CN102120030A - Medicament of ilaprazole chemical structure and application thereof - Google Patents
Medicament of ilaprazole chemical structure and application thereof Download PDFInfo
- Publication number
- CN102120030A CN102120030A CN 201010001215 CN201010001215A CN102120030A CN 102120030 A CN102120030 A CN 102120030A CN 201010001215 CN201010001215 CN 201010001215 CN 201010001215 A CN201010001215 A CN 201010001215A CN 102120030 A CN102120030 A CN 102120030A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- ilaprazole
- salt
- described pharmaceutical
- antibiotic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a medicament of an ilaprazole chemical structure and application thereof. The medicament comprises the following components in parts by weight: 200 parts of ilaprazole or pharmaceutically acceptable salts and hydrates thereof, 0.5-2 parts of nitromidazoles antibiotics and 1-5 parts of quinolones antibiotics. The inhibition activity of the medicament composition is at least 3-4 times higher than the activities of the omeprazole and the antibiotic medicaments or the combined activity of ilaprazole, amoxicillin and clarithromycin, the medicament can be used for more effectively inhibiting or killing helicobacter pylori and treating duodenal ulcer, gastric ulcer and/or chronic gastritis.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that is used to suppress or kill helicobacter pylori, be specifically related to a kind of medical composition and its use that comprises ilaprazole.
Background technology
Helicobacter pylori (Hp) is the important virulence factor of chronic gastritis and peptic ulcer, and Hp also takes place relevant with gastric cancer.Epidemiological study shows that Hp infects increases the danger that gastric cancer takes place; Eradicate Hp and can block or delay further developing of gastric mucosa atrophy and intestinalization, but whether can reverse the further research of still needing of these two kinds of pathological changes; Eradicate Hp and can reduce early gastric cancer post operative recurrence rate; Simple Hp infects and can induce gastric cancer in mongolian gerbils; The Hp that carries some virulence gene may have closer relation with gastric cancer, but does not still have clear conclusions at present.Gastric cancer be coefficient results such as Hp infection, host and environmental factors, gene pleiomorphism such as host's interleukin-1 ' beta ' is relevant with the danger that metainfective gastric acid state of Hp and gastric cancer take place.
Summary of the invention
Therefore, the purpose of this invention is to provide a kind of pharmaceutical composition that is used to suppress or kill helicobacter pylori.
Another object of the present invention provides the purposes of aforementioned pharmaceutical compositions.
The objective of the invention is to realize by the following technical solutions.
On the one hand, the invention provides a kind of pharmaceutical composition that is used to suppress or kill helicobacter pylori, wherein calculate by weight, this pharmaceutical composition comprises:
200 parts of ilaprazoles or its pharmaceutically acceptable salt, hydrate;
0.5～2 parts of nitro glyoxaline antibiotic; With
1～5 part of quinolone antibiotic.
In aforementioned pharmaceutical compositions, the pharmaceutically acceptable salt of ilaprazole can be selected from one or more in sodium salt, potassium salt, calcium salt, magnesium salt and the zinc salt of ilaprazole; The hydrate of ilaprazole can be selected from one or more in semihydrate, monohydrate, dihydrate, trihydrate and the tetrahydrate of ilaprazole.
In aforementioned pharmaceutical compositions, the nitro glyoxaline antibiotic can be selected from one or more in metronidazole, tinidazole, ornidazole and the secnidazole, is preferably metronidazole.
In aforementioned pharmaceutical compositions, quinolone antibiotic can be selected from the husky star of levofloxacin, ofloxacin, Moxifloxacin, Gemifloxacin, lomefloxacin, tosufloxacin, temafloxacin, rufloxacin, fleroxacin, Sparfloxacin, sodium Burmannia coelestis D. Don. star, grepafloxacin, curve, alafloxacin, balofloxacin, Pazufloxacin, clinafloxacin, lattice in husky star and the prulifloxacin one or more, is preferably levofloxacin.
