CN109223825A - Hydrogen peroxide is in the drug for preparing application and preparation in Helicobacter pylori eradication drug - Google Patents
Hydrogen peroxide is in the drug for preparing application and preparation in Helicobacter pylori eradication drug Download PDFInfo
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Abstract
The present invention provides hydrogen peroxide in the drug for preparing application and preparation in Helicobacter pylori eradication drug.The hydrogen peroxide of suitable concentration decomposes rapidly in stomach discharges a large amount of oxygen, significantly improves oxygen concentration in stomach, helicobacter pylori infections is enable effectively to eradicate.It is demonstrated experimentally that the hydrogen peroxide of suitable concentration all has preferable killing effect to helicobacter pylori international standard bacterial strain and helicobacter pylori wild-type strain, helicobacter pylori can especially be effectively prevent to generate drug resistance and recurrent infection.Helicobacter pylori infection in mice model, without recurrence, can have the function that elimination after hydrogen peroxide is treated, and provide new selection to eradicate anti-Heliobactorpylori drug, new thinking is provided for clinical prevention helicobacter pylori infections.
Description
Technical field
The invention belongs to medicines, are related to hydrogen peroxide in preparing Helicobacter pylori eradication drug
Using and preparation drug.
Background technique
Helicobacter pylori (Helicobacter pylori, Hp) be a kind of Gram-negative, it is micro- it is aerobic, to growth conditions
It is required that harsh bending corynebacteria.It is found so far from nineteen eighty-three Australia scholar Warren and Marshall, pylorus spiral shell
Bacillus have been found in the world be chronic gastritis, peptic ulcer and gastric lymphoma of mucosa-associated lymphoid tissue principal causative because
Son, it is especially close with being related for gastric cancer.Helicobacter pylori is classified as I class carcinogen by the World Health Organization in 1994
(1.Peleteiro B,Bastos A,Ferro A,et al.Prevalence of Helicobacter pylori
infection worldwide:a systematic review of studies with national coverage[J]
.Dig Dis Sci,2014,59(8):1698-1709；2.Grad YH,Lipsitch M,Aiello AE.Secular
trends in Helicobacter pylori seroprevalence in adults in the United States:
evidence for sustained race/ethnic disparities[J].Am J Epidemiol,2012,175(1):
54-59；3. ten thousand Mount Tais, Hu Fulian, Xiao Shudong wait epidemiological survey [J] of China general population helicobacter pylori infections
Modern times digestion and intervention diagnosis and therapy, 2010,15 (5): 265-270；4.Moeller H,Correa P.Carcinogenicity of
some biological agents[J].Cancer Epidemiol Biomarkers Prev,1994,3(7):627).Mesh
Preceding data shows that there are different degrees of helicobacter pylori infections in global every country and area, and range is more than 50%, wherein drawing
Fourth America and Latvian infection rate are up to 79%.According to the investigation result (Liu Li of Helicobacter pylori in China Collaboration on Scientific Research group
It is raw, Wang Wen, China of Yao Chong China hypertension prevention and control guide (2009) [J] China hypertension magazine, 2010,18 (1): 1-30), I
Average rate 64% in state's helicobacter pylori general population, (the Hu Fulian pylorus of average rate 85% of Tibet Autonomous Region
Helicobacter research focuses and progress [J] gastroenterology, 2015 (12): 705-707).
