520-27-4 Usage
Pharmacological Effects
Diosmin is also called Alvenor. It is a kind of drug for the treatment of hemorrhoid symptoms related to acute episodes, can also be used in the treatment of symptoms associated with venous lymphatic insufficiency (leg heavy, pain, morning acid swells discomfort).
The effects of diosmin are as below:
1, Has specific affinity to the venous system, enhance the tension system without affecting the artery of vein;
2, To the microcirculation system, decrease the blood viscosity, improve the velocity of reducing silt up;
3, Contract the lymphatic system, which can enhance lymphatic and lymph drainage speed, speed up the return relieve edema.
4, Commercially available diosmin uses micronization technology, increase the contact area after using medicine, absorb more and higher bioavailability. Suitable for all kinds of hemorrhoids and acute hemorrhoids, also can be used for the treatment of chronic venous insufficiency, such as varicose veins, leg ulcers, etc.
This information is edited by lookchem Xiao Nan.
Chemical Properties
Diosmin is a natural flavonoid mainly present in the peel of some citrus fruits, such as oranges and lemons. Flavonoids are anti-inflammatory plant compounds that protect your body from free radicals and other unstable molecules. The most prevalent uses for Diosmin include hemorrhoids and leg sores caused by poor blood flow. Diosmin was first found in 1925 in the wort plant and has since been used as a natural treatment for hemorrhoids, varicose veins, venous insufficiency, leg ulcers, and other circulatory issues.
Physical properties
Appearance: Grayish yellow or light yellow hygroscopic powder. Solubility: Practically insoluble in water, soluble in dimethyl sulfoxide, practically insoluble in alcohol. It dissolves in dilute solutions of alkali hydroxides. Melting point: 277–278°C.
Originator
Diosmil,Bellon,France,1971
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
30?years 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.
Application
Diosmin is a naturally occurring flavonic glycoside isolated from various plants. Diosmin is a capillary protectant and It is used for the improvement of capillary fragility or venous insufficiency, including chronic venous insufficiency (CVI) and hemorrhoids. Diosmin is widely available over-the-counter and demonstrates a favourable a favorable safety profile.
Indications
The clinical indications of diosmin are those symptoms related to venous-lymphatic
dysfunction such as leg heaviness, pains, soreness, and swelling in the morning.
Besides, the symptoms related to acute hemorrhoids could also be treated with
diosmin.
Definition
ChEBI: 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.
Manufacturing Process
A mixture of 72 g hesperidin, 288 ml acetic anhydride and 300 ml glacial
acetic acid were boiled in reflux with 15 ml pyridine as the catalyst for 144
hours until during the control of the reaction the band disappeared at a wave
length between 264 to 280 nm, and a new maximum appeared at 330 nm.
Thereafter in a rotation evaporator the reaction mixture was concentrated by
evaporation under vacuum conditions. The residue was absorbed in 1,200 ml ethyl acetate, admixed with 20 ml ethanol and boiled for one hour under reflux action. The solution was filtered
and compressed to dryness. The residue was dried in a vacuum drying
cabinet. The yield amounted to 107.5 g. 35.8 g thereof were then dissolved in 280 ml glacial acetic acid and
ominated with a solution of 6.05 g omine in 30 ml glacial acetic acid.
Thereafter the mixture compressed to dryness by means of the rotation
evaporator, there being obtained a residue of 41.8 g. Such was dissolved in
150 ml methanol, admixed with a solution of 36 g sodium hydroxide in 180 ml
water and stirred for one hour at 50°C. The diosmin was precipitated out by adding 120 ml glacial acetic acid and
stirring at 70°C for 30 minutes. The precipitate was filtrated in a suction filter
or strainer, washed with methanol, water and again methanol and dried at
60°C in the drying cabinet. Raw yield: 17.0 g corresponding to 71% yield.
omine content 0.51%. 10 g of the thus-obtained diosmin was dissolved in a solution of 24 g sodium
hydroxide in 120 ml water, admixed with 100 ml methanol and 100 ml
pyridine and stirred for one hour at 50°C. The diosmin was precipitated by the
addition of 100 ml glacial acetic acid and stirred for 30 minutes at 70°C,
filtered and washed with methanol and water and again methanol. After drying at 60°C there was obtained a pure yield of 9.2 g diosmin (65%
based upon the employed hesperidin) having a omine content of 0.07%.