Aforementioned pharmaceutical compositions can also comprise beta-lactam antibiotic, for example amoxicillin.
Aforementioned pharmaceutical compositions can also comprise macrolide antibiotics, for example clarithromycin.
Aforementioned pharmaceutical compositions also comprises pharmaceutically acceptable carrier and/or excipient.
On the other hand, the invention provides the purposes of aforementioned pharmaceutical compositions in the medicine of preparation treatment duodenal ulcer, gastric ulcer and/or chronic gastritis.
Bacteriostatic experiment proves that the independent medication of ilaprazole has demonstrated the remarkable vitro inhibition activity to the growth of helicobacter pylori clinical separation strain.Ilaprazole is 12.5-6.25 μ g/ml to the minimum inhibitory concentration (MIC) of the bacterial strain type (American type culture collection ATCC or the typical culture presevation NCTC of institute of Britain country) of strain of helicobacter pylori clinical isolates and preservation, is lower than omeprazole.The present invention finds that further ilaprazole is with other antibiont medicine three coupling medicines the time, can suppress 50% clinical isolates strain, at least than omeprazole and these antibiotic medicines, perhaps the active high 3-4 of ilaprazole, amoxicillin and clarithromycin coupling doubly comprising the inhibition activity of the pharmaceutical composition of ilaprazole, nitroimidazoles medicine (as metronidazole) quinolones (levofloxacin).
In addition, pharmacokinetic shows, the multiple dose ilaprazole group that the infiltration rate of three coupling medicine group ilaprazoles and degree all are lower than non-coupling scheme, and peak concentration decline 29.4%, area under curve dwindle 8.2%, and relative bioavailability is 91.7%; The infiltration rate of metabolite ilaprazole sulfone and degree all are lower than the multiple dose ilaprazole group of non-coupling scheme; And the infiltration rate of metabolite ilaprazole thioether and degree all are higher than non-coupling scheme multiple dose ilaprazole group; The infiltration rate of three coupling medicine metronidazole groups is higher than non-coupling scheme multiple dose metronidazole group, and peak concentration raises 24.37%, but area under curve do not become, and relative bioavailability is 104%.
The specific embodiment
Followingly the present invention is described with reference to specific embodiment.It will be appreciated by those skilled in the art that these embodiment only are used to illustrate the present invention, the scope that it does not limit the present invention in any way.
Embodiment 1: comprise the research of the pharmaceutical composition anti-helicobactor pylori activity of ilaprazole
Present embodiment is investigated and is comprised the inhibitory action of the pharmaceutical composition of ilaprazole to the strain of helicobacter pylori clinical isolates.Adopt agar dilution to measure the bigeminy medication, i.e. the pharmaceutical composition of pharmaceutical composition of ilaprazole and levofloxacin, and ilaprazole and metronidazole is to the minimum inhibitory concentration (MICs) of clinical isolating helicobacter pylorus bacteria strain.
With sterilized water with 2 times of ilaprazole and antibiotic (levofloxacin or metronidazole) serial dilutions, concrete concentration is as follows: levofloxacin is 1.57-0.05 μ g/ml, metronidazole is 0.4-0.013 μ g/ml, and ilaprazole (IY) and omeprazole (OMP) are 12.5-1.57 μ g/ml.The grouping situation of bigeminy medication and the minimum inhibitory concentration of anti-helicobacter pylori the results are shown in Table 1.
The minimum inhibitory concentration result (μ g/ml) of table 1 bigeminy medication anti-helicobacter pylori
As shown in Table 1, ilaprazole+levofloxacin can suppress 62.5% clinical isolates strain when Cmin.Although do not suppress all clinical isolates strains when Cmin, ilaprazole+levofloxacin group demonstrates activity than omeprazole+the levofloxacin group is stronger to #81, #152, #179 bacterial strain.