The nineties in last century, standard Triple therapy (proton pump inhibitor+clarithromycin+Amoxicillin/metronidazole) is root
Except the most common scheme of helicobacter pylori, good effect (Lind T, et al.Eradication of Helicobacter
pylori using one-week triple therapies combining omeprazole with two
antimicrobials:the MACH I Study[J].Helicobacter,1996；1 (3): 138-44), but with bacterium
Significant changes have occurred in the elimination effect of the significant raising of resistant rate, helicobacter pylori.The U.S., Europe, South Korea helicobacter pylori
Eradication rate be lower than 80%, in recent years the eradication rate of China's report down to 60% (Malfertheiner P, Bazzoli F,
Delchier J C.Helicobacter pylori eradication with a capsule containing
bismuth subcitrate potassium,metronidazole,and tetracycline given with
omeprazole versus clarithromycin-based triple therapy:a randomised,open-
label,non-inferiority,phase 3trial(vol377,pg 905,2011)[J].LANCET,2011,378
(9805):1778-1778).For the eradication rate for improving helicobacter pylori, the strategy taken is concentrated mainly on: triple therapy changes
Into with reinforcement, Chinese medicine antibacterial and the aspect of helicobacter pylori vaccine three.First, take improvement to arrange with reinforcement for triple therapy
It applies, the course for the treatment of was increased to 14 days from 7 days, while increasing antimicrobial dosage, medicament categories increase to 4 kinds by 3 kinds；Second, it uses
Chinese medicine replaces antimicrobial to play antibacterial action, and resistant rate is avoided to increase, such as banxia xiexin decoction, stomach dissipate again, Jingjiang reach
And sanjiu weitai capsules；Third, helicobacter pylori vaccine, such as helicobacter pylori recombinant vaccine, helicobacter pylori whole-bacterial-vaccine.Root
Though the method except helicobacter pylori is more, to reach effectively elimination and be not easy to.First, increase medicine on the basis of triple therapy
Species, the shortcomings that extending the period for the treatment of: with the long-time large dosage application of antimicrobial, cause in the resistant rate of helicobacter pylori
It rises, becomes the principal element for influencing Eradication Therapy of Helicobacter pylori effect；Second, Chinese patent drug replace antibiotic the shortcomings that: drug
Complicated component, antibacterial effect are unstable；The shortcomings that third, helicobacter pylori vaccine: the research and development of vaccine are still in primary stage, epidemic disease
Seedling effect is influenced vulnerable to factors such as adjuvants, and the safety of human body is still not clear in the immune response that vaccine causes.
Hydrogen peroxide is a kind of oxidant, and aqueous solution is commonly called as hydrogen peroxide, is colourless transparent liquid, and aqueous solution is widely applied
It is sterilized in medical wound, food, environment etc., helicobacter pylori infections can be treated about hydrogen peroxide and had not been reported.
Summary of the invention
Aiming at the problems existing in the prior art, the present invention provide hydrogen peroxide prepare helicobacter pylori infections elimination control
Treat the drug of the application and preparation in drug.
The present invention is to be achieved through the following technical solutions:
Hydrogen peroxide is preparing the application in Helicobacter pylori eradication drug.
Preferably, the helicobacter pylori includes helicobacter pylori international standard bacterial strain and helicobacter pylori wild-type bacteria
Strain.
Further, the helicobacter pylori wild-type strain includes helicobacter pylori wild-type strain I, helicobacter pylori
Wild type II and helicobacter pylori wild type III.
Preferably, the position of the helicobacter pylori infections is alimentary canal.
Further, the alimentary canal includes stomach and duodenum.
Hydrogen peroxide is preparing the application in eradication therapy helicobacter pylori infections disease medicament, the helicobacter pylori
Infectious diseases includes chronic gastritis, peptic ulcer, gastric lymphoma of mucosa-associated lymphoid tissue and gastric cancer.
A kind of drug of eradication therapy helicobacter pylori infections, is made oral solution, tablet, capsule, powder for hydrogen peroxide
Agent or granule obtain.
Preferably, the mass concentration of hydrogen peroxide is 0.2%~1%.
Compared with prior art, the invention has the following beneficial technical effects:
For helicobacter pylori as a kind of obligate microaerobion, the optimum oxygen concentration of growing environment is 5%-6%, is improved
Cause helicobacter pylori dead rapidly if oxygen concentration (such as atmospheric environment oxygen concentration).Therefore, the hydrogen peroxide of suitable concentration is in stomach
Interior rapid decomposition discharges a large amount of oxygen, significantly improves oxygen concentration in stomach, helicobacter pylori infections is enable effectively to eradicate.Experiment card
Bright, the hydrogen peroxide of suitable concentration all has preferably helicobacter pylori international standard bacterial strain and helicobacter pylori wild-type strain
Killing effect, can especially effectively prevent helicobacter pylori to generate drug resistance and recurrent infection.Helicobacter pylori infection in mice
Model, without recurrence, can have the function that elimination after hydrogen peroxide is treated, and provide new selection to eradicate anti-Heliobactorpylori drug.
Hydrogenperoxide steam generator is decomposed rapidly by the enzymatic of stomach hydrogen peroxide and generates a large amount of oxygen and water, and the two is harmless, and
Since concentration is low, oxidation is weak, is not enough to cause human body gastric mucosa damage.Therefore the present invention, will using " oxygen environment " strategy
" helicobacter pylori eradication problem " is converted into the problem of " depriving the necessary condition of growth of H. pylori ", effectively prevents existing treatment
The defect of method provides new thinking for clinical prevention helicobacter pylori infections.