Therapeutic Function
Bioflavonoid
Flammability and Explosibility
Notclassified
Pharmacology
Diosmin is a micronized, purified, flavonoid-structure drug. It is helpful for lymphatic return and stimulating microcirculation, treating hemorrhoids and venous
dysfunction by increasing the venous tension.1. Increasing the venous tension. Diosmin could strengthen the tensile force of the
venous wall even under high temperature. Diosmin’s action in venous constriction is stronger than other drugs like rutin. Even under the acidic toxicity in the
body, it could still raise the venous tension. Diosmin has special affinity to the
venous other than the arterial system.2. Improving the microcirculation. Diosmin could effectively reduce adhesion and
migration of leukocyte and vascular endothelial cells. It could also release
inflammatory substances such as histamine, bradykinin, alexin, leukotriene,
prostaglandin, and surplus free radicals. Hence, the penetration of capillary
blood vessel was reduced, and the tension was enhanced. Besides, diosmin could
decrease blood viscosity, accelerate erythrocyte flow rate, and finally reduce the
chances of microcirculatory stasis3. Stimulating the lymphatic return. Diosmin could effectively increase the speed
of lymphatic drainage and the lymphatic contraction, accelerating the circumfluence of interstitial fluid, improving lymphatic return, and relieving edema.
Clinical Use
Diosmin was mainly used to treat diseases like chronic venous dysfunction, haemorrhoids, lymphedema, phlebeurysm, etc.
Side effects
Diosmin can cause some side effects such as nausea, stomach pain, diarrhea, insomnia, dizziness, headache, drowsiness, skin redness and hives, muscle pain, blood problems, and altered heart rate.There may be a few of minor gastrointestinal reactions and adverse reactions such as plant nerve function disorder, but generally mild and don't have to stop the drug.Pregnant women and nursing mothers with hemorrhoids are safe to use this product.
Mode of action
1. Enhance the vein tension, even not exceptional under high temperature condition. It has a stronger effect causing the constriction of vein than other drugs such as rutin, still can enhance the tension of the vein when the body was acidosis. Diosmin has specific affinity for vein without affecting the arterial system.2. Improve microcirculation. Diosmin can obviously reduce the white blood cells and vascular endothelial cell adhesion, migration, disintegrating the release of inflammatory substances, such as histamine, slow excitation peptide, complement, leukotriene, prostaglandins, and too many free radicals, reducing the permeability of capillaries and enhance its tension. Diosmin can lower blood viscosity, enhance the function of red blood cell velocity, thus reduce the microcirculation clogged.3. Promote lymphatic circumfluence. Diosmin can increase the speed of lymphatic drainage.
Check Digit Verification of cas no
The CAS Registry Mumber 520-27-4 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,2 and 0 respectively; the second part has 2 digits, 2 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 520-27:
(5*5)+(4*2)+(3*0)+(2*2)+(1*7)=44
44 % 10 = 4
So 520-27-4 is a valid CAS Registry Number.
InChI:InChI=1/C28H32O15/c1-10-21(32)23(34)25(36)27(40-10)39-9-19-22(33)24(35)26(37)28(43-19)41-12-6-14(30)20-15(31)8-17(42-18(20)7-12)11-3-4-16(38-2)13(29)5-11/h3-8,10,19,21-30,32-37H,9H2,1-2H3/t10-,19-,21-,22-,23+,24+,25+,26-,27+,28-/m1/s1
520-27-4Relevant articles and documents
Continuous flow microchannel synthesis process of flavonoid compounds
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Paragraph 0042-0052; 0063-0071; 0078-0085; 0090-0104; ..., (2021/06/22)
The invention provides a continuous flow microchannel synthesis process of flavonoid compounds. According to the process, hesperidin and iodine elementary substance are used as raw materials and react in a continuous flow microchannel reactor in the presence of a reaction solvent to synthesize the flavonoid compound as shown in a formula A. Compared with a traditional kettle-type preparation process, the process disclosed by the invention has the advantages that the preparation time is obviously shortened, and the conversion rate of raw materials and the yield of products are obviously improved; and especially, when the diosmin is prepared under optimal process conditions of continuous flow microchannel synthesis, the conversion rate of the raw material hesperidin is as high as 96.48%, and the yield of the product diosmin is as high as 81.96%. The continuous flow micro-channel synthesis process provided by the invention is beneficial to realizing safe, efficient and rapid industrial production of flavonoid compounds, and has a wide application prospect.