Embodiment 2: comprise the research of the pharmaceutical composition anti-helicobactor pylori activity of ilaprazole
Present embodiment is investigated and is comprised the inhibitory action of the pharmaceutical composition of ilaprazole to the strain of helicobacter pylori clinical isolates.Adopt agar dilution to measure three coupling medicines, promptly the pharmaceutical composition of ilaprazole, levofloxacin and metronidazole is to the minimum inhibitory concentration (MICs) of clinical isolating helicobacter pylorus bacteria strain.
Three coupling medicines are divided into following 4 groups: ilaprazole (IY) 1.57 μ g/ml+ metronidazole+levofloxacin; Ilaprazole (IY) 1.57 μ g/ml+ metronidazole+Gemifloxacins; Omeprazole (OMP) 1.57 μ g/ml+ metronidazole+levofloxacin; The minimum inhibitory concentration of ilaprazole (IY) 1.57 μ g/ml+ amoxicillin+clarithromycins three coupling medicine anti-helicobacter pyloris the results are shown in Table 2.
The minimum inhibitory concentration result (μ g/ml) of table 2 three coupling medicine anti-helicobacter pyloris
As shown in Table 2, the bacteriostatic activity of omeprazole+metronidazole+levofloxacin group is obviously not as remaining ilaprazole group.There are 6 strain clinical isolates strains on all flat boards of ilaprazole+metronidazole+levofloxacin group and ilaprazole+metronidazole+Gemifloxacin group, all not grow.Although the activity of ilaprazole+amoxicillin+clarithromycin group is similar to ilaprazole+metronidazole+levofloxacin group and ilaprazole+metronidazole+Gemifloxacin group, but on the whole, ilaprazole+metronidazole+levofloxacin group and ilaprazole+metronidazole+Gemifloxacin group is better than ilaprazole+amoxicillin+clarithromycin group to the inhibition activity of isolated strains.
Embodiment 3: preparation of drug combination method of the present invention
The preparation of drug combination method of present embodiment may further comprise the steps:
1) gets material by following parts by weight proportioning: 1 part of ilaprazole, 100 parts of metronidazoles, 200 parts of levofloxacin, microcrystalline Cellulose 10-75 part, mannitol 5-50 part, hydroxypropyl emthylcellulose 0.2-30 part, polyvinylpolypyrrolidone 1-30 part, magnesium stearate 0.1-5.0 part; 2) ilaprazole, metronidazole and levofloxacin are crossed 60-100 order nylon mesh at lucifuge, ambient humidity under less than the condition of 50%RH, microcrystalline Cellulose and polyvinylpolypyrrolidone are crossed 60-100 order nylon mesh respectively, mannitol is pulverized the back cross 80-120 order (being preferably 100 orders) nylon mesh sieve;
3) be that the medicinal alcohol of 50-95% is mixed with the binding agent that viscosity is the 5-35 centipoise with hydroxypropyl emthylcellulose with concentration expressed in percentage by volume, and stir and make it abundant swelling;
4) with step 2) ilaprazole, metronidazole, levofloxacin, the microcrystalline Cellulose that sieve and partly measure polyvinylpolypyrrolidone and fully mix;
5) the mixture vacuum that step 4) is obtained sucks in the fluid bed, starts fluidisation operating system, makes it abundant mixing;
6) granulate on hydroxypropyl emthylcellulose alcoholic solution atomizing that step 3) is obtained and the mixture that is sprayed on the step 5) acquisition equably;
7) mixture that step 6) is obtained is partly measured polyvinylpolypyrrolidone and magnesium stearate mixing with residue, obtains pharmaceutical composition provided by the present invention.
