CN102861067B - Application of Houttuynoid E in preparing anti-helicobacter pylori (Hp) medicine - Google Patents
Application of Houttuynoid E in preparing anti-helicobacter pylori (Hp) medicine Download PDFInfo
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- CN102861067B CN102861067B CN201210418406.2A CN201210418406A CN102861067B CN 102861067 B CN102861067 B CN 102861067B CN 201210418406 A CN201210418406 A CN 201210418406A CN 102861067 B CN102861067 B CN 102861067B
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Abstract
An in vitro activity experiment shows that Houttuynoid E has very strong anti-Hp activity. Houttuynoid E can be utilized to treat diseases, such as acute gastritis, chronic gastritis, gastrohelcosis ulcer and duodenal ulcer and applied to preparation of the medicines for treating acute gastritis, chronic gastritis, gastrohelcosis ulcer and duodenal ulcer. Application of Houttuynoid E in preparation of an anti-Hp medicine provided by the invention is disclosed firstly. The skeleton type belongs to new skeleton type, and the inhibitory activity of Houttuynoid E on Hp is unexpectedly strong; and the probability that any revelation is provided by other compounds does not existe, Houttuynoid E has the excellent substantive features, and Houttuynoid E obviously has a remarkable progress when being used for preventing and treating Hp infection.
Description
Technical field
The invention belongs to biological pharmacy technical field, relate in particular to Houttuynoid E in the application of preparing in 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 by Hp, and it plays a leading role in gastric cancer development.The scheme that at present popular treatment Hp infects is to take the triple therapy that proton pump inhibitor (PPI) adds two kinds of antibiotic (clarithromycin, amoxicillin, tetracycline, metronidazole etc. select two kinds) simultaneously.The main factor that affects 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 cause 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 compound H outtuynoid E the present invention relates to is one and within 2012, delivers (Chen, S. D. et al., 2012. Houttuynoid E_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.) New skeleton compound, this compound has brand-new framework types, current purposes only relates to anti-herpes simplex virus activity (Chen, S. D. et al., 2012. Houttuynoid E_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.), purposes for the Houttuynoid E 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 compounds, possesses outstanding substantive distinguishing features, for the control of helicobacter pylori infections, obviously there is significant progress simultaneously.
Summary of the invention
The object of the invention is to study the application of Houttuynoid E in Anti-helicobacter pylori drugs.
Described compound H outtuynoid E structure is as shown in formula I:
The experiment in vitro of Houttuynoid E shows, Houttuynoid E has very strong anti Helicobacter pylori activity, and paper disk method shows that its antibacterial circle diameter is 19 mm (ATCC43504).With agar dilution, show that it can suppress the growth of 5 random clinical strains (Hp001, Hp003, Hp004, Hp018 and Hp036) and 1 reference culture (ATCC43504) completely, minimal inhibitory concentration (MIC) is 1.0 μ g/ml.With making positive control in ampicillin, its Cmin (MIC) that 6 strain test bacterium are suppressed is completely 2.0 μ g/ml.
This result of study shows, the energy force rate ampicillin of the inhibition helicobacter pylori activity of Houttuynoid E is strong, explanation for the diseases such as the closely-related acute and chronic gastritis of helicobacter pylori, duodenal ulcer, Houttuynoid E 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 Houttuynoid E 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 compounds, possess outstanding substantive distinguishing features, for the control of helicobacter pylori infections, obviously there is significant progress simultaneously.
The specific embodiment
The preparation method of compound H outtuynoid E involved in the present invention is referring to document (Chen, S. D. et al., 2012. Houttuynoid E_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subject to any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of compound H outtuynoid E tablet involved in the present invention:
Get 20 and digest compound Houttuynoid E, add 180 grams of conventional adjuvants preparing tablet, mix, conventional tablet machine is made 1000.
Embodiment 2: the preparation of compound H outtuynoid E capsule involved in the present invention:
Get 20 and digest compound Houttuynoid E, add the conventional adjuvant of preparing capsule as 180 grams of starch, mix, encapsulatedly make 1000.
Below by pharmacodynamic experiment, further illustrate its pharmaceutically active.
The pharmacological evaluation of Houttuynoid E
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 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; Patient to peptic ulcer, duodenal bulbar inflammation or gastritis verrucosa in continuous gastroscopy, first through RUT experiment, be defined as Hp positive, get again antral gastric mucosa 1-2 piece, after chopping, be inoculated in containing 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 micro-oxygen environment
2, 10% CO
2with 85% N
2) cultivate 72 hours.Collect antibacterial, through smear Gram’s staining, oxidase, catalase and urease are accredited as after the positive, the pure culture of going down to posterity, and 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 can produce the needed micro-aerobic environment of Hp by chemical reaction.
