Diosmin
DIOSMETIN-7-O-RUTINOSIDE · Hesperedin · DIOSIMIN · DIOSMINE · SiF6 · Rubber powder · Daflon · Diosmin CRS
Identifiers & Physical Properties
| CAS No. | 520-27-4 |
|---|---|
| Molecular formula | C28H32O15 |
| Average molar mass | 608.5 g/mol |
| Monoisotopic mass | 608.17412032 g/mol |
| SMILES | COc1ccc(-c2cc(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3o2)cc1O |
| InChIKey | GZSOSUNBTXMUFQ-YFAPSIMESA-N |
| PubChem CID | 5281613 |
| ChEMBL | CHEMBL231884 |
| ChEBI | CHEBI:4631 |
| EC No. | 208-289-7 |
| DTXSID | DTXSID4045892 |
Chemical & Physical Properties
| XLogP | -0.8 |
|---|---|
| Topological polar surface area | 234 |
| Hydrogen bond donors | 8 |
| Hydrogen bond acceptors | 15 |
| Rotatable bonds | 7 |
| Heavy atoms | 43 |
| Formal charge | 0 |
| Complexity | 995 |
| Drugs | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Used in Switzerland |
| Lipids | Polyketides [PK] -> Flavonoids [PK12] -> Flavones and Flavonols [PK1211] |
| Cosmetics | Antioxidant |
| LogP (partition coefficient) | 0.14 |
| Boiling point | 926.8±65.0926.8±65.0 °C(Predicted) |
| Melting point | 277-278277-278°C |
| Dissociation Constants | 6.10±0.40 |
| Collision Cross Section | 243.33 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]242.5 Ų [M+H]+ [CCS Type: TW |
| Density | 1.68±0.1 g/cm3(Predicted) |
| Vapor pressure | 0Pa at 20℃ |
| Storage conditions | Sealed in dry,2-8°C |
| Solubility | Practically insoluble in water, soluble in dimethyl sulfoxide, practically insoluble in alcohol. It dissolves in dilute solutions of alkali hydroxides.Soluble in DMSO (50 mg/ml), water (122 mg/ml at 25°C), and ethanol (<1 mg/ml at 25°C). |
| Physical state | Solid |
| pKa (acidity coefficient) | 6.10±0.40(Predicted) |
| Color | Pale Beige to Brown |
| λmax | 345nm(EtOH)(lit.) |
| Merck | 14,3297 |
| Major applications | food and beverages |
| Cosmetics Ingredients Functions | ANTIOXIDANT |
| InChIKey | GZSOSUNBTXMUFQ-YFAPSIMESA-N |
| SMILES | COc1ccc(cc1O)C2=CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 |
| LogP (partition coefficient) | 0.14 at 20℃ |
| CAS DataBase Reference | 520-27-4(CAS DataBase Reference) |
| EWG's Food Scores | 1 |
| FDA UNII | 7QM776WJ5N |
| ATC code | C05CA03,C05CA53 |
| UNSPSC Code | 41116107 |
| NACRES | NA.24 |
| GHS pictogram | GHS07 |
| Signal word | Warning |
| GHS hazard statements | H302-H315-H319-H412 |
| GHS precautionary statements | P501-P273-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330 |
| Hazard symbols | Xi |
| Risk statements (R) | 36/37/38 |
| Safety statements (S) | 26-36-36/37-24/25 |
| Water hazard class (WGK) | 3 |
| Customs code | 29381000 |
| Storage class | 11 - Combustible Solids |
| REACH registrations | Active |
Safety & Regulations
| GHS classification | This chemical does not meet GHS hazard criteria for 90.8% (89 of 98) of all reports.Not ClassifiedAggregated GHS information provided per 98 reports by companies from 2 notifications to the ECHA C&L Inventory. |
|---|---|
| Regulatory information | Status: Active Update: 13-11-2017 https://echa.europa.eu/registration-dossier/-/registered-dossier/21071 |
| Hazard Classes and Categories | Not Classified |
| Water hazard class (WGK) | 3 |
| Customs code | 29381000 |
| Risk statements (R) | 36/37/38 |
| Signal word | Warning |
| GHS pictogram | GHS07 |
| Hazard symbols | Xi |
| Safety statements (S) | 26-36-36/37-24/25 |
| Storage class | 11 - Combustible Solids |
| GHS hazard statements | H302-H315-H319-H412 |
| REACH registrations | Active |
| GHS precautionary statements | P501-P273-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330 |
Applications & Uses
Description
Diosmin 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.
History
Diosmin 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.
Uses
Diosmin 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.
Preparation & Synthesis
Preparation
Currently, 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.