinic to receive treatment and are often performed after a disease has already progressed to a certain extent. For this reason, periodontal diseases often fail to be treated effectively and become chronic. Antibiotics prescribed in addition to treatment can cause side effects when delivered to untargeted sites in an excessive amount. A recent study reported isolating antibiotic-resistant bacteria from patients with periodontal diseases.

To overcome the limitations of surgical methods and antibiotic use and improve the prevention and treatment of periodontal diseases, drugs that can restore damaged or lost periodontal tissue must be developed. To develop a safe medication that can safely restore periodontal tissue, this study was conducted to examine various herbal medicines that can inhibit the activity of inflammatory cytokines and have intracellular activities related to bone resorption and formation. P.notoginseng, which showed excellent anti-inflammatory activity, and R.Radix P., which effectively inhibited bone resorption and promoted bone formation, were selected as candidate raw materials. Using these raw materials, YH23537, an active ingredient for periodontal dysfunction, was developed.

Major cytokines associated with bone loss, inflammation, and connective tissue damage caused by periodontal diseases include interleukin-1 (IL-1) and TNF-α). A study reported that blocking these cytokines in an animal model of periodontal disease inhibited connective tissue attachment and the loss of alveolar bone height). Activating monocyte-derived osteoclasts and macrophages within bone marrow promotes bone resorption, causing alveolar bone loss. Receptor activator of nuclear factor kappa-B ligand (RANKL) is essential for osteoclast-mediated bone resorption, and osteoprotegerin (OPG) produced by ligament cells, gingival fibroblasts, and epithelial cells inhibit the binding between RANKL and receptor activator of nuclear factor kappa-B (RANK), thereby inhibiting osteoclastogenesis.

Gingivitis is an inflammatory process limited to the mucosal epithelial tissue surrounding the cervical portion of the teeth and the alveolar processes. Gingivitis has been classified by clinical appearance (eg, ulcerative, hemorrhagic, necrotizing, purulent), etiology (eg, drug-induced, hormonal, nutritional, infectious, plaque-induced), and duration (acute, chronic). The most common type of gingivitis is a chronic form induced by plaque.

Gingivitis is generally regarded as a site-specific inflammatory condition initiated by dental biofilm accumulation and characterized by gingival redness and edema and the absence of periodontal attachment loss. Gingivitis is commonly painless, rarely leads to spontaneous bleeding, and is often characterized by subtle clinical changes, resulting in most patients being unaware of the disease or unable to recognize it.

Based on various previous in vitro and in vivo tests on, it is aimed to assess the safety and efficacy of YH23537 as an individually approved ingredient for gingival health at the optimal clinical dose and method of administration.