3) biological activity determination
Adopt paper disk method (Microbiological paper method) to measure the inhibitory action of compound to helicobacter pylori, with agar dilution, measure the minimum inhibitory concentration (minimal inhibitory concentration, MIC) of test sample.
I. paper disk method experiment
(A) prepare culture medium by the Columbia culture medium preparing after high pressure steam sterilization, be cooled to 50-60 ℃, add 8% horse serum or Sheep Blood, mix in the culture dish that is poured into sterilizing, every ware 7-10 ml, culture medium thickness is 1.5 mm (sterile workings).
(B) switching experimental bacteria (be coated with bacterium) with microscale sampler get diluted 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 37oC drying baker and take out after 15 min, object makes agar surface dry, standby.
(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 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 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) cultivate each plate is placed in to micro-aerobic bag, sealing, opens gas generator, then is placed in 37oC incubator and cultivates 72h.
(E) survey antibacterial circle diameter and take out after flat board, measure respectively each scraps of paper size of antibacterial circle diameter around.With reference to the result of matched group, can draw the result of testing sample sensitive experiment.In triplicate.
II. agar dilution is measured MIC
(A) first the preparation of medicine flat board becomes dimethyl sulfoxide for compound (DMSO) solution preparation of test the mother solution of 0.5 mg/ml, 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, the concentration of DMSO in medium is less than 1%.The test compounds solution that 1 ml is prepared separately adds 1 ml in the 9 ml Colombia culture medium of 50 ° of C and is incubated in the horse serum of 50 ° of C and fully mixes with being incubated, and casts in culture dish cooling.
(B) switching experimental bacteria (be coated with bacterium) with microscale sampler draw diluted 1 × 10
8bacteria suspension 0.1 ml of CFU/ml Hp spreads upon culture dish surface equably, is inverted in 37oC drying baker and takes out after 15 min, and object makes agar surface dry, standby.
(C) determine that MIC (contains culture dish to be measured: 85% N at micro-aerobic bag
2, 10% CO
2with 5% O
2) in, insulation 37
oc cultivates 72 hours, observes Hp growing state, with blank group contrast, there is no the sample least concentration of bacteria growing completely as minimum inhibitory concentration (minimal inhibitory concentration, MIC) value.Positive control is ampicillin (Ampicillin).
3, the pharmacological results of Houttuynoid E
Experiment in vitro shows, Houttuynoid E has very strong anti Helicobacter pylori activity, and paper disk method shows that its antibacterial circle diameter is 19 mm (ATCC43504).With agar dilution, show that it can suppress the growth of 5 random clinical strains (Hp001, Hp003, Hp004, Hp018 and Hp036) and 1 reference culture (ATCC43504) completely, minimal inhibitory concentration (MIC) is 1.0 μ g/ml.With making positive control in ampicillin, its Cmin (MIC) that 6 strain test bacterium are suppressed is completely 2.0 μ g/ml.
Conclusion: it is strong that Houttuynoid E 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, Houttuynoid E 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.Houttuynoid E is in the application of preparing in Anti-helicobacter pylori drugs, described compound H outtuynoid E structure as
formula Ishown in:
formula I.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101327266A (en) * | 2008-07-18 | 2008-12-24 | 南方医科大学 | Oral cavity nursing agent for preventing and treating oral disease induced by Helicobacter pylori infection contamination |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101327266A (en) * | 2008-07-18 | 2008-12-24 | 南方医科大学 | Oral cavity nursing agent for preventing and treating oral disease induced by Helicobacter pylori infection contamination |
Non-Patent Citations (4)
| Title |
|---|
| Houttuynoids A-E, anti-herpes simplex virus active flavonoids with novel skeletons from houttuynia cordata;Shao-Dan Chen et al;《Organic Letters》;20120313;第14卷(第7期);第1773页 * |
| Shao-DanChenetal.HouttuynoidsA-E anti-herpes simplex virus active flavonoids with novel skeletons from houttuynia cordata.《Organic Letters》.2012 |
| 李爽 等.鱼腥草的有效成分、药理作用及临床应用的研究进展.《沈阳药科大学学报》.1997,第14卷(第2期),第144-146页. |
| 鱼腥草的有效成分、药理作用及临床应用的研究进展;李爽 等;《沈阳药科大学学报》;19970430;第14卷(第2期);第144-146页 * |
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