CN103690527B - Aphanamgrandiol A is preparing the application in Anti-helicobacter pylori drugs - Google Patents
Aphanamgrandiol A is preparing the application in Anti-helicobacter pylori drugs Download PDFInfo
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- CN103690527B CN103690527B CN201310405608.8A CN201310405608A CN103690527B CN 103690527 B CN103690527 B CN 103690527B CN 201310405608 A CN201310405608 A CN 201310405608A CN 103690527 B CN103690527 B CN 103690527B
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Abstract
Do you the invention discloses Aphanamgrandiol? the application purpose of A in preparation treatment Anti-helicobacter pylori drugs, does external activity experiment show Aphanamgrandiol? does A have very strong anti-helicobacter pylori (Helicobacter? pylori, Hp) active, can be used for the diseases such as acute and chronic gastritis, duodenal ulcer, therefore Aphanamgrandiol? A may be used for preparation treatment Anti-helicobacter pylori drugs, this application purposes belongs to first public, and it is active strong, possess outstanding substantive distinguishing features and significant progress.
Description
Technical field
The present invention relates to the novelty teabag of compd A phanamgrandiolA, particularly relate to AphanamgrandiolA and preparing the application in Anti-helicobacter pylori drugs.
Background technology
Helicobacter pylori (Helicobacterpylori, Hp) is a kind of Gram-negative spiral bacteria.Research display, helicobacter pylori is the primary pathogenic event of acute and chronic gastritis and taste-blindness rate, and may fall ill relevant with gastric cancer stomach function regulating mucosa-associated lymphoid tissue (MALT) malignant lymphoma.Recently, Hp is classified as I class carcinogen by World Health Organization (WHO), and it plays a leading role in stomach cancer development.Simultaneously the scheme that popular at present treatment Hp infects takes the triple therapy that proton pump inhibitor (PPI) adds two kinds of antibiotic (clarithromycin, amoxicillin, tetracycline, metronidazole etc. select two kinds).The main factor affecting triple therapy is considered to the drug resistance of Hp to antibacterial; Another serious problems are that proton pump inhibitor can bring out dyspepsia, and a large amount of antibacterial then causes the serious destruction of flora in digestive tract.Therefore, find the active kind new medicine thing of efficient, safe anti-Hp and become an important and urgent task.
The compd A phanamgrandiolA that the present invention relates to is one and delivers (QiZeng in 2013, BinGuan, JieRen, etal.AphanamgrandiolA, anewtriterpenoidwithauniquecarbonskeletonfromAphanamixis grandifolia.Fitoterapia, 86 (2013) 217 – 221.) noval chemical compound, this compound has brand-new framework types, current purposes only relates to suppression gastric cancer, ovarian cancer, colon cancer, increment (the QiZeng of liver epithelial cancerous cell, BinGuan, JieRen, etal.AphanamgrandiolA, anewtriterpenoidwithauniquecarbonskeletonfromAphanamixis grandifolia.Fitoterapia, 86 (2013) 217 – 221.), the AphanamgrandiolA that the present invention relates to belongs to first public preparing the purposes in Anti-helicobacter pylori drugs, belong to brand-new structure type.
Summary of the invention
The object of the invention is to not find that it has the present situation of the report of anti-helicobactor pylori activity according in existing AphanamgrandiolA research, provide AphanamgrandiolA and preparing the application in Anti-helicobacter pylori drugs.
Described compd A phanamgrandiolA, structure is as shown in formula I:
The experiment in vitro of AphanamgrandiolA shows, AphanamgrandiolA has very strong anti Helicobacter pylori activity, and it is 16mm (ATCC43504) that paper disk method shows its antibacterial circle diameter.With agar dilution display, it can suppress the growth of 5 random clinical strains (Hp001, Hp003, Hp004, Hp018 and Hp036) and 1 reference culture (ATCC43504) completely, and minimal inhibitory concentration (MIC) is 0.31 μ g/ml.Make positive control with ampicillin, its Cmin (MIC) suppressed completely 6 strain test bacterium is 4.0 μ g/ml.
