Hydrophilic polymer-puerarin specific conjugated non-hemolytic conjugate

Abstract

The invention relates to a conjugate shown in formula 1 or pharmaceutically acceptable salt thereof. The conjugate has good water solubility, overcomes the defects of poor water solubility, low bioavailability and the like of puerarin, greatly reduces or eliminates the adverse reactions such as puerarin haemolysis and the like, has simple synthesis method and low preparation cost, and is suitable for industrialized production. In addition, the invention also relates to a pharmaceutical composition based on the conjugate, a preparation method and the application in the medicine aspect.Formula 1.

Description

technical field The invention belongs to the field of medicinal chemistry, in particular, the invention relates to a conjugate formed by specifically conjugating biodegradable puerarin and its derivatives with polyethylene glycol through the 7-position phenolic hydroxyl group. In addition, the present application also relates to the pharmaceutical composition based on the conjugate, the preparation method and the application as a medicine. Background technique Puerarin (Puerarin, hereinafter referred to as Pur, chemical name 7,4'-dihydroxy-β-C-D-glucosyl isoflavone) is produced from the roots of leguminous plants Pueraria lobata and Pueraria thomsonii. An extracted isoflavone glycoside, which has the functions of myocardial protection, renal protection, brain tissue protection, anti-oxidation, anti-inflammation, anti-atherosclerosis, anti-arrhythmia, anti-ischemia-reperfusion injury, anti-alcohol central inhibition, anti-cancer It has important pharmacological activities in...

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Problems solved by technology

However, this patent not only describes in general terms, but also fails to scientifically evaluate the efficacy of the final product, water solubility, hemolysis, etc., and more seriously, the conjugation of PEG to puerarin is not specific, or the conjugation is carried out by excessive PEG. All hydroxyl groups on puerarin, or conjugation to carboxyl groups on the flavone sugar ring

The former has many by-products due to various incomplete conjugations, which makes preparation and purification difficult, and the quality of the final product is not easy to control, and because the proportion of PEG in the final product is too high, the activity of active ingredients (flavonoids) is greatly reduced. valence, which increases the final dosage; the latter cannot be applied because puerarin just does not have a carboxyl group on the sugar ring.

Especially the former, there is no selectivity for the conjugation of flavonoids, such excessive conjugation will lose or reduce the activity of the drug

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