Flavonoid glycoside and isoquinoline alkaloid complex for inhibiting multi-drug-resistant staphylococcus aureus and preparation of carrier-free nano-drug of flavonoid glycoside and isoquinoline alkaloid complex

A technology of isoquinoline alkaloids and flavonoid glycoside complexes, which is applied in the preparation of sugar derivatives, sugar derivatives, sugar derivatives, etc., and can solve problems such as no therapeutic effect, toxicity and inflammation, and low drug loading capacity

Inactive Publication Date: 2020-12-01
BEIJING UNIV OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, many nano-adjuvants exhibit low drug-loading capacity and no therapeutic effect, and some even cause toxicity and inflammation during degradation and metabolism.

Method used

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  • Flavonoid glycoside and isoquinoline alkaloid complex for inhibiting multi-drug-resistant staphylococcus aureus and preparation of carrier-free nano-drug of flavonoid glycoside and isoquinoline alkaloid complex
  • Flavonoid glycoside and isoquinoline alkaloid complex for inhibiting multi-drug-resistant staphylococcus aureus and preparation of carrier-free nano-drug of flavonoid glycoside and isoquinoline alkaloid complex
  • Flavonoid glycoside and isoquinoline alkaloid complex for inhibiting multi-drug-resistant staphylococcus aureus and preparation of carrier-free nano-drug of flavonoid glycoside and isoquinoline alkaloid complex

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] This example prepares the complex by the method comprising the following steps.

[0051] The selected raw materials are natural flavonoid glycosides represented by baicalin, scutellarin, and wogonin and their derivative products, as well as berberine, palmatine, coptisine, jatrorrhizine, epiberberine, and cork Alkali is a representative natural isoquinoline alkaloid and its derivatives.

[0052] Taking the baicalin-berberine complex as an example, weigh baicalin and berberine with a molar ratio of 10:1 to 1:10 and dissolve them in water respectively, heat, and adjust the flavonoid glycosides to pH=6-10 to obtain clarification Clear solution. Mix and stir, centrifuge to obtain a precipitate, wash three times with water, and freeze-dry to obtain a brownish-yellow powder, which is the complex. The preparation method of other 23 kinds of complexes is the same.

[0053] The complex prepared in Example 1 was further analyzed by mass spectrometry (static spray-HRMS, Waters,...

Embodiment 2

[0060] In the present embodiment, part of the complex prepared in Example 1 is characterized by NMR (Avance IIIHD400MHz spectrometer, Bruker, America), and the results are as follows:

[0061] NMR attribute of baicalin-berberine complex: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 6.93 (overlap, 2H, H-3, 8, BA), 8.03 (d, J=7.2Hz, 1H, H-2', 6', BA), 7.55-7.62 (m, 3H , H-3', 4', 5', BA), 4.97 (d, J=5.1Hz, 1H, H-1", BA), 3.23-3.36 (m, 3H, H-2", 3", 4″, BA), 3.60 (d, J=9.6Hz, 1H, H-5″, BA), 7.74 (s, 1H, H-1, BBR), 7.02 (s, 1H, H-4, BBR) , 3.19 (m, 2H, 5-CH 2 -, BBR), 4.93 (m, 2H, 6-CH 2 -, BBR), 9.94 (s, 1H, H-8, BBR), 8.08 (d, J=9.0Hz, 1H, H-11, BBR), 7.93 (d, J=9.0Hz, 1H, H-12 , BBR), 8.90 (s, 1H, H-13, BBR), 6.14 (s, 2H, 15-CH 2 -, BBR), 4.07 (s, 3H, 9-OCH 3 , BBR), 3.97(s, 3H, 10-OCH 3 , BBR).

[0062] NMR assignment of scutellarin-berberine complex: SCU-BBR NPs 1 HNMR (400MHz, DMSO-d 6 ): 6.81 (s, 1H, H-8, SCU), 6.99 (s, 1H, H-4, BBR), 7.75 (d, J=7.4Hz, 2H, H-2′, 6′, SCU)...

Embodiment 3

[0065] In the present embodiment, the antibacterial activity of the complex prepared in Example 1 is measured, and the method is as follows:

[0066] The inhibitory effect of the complex on pathogenic bacteria Staphylococcus aureus, opportunistic pathogenic bacteria Escherichia coli, probiotics Bacillus subtilis and Enterococcus faecium, and clinically isolated multidrug-resistant Staphylococcus aureus were observed by turbidimetric method. Staphylococcus aureus, Escherichia coli, probiotics Bacillus subtilis and Enterococcus faecium were all obtained from the College of Life Sciences, Beijing University of Traditional Chinese Medicine. Multidrug-resistant Staphylococcus aureus was obtained from the Laboratory Department of Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine (sample number: 19PXTH0119). The complex powder prepared in Example 1 was sealed and stored at 4°C. Dissolve in LB medium to 1×10 4 The μg / mL stock solution is ready for use (DMSO con...

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Abstract

The invention provides a novel flavonoid glycoside and isoquinoline alkaloid complex structure, preparation, antibacterial application and three complex carrier-free nano-drugs with self-assembly performance. The structural general formula of the complex is shown in the specification, the complex has excellent selective antibacterial ability, and the activity of endophyte escherichia coli and probiotics bacillus subtilis and enterococcus faecium is not influenced while pathogenic bacteria staphylococcus aureus is killed; meanwhile, the compound has a good inhibition effect on multiple drug-resistant staphylococcus aureus, and is superior to norfloxacin, oxacillin, tetracycline and ciprofloxacin. The nano-drug formed by self-assembling the three complexes is uniform in form and good in dispersity and stability, gel or fiber is formed under the condition that auxiliary materials are not needed, and support is provided for development of a carrier-free pure drug delivery preparation.

Description

technical field [0001] The present invention relates to the preparation method and antibacterial application of 24 kinds of flavonoid glycoside-isoquinoline alkaloid complexes, especially have good inhibitory activity to clinically multi-drug resistant Staphylococcus aureus; wherein three kinds of complexes have The self-assembly property can prepare carrier-free nano-medicine, and belongs to the field of medicinal chemistry. Background technique [0002] Bacterial infection is one of the great threats facing mankind at present. With the abuse of antibiotics, more and more drug-resistant bacteria, even multi-drug-resistant "super bacteria" have emerged. Drug-resistant infections kill about 700,000 people worldwide each year, mostly in developing countries; by 2050, bacterial resistance will kill 10 million people a year globally. At the same time, long-term extensive use of broad-spectrum antibiotics will also cause damage to the homeostasis of human intestinal flora, ther...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D455/03C07H17/07C07H1/00A61K31/4375A61K31/7048A61P31/04A61P31/02
CPCC07D455/03C07H17/07C07H1/00A61K31/4375A61K31/7048A61P31/04A61P31/02Y02A50/30
Inventor 王鹏龙雷海民李桐
Owner BEIJING UNIV OF CHINESE MEDICINE
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