Detailed description of the invention
Fig. 1 is minimal inhibitory concentration of the hydrogen peroxide to Liquid Culture helicobacter pylori international standard bacterial strain；Mean ± mark
Poor, the n=6 of standard, compared with the control group * p < 0.05, p < 0.01 * *.
Fig. 2 is minimal inhibitory concentration of the hydrogen peroxide to solid culture helicobacter pylori international standard bacterial strain；CBS is bismuth agent
Group, NS are physiological saline；Mean ± standard deviation, n=5, compared with the control group * p < 0.05, p < 0.01 * *.
Fig. 3 is minimal inhibitory concentration of the hydrogen peroxide to Liquid Culture helicobacter pylori wild-type strain-I, II, III；?
Number ± standard deviation, n=6, compared with the control group * p < 0.05, p < 0.01 * *.
Fig. 4 is minimal inhibitory concentration of the hydrogen peroxide to solid culture helicobacter pylori wild-type strain-I, II, III；?
Number ± standard deviation, n=6, compared with the control group * p < 0.05, p < 0.01 * *.
Fig. 5 is that the effect to gerbil jird helicobacter pylori infections in 14 days is administered in hydrogen peroxide；Giemsa staining, 1000 ×, PBC
For Bismuth Potassium Citrate group, mean, n=8, compared with the control group * p < 0.05, p < 0.01 * *.
Fig. 6 is that the effect to Helicobacter pylori infection in mice in 4,7,14 days is administered in hydrogen peroxide；Giemsa staining, 1000
×, mean, n=12, compared with the control group * p < 0.05, p < 0.01 * *.
Fig. 7 is that hydrogen peroxide removes the recurrence after Helicobacter pylori infection in mice；Giemsa staining, 1000 ×, n=
12, * p < 0.05 compared with the control group, p < 0.01 * *.
Specific embodiment
Below with reference to specific embodiment, the present invention is described in further detail, it is described be explanation of the invention and
It is not to limit.
Experiment 1: effect of the hydrogen peroxide to helicobacter pylori international standard bacterial strain
(1) minimal inhibitory concentration of Liquid Culture based assays hydrogen peroxide
Helicobacter pylori international standard strains A TCC43504, which is prepared, becomes 1.0 × 108CFU/mL bacteria suspension, matches simultaneously
Make the helicobacter pylori fluid nutrient medium of the hydrogen peroxide containing concentration gradient.It draws 0.12mL bacteria suspension and 11.88mL is added containing concentration
The helicobacter pylori fluid nutrient medium of gradient hydrogen peroxide makes entire fluid nutrient medium volume 12mL (bacterium solution: fluid nutrient medium
=1:100).37 DEG C of isothermal vibration incubators are set, are cultivated 5 days under micro- aerobic environment with 150r/min, helicobacter pylori is observed
Growing state measures fluid nutrient medium OD600And draw growth curve.
Helicobacter pylori international standard strains A TCC43504 is prepared respectively becomes 1.0 × 106CFU/mL、1.0×
107CFU/mL、1.0×108CFU/mL、1.0×109CFU/mL bacteria suspension is drawn 0.12mL respectively and is inoculated in containing 0.21% peroxide
The helicobacter pylori fluid nutrient medium for changing hydrogen, makes culture volume 12mL (bacterium solution: culture medium=1:100).Set 37 DEG C of constant temperature
Concussion and cultivate case is cultivated 5 days under micro- aerobic environment with 150r/min, observes growth of H. pylori situation, measures culture medium
OD600And draw growth curve.
Figure 1A the results show that hydrogen peroxide to the minimal inhibitory concentration of helicobacter pylori international standard strains A TCC43504
It is 0.21%, when concentration of hydrogen peroxide is greater than 0.21%, helicobacter pylori reference culture is not grown.Figure 1B the results show that
It is respectively 10 by concentration6、107、108、109The helicobacter pylori international standard strains A TCC43504 of CFU/mL is inoculated in respectively to be contained
When the fluid nutrient medium of 0.21% hydrogen peroxide, there is difference, inoculum density highest 10 in the growth curve of four groups of bacterial strains9CFU/
ML group takes the lead in growing, and then respectively 108、107、106CFU/mL group.