Synthesis of 5-Hydroxy-3′,4′,7-trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2-Mediated Anticancer Drug Resistance
Tsunekawa, Ryuji,Katayama, Kazuhiro,Hanaya, Kengo,Higashibayashi, Shuhei,Sugimoto, Yoshikazu,Sugai, Takeshi
, p. 210 - 220 (2018/10/15)
3′,4′,7-Trimethoxyflavone (TMF) has been reported to show a potent reversal effect on drug resistance mediated by breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we designed and synthesized five derivatives with either a hydroxy group or a fluorine atom at C-5 and several kinds of capping moiety at the C-7 hydroxy group, on the same 3′,4′-dimethoxy-substituted flavone skeleton. We subsequently evaluated the efficacies of these compounds against BCRP-expressing human leukaemia K562/BCRP cells. Reversal of drug resistance was expressed as the concentration of compound causing a twofold reduction in drug sensitivity (RI50). Of the synthesized compounds, the reversal effect of 5-hydroxy-3′,4′,7-trimethoxyflavone (HTMF, RI50 7.2 nm) towards 7-ethyl-10-hydroxycamptothecin (SN-38) was stronger than that of TMF (RI50 18 nm). Fluoro-substituted 5-fluoro-3′,4′,7-trimethoxyflavone (FTMF, RI50 25 nm) and monoglycosylated 7-(β-glucosyloxy)-5-hydroxy-3′,4′-dimethoxyflavone (GOHDMF, 91 nm) also exhibited reversal effects, whereas the di- and triglycoside derivatives did not. TMF, HTMF and FTMF at 0.01–10 μm upregulated the K562/BCRP cellular accumulation of Hoechst 33342 nuclear staining dye. In addition, western blotting revealed that treatment of K562/BCRP cells with 0.1 μm TMF, HTMF or FTMT suppressed the expression of BCRP. HTMF showed the strongest inhibition of BCRP-mediated efflux and suppression of BCRP expression of the three effective synthesized flavones.
Semi-synthesis method of diosmetin
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Paragraph 0027-0030; 0035-0038; 0043-0046; 0051-0054, (2019/01/23)
The invention provides a semi-synthesis method of diosmetin. A purpose of the present invention is to solve the problems of high production cost and low synthesis efficiency of the existing synthesismethod. According to the present invention, neohesperidin, pyridine and iodine are heated and react to prepare neodiosmin, and the neodiosmin is hydrolyzed with a sodium hydroxide solution to preparediosmetin; and the semi-synthesis method has characteristics of short process time, simple post-treatment, low production cost, high product purity and high yield, and is suitable for the industrial production of diosmetin.
PROCESS FOR THE PREPARATION OF DIOSMIN
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, (2016/09/22)
The present invention relates to a process for the preparation of diosmin from hesperidin. The process involves the oxidation of acylated hesperidin with iodine or bromine in a C2-C4 carboxylic acid medium and subsequent treatment with an inorganic base to partially neutralize the acidic media. The process allows obtaining diosmin with low iodine or bromine content, avoiding the use of organic solvents.
Method for preparing green and economic diosmin
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Paragraph 0040; 0041, (2016/10/17)
The invention discloses a method for preparing green and economic diosmin. The method comprises three main steps of preparation, recycling and refining. Compared with a conventional method, the method thoroughly avoids use of pyridine and inorganic base, the production environment is greatly improved, the aftertreatment is simple, iodine and solvents can be recycled, the reaction conditions are gentle, the production cost is low, and meanwhile in the method, a crude product is not refined in a classic alkali solution acidification mode instead of a mode that diosmin is separated out, then the purity of a finished product can be up to 99%, the product quality can be improved, and moreover the method is simple and convenient to operate and applicable to industrial production.
