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Application of a spirocyclic alkaloid in the preparation of drugs for preventing or treating pulmonary fibrosis

A pulmonary fibrosis and alkaloid technology, applied in the field of alkaloids, can solve problems such as no compound reported in literature to prevent or treat pulmonary fibrosis diseases, no research reports, etc. Inexpensive effect

Active Publication Date: 2017-01-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The spirocyclic alkaloids shown in structural formula I, such as stemospironine, croomine, etc., are more commonly distributed in plants of the genus Libeta, but so far, except for the antitussive activity of croomine, there are no other research reports on activities, and there are no literature reports yet. The compound has the effect of preventing or treating pulmonary fibrosis or its application in medicine for treating pulmonary fibrosis

Method used

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  • Application of a spirocyclic alkaloid in the preparation of drugs for preventing or treating pulmonary fibrosis
  • Application of a spirocyclic alkaloid in the preparation of drugs for preventing or treating pulmonary fibrosis
  • Application of a spirocyclic alkaloid in the preparation of drugs for preventing or treating pulmonary fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1 Preparation and structure identification of alkaloids

[0059] 1. Medicinal materials and reagents

[0060] The medicinal material is the dried root of Stemona tuberosa Lour., purchased from the medicinal material market in Haozhou, Anhui. Reagents such as ethanol, dichloromethane, and methanol were all analytically pure.

[0061] 2. Extraction and separation

[0062] Extract 95% ethanol for 3 times, concentrate under reduced pressure until there is no alcohol smell, add 5% dilute hydrochloric acid to acidify to pH 1-2, filter, alkalinize the filtrate to pH 10 with concentrated ammonia water, extract with chloroform, and recover chloroform to obtain Total alkaloid sites. The total alkaloids were subjected to silica gel column chromatography, eluted with dichloromethane-methanol gradient (100:0~100:10), and the same fractions were combined according to the TLC results, and then subjected to repeated silica gel column chromatography and separated by Sephadex ...

Embodiment 2

[0072] Example 2 Preparation of pulmonary fibrosis animal model

[0073] 1. Main reagents and experimental animals

[0074] The bleomycin used in the experiment was purchased from Nippon Kayaku Co., Ltd., batch number 730342.

[0075] The SPF grade C57BL / 6 mice (female, 8 weeks old) used in the experiment were purchased from the Comparative Medical Center of Yangzhou University.

[0076] 2. Model Preparation

[0077] Bleomycin-induced pulmonary fibrosis in mice is an internationally recognized animal model for screening anti-pulmonary fibrosis drugs. After bleomycin modeling, acute lung injury was caused. The initial manifestation was inflammation, and fibrosis began to appear in about 10 days. A large amount of collagen appeared in the lungs. These pathological changes were very similar to the pathological changes of idiopathic pulmonary fibrosis in clinical practice. resemblance. Although the pathogenesis and mechanism of idiopathic pulmonary fibrosis are unclear, both b...

Embodiment 3

[0079] Example 3 Identification of four alkaloids and carboxylate against pulmonary fibrosis in mice

[0080] The purpose of this example is to study the anti-pulmonary fibrosis activity of the alkaloids isolated in Example 1 to identify whether it has an anti-pulmonary fibrosis effect. Since these alkaloids are all effective cough-relieving ingredients of the Chinese medicine Baibu, in order to know whether the cough-relieving medicine can resist pulmonary fibrosis, the present embodiment selects the commonly used clinical cough-relieving medicine - pentoxyverine (pentoxyverine, citrate pentoxyverine tablets, cough medicine) Positive control drugs commonly used in pharmacological experiments) were simultaneously screened for anti-pulmonary fibrosis activity.

[0081] 1. Main reagents and experimental animals

[0082] Compounds I to IV were obtained according to Example 1, and the purity was more than 98%. Kebiqing was purchased from Sinopharm Rongsheng Pharmaceutical Co., L...

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Abstract

The invention discloses the use of the alkaloid with the structural formula I in the preparation of medicines for preventing and / or treating pulmonary fibrosis. It has the alkaloid shown in structural formula I, which can significantly reduce the degree of inflammation in diseased lung tissue, reduce the content of pro-fibrosis factor TGF-β1 in diseased lung tissue, reduce the excessive deposition of collagen in diseased lung tissue, and have a significant effect on pulmonary fibrosis. prevention and treatment of

Description

technical field [0001] The present invention relates to a class of alkaloids with anti-pulmonary fibrosis activity, in particular to the application of the alkaloids represented by structural formula I in the preparation of pharmaceutical compositions for preventing or treating pulmonary fibrosis. Background technique [0002] Pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), is a diffuse lung disease of unknown etiology. Mainly manifested as diffuse alveolitis, alveolar unit structural disorder and pulmonary fibrosis, which eventually led to severe damage to lung structure and function. As a result, it replaces the normal lung tissue structure, seriously affects the ventilation and ventilation function of the lung, and eventually leads to respiratory failure and death. Its pathogenesis has not been fully elucidated, there is currently no effective clinical treatment, and the mortality rate is high. [0003] Lung interstitial tissue is composed of collage...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/537A61P11/00
Inventor 张勉张朝凤吴艳许翔鸿向娟贺艳慧
Owner CHINA PHARM UNIV
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