(2) minimal inhibitory concentration of solid culture based assays hydrogen peroxide
Helicobacter pylori international standard strains A TCC43504, which is prepared, becomes 1.0 × 108CFU/mL bacteria suspension, is poured respectively
Build the helicobacter pylori solid medium of hydrogen peroxide containing concentration gradient, bismuth agent.It draws 0.1mL bacteria suspension and is added and contain concentration gradient
The helicobacter pylori solid medium of hydrogen peroxide, aseptic inoculation ring are smeared uniform.37 DEG C of constant incubators are set, in micro- aerobic ring
After cultivating 5 days under border, by the elution of whole bacterium colonies in 2mL sterile saline, bacterium colony eluent OD is measured600.Fig. 2 result is aobvious
Show, compared with blank control group, helicobacter pylori international standard strains A TCC43504 is trained in the solid containing 0.1% hydrogen peroxide
Growth restriction in base is supported, the growth inhibition in the solid medium containing 0.2% hydrogen peroxide, in consolidating containing 0.8% hydrogen peroxide
Growth significantly inhibits in body culture medium.With the increase of concentration of hydrogen peroxide in solid medium, reference culture increment is significant
It reduces.
(3) measurement of hydrogen peroxide minimum bactericidal concentration
Helicobacter pylori border reference culture ATCC43504 is made for 1.0 × 108CFU/mL bacteria suspension, while preparing and containing
The helicobacter pylori of the helicobacter pylori fluid nutrient medium (concentration be higher than minimal inhibitory concentration) of concentration gradient hydrogen peroxide, blank
Solid medium.0.12mL bacteria suspension is added to the fluid nutrient medium of 11.88mL hydrogen peroxide containing concentration gradient, is placed in 37 DEG C
Isothermal vibration incubator is cultivated 3 days under micro- aerobic environment with 150r/min.The bacteria suspension that 0.1mL is cultivated 3 days is drawn, respectively
Blank solid medium is added, aseptic inoculation ring is smeared uniform.37 DEG C of constant incubators are placed in, are cultivated under micro- aerobic environment
After 5 days, the growing state of observation caliber bacterial strain.Table 1 the results show that helicobacter pylori international standard strains A TCC43504 through containing
After the fluid nutrient medium culture of 2.28% hydrogen peroxide, transferred species to blank helicobacter pylori solid medium, sterile length of being born.
Minimum bactericidal concentration of 1 hydrogen peroxide of table to helicobacter pylori ATCC43504
Experiment 2: effect of the hydrogen peroxide to helicobacter pylori wild-type strain
(1) minimal inhibitory concentration of Liquid Culture based assays hydrogen peroxide
Helicobacter pylori wild-type strain-I, II, III is prepared respectively becomes 1.0 × 108CFU/mL bacteria suspension, matches simultaneously
Make the helicobacter pylori fluid nutrient medium of the hydrogen peroxide containing concentration gradient.Tri- kinds of bacteria suspensions of 0.12mL are drawn respectively to be added
The helicobacter pylori fluid nutrient medium of 11.88mL hydrogen peroxide containing concentration gradient makes entire fluid nutrient medium volume 12mL (bacterium
Liquid: culture medium=1:100).37 DEG C of isothermal vibration incubators are placed in, are cultivated 5 days under micro- aerobic environment with 150r/min, are seen
Growth of H. pylori situation is examined, entire fluid nutrient medium OD is measured600And draw growth curve.
Helicobacter pylori wild-type strain-I, II, III is prepared respectively becomes 1.0 × 106、107、108、109CFU/mL bacterium
Suspension draws 0.12mL respectively and is inoculated in the helicobacter pylori Liquid Culture containing 0.04%, 0.08%, 0.04% hydrogen peroxide
Base makes culture volume 12mL (bacterium solution: culture medium=1:100).37 DEG C of isothermal vibration incubators are placed in, with 150r/min
It is cultivated 5 days under micro- aerobic environment, observes growth of H. pylori situation, measure entire fluid nutrient medium OD600And draw growth
Curve.
A, B, C in Fig. 3 are the results show that the minimal inhibitory concentration of helicobacter pylori wild-type strain I, II, III is respectively
0.08%, 0.16%, 0.05%.D, E, F in Fig. 3 are the results show that be respectively 10 by concentration6、107、108、109CFU/mL's is deep and remote
Helicobacter pylori wild-type strain I, II, III is inoculated in the fluid nutrient medium containing 0.04%, 0.08%, 0.04% hydrogen peroxide respectively
When, there is difference, inoculum density highest 10 in the growth curve of each group bacterial strain9CFU/mL group is first grown, and then substantially 108、
107、106CFU/mL group.
