Rhein berberine ion pair compound, preparation method and application

Abstract

The invention relates to a rheinic acid berberine ion pair compound with a formula (I) structure and a preparation method thereof, comprising the following steps of: (1) preparing a berberine hydrochloride solution, (2) adding rheinic acid or an alkali metal salt of rheinic acid into the solution obtained in the step (1), heating, stirring and fully reacting; and (3) filtering, washing, refining and drying the reaction products to obtain the rheinic acid berberine ion pair compound. The invention further relates to pharmaceutical compositions containing the ion pair compound, wherein the weight of the ion pair compound is 0.1-99.9% that of the compositions. The invention also relates to applications of the ion pair compound and the compositions thereof for preparing medicines for treating bacterial infection, peptic ulcer, diabetes, hyperlipemia, obesity, arthritis, heart failure, arrhythmia, platelet aggregation, hypertension, intestinal adhesion, etc. The rheinic acid berberine ion pair compound can increases lipid solubility of rheinic acid and berberine, and substantially raises a biological utilization degree.

Description

technical field [0001] The invention relates to a rhein berberine ion-pair compound and a preparation method, as well as the application of the drug in the preparation of drugs for treating antibacterial, peptic ulcer, diabetes and the like. Background technique [0002] Rhein is obtained from Rheum palmatum L., Rheum tanguticum Maxim.ex Balf. or Rheum officinale Baill.), Polygonum cuspidatum Sieb.et Zucc., Folium sennae, Polygonum multiflorum Thunb. ), Semen cassiae (Semen cassiae) and other plants, the compound of formula (II) is prepared by extraction, refinement or appropriate chemical modification. Rhein has pharmacological effects such as lowering blood sugar, lowering fat, improving insulin resistance and reducing urinary protein excretion, and can play multi-target and multi-level effects in diabetes and its complication diabetic nephropathy (CN 1899277A); rhein compounds It has been studied in the preparation of osteoarthritis, rheumatoid arthritis and rheumatoid a...

AI Technical Summary

Problems solved by technology

[0007] Because rhein is insoluble in water and cannot be completely absorbed by the gastrointestinal tract, resulting in low bioavailability, these have limited the application of rhein, and the formation of salts between rhein and metal ions increases the water solubility of rhein. properties, improve the bioavailability of oral route, but rhein sodium salt, potassium salt (US6197818, CN97107137) are strong base and weak salt, the aqueous solution is alkaline, and the pH value of making water injection is higher, which will cause physiological damage to the human body. Discomfort; if the pH value is lowered, the stability of the preparation is not good

However, berberine hydrochloride has very little water solubility, even less fat solubility, and poor absorption in the gastrointestinal tract, resulting in low oral bioavailability, which affects its systemic therapeutic effect.

[0008] Although rhein and berberine have many similar pharmacological activities, their clinical use is limited to a certain extent due to their low bioavailability. The method of synergistic effect of patients will have very important clinical significance

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