This result of study shows, the energy force rate ampicillin of the suppression helicobacter pylori activity of AphanamgrandiolA is strong, illustrate for the diseases such as the closely-related acute and chronic gastritis of helicobacter pylori, duodenal ulcer, AphanamgrandiolA is the compound of a great exploitation potential for its.It can be directly used in the treatment of corresponding disease and the preparation of related drugs.
The purposes of the AphanamgrandiolA that the present invention relates in preparation treatment Anti-helicobacter pylori drugs belongs to first public, because framework types belongs to brand-new framework types, and it is active strong, possess outstanding substantive distinguishing features, the control simultaneously for helicobacter pylori infections obviously has significant progress.
Detailed description of the invention
The preparation method of compd A phanamgrandiolA involved in the present invention is see document (QiZeng, BinGuan, JieRen, etal.AphanamgrandiolA, anewtriterpenoidwithauniquecarbonskeletonfromAphanamixis grandifolia.Fitoterapia, 86 (2013) 217 – 221.)
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of compd A phanamgrandiolA tablet involved in the present invention:
Get 5 g of compound AphanamgrandiolA, add 195 grams, dextrin, mixing, Conventional compression makes 1000.
Embodiment 2: the preparation of compd A phanamgrandiolA capsule involved in the present invention:
Get 5 g of compound AphanamgrandiolA, add starch 195 grams, mixing, encapsulatedly makes 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
1) strains tested
Helicobacter pylori (Helicobacterpylori, Hp) reference culture ATCC43504 is purchased from U.S.'s Culture Collection (AmericanTypeCultureCollection, ATCC).15 strain Hp clinical strains are picked up from Jiangsu Prov. People's Hospital Gastroenterology dept., clinical laboratory of Jiangsu TCM Hospital and Nanjing Children's Hospital Dndoscope Laboratory and are accepted gastroscopic patient; To the patient of peptic ulcer, duodenal bulbar inflammation or gastritis verrucosa in continuous gastroscopy, first be defined as Hp positive through RUT experiment, get antral gastric mucosa 1-2 block again, be inoculated in containing 8% horse serum, trimethoprim (trimethropin after chopping, in the Columbia selectivity agar culture medium of TMP) 1.25g/L, polymyxin (polymyxin) B2500U/L, vancomycin (vancomycin) 10mg/L, in 37 DEG C of (5%O under micro-oxygen environment
2, 10%CO
2and 85%N
2) cultivate 72 hours.Collect antibacterial, through smear Gram’s staining, after oxidase, catalase and urease are accredited as the positive, pure culture of going down to posterity, obtained strains is as experimental strain.
2) strain culturing
We adopt micro-aerobic bag (purchased from Shanghai Medical Univ) to carry out the strain culturing of HP, and it produces the micro-aerobic environment required for Hp by chemical reaction.
3) biological activity determination
Paper disk method (Microbiologicalpapermethod) is adopted to measure the inhibitory action of compound to helicobacter pylori, the minimum inhibitory concentration (minimalinhibitoryconcentration, MIC) of test sample is measured with agar dilution.
I. paper disk method experiment
(A) culture medium is prepared by the Columbia culture medium for preparing after high pressure steam sterilization, be cooled to 50-60 DEG C, add 8% horse serum or Sheep Blood, mixing is poured in the culture dish of sterilizing, every ware 7-10ml, culture medium thickness is 1.5mm (sterile working).
(B) experimental bacteria of transferring (being coated with bacterium) gets 108CFU/ml (1OD660=108CFU/ml) Hp diluted bacteria suspension 0.1ml with microscale sampler spreads upon suitable culture dish surface equably.Be inverted in 37 DEG C of drying bakers and take out after 15min, object makes agar surface dry, for subsequent use.
(C) paste sample scraps of paper microscale sampler to get 6 μ l testing samples (mass concentration 2mg/ml) and inject on the round filter paper of sterilizing.With aseptic nipper tweezer containing the scraps of paper of sample and the blank scraps of paper of contrast, by sterile working respectively the scraps of paper be close to containing bacterio-agar surface, paste a piece of paper sheet at a certain distance.Often kind of bacterium is cooked 3 wares, and acquired results asks its meansigma methods.