(2) minimal inhibitory concentration of solid culture based assays hydrogen peroxide
Helicobacter pylori wild-type strain-I, II, III is prepared respectively becomes 1.0 × 108CFU/mL bacteria suspension, is poured respectively
Build the helicobacter pylori solid medium of hydrogen peroxide containing concentration gradient, bismuth agent.It draws 0.1mL bacteria suspension and is added and contain concentration gradient
The helicobacter pylori solid medium of hydrogen peroxide, aseptic inoculation ring are smeared uniform.37 DEG C of constant incubators are placed in, in micro- need
After cultivating 5 days under oxygen environment, by the elution of whole bacterium colonies in 2mL sterile saline, bacterium colony eluent OD is measured600.Fig. 4 knot
Fruit shows, compared with blank control group, helicobacter pylori wild-type strain-I, II, III is containing 1.6%, 0.8%, 0.2% peroxide
Change growth restriction in the solid medium of hydrogen, growth is aobvious in the solid medium containing 3.2%, 1.6%, 0.4% hydrogen peroxide
It writes and inhibits.With the increase of concentration of hydrogen peroxide in solid medium, three kinds of wild-type strain increments are significantly reduced.
(3) measurement of hydrogen peroxide minimum bactericidal concentration
Helicobacter pylori wild-type strain-I, II, III is made for 1.0 × 108CFU/mL bacteria suspension, while preparing containing dense
Helicobacter pylori fluid nutrient medium (concentration is higher than minimal inhibitory concentration), the helicobacter pylori of blank for spending gradient hydrogen peroxide are solid
Body culture medium.0.12mL bacteria suspension is added to the fluid nutrient medium of 11.88mL hydrogen peroxide containing concentration gradient, is placed in 37 DEG C of perseverances
Warm concussion and cultivate case is cultivated 3 days under micro- aerobic environment with 150r/min.Draw 0.1mL and cultivate 3 days bacteria suspensions, respectively plus
Enter blank solid medium, aseptic inoculation ring is smeared uniform.37 DEG C of constant incubators are placed in, cultivate 5 under micro- aerobic environment
After it, the growing state of three kinds of wild-type strains is observed.Table 2 is the results show that-I, II, III point of helicobacter pylori wild-type strain
Not after the fluid nutrient medium culture containing 0.24%, 0.32%, 0.32% hydrogen peroxide, transferred species is solid to blank helicobacter pylori
Body culture medium, sterile length of being born.
Minimum bactericidal concentration of 2 hydrogen peroxide of table to 3 kinds of helicobacter pylori wild-type strains
| Bacterial strain | The minimum bactericidal concentration (%) of hydrogen peroxide |
| Bacterial strain I | 0.24 |
| Bacterial strain II | 0.32 |
| Bacterial strain III | 0.32 |
Experiment 3: the minimal inhibitory concentration variation of helicobacter pylori international standard bacterial strain under hydrogen peroxide screening pressure
It is above-mentioned it is experimentally confirmed that hydrogen peroxide is 0.21% to the minimal inhibitory concentration of helicobacter pylori international standard bacterial strain,
To make the continued growth under hydrogen peroxide screening pressure of helicobacter pylori international standard bacterial strain, choose lower than minimal inhibitory concentration
Induced concentration of the concentration of hydrogen peroxide 0.20% as helicobacter pylori international standard bacterial strain.It prepares containing 0.20% hydrogen peroxide
Helicobacter pylori fluid nutrient medium 50mL draws 3.6mL culture respectively and is based on 50mL sterile test tube, and every pipe equivalent addition 1 ×
108CFU/mL helicobacter pylori international standard strains A TCC43504 bacterium solution 0.4mL, repeats 5 pipes, and every pipe is placed in isothermal vibration
Incubator is cultivated under the conditions of 37 DEG C, 150r/min and is denoted as within 24 hours induction 1 time, when inducing 10,20,30 times respectively, measurement
The MIC of helicobacter pylori international standard bacterial strain after hydrogen peroxide-induced10、MIC20、MIC30.Table 3 is the results show that 0.20% peroxide
After changing hydrogen induction 10,20,30 generation of helicobacter pylori international standard bacterial strain, minimal inhibitory concentration is respectively 0.25%, 0.29%,
0.37%.