Method for semi-synthesizing 3-deoxyanthocyanidin from 5-OH-7-O-substituted flavanone
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Paragraph 0025, (2016/11/28)
The invention relates to a method for semi-synthesizing 5-OH-7-O-substituted-3-deoxyanthocyanidin from 5-OH-7-O-substituted flavanone, and relates to the fields of chemistry and pharmacy, food and cosmetics. According to the invention, 5-OH-7-O-substituted flavanone is reduced into 5-OH-7-O-substituted flavan-4-ol with reducing agents such as potassium borohydride; direct acid dehydration is carried out, such that a 5-OH-7-O-substituted flavan-4-carbonium ionic compound is produced; water is removed, and iodine-pyridine solvent dehydrogenation is carried out, such that 5-OH-7-O-substituted-3-deoxyanthocyanidin is produced. The 5-OH-7-O-substituted-3-deoxyanthocyanidin is subjected to macroporous absorption resin enrichment, and harmful impurities such as pyridine are removed; and ethanol elution and reduced-pressure recovery are carried out, such that the final product is obtained. According to the invention, multiple reaction steps are integrated into a one-step reaction; operation is simple; and yield is relatively high. The method is suitable for industrial productions. With the method, flavanone glycosides such as hesperidin and naringin can be prepared into 3-deoxyanthocyanidin with good water solubility and oxidation resistance.
A new technology for producing crane wooden glucoside
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Paragraph 0016, (2017/01/26)
The invention discloses a novel production technology of diosmin, which comprises the following steps that a dehydrogenation reaction is performed; a crude diosmin product is prepared, dried, and subjected to iodine residual removal; a solvent residual of diosmin is removed; a fine diosmin product is dried, and subjected to a diosmin micronization technology; and micronized diosmin meeting a requirement of EP8.0 (European Pharmacopoeia 8.0) is obtained. The novel production technology has the characteristic of sociometric sustainable development; no harmful effect is exerted on an environment in a production process; more importantly, the consumption of a dehydrogenation agent is reduced to be 2-5% of that of hesperidin in the production process, so that a raw material resource is used fully to the greatest extent; the solvent and iodine residuals are removed effectively; and development requirements of a resource-saving and environment-friendly society are met.
PROCESS FOR THE PREPARATION OF DIOSMIN
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Page/Page column 9; 10, (2010/09/03)
The process of preparation of pure diosmin that is independent of hesperidine used for conversion is described. Process is effective in controlling the impurity by crystallization. The cost effective and ecofriendly process enables recovery and recycling of the reagents involved in the manufacturing process.
Mild alkaline hydrolysis of some 7-O-flavone glycosides. Application to a novel access to rutinose heptaacetate
Quintin, Jér?me,Lewin, Guy
, p. 4341 - 4343 (2007/10/03)
Alkaline hydrolysis of some 7-O-flavone glycosides was performed through the 6,8-dibromo derivative. When the sugar linked to the aglycon has a 2-hydroxy group trans to the sugar-aglycon bond as in β-D-glucosides or rutinosides, hydrolysis occurred at room temperature under very mild conditions. Application to a novel preparation of rutinose heptaacetate by hydrolysis of a diosmin derivative is described.
Novel use of flavones
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, (2008/06/13)
A pharmaceutical composition for inhibiting COX-2 biosynthesis comprising a therapeutically effective amount of the compound of formula I and a pharmaceutrically acceptable carrier. wherein R1 and R4 represent either Hydrogen or together a bond R5, R6, R7, R8 represent independently of each other Hydrogen, Hydroxy or Methoxy; in addition R7 represents a sugar substituent like glucoside, rutinosid, manno gluco pyransyl, aprosylglucoside R2 and R3 represent Hydrogen, Hydroxy, Methoxy or wherein R2′, R3′, R4′, R5′ and R6′ are independently or each other Hydrogen, Hydroxy or Methoxy with the proviso, that R2 or R3 is represented by the optionally substituted Phenylring.