(D) cultivate each plate is placed in micro-aerobic bag, sealing, opens gas generator, then is placed in 37 DEG C of incubators and cultivates 72h.
(E), after surveying antibacterial circle diameter taking-up flat board, the size of antibacterial circle diameter around each scraps of paper is measured respectively.With reference to the result of matched group, the result of testing sample sensitive experiment can be drawn.In triplicate.
II. agar dilution measures MIC
(A) first compound dimethyl sulfoxide (DMSO) solution preparation of test is become the mother solution of 0.5mg/ml by the preparation of Drug plates, then with sterilized water dilution, is finally made into 10.0,8.0,6.0,4.5,4.0,3.5,3.0,2.5,2.0,1.5,1.0, the concentration series of 0.5 and 0.25 μ g/ml, DMSO concentration is in media as well less than 1%.The test compounds solution prepared by 1ml separately adds in the 9ml Columbia medium of 50 DEG C the horse serum that 1ml is incubated in 50 DEG C and fully mixes with being incubated, and casts in culture dish to cool.
(B) experimental bacteria of transferring (being coated with bacterium) draws the 1 × 108CFU/mlHp diluted bacteria suspension 0.1ml with microscale sampler spreads upon culture dish surface equably, is inverted in 37 DEG C of drying bakers and takes out after 15min, and object makes agar surface dry, for subsequent use.
(C) determine that test dish (contains: 85%N at micro-aerobic bag by MIC
2, 10%CO
2and 5%O
2) in, be incubated 37 DEG C and cultivate 72 hours, observe Hp growing state, contrast with blank group, there is no the sample least concentration of bacteria growing completely for minimum inhibitory concentration (minimalinhibitoryconcentration, MIC) value.Positive control is ampicillin (Ampicillin).
3, the pharmacological results of AphanamgrandiolA
Experiment in vitro shows, AphanamgrandiolA has very strong anti Helicobacter pylori activity, and it is 16mm (ATCC43504) that paper disk method shows its antibacterial circle diameter.With agar dilution display, it can suppress the growth of 5 random clinical strains (Hp001, Hp003, Hp004, Hp018 and Hp036) and 1 reference culture (ATCC43504) completely, and minimal inhibitory concentration (MIC) is 0.31 μ g/ml.Make positive control with ampicillin, its Cmin (MIC) suppressed completely 6 strain test bacterium is 4.0 μ g/ml.
Conclusion: AphanamgrandiolA suppresses the energy force rate ampicillin of helicobacter pylori activity strong, illustrate for the diseases such as the closely-related acute and chronic gastritis of helicobacter pylori, duodenal ulcer, AphanamgrandiolA is the compound of a great exploitation potential for its.It can be directly used in the treatment of corresponding disease and the preparation of related drugs.
Claims (1)
1.AphanamgrandiolA is preparing the application in Anti-helicobacter pylori drugs, and described compd A phanamgrandiolA structure is as shown in formula I:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310405608.8A CN103690527B (en) | 2013-09-06 | 2013-09-06 | Aphanamgrandiol A is preparing the application in Anti-helicobacter pylori drugs |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310405608.8A CN103690527B (en) | 2013-09-06 | 2013-09-06 | Aphanamgrandiol A is preparing the application in Anti-helicobacter pylori drugs |
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| Publication Number | Publication Date |
|---|---|
| CN103690527A CN103690527A (en) | 2014-04-02 |
| CN103690527B true CN103690527B (en) | 2016-03-23 |
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|---|---|---|---|
| CN201310405608.8A Expired - Fee Related CN103690527B (en) | 2013-09-06 | 2013-09-06 | Aphanamgrandiol A is preparing the application in Anti-helicobacter pylori drugs |
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Inventor after: Cao Aiyun Inventor before: Zhang Zhilian |
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Effective date of registration: 20160229 Address after: 311800 Zhejiang city of Shaoxing province Zhuji City Tao Zhan Shan Street Road No. 17 Applicant after: Cao Aiyun Address before: The 3 groups after the deep Tangxia village of Yiwu city street 322008 Zhejiang city of Jinhua Province Applicant before: Zhang Zhilian |
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