Minimal inhibitory concentration (MIC) variation of helicobacter pylori ATCC 43504 under 3 hydrogen peroxide screening pressure of table
| It induces number (secondary) | MIC (%) |
| 0 | 0.21 |
| 10 | 0.25 |
| 20 | 0.29 |
| 30 | 0.37 |
Experiment 4: the minimal inhibitory concentration variation of helicobacter pylori wild-type strain under hydrogen peroxide screening pressure
It is above-mentioned it is experimentally confirmed that hydrogen peroxide distinguishes the minimal inhibitory concentration of helicobacter pylori wild-type strain-I, II, III
Are as follows: 0.08%, 0.16%, 0.05%, to make three kinds of wild-type strain continued growths under hydrogen peroxide screening pressure, therefore select
Take the concentration of hydrogen peroxide of slightly less than minimal inhibitory concentration: 0.04%, 0.08%, 0.04% is wild respectively as helicobacter pylori
The induced concentration of type bacterial strain-I, II, III.Table 4 the results show that hydrogen peroxide induce respectively helicobacter pylori wild-type strain-I,
II, after III 10,20,30 generations of growth, it is 0.08% that the minimal inhibitory concentration of helicobacter pylori wild-type strain-I is unchanged；
The minimal inhibitory concentration of helicobacter pylori wild-type strain-II increases to 0.40%；Helicobacter pylori wild-type strain-III is most
Small Mlc increases to 0.30%.
The minimal inhibitory concentration (MIC) of helicobacter pylori wild-type strain-I, II, III under 4 hydrogen peroxide screening pressure of table
Variation
Experiment 5: the scavenging effect that hydrogen peroxide is colonized gerbil jird and mouse helicobacter pylori
1. gerbil jird takes 4 week old mongolian gerbil 80, weight 40-50g, adaptive feeding 1 week.The helicobacter pylori world is marked
Quasi- strains A TCC43504 is made for 1.0 × 108CFU/mL bacteria suspension, 15mL/kg stomach-filling, one time a day, continuous 2 weeks.Confirmation is deep and remote
Mongolian gerbil is grouped by Helicobacter pylori model after succeeding: 1. blank control group, 2. model group, 3.~it is 5. respectively hydrogen peroxide
0.1%, 0.2%, 0.4% group, 6. Lizhuwei Sanlian group (Bismuth Potassium Citrate, metronidazole, clarithromycin), 7. Bismuth Potassium Citrate
Group.Each group carries out gastric infusion with 15mL/kg and puts to death after continuous 2 weeks one time a day, carries out Giemsa staining, counts under microscope
Number helicobacter pylori number.For Fig. 5 the results show that compared with blank control group, it is obvious that model group gerbil jird infects helicobacter pylori；It crosses
Compared with blank control group, the two is better than 0.2% without significant difference, 0.4% hydrogen peroxide group bactericidal effect for hydrogen oxide treatment group
Hydrogen peroxide group, while hydrogen peroxide group bactericidal effect is better than three medicine groups.
2. mouse chooses 6-8 week old kunming mice 81, weight 15-22g, adaptive feeding 1 week.By helicobacter pylori state
Border reference culture ATCC43504 is made for 1.0 × 108CFU/mL bacteria suspension carries out stomach-filling with 20mL/kg, one time a day, continuously
10 days.Kunming mice is grouped by confirmation helicobacter pylori model after succeeding: 1. blank control group, 2. model group, 3. hydrogen peroxide
Group, 4. Lizhuwei Sanlian group (Bismuth Potassium Citrate, metronidazole, clarithromycin).Each group gastric infusion, 20mL/kg, one time a day, even
It is 14 days continuous.4th, 7, the 14 dead one third animals in natural gift other places carry out Giemsa staining, count helicobacter pylorus bacterium number under microscope
Mesh.
Fig. 6 A is the results show that helicobacter pylori number is significantly higher than blank control group, explanation in model group kunming mice stomach
Modeling success；Helicobacter pylori number and blank control group indifference in stomach after hydrogen peroxide group kunming mice is treated 4 days；Three
Helicobacter pylori number is still higher than blank control group in medicine group kunming mice stomach, and three drug bactericidal effects are weaker than hydrogen peroxide
Group.For Fig. 6 B the results show that by 7 days drug treatments, the bactericidal effect of hydrogen peroxide group is better than three medicine groups.Fig. 6 C result is aobvious
Show, by 14 days drug treatments, the bactericidal effect of hydrogen peroxide group was substantially better than three medicine groups.
Experiment 6: kunming mice helicobacter pylori is recurred after removing
Choose 6-8 week old kunming mice 105, weight 15-22g, adaptive feeding 1 week.The helicobacter pylori world is marked
Quasi- strains A TCC43504 is made for 1.0 × 108CFU/mL bacteria suspension, with 20mL/kg stomach-filling, one time a day, continuous 10 days.Confirmation
Kunming mice is grouped after the success of helicobacter pylori model: 1. blank control group, 2. model group, 3. hydrogen peroxide group, 4. three
Medicine group.Each group gastric infusion, 20mL/kg, one time a day, continuous 10 days.Each one third of putting to death is moved within gastric infusion the 5th, 10 day
Object detects helicobacter pylori respectively.After remaining animal normal feeding is not administered 14 days, whether observation helicobacter pylori recurs sense
Dye.
