CN102988355A - Application of Aphanamixoid A for preparing helicobacter pylori resistant medicine - Google Patents
Application of Aphanamixoid A for preparing helicobacter pylori resistant medicine Download PDFInfo
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- CN102988355A CN102988355A CN2012104702343A CN201210470234A CN102988355A CN 102988355 A CN102988355 A CN 102988355A CN 2012104702343 A CN2012104702343 A CN 2012104702343A CN 201210470234 A CN201210470234 A CN 201210470234A CN 102988355 A CN102988355 A CN 102988355A
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- aphanamixoid
- helicobacter pylori
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- ulcer
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Abstract
In-vitro activity experiments show that Aphanamixoid A has strong helicobacter pylori (Hp) resistant activity. Aphanamixoid A can be used for treating diseases, such as acute and chronic gastritis, gastric ulcer, duodenum ulcer and the like and applied for preparing medicines for treating acute and chronic gastritis, gastric ulcer and duodenum ulcer. The application of Aphanamixoid A for preparing the helicobacter pylori resistant medicine is disclosed for the first time; because the skeleton type belongs to a brand new skeleton type and the helicobacter pylori inhibitory activity of Aphanamixoid A is strong unexpectedly, the possibility that other compounds give any inspiration does not exist; Aphanamixoid A has outstanding substantive characteristics; and simultaneously, Aphanamixoid A has obvious progress for preventing and treating helicobacter pylori infection.
Description
Technical field
The invention belongs to biological pharmacy technical field, relate in particular to the application of Aphanamixoid A in the preparation Anti-helicobacter pylori drugs.
Background technology
Helicobacter pylori (Helicobacter pylori, Hp) is a kind of Gram-negative spiral bacteria.Studies show that helicobacter pylori is the main pathogenesis of acute and chronic gastritis and Stomach duodenum ulcer, and may be relevant with the morbidity of gastric cancer stomach function regulating mucosa-associated lymphoid tissue (MALT) malignant lymphoma.Recently, World Health Organization (WHO) is classified as I class carcinogen with Hp, and it plays a leading role in the gastric cancer development.The scheme that at present popular treatment Hp infects is to take simultaneously the triple therapy that proton pump inhibitor (PPI) adds two kinds of antibiotic (clarithromycin, amoxicillin, tetracycline, metronidazole etc. select two kinds).The main factor that affects triple therapy is considered to Hp to the drug resistance of antibacterial; Another serious problems are that proton pump inhibitor can bring out dyspepsia, and a large amount of antibacterial then cause the serious destruction of flora in the digestive tract.Therefore, seek the active kind new medicine thing of efficient, safe anti-Hp and become an important and urgent task.
The compd A phanamixoid A that the present invention relates to is one and delivered (Cai in 2012, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to insect antifeedant activity (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.), belong to open first for the purposes of the Aphanamixoid A that the present invention relates in preparation treatment Anti-helicobacter pylori drugs, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for helicobacter pylori, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, the control that is used for simultaneously helicobacter pylori infections obviously has significant progress.
Summary of the invention
The objective of the invention is to study the application of Aphanamixoid A in Anti-helicobacter pylori drugs.
Described compd A phanamixoid A structure is shown in formula I:
The experiment in vitro of Aphanamixoid A shows that Aphanamixoid A has very strong anti Helicobacter pylori activity, and paper disk method shows that its antibacterial circle diameter is 24 mm (ATCC43504).With agar dilution show it can suppress fully 5 at random clinical strains (Hp001, Hp003, Hp004, Hp018 and Hp036) and the growth of 1 reference culture (ATCC43504), minimal inhibitory concentration (MIC) is 0.5 μ g/ml.Make positive control with the ampicillin, it is 2.0 μ g/ml to the Cmin (MIC) that 6 strains test bacterium suppresses fully.
This result of study shows, the energy force rate ampicillin of the inhibition helicobacter pylori activity of Aphanamixoid A is strong, explanation for the diseases such as the closely-related acute and chronic gastritis of helicobacter pylori, duodenal ulcer, Aphanamixoid A is the chemical 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 Aphanamixoid A that the present invention relates in preparation treatment Anti-helicobacter pylori drugs belongs to open first, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for helicobacter pylori, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, the control that is used for simultaneously helicobacter pylori infections obviously has significant progress.
The specific embodiment
The preparation method of compd A phanamixoid A involved in the present invention is referring to document (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.
