Diosmin

DescriptionDiosmin was separated from the root of Scrophularia nodosa L. in 1925. The root of Scrophularia nodosa L. has the function of nourishing, reducing fever, relieving internal heat, and detoxicating. It was firstly recorded in the Shen Nong’s Classic of Materia Medica, as a class of middle-grade drug and is currently recorded in the Ch.P 2015, Volume I. The natural resource was abundant in China, mainly provided from Zhejiang, Sichuan, Hubei, Anhui, and Jiangsu provinces. In the clinical practice, Scrophularia nodosa L. was employed to eliminate pathogenic heat from the blood. In the clinical indication, diosmin was mainly applied to treat fever, polydipsia, maculitis, gingivitis, amygdalitis, laryngopharyngitis, acute lymphadenitis, etc. It also has the biological function of antiplatelet aggregation and antitumor. The chemical components include iridoids, phenylpropanoid glycoside, flavonoids, and fatty acids.

HistoryDiosmin was firstly introduced as a medicine in 1969. It was launched in France in 1987 with the product name “Alvenor.” As the protecting agent for blood vessel and therapeutic agent for chronic venous disease, diosmin has been used for over 30years in EuropeDiosmin is a typical flavonoid. It could be prepared from natural resources or semisynthesized from the natural product hesperidin by dehydrogenation reaction.

UsesDiosmin is an agonist of the aryl hydrocarbon receptor (AhR) and exhibits anti-proliferative and anti-inflammatory. It is used in the treatment of venous disease, i.e., chronic venous insufficiency (CVI) and hemorrhoidal disease (HD). Diosmin also reduces capillary hyperpermeability and expression of endothelial adhesion molecules (ICAM1, VCAM1). It effectively inhibits the P-glycoprotein (Pgp)-mediated efflux in cells.

PreparationCurrently, diosmin is mainly synthesized from hesperidin extracted from natural plants through semi-synthesis. Chinese patent CN104250276-A discloses an industrial production method for diosmin. The specific steps are as follows: hesperidin is added to a mixed solvent of pyridine and dimethyl sulfoxide, followed by a dehydrogenation reaction with potassium iodide and sulfuric acid to obtain a reaction intermediate; a methanol solution containing sodium hydroxide is added to the reaction intermediate for further reaction; then acid is added to adjust the pH value, and the mixture is allowed to stand for crystallization to obtain diosmin. The purity of diosmin produced by this method is generally below 95%, making it unsuitable for sale as a drug and requiring further separation and purification. CN201810382522.0 proposes a method for preparing high-purity diosmin. To achieve the above objective, the technical solution of this invention is: this invention uses column chromatography to purify crude diosmin, with the chromatographic column filled with polymer chromatographic packing material. Polymer chromatography packing materials refer to chromatographic packing materials that use styrene, methacrylate, and styrene-methacrylate copolymers as matrices, and achieve particle sizes less than 100 μm and pore sizes less than [specific parameters missing] through precise control of particle size, morphology, particle size distribution, specific surface area, pore structure, and surface functional groups. The polymer chromatography packing material described herein is PSN 30-300. The method specifically includes the following steps: 1) Sample solution preparation: Take crude diosmin, add it to an alkaline solvent and stir thoroughly. After dissolution, filter to obtain a crude diosmin solution for later use; 2) Chromatographic separation process: After packing the polymer chromatographic packing material into the chromatographic column, rinse with deionized water. After equilibration, inject the crude diosmin solution obtained in step 1) into the chromatographic column using a pump for sample loading. After sample loading, rinse with deionized water, and then elute with the first eluent and the second eluent successively. Collect each eluent and perform purity testing. Combine the diosmin eluents with a purity greater than 99%, precipitate diosmin with acid, filter, wash, and finally dry to obtain a high-purity diosmin product.

DefinitionChEBI: Diosmin is a disaccharide derivative that consists of diosmetin substituted by a 6-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage. It has a role as an antioxidant and an anti-inflammatory agent. It is a glycosyloxyflavone, a rutinoside, a disaccharide derivative, a monomethoxyflavone and a dihydroxyflavanone. It derives from a diosmetin.