Scutellarin prodrug and preparation method thereof

A technology of scutellarin and prodrugs, which is applied in the field of scutellarin prodrugs and its preparation, can solve the problems of poor selective release characteristics, etc., achieve improved bioavailability, avoid release and destruction, and have good biocompatibility Effect

Active Publication Date: 2012-09-19
KPC PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these two classes of prodrugs have poor selective release properties at the target site

Method used

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  • Scutellarin prodrug and preparation method thereof
  • Scutellarin prodrug and preparation method thereof
  • Scutellarin prodrug and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] 1. Preparation of sulfonylated cyclodextrin

[0058] Refer to existing literature [R.C.Petter, J.S.Salek, C.T.Sikorski, G.Kumaravel, and F.-T.Lin: J.Am.Chem.Soc.112, 3860-3868 (1990)].

[0059]Take 210g of the recrystallized β-cyclodextrin, dissolve it in 1300mL of distilled water, and stir the solution into a white emulsion, add sodium hydroxide solution (17.2g, 50mL), and stir for 1.5h. Weigh 26.0g of p-toluenesulfonyl chloride, dissolve it in 80mL of acetonitrile solution, slowly add the solution dropwise to β-cyclodextrin lye, stir at room temperature for 2 hours, remove a small amount of insoluble matter by suction filtration, and adjust the pH value of the filtrate with 2M hydrochloric acid To 7.5, at this time a large amount of precipitation occurs, and the filtrate is removed by suction filtration. Dissolve the precipitate in 450mL of water under heating, filter out the insoluble matter while it is hot, recrystallize the filtrate at 0°C for 12 hours, recrystall...

Embodiment 2

[0067] Dissolve 2.61g (2mmol) of mono-[2-(ethylenediamino)-6-deoxy]-β-cyclodextrin in anhydrous N,N-dimethylamide (50mL) and cool to about 0°C . Add 1.2 g of dicyclohexylcarbodiimide (DCC) and 0.9 g of 1-hydroxybenzotriazole (HOBT) to this solution, add scutellarin 2.77 g (6 mmol) after stirring in an ice bath for 5 h, and the reaction solution is Stir in ice bath for 20 h, and stir at room temperature for 10 h (using TCL tracking detection, developer: methanol: ethyl acetate: water = 7:7:1). The reaction solution was evaporated to dryness under reduced pressure at 60°C, the residue was fully dissolved in water, fully dissolved in water, filtered, the filtrate was concentrated, dropped into 100mL chloroform for filtration, the precipitate was collected, and vacuum-dried at 50°C for 24 hours to obtain 2-scutellarin bonded β-cyclodextrin, 65% yield.

Embodiment 3

[0069] Dissolve 2 mmol of mono-[3-(methylamino)-6-deoxy]-α-cyclodextrin in anhydrous DMF (50 mL), and cool to about 0°C. Add 0.4 g of dicyclohexylcarbodiimide and 0.3 g of 1-hydroxybenzotriazole to the solution, stir in an ice bath for 3 h, then add 2.77 g (6 mmol) of scutellarin, and stir the reaction solution in an ice bath for 6 h. Stir for 12 h (using TCL tracking detection, the developer is methanol: ethyl acetate: water = 7:7:1). The reaction solution was evaporated to dryness under reduced pressure at 60°C, the residue was fully dissolved in 50g of water, filtered, the filtrate was concentrated, 100mL of ethanol was added dropwise, filtered, the precipitate was collected, and vacuum-dried at 50°C for 24 hours to obtain 3-scutellarin bonded α - Cyclodextrin, yield 56%.

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Abstract

The invention relates to the field of drug synthesis and discloses a scutellarin prodrug and a preparation method thereof. According to the scutellarin prodrug, cyclodextrin is used as a carrier, and scutellarin molecules are connected with the cyclodextrin through amido bonds formed by carboxyl groups of the scutellarin molecules with amido modified on any hydroxyl group. Compared with scutellarin, the scutellarin prodrug has more hydrophilic active groups, so the biocompatibility and water solubility are better; on the other hand, the scutellarin prodrug has the straight cecum release characteristic and can effectively enter the body of a patient to release the scutellarin at a straight cecum target spot and selectively induce rectum cancer cells of the human body to die, so that the scutellarin is avoided being released and broken in the digestive tract, and the bioavailability is high. The preparation method for the scutellarin prodrug has the advantages of simple operation, easiness of obtaining raw materials and moderate reaction condition and can be used for preparing the scutellarin prodrugs in a large scale.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a scutellarin prodrug and a preparation method thereof. Background technique [0002] Breviscapus is a flavonoid mixture extracted from the Chinese medicinal plant Asteraceae Erigerin breviscapus (Vant.) Hand.-Mazz. It is often used clinically to treat cardiovascular and cerebrovascular diseases. Scutellarin, also known as scutellarin, is the main component of scutellarin and the main medicinal component. Modern pharmacological studies have shown that scutellarin has the effects of dilating blood vessels, increasing arterial flow, reducing blood viscosity, reducing peripheral resistance, reducing platelet count and inhibiting platelet aggregation, so it is mainly used in the treatment of coronary heart disease, angina pectoris, myocardial ischemia injury and cerebral thrombosis. The latest research reports that scutellarin can weaken H 2 o 2 - Induced cytotoxicity, attenuated ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K31/7048A61P9/10
Inventor 杨波杨兆祥杨健张伟赵俞林
Owner KPC PHARM INC
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