Treatment of a condition in a mammal with administration of compounds and methods of use
A mammalian and compound technology, applied in the direction of carbohydrate active ingredients, medical preparations containing active ingredients, drug combinations, etc., can solve the problem of not preventing or slowing the progression of OA
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Embodiment 1
Treatment of cultured osteoarthritic human articular chondrocytes with amino sugars
[0145]Human osteoarthritic cartilage was obtained from an informed donor following routine total knee replacement. Articular cartilage from the femoral condyles and tibial plateaus were aseptically dissected. Cartilage scrapings were harvested and placed in tissue culture medium (DMEM, 10% FBS, penicillin, streptomycin) and stored at 4°C until they were processed.
[0146] After sequential digestion with pronase (Roche, 10 g / l) for 30 minutes and collagenase type IV (Sigma, 1 g / l) for 6 hours, both digestions were carried out in 0.9% NaCl, Chondrocytes were isolated from cartilage. In DMEM (BioWhittaker) supplemented with 10% fetal bovine serum (BioWhittaker), 60 U / ml penicillin, 60 μg / ml streptomycin and 2 mmol / l glutamine (BioWhittaker) at 37 °C in the presence of 5% CO 2 chondrocytes were allowed to grow to confluence.
[0147] Experiment with first or second passage cells. Chondrocy...
Embodiment 2
Effects of amino sugars on NO induced by IL-1β in cultured chondrocytes
[0148] IL-1β-induced inflammatory mediator·NO was measured according to the method of Griess reaction (Hevel, et. al. Methods Enzymol. 233:250) and by protein ELISA (R&D Systems, Minneapolis, MN).
[0149] Amino sugars such as GlcN and GlcNAc are known to inhibit IL-1β and TNFα-induced nitric oxide (·NO) production in osteoarthritic human articular chondrocytes (PCT Publication WO 02 / 078445A1). Therefore, the effect of the amino sugar derivatives of the present invention on IL-1β-induced NO production will be measured and compared according to the Griess reaction method, and the amino sugar derivatives include but not limited to derivatives of glucosamine, semi-glucosamine Derivatives of lactosamine, derivatives of cyclodol and derivatives of iminocyclitol.
[0150] In an oxygenated solution, NO decomposes to form NO 2 - and NO 3 - , as shown in equations (1)-(3).
2 NO+O 2 →2·NO 2 ...
Embodiment 3
Effects of amino sugars on IGF-stimulated synthesis of sulfated glycosaminoglycans (SGAG)
[0155] Basal sulfated glycosaminoglycan (SGAG) synthesis and IGF-stimulated sulfated glycan synthesis in vitro and in vivo can be assayed by methods similar to those described elsewhere (Scharstuhl et al. Ann. Rheum. Dis. 61: 1095). Saminoglycan (SGAG) synthesis. Can be measured in the extracellular fraction 35 Levels of incorporation of S-sodium sulfate (ICN Radiochemicals, Irvine, CA) into SAGA. This can be done in the presence or absence of aminosugar derivatives of the invention, including but not limited to derivatives of glucosamine, galactosamine, cyclodol and Derivatives of iminocyclitols.
In vivo SGAG synthesis:
[0156] The right knee joints of mice aged 3 to 18 months can be injected with IGF in PBS supplemented with 0.1% bovine serum albumin and amino sugar derivatives of the present invention, including but not It is limited to derivatives of glucosamine, galactosa...
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