Embodiment 1: the preparation of compd A phanamixoid A tablet involved in the present invention:
Get 20 and digest compound Aphanamixoid A, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of compd A phanamixoid A capsule involved in the present invention:
Get 20 and digest compound Aphanamixoid A, add conventional adjuvant such as starch 180 grams of preparation capsule, mixing is encapsulatedly made 1000.
Further specify its pharmaceutically active below by pharmacodynamic experiment.
The pharmacological evaluation of Aphanamixoid A
1) strains tested
Helicobacter pylori (Helicobacter pylori, Hp) reference culture ATCC 43504 is purchased from U.S.'s strain and preserves center (American Type Culture Collection, ATCC).15 strain Hp clinical strains are picked up from Nanjing drum tower hospital, Jiangsu Prov. People's Hospital, Jiangsu TCM Hospital and Nanjing Children's Hospital and are accepted gastroscopic patient; In continuous gastroscopy to the patient of peptic ulcer, duodenal bulbar inflammation or gastritis verrucosa, be defined as the Hp positive through the RUT experiment first, get again antral gastric mucosa 1-2 piece, be inoculated in after the chopping and contain 8% horse serum, trimethoprim (trimethropin, TMP) in the Columbia selectivity agar culture medium of 1.25 g/L, polymyxin (polymyxin) B2500 U/L, vancomycin (vancomycin) 10 mg/L, in 37 ° of C (5% O under little oxygen environment
2, 10% CO
2With 85% N
2) cultivated 72 hours.Collect antibacterial, through the smear Gram’s staining, after oxidase, catalase and urease are accredited as the positive, the pure culture of going down to posterity, obtained strains is as experimental strain.
2) strain culturing
We adopt little aerobic bag (available from Shanghai Medical Univ) to carry out the strain culturing of HP, and it can produce the needed little aerobic environment of Hp by chemical reaction.
3) biological activity determination
Adopt paper disk method (Microbiological paper method) to measure chemical compound to the inhibitory action of helicobacter pylori, measure the minimum inhibitory concentration (minimal inhibitory concentration, MIC) of test sample with agar dilution.
I. paper disk method experiment
(A) prepare culture medium with the Columbia culture medium for preparing behind high pressure steam sterilization, be cooled to 50-60 ℃, add 8% horse serum or Sheep Blood, mixing is poured in the culture dish of having sterilized, every ware 7-10 ml, culture medium thickness are 1.5 mm (sterile workings).
(B) switching experimental bacteria (being coated with bacterium) with microscale sampler get dilution good 10
8CFU/ml (1OD
660=10
8CFU/ml) bacteria suspension 0.1 ml of Hp spreads upon suitable culture dish surface equably.Be inverted in the 37oC drying baker and take out behind 15 min, purpose makes agar surface dry, for subsequent use.
(C) pasting the sample scraps of paper gets 6 μ l testing samples (mass concentration 2 mg/ml) with microscale sampler and injects on the round filter paper of having sterilized.Contain the scraps of paper and the blank scraps of paper of contrast of sample with the aseptic nipper tweezer, by the sterile working respectively the scraps of paper be close to and contain the bacterio-agar surface, paste at a certain distance a piece of paper sheet.Every kind of bacterium is cooked 3 wares, and acquired results is asked its meansigma methods.
(D) cultivation places little aerobic bag with each plate, and gas generator is opened in sealing, places the 37oC incubator to cultivate 72h again.
(E) after the survey antibacterial circle diameter takes out flat board, measure respectively each scraps of paper size of antibacterial circle diameter on every side.With reference to the result of matched group, can draw the result of testing sample sensitive experiment.Triplicate.
II. agar dilution is measured MIC
(A) preparation of medicine flat board at first becomes the mother solution of 0.5 mg/ml with the chemical compound of test with dimethyl sulfoxide (DMSO) solution preparation, dilutes with sterilized water again, finally is made into 10.0,8.0,6.0,4.5,4.0,3.5,3.0,2.5,2.0,1.5,1.0,0.5 with the concentration series of 0.25 μ g/ml, the concentration of DMSO in medium is less than 1%.The test compounds solution that 1 ml is prepared adds in addition 1 ml in the 9 ml Colombia culture medium of 50 ° of C and is incubated in the abundant mixing of the horse serum of 50 ° of C with being incubated, and casts to cool off in the culture dish.
