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1.Single Compound for Osteoarthritis Treatment Which Contains KH-207 as the Cartilage Regeneration Agent(KH-207), 2. Herbal Pharmaceutical Composition for Regenerative Agent of Cartilaginous Tissue and Treatment of Osteoarthritis(KD-30)
Korea Health Industry Development Institute (KHIDI) South Korea flag South Korea
Abstract ID:
Our products (KH-207 and KD-30) related to treatment of osteoarthritis focus on increase of chondrogenesis through cartilage protection as well as beneficial effects (decrease of pain and stiffness and improvement of function). We propose an alterna...
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MECHANISM OF ACTION
1.Excellent anti-inflammatory and analgesic effect through suppressing nitric oxide and prostaglandin-E2 derived from osteoarthritis.

181 sorts of herbal products were screened in pharmacological experiment in vitro.The natural product, containing efficacy indicating material of KH-207, was found among the tested natural products. The natural product is similar to KH-207 in term of pharmacological effect. We call the natural product the KD-30. I. Anti-inflammatory effect Formation of NO2- is pivotal factor in inflammation process.


To evaluate anti-inflammatory effects of KH-207 and KD - 30, NO2- was examined in mouse macrophage RAW 264.7 cells and chondrocyte of rabbit. This agent dramatically exhibited formation of NO2- compared with control group. Also, KH-207 and KD-30 effectively suppressed inflammation response of the carrageenan-induced edema. II. Analgesic effect In analysis of analgesic effects of KH-207 and KD-30, this agent suppressed production of prostaglandin E2 (PDE2), which is inflammatory compound, in RAW 264.7 cells and chondrocytes.


It also inhibited cyclooxygenase-2 (COX-2) expression to normal level, which is enzyme for generation of PDE2. Together, the agent has excellent effect in formalin and writhing test . III. Cartilage protection KH-207 and KD-30 prevented not only hydrolysis of proteoglycan but also MMP-1, MMP-3, and MMP-13 gene expression. And this agent inhibited MMP-9 activity, which is the enzyme involvedin hydrolysis of cartilage. IV. Pharmacological effect test involved in osteoarthritis After an administration of KH-207 and KD-30 for four weeks, synovial fluid was collected in the osteoarthritis-induced New Zealand white rabbit. The synovial fluid is used to pharmacological experiments. Pharmacological experiments included total protein (anti-inflammation), proteoglycan (protection of cartilage), prostaglandin E2 (analgesic effect), and volume of synovial fluid (anti-inflammation).


As a result of experiment, it demonstrated that KH-207 and KD-30 has excellent effect related to osteoarthritis treatments. Particularly, regeneration of cartilage is observed in histopathological and gross finding. V. Comparison of KD-30 with commercially available drugs -Anti-inflammation effect: To compare anti-inflammatory effect, NO2- generation of drugs was measured in the chondrocyte of rabbit. The KD-30 had the excellent efficacy of inflammation in all drugs, next to KH-207 and Diclofenac. -Analgesic effect: The Piroxicam and Ketoprofen had the excellent inhibition effect of PGE2, however, its drugs were not related to anti-inflammation and cartilage protection. The KH-207 showed the similar effect to the Diclofenac in the activity of PGE2 inhibition. The KD-30 as herbal extract showed the good effect than CM (negative control), and showed the similar effect to JOINS, which the new drug in Korea, in the activity of PGE2 inhibition. -Cartilage protection: KH-207 and KD-30 showed the excellent inhibition of proteoglycan decomposition next to the Celecoxib in the DMB assay using the rabbit chondrocyte, Especially, KH-207 and KD-30 were the excellent inhibitor of MMP-9, which is the enzyme involved in hydrolysis of cartilage.


These results mean that KH-207 and KD-30 have the excellent protection of cartilage. VI.Cytotoxicity test (KGLP Chemon Co., Ltd.) Acutic Toxicity of KD-30 did not observe in all animal models (female and male). The LD50 was more than 5.0 g/kg.To determine volume of chronic toxicity test of KD-30, 4 weeks repeated toxicity test was performed in animal models. As results of toxicity test, maximal volume is determined at 1,000 mg/kg. To date, toxicity and side effect were not found in all animal models in 26 weeks repeated toxicity test. The chronic toxicity test will be finished on August 2006.



FEATURED
Last Updated Jun 2016
Technology Type THERAPEUTIC
Phase of Development PRECLINICAL
GOVERNMENT INSTITUTE