Dosage foundation: Bismuth Potassium Citrate, metronidazole and clarithromycin clinic consumption per day be respectively as follows: 440,1000,
500mg.Human body presses 60kg calculating again, and the dosage of above-mentioned three kinds of drugs is respectively as follows: 7.3,16.7,8.3mg/kg.Kunming is small
Mouse dosage by 9 times of people's dosage calculating, the dosage of Bismuth Potassium Citrate, metronidazole and clarithromycin is respectively as follows: 65,150,
75mg/kg。
5 helicobacter pylori infections model kunming mice dosage regimen of table
Fig. 7 A illustrates modeling the results show that helicobacter pylori number is significantly higher than blank control group in model group Mouse Stomach
Success；Hydrogen peroxide group mouse treat 5 days after in stomach helicobacter pylori number and blank control group without difference；And three
Helicobacter pylori number is still higher than blank control group in medicine group kunming mice stomach, and three drug bactericidal effects are weaker than hydrogen peroxide
Group.Fig. 7 B is the results show that by 10 days drug treatments, hydrogen peroxide group and blank control group helicobacter pylori number indifference,
And three medicine groups are compared with blank control group, there are still helicobacter pylori infections, the bactericidal effect of hydrogen peroxide group is better than three
Join medicine group.Fig. 7 C after administration the results show that observe 14 days, three medicine groups are compared with blank control group, helicobacter pylorus
Bacterium number mesh significantly increases, and hydrogen peroxide group helicobacter pylori number and blank control group indifference, illustrates that hydrogen peroxide group is deep and remote
Helicobacter pylori is substantially without recurrence, the three significant recurrent infections of medicine group helicobacter pylori.
Experiment 7: the preparation of hydrogen peroxide peroral dosage form
Oral solution, pulvis, tablet, capsule is made in hydrogen peroxide by the present invention, and hydrogen peroxide mass concentration is
0.2%-1%, preferably 0.4%.
The oral solution includes following raw material: pure water, 30% hydrogenperoxide steam generator (medicinal), xylitol, citric acid.
(1) 30% hydrogenperoxide steam generator 13.3mL is measured according to above-mentioned formula, weighs xylitol 200g, citric acid 3g is standby
With；
(2) add dissolved in purified water to 1L, 0.4% hydrogenperoxide steam generator of gained and xylose above-mentioned 30% hydrogenperoxide steam generator
Alcohol, citric acid are added into blend tank together, are thoroughly mixed uniformly by blender；
(3) through in filtering, sterilization, the filling bottle to 50mL and automatic sealing, most afterwards through labelling vanning to get finished product mouth
Take liquid.
It is identical as above-mentioned oral liquor, the amount of 30% hydrogenperoxide steam generator is only changed to 6.5mL, makes gained mouth
Taking concentration of hydrogen peroxide in liquid is 0.2%.
The pulvis includes following raw material: starch, solid hydrogen peroxide (2Na2CO3·3H2O2), anhydrous citric acid.
(1) starch 4g, solid hydrogen peroxide (2Na are weighed according to above-mentioned formula2CO3·3H2O2) 0.06g, anhydrous citric acid
0.9g, it is spare；
(2) above-mentioned raw materials are mixed, is crushed to 200 mesh
(3) packaging into the bag of 5g and seals, labels to get finished product pulvis after sterilizing.
It is identical as above-mentioned pulvis preparation method, the amount of solid hydrogen peroxide is only changed to 0.15g, makes mistake in gained pulvis
Hydrogen peroxide concentration is 1%.
The tablet includes following raw material: lactose, sodium bicarbonate, magnesium stearate, solid hydrogen peroxide (2Na2CO3·
3H2O2), citric acid.
(1) lactose 73.8g, sodium bicarbonate 18g, magnesium stearate 5g, solid hydrogen peroxide are weighed according to above-mentioned formula
(2Na2CO3·3H2O2) 1.2g, citric acid 2g, it is spare；
(2) above-mentioned raw materials are mixed, is crushed to 100 mesh, mixed, sterilization；
The granulation of (3) 20 meshes, stiffened fatty acid magnesium, tabletting are made 100, and film coating gets product tablet.
