Effect of SKI 306X, a new herbal anti-arthritic agent, in patients with osteoarthritis of the knee: a double-blind placebo controlled study

Abstract: SKI 306X is a purified extract from a mixture of three oriental herbal medicines (Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris) that have been widely used for the treatment of inflammatory diseases similar as lymphadenitis and arthritis in far East Asia. A double-blind, controll research was performed to evaluate the efficacy and safety of SKI 306X with placebo in 96 patients with classical osteoarthritis of the knee Patients were randomized to four treatment groups: placebo, 200 mg 400 mg and 600 mg of SKI 306X t.i.d.. Clinical efficacy and safety were evaluated for 4 weeks continuous treatment. SKI 306X demonstrated its clinical efficacy, as assessed by dint of 100 mm visual analogue scale (VAS), Lequesne index and patients' and investigators opinion of the therapeutic consequence compared with placebo (p<0.01). No significant adverse occurrences were observed in patients treated with SKI 306X This investigation demonstrated that SKI 306X, a novel herbal anti-arthritic agent provided clinical efficacy in patients with osteoarthritis.

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Osteoarthritis is a degenerative joint disease showed by failure of the diarthrodial joint and leading to disability in the somewhat old It is distinguished by the progressive los of articular cartilage and through reactive changes in the subchondral bone (Brandt, 1985) Slowly developing joint pain with acute flares, joint enlargement and limitation of motion are the most frequent manifestations and require immediate attention (Altman, 1991) above the last decade, several non steroidal anti-inflammatory medicines (NSAIDs) have been used to treat osteoarthritis, on the contrary their usefulness has been limited because of their simple anti-inflammatory and analgesic activity and by the agency of adverse gastrointestinal and renal side issues (Murray and Brater, 1990). novel classes of selective cyclooxygenase type-II inhibitors provide a serviceable safety profile, particularly with reverence to reduced gastrointestinal adverse circumstances compared with other NSAIDs (Vane and Botting, 1995) Unfortunately, these therapeutic approaches are not curative and just relieve the clinical signs and symptoms of the disease. For a curative treatment of osteoarthritis, numerous efforts have been made to unravel a more effective and safer physic As one of the continuing efforts, we tried to find a of recent origin type of herbal extract, which has multi-functions similar as anti-inflammatory and analgesic actions, activation of life-blood micro-circulation and protection against joint cartilage degeneration.

Among 600 oriental herbal medicines that have been widely used for the treatment of inflammatory diseases like as lymphadenitis and arthritis in far East Asia, we fix uponed 53 and studied their anti-inflammatory and analgesic activity, anti-arthritic activity, vital fluid micro-circulation enhancing activity and inhibition of cartilage degeneration enzyme activity using various biological screening a whole s On the basis of these studies, we prepared a fresh herbal extract (SKI 306X) from a combination of Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris (Park et al., 1995; Ahn et al., 1996; Kim et al., 1996)

For the design of evaluating the clinical efficacy and optimal dosage of SKI 306X a double-blind placebo controll outpatients clinical trial was performed.

Patients and Methods

Preparation and Composition of SKI 306X

SKI 306X was prepared by means of extracting a mixture of 3 in a raw state herbal components (dried root of Clematis mandshurica, dried flower and trunk of Prunella vulgaris and dried foundation of Trichosanthes kirilowii, 1:1:2 (w/w) respectively) in 7 times of 30% (v/v) ethanol-water, at 85 [degrees] C for 6 hr The extract solution was filtered and evaporated below vacuum. The residue was partitioned between butanol and water. The butanol layer was evaporated below vacuum for complete removal of residual menstrum and the resulting residue was lyophilized to yield 25% (w/w) of a dark-brown powder

SKI 306X was standardized conforming to the regulations imposed by dint of Korea Food and Drug Administration (KFDA). Typical active ingredients are oleanolic acid for Clematis mandshurica, rosmarinic acid and ursolic acid for Prunella vulgaris, and 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid and trans-cinnamic acid for Trichosanthes kirilowii, which should be at hand in more than 4.00, 020 050 003 003 and 005% (w/w) respectively, in SKI 306X These typical active ingredients were isolated, purified and analyzed through High Performance Liquid Chromatography (HPLC) system

For the convenience of treatment, tablets were made through 200 mg of SKI 306X with general additives (SKI 306X tablet).

Patients and Treatment

Patients were registered in 2 general practitioner center in Seoul Korea and 96 patients with classical osteoarthritis of the knee were allocated in this research This study was approved by dint of a local ethics committee and carried on the outside in accordance with revised Declaration of Helsinki guidelines. Patients with clinically and radiographically confirmed osteoarthritis of the knee were eligible for this close attention and their age ranged from 35 to 75 years. Other criteria included moderate pain in the affected knee joint, more than a score of 35 mm as assessed through a visual analogue scale (VAS) ranging from 0 mm (no pain) to 100 mm (unbearable pain) and normal hepatic and renal function.