(B) switching experimental bacteria (being coated with bacterium) with microscale sampler draw dilution good 1 * 10
8Bacteria suspension 0.1 ml of CFU/ml Hp spreads upon the culture dish surface equably, is inverted in the 37oC drying baker and takes out behind 15 min, and purpose makes agar surface dry, for subsequent use.
(C) determine that MIC (contains culture dish to be measured: 85% N at little aerobic bag
2, 10% CO
2With 5% O
2) in, insulation 37
oC cultivated 72 hours, observed the Hp growing state, contrasted with the blank group, take the sample least concentration that do not have bacteria growing fully as minimum inhibitory concentration (minimal inhibitory concentration, MIC) value.Positive control is ampicillin (Ampicillin).
3, the pharmacological results of Aphanamixoid A
Experiment in vitro shows that Aphanamixoid A has very strong anti Helicobacter pylori activity, and paper disk method shows that its antibacterial circle diameter is 24 mm (ATCC43504).With agar dilution show it can suppress fully 5 at random clinical strains (Hp001, Hp003, Hp004, Hp018 and Hp036) and the growth of 1 reference culture (ATCC43504), minimal inhibitory concentration (MIC) is 0.5 μ g/ml.Make positive control with the ampicillin, it is 2.0 μ g/ml to the Cmin (MIC) that 6 strains test bacterium suppresses fully.
Conclusion: it is strong that Aphanamixoid A suppresses the energy force rate ampicillin of helicobacter pylori activity, explanation for the diseases such as the closely-related acute and chronic gastritis of helicobacter pylori, duodenal ulcer, Aphanamixoid A is the chemical 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.Aphanamixoid the application of A in the preparation Anti-helicobacter pylori drugs, described compd A phanamixoid A structure is shown in formula I:
Formula I.
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| CN2012104702343A CN102988355A (en) | 2012-11-19 | 2012-11-19 | Application of Aphanamixoid A for preparing helicobacter pylori resistant medicine |
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| CN2012104702343A CN102988355A (en) | 2012-11-19 | 2012-11-19 | Application of Aphanamixoid A for preparing helicobacter pylori resistant medicine |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103251639A (en) * | 2013-06-03 | 2013-08-21 | 南京正亮医药科技有限公司 | Application of Polyflavanostilbene A in preparing anti-helicobacter pylori medicine |
| CN103520185A (en) * | 2013-10-29 | 2014-01-22 | 杨文君 | Application of compound in preparing monoamine oxidase MAO inhibitor |
| CN103520184A (en) * | 2013-10-29 | 2014-01-22 | 杨文君 | Application of compound in preparing antibacterial medicine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101239058A (en) * | 2007-02-07 | 2008-08-13 | 上海华珠生物科技有限公司 | Proanhocyanidins compounds for preparing medicaments and health care food for preventing and controlling helicobacter pylori associated gastritis |
| CN102327489A (en) * | 2011-09-21 | 2012-01-25 | 浙江天皇药业有限公司 | Application of Dendrobium candidum in preparation of medicaments for treating Helicobacter pylori infection |
-
2012
- 2012-11-19 CN CN2012104702343A patent/CN102988355A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101239058A (en) * | 2007-02-07 | 2008-08-13 | 上海华珠生物科技有限公司 | Proanhocyanidins compounds for preparing medicaments and health care food for preventing and controlling helicobacter pylori associated gastritis |
| CN102327489A (en) * | 2011-09-21 | 2012-01-25 | 浙江天皇药业有限公司 | Application of Dendrobium candidum in preparation of medicaments for treating Helicobacter pylori infection |
Non-Patent Citations (2)
| Title |
|---|
| JIE-YUN CAI等: "Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya", 《ORGANIC LETTERS》, vol. 14, no. 10, 27 April 2012 (2012-04-27), pages 2524 - 2527 * |
| 孙崇德等: "柑桔果实柠檬苦素类化合物的研究与应用", 《浙江农业学报》, vol. 14, no. 5, 31 December 2002 (2002-12-31), pages 297 - 302 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103251639A (en) * | 2013-06-03 | 2013-08-21 | 南京正亮医药科技有限公司 | Application of Polyflavanostilbene A in preparing anti-helicobacter pylori medicine |
| CN103520185A (en) * | 2013-10-29 | 2014-01-22 | 杨文君 | Application of compound in preparing monoamine oxidase MAO inhibitor |
| CN103520184A (en) * | 2013-10-29 | 2014-01-22 | 杨文君 | Application of compound in preparing antibacterial medicine |
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Application publication date: 20130327 |