The capsule includes following raw material: starch, solid hydrogen peroxide (2Na2CO3·3H2O2), anhydrous citric acid.
(1) starch 96g, solid hydrogen peroxide (2Na are weighed according to above-mentioned formula2CO3·3H2O2) 1.2g, anhydrous citric acid
2.8g, it is spare；
(2) above-mentioned raw materials are mixed, is crushed to 200 mesh；
(3) the filling capsule after sterilizing, every weight 0.3g is to get finished capsule product agent.
The present invention relates to hydrogen peroxide to eradicate the new application in helicobacter pylori.The hydrogen peroxide is to helicobacter pylorus
Bacterium has good killing effect, and helicobacter pylori can especially be effectively prevent to generate drug resistance and recurrent infection.Hydrogen peroxide is to deep and remote
The minimal inhibitory concentration range of Helicobacter pylori international standard bacterial strain and clinical wildtype bacterial strain is 0.05%-0.21%.Peroxidating
After hydrogen acts on 30 generation of helicobacter pylori, minimal inhibitory concentration range is 0.08%-0.40%.Helicobacter pylori infection in mice mould
Type is after hydrogen peroxide is treated without recurrence.The new application of the hydrogen peroxide provides new choosing to eradicate anti-Heliobactorpylori drug
It selects, disease caused by treatment helicobacter pylori infections, including chronic gastritis, peptic ulcer, gastric mucosa associated lymphatic can be used
Tumor and gastric cancer.
Claims (8)
1. hydrogen peroxide is preparing the application in Helicobacter pylori eradication drug.
2. application according to claim 1, which is characterized in that the helicobacter pylori includes helicobacter pylori international standard
Bacterial strain and helicobacter pylori wild-type strain.
3. application according to claim 2, which is characterized in that the helicobacter pylori wild-type strain includes helicobacter pylorus
Bacterium wild-type strain I, helicobacter pylori wild type II and helicobacter pylori wild type III.
4. application according to claim 1, which is characterized in that the position of the helicobacter pylori infections is alimentary canal.
5. application according to claim 4, which is characterized in that the alimentary canal includes stomach and duodenum.
6. hydrogen peroxide is preparing the application in eradication therapy helicobacter pylori infections disease medicament, which is characterized in that described
Helicobacter pylori infections disease includes chronic gastritis, peptic ulcer, gastric lymphoma of mucosa-associated lymphoid tissue and gastric cancer.
7. a kind of drug of eradication therapy helicobacter pylori infections, which is characterized in that by hydrogen peroxide be made oral solution, tablet,
Capsule, pulvis or granule obtain.
8. the drug of eradication therapy helicobacter pylori infections according to claim 7, which is characterized in that the matter of hydrogen peroxide
Measuring concentration is 0.2%~1%.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811230316.4A CN109223825A (en) | 2018-10-22 | 2018-10-22 | Hydrogen peroxide is in the drug for preparing application and preparation in Helicobacter pylori eradication drug |
| PCT/CN2019/098129 WO2020082840A1 (en) | 2018-10-22 | 2019-07-29 | Use of hydrogen peroxide in preparation of drugs for eradication of helicobacter pylori infection and prepared drugs |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811230316.4A CN109223825A (en) | 2018-10-22 | 2018-10-22 | Hydrogen peroxide is in the drug for preparing application and preparation in Helicobacter pylori eradication drug |
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| Publication Number | Publication Date |
|---|---|
| CN109223825A true CN109223825A (en) | 2019-01-18 |
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| WO (1) | WO2020082840A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020082840A1 (en) * | 2018-10-22 | 2020-04-30 | 西安交通大学 | Use of hydrogen peroxide in preparation of drugs for eradication of helicobacter pylori infection and prepared drugs |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107519201A (en) * | 2017-07-08 | 2017-12-29 | 陈加良 | Three hydrogen peroxide, glacial acetic acid, hypochlorous acid chemical synthesis strong oxidizers |
| CN109223825A (en) * | 2018-10-22 | 2019-01-18 | 西安交通大学 | Hydrogen peroxide is in the drug for preparing application and preparation in Helicobacter pylori eradication drug |
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2018
- 2018-10-22 CN CN201811230316.4A patent/CN109223825A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2020082840A1 (en) * | 2018-10-22 | 2020-04-30 | 西安交通大学 | Use of hydrogen peroxide in preparation of drugs for eradication of helicobacter pylori infection and prepared drugs |
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| WO2020082840A1 (en) | 2020-04-30 |
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Application publication date: 20190118 |