Embodiment 4: preparation of drug combination method of the present invention
The preparation of drug combination method of present embodiment may further comprise the steps:
1) gets material by following parts by weight proportioning: 1 part of ilaprazole, 100 parts of metronidazoles, 100 parts of levofloxacin, microcrystalline Cellulose 10-75 part, mannitol 5-50 part, hydroxypropyl emthylcellulose 0.2-30 part, polyvinylpolypyrrolidone 1-30 part, magnesium stearate 0.1-5.0 part; 2) ilaprazole, metronidazole and levofloxacin are crossed 60-100 order nylon mesh at lucifuge, ambient humidity under less than the 50%RH condition, microcrystalline Cellulose and polyvinylpolypyrrolidone are crossed 60-100 order nylon mesh respectively, mannitol is pulverized the back cross 80-120 order (being preferably 100 orders) nylon mesh sieve;
3) be that the medicinal alcohol of 50-95% is mixed with the binding agent that viscosity is the 5-35 centipoise with hydroxypropyl emthylcellulose with concentration expressed in percentage by volume, and stir and make it abundant swelling;
4) with step 2) ilaprazole, metronidazole, levofloxacin, the microcrystalline Cellulose that sieve and partly measure polyvinylpolypyrrolidone and fully mix;
5) the mixture vacuum that step 4) is obtained sucks in the fluid bed, starts fluidisation operating system, makes it abundant mixing;
6) granulate on hydroxypropyl emthylcellulose alcoholic solution atomizing that step 3) is obtained and the mixture that is sprayed on the step 5) acquisition equably;
7) mixture that step 6) is obtained is partly measured polyvinylpolypyrrolidone and magnesium stearate mixing with residue, obtains pharmaceutical composition provided by the present invention.
Claims (8)
1. a pharmaceutical composition that is used to suppress or kill helicobacter pylori wherein calculates by weight, and this pharmaceutical composition comprises:
200 parts of ilaprazoles or its pharmaceutically acceptable salt, hydrate;
0.5～2 parts of nitro glyoxaline antibiotic; With
1～5 part of quinolone antibiotic.
2. pharmaceutical composition according to claim 1 is characterized in that, the pharmaceutically acceptable salt of described ilaprazole is selected from one or more in the sodium salt of ilaprazole, potassium salt, calcium salt, magnesium salt and the zinc salt; The hydrate of described ilaprazole is selected from one or more in semihydrate, monohydrate, dihydrate, trihydrate and the tetrahydrate of ilaprazole.
3. pharmaceutical composition according to claim 1 and 2 is characterized in that, described nitro glyoxaline antibiotic is selected from one or more in metronidazole, tinidazole, ornidazole and the secnidazole, is preferably metronidazole.
4. according to each described pharmaceutical composition in the claim 1 to 3, it is characterized in that, described quinolone antibiotic is selected from the husky star of levofloxacin, ofloxacin, Moxifloxacin, Gemifloxacin, lomefloxacin, tosufloxacin, temafloxacin, rufloxacin, fleroxacin, Sparfloxacin, sodium Burmannia coelestis D. Don. star, grepafloxacin, curve, alafloxacin, balofloxacin, Pazufloxacin, clinafloxacin, lattice in husky star and the prulifloxacin one or more, is preferably levofloxacin.
5. according to each described pharmaceutical composition in the claim 1 to 4, it is characterized in that described pharmaceutical composition also comprises beta-lactam antibiotic, for example amoxicillin.
6. according to each described pharmaceutical composition in the claim 1 to 5, it is characterized in that described pharmaceutical composition also comprises macrolide antibiotics, for example clarithromycin.
7. according to each described pharmaceutical composition in the claim 1 to 6, it is characterized in that described pharmaceutical composition also comprises pharmaceutically acceptable carrier and/or excipient.
