Pentacyclic triterpene and melbine salt of derivative thereof, preparation method and medical application of pentacyclic triterpene

A technology of metformin salt and pentacyclic triterpene, which is applied in the fields of natural medicine and medicinal chemistry, and can solve problems such as high water solubility, side effects, and limited application

Inactive Publication Date: 2010-05-12
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The absorption of metformin is saturated and very incomplete
[0011] However, the water solubility of pentacyclic triterpenoids is generally poor, and the bioavailability of its preparations is low, which greatly limits its clinical application.
However, the extremely high water solubility of metformin hydrochloride used clinically and the poor absorption performance in the gastrointestinal tract have partially caused its more serious gastrointestinal side effects (diarrhea, vomiting, etc.)

Method used

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  • Pentacyclic triterpene and melbine salt of derivative thereof, preparation method and medical application of pentacyclic triterpene
  • Pentacyclic triterpene and melbine salt of derivative thereof, preparation method and medical application of pentacyclic triterpene
  • Pentacyclic triterpene and melbine salt of derivative thereof, preparation method and medical application of pentacyclic triterpene

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] 3-O-Succinyl Glycyrrhetinic Acid Hemimetformin Salt

[0084]

[0085] Dissolve 113mg (0.88mmol, 1eq) of metformin in 15ml of methanol, then add 500mg (0.88mmol) of 3-O-succinylglycyrrhetinic acid, and stir at room temperature until dissolved. After 3 hours, filter to remove insoluble impurities, then put it into the refrigerator to cool and crystallize, filter with suction, and dry to obtain a white solid product which is 3-O-succinylglycyrrhetinic acid hemimetformin salt. M.p. 256-258°C. 1 H NMR (DMSO-d 6 , 300MHz) δ0.75(s, 3H), 0.82(s, 6H), 1.04(s, 3H), 1.06(s, 6H), 1.36(s, 3H), 2.34-2.47(m, 4H), 2.92 (s, 3H), 4.40-4.45 (m, 1H), 5.41 (s, 1H); Anal. Calcd for C 72 h 111 o 14 N 5 0.5H 2 O: C 67.57, H 8.82, N 5.47, Found: C 67.38, H 8.78, N 5.92.

Embodiment 2

[0087] 3-O-Succinyl Glycyrrhetinic Acid Monometformin Salt

[0088]

[0089] Dissolve 227mg (1.76mmol, 2eq) of metformin in 26ml of methanol, then slowly add 500mg (0.88mmol, 1eq) of 3-O-succinylglycyrrhetinic acid, stir at room temperature for 1h, heat up to 60°C to dissolve the reactant, filter, and filtrate Cooling and crystallization, suction filtration and drying, the white solid product obtained was 3-O-succinylglycyrrhetinic acid monometformin salt. M.p. 232-234°C. 1 H NMR (DMSO-d 6 , 300MHz) δ0.74(s, 3H), 0.82(s, 6H), 1.02(s, 3H), 1.04(s, 3H), 1.06(s, 3H), 1.36(s, 3H), 2.26-2.39 (m, 4H), 2.92 (s, 6H), 4.38-4.44 (m, 1H), 5.42 (s, 1H).

Embodiment 3

[0091] 18β-Glycyrrhizinate Monometformin Salt

[0092] Dissolve 314.76mg (2.44mmol, 2eq) of metformin in 25ml of methanol, then slowly add 1.02g (1.22mmol, 1eq) of 18β-glycyrrhizic acid, and stir at room temperature for 1h. When the temperature was raised to 70°C, the reactant still could not be completely dissolved, and methanol was added until the total amount was 40ml, and the reactant was dissolved. After 2 hours, the reaction was stopped, cooled and crystallized, filtered with suction, and dried to obtain a white solid product which was 18β-glycyrrhizic acid monometformin salt. M.P. 205-206°C. 1 H NMR (DMSO-d 6 +D 2 O, 300MHz) δ0.66(s, 3H), 0.70(s, 3H), 0.89(s, 3H), 0.97(s, 6H), 1.05(s, 3H), 1.27(s, 3H), 2.89( s, 6H), 4.30 and 4.33 (d, J = 6.4Hz, each 1H), 4.50 and 4.53 (d, J = 7.5Hz, each 1H), 5.38 (s, 1H).

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PUM

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Abstract

The invention relates to field of natural medicine and medicinal chemistry, in particular to novel pentacyclic triterpene and melbine salt I of the derivative thereof. The salt compound can be used for preparing medicaments curing diabetes mellitus and complicating disease thereof, cerebral ischemia, angiocardiopathy, atherosclerosis, hepatitis, fatty liver and metabolic syndrome or tumour, descendens blood fat drugs and anti-obesity drugs. The invention also relates to the preparation method of the salt compound.

Description

technical field [0001] The invention relates to the fields of natural medicine and medicinal chemistry, in particular to a new class of metformin salts of pentacyclic triterpenes and derivatives thereof. Such salt compounds can be used to prepare anti-diabetes and its complications drugs, anti-cerebral ischemia drugs, anti-cardiovascular disease drugs, blood lipid-lowering drugs, weight-loss drugs, anti-atherosclerosis drugs, anti-hepatitis drugs, anti-fatty liver drugs, Drugs for metabolic syndrome or antineoplastic drugs. The present invention also relates to the preparation method of the salt compound. Background technique [0002] Metformin is an oral drug for the treatment of type 2 diabetes. It has been used in the treatment of type 2 diabetes for more than 50 years. It belongs to the biguanide hypoglycemic drug and does not stimulate the secretion of insulin by pancreatic β cells. It is mainly used for obese non-insulin-dependent mild diabetic patients. Its general ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J63/00C07H15/256C07C279/26C07J75/00C07H1/00C07C277/08A61K31/704A61K31/56A61K31/155A61P3/10A61P9/10A61P3/06A61P3/04A61P1/16A61P3/00A61P35/00A61P13/12A61P25/00A61P9/06
Inventor 孙宏斌张迎霞洪浩
Owner CHINA PHARM UNIV
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