8. according to the purposes of each described pharmaceutical composition in the claim 1 to 7 in the medicine of preparation treatment duodenal ulcer, gastric ulcer and/or chronic gastritis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010001215 CN102120030B (en) | 2010-01-08 | 2010-01-08 | Medicament of ilaprazole chemical structure and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010001215 CN102120030B (en) | 2010-01-08 | 2010-01-08 | Medicament of ilaprazole chemical structure and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102120030A true CN102120030A (en) | 2011-07-13 |
| CN102120030B CN102120030B (en) | 2013-07-10 |
Family
ID=44248758
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010001215 Active CN102120030B (en) | 2010-01-08 | 2010-01-08 | Medicament of ilaprazole chemical structure and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102120030B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104857017A (en) * | 2015-05-14 | 2015-08-26 | 邓学峰 | Ilaprazole pharmaceutical composition |
| CN106031711A (en) * | 2015-03-18 | 2016-10-19 | 邓学峰 | Preparation method and applications of ilaprazole sodium liposome |
| CN110082487A (en) * | 2019-05-13 | 2019-08-02 | 丽珠医药集团股份有限公司 | Detection reagent, detection system and the test method for drawing azole drug intestinal absorption |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101600432A (en) * | 2006-10-27 | 2009-12-09 | 密苏里大学董事会 | Comprise the proton pump inhibitor of at least a acid labile, the compositions of optional other medicines activating agent and the method for using them |
| CA2702356C (en) * | 2007-10-12 | 2014-02-11 | Takeda Pharmaceuticals North America, Inc. | Pharmaceutical formulation comprising a proton pump inhibitor for the treatment of gastrointestinal conditions independent of food intake |
-
2010
- 2010-01-08 CN CN 201010001215 patent/CN102120030B/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106031711A (en) * | 2015-03-18 | 2016-10-19 | 邓学峰 | Preparation method and applications of ilaprazole sodium liposome |
| CN104857017A (en) * | 2015-05-14 | 2015-08-26 | 邓学峰 | Ilaprazole pharmaceutical composition |
| CN110082487A (en) * | 2019-05-13 | 2019-08-02 | 丽珠医药集团股份有限公司 | Detection reagent, detection system and the test method for drawing azole drug intestinal absorption |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102120030B (en) | 2013-07-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101645069B1 (en) | Capsule formulation of pirfenidone and pharmaceutically acceptable excipients | |
| US20100266590A1 (en) | Combination therapy | |
| CN103087042B (en) | Salts of sitafloxacin and pharmaceutical purposes thereof | |
| CN102120030B (en) | Medicament of ilaprazole chemical structure and application thereof | |
| EP2658539B1 (en) | Composition for prevention of nausea or vomiting | |
| CN101507717B (en) | Composite tablet capable of treating peptic ulcer and preparation method thereof | |
| CN101805285A (en) | Nicotinic acid-contained curcumin ester derivative and preparation method and application thereof | |
| US20080207644A1 (en) | Therapeutic materials and methods | |
| US6426369B1 (en) | Oxethazaine as antimicrobial agent | |
| CN101301280A (en) | Sustained release tablet products used as helminthic of livestock | |
| CN100425234C (en) | Pharmaceutical composition containing anti-ulcerative drug and mucosa-protecting agent for treating gastrosis | |
| CN112791087B (en) | Application of BPTES in preparation of medicine for preventing or treating anthracnose | |
| CN102579453A (en) | Compound preparation for treating gastric ulcer and preparation method of same | |
| CN101497616B (en) | Imidazopyridine compound containing aminoxy substituted pyridine | |
| CN101497623B (en) | Compound containing imidazopyridine | |
| CN103417513B (en) | Compound containing Lafutidine and preparation containing Lafutidine | |
| CN101492463B (en) | Imidazopyridine derivative containing dioxane-pyridine | |
| CN101492464B (en) | Sulfhydryl imidazopyridine derivative containing dioxepane-pyridine | |
| CN101492446A (en) | Novel pyridine-imidazole derivative | |
| CN101497604B (en) | Benzimidazole derivative containing alkoxy acetamide substituted pyridine | |
| CN101497603B (en) | Benzimidazole derivative containing alkoxy alkanamine oxyl substituted pyridine | |
| CN101492452A (en) | Sulfhydryl benzimidazole derivative containing dioxepane-pyridine | |
| JPH0920668A (en) | Antibacterial agent for helicobacter pylori as slightly aerobic gram-negative bacillus | |
| AU2013201986A1 (en) | Capsule Formulation Of Pirfenidone And Pharmaceutically Acceptable Excipients | |
| JPH03161440A (en) | Antibacterial agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |