CN105147682A - Pharmaceutical ilaprazole sodium composition for treating gastric ulcer - Google Patents
Pharmaceutical ilaprazole sodium composition for treating gastric ulcer Download PDFInfo
- Publication number
- CN105147682A CN105147682A CN201510629814.6A CN201510629814A CN105147682A CN 105147682 A CN105147682 A CN 105147682A CN 201510629814 A CN201510629814 A CN 201510629814A CN 105147682 A CN105147682 A CN 105147682A
- Authority
- CN
- China
- Prior art keywords
- ilaprazole
- sodium
- crystal
- ilaprazole sodium
- gastric ulcer
- 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.)
- Withdrawn
Links
Abstract
The invention discloses a pharmaceutical ilaprazole sodium composition for treating gastric ulcer and belongs to the technical field of medicines. The pharmaceutical ilaprazole sodium composition is prepared from ilaprazole sodium and arginine, wherein the ilaprazole sodium is a crystal, as shown in Figure 1 of an X-ray powder diffraction diagram obtained through Cu-KAlpha ray measurement. The novel crystal-form ilaprazole sodium is different from a crystal-form structure in the prior art. It is found that the novel crystal-form compound is high in purity, good in liquidity and stability, low in impurity content and is safe and reliable in clinic application and does not easily absorb moisture though test verification. The injection powder prepared by utilizing the novel crystal-form compound is high in medicinal effect and bioavailability and good in stability, has good stability after being compatible with a solvent, is very low in insoluble particle content and is very suitable for clinic application.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine ilaprazole composition of sodium for the treatment of gastric ulcer.
Background technology
Ilaprazole, have another name called IY-81149, it is the novel proton pump inhibitor of a kind of irreversible developed by foreign drugmaker of Korea S one, it suppresses helicobacter pylori (HP) effect stronger than omeprazole, effective dose is only 1/4 of omeprazole, not easily develop immunity to drugs, and toxic and side effects is not obvious; Ilaprazole is compared with original like product, causing delayed gastric emptying, parietal cell swelling and the defect significantly after drug withdrawal in gastric acid secretion bounce-back etc. overcoming original like product in varying degrees, the curative effect to dyskinesis sample functional dyspepsia (GERD) and other acid-related diseases can be strengthened simultaneously, and onset is faster, acid suppression better effects if, t1/2 is longer, can continue acid suppression and control night time acid breakthrough; The dependency of its metabolism to CYP2C19 is little, affects little by enzyme gene pleiomorphism.Long half time, whole day maintains higher acid suppression level, and the time of stomach pH>4 obviously extends, and effectively reduces the phenomenon of Control of Nocturnal Gastric Acid Breakthrough; Curative effect is not by the medicine that hepatocyte inner cell pigment isozyme CYP2C19 metabolic polymorphism affects, and individual variation is little; It is that treatment comprises taste-blindness rate, and reflux esophagitis and Zollinger-Ellisonsyndrome syndrome are at interior potent drug for the treatment of with gastric acid-related diseases.
The novel potent proton pump of ilaprazole Shi Li pearl group first listing of the whole world in 2007 suppresses enteric coatel tablets, is applicable to duodenal ulcer and reflux esophagitis.Its acid suppression activity is more than 4 times of omeprazole, and the day dosing of omeprazole enteric-coated preparation is 40mg, and ilaprazole then only needs 5-10mg; Long half time, long action time in body, without CYP2C19 metabolism, also seldom by CYP3A4 enzymes metabolism, to different genotype patient without individual variation; Less adverse effect.For adapting to the patient of digestive tract hemorrhage, playing the feature that ilaprazole Acidinhibitor is strong, making gastric pH reach more than 6 rapidly, hemostatic factor quick acting.
Ilaprazole is alkalescence, and very poor at light, heat, water, oxygen, stable under acidic conditions, the approach of existing solution ilaprazole stability problem mainly comprises the crystal formation changing dosage form or change medicine.
Chinese patent CN102038648B discloses a kind of injection and preparation method for the treatment of peptic ulcer, and selected active component is Ilaprazole Sodium.Said preparation is made up of Ilaprazole Sodium, excipient, antioxidant and/or metal ion chelation agent, and wherein above-mentioned each constituent mass mark is than being ilaprazole 1 part, excipient 1-30, antioxidant 0-10 part and/or metal ion chelation agent 0-0.3 part.Effectively improve the problem of Ilaprazole Sodium stable under acidic conditions difference.But, add sodium thiosulfate in this patent of invention prescription, add the risk of medicine to blood vessel irritation.Simultaneously according to actual production, on the basis ensureing curative effect of medication, solubility and product appearance, the kind of adjuvant and consumption are more few better, are not only conducive to reducing corresponding toxic and side effects, increase Drug safety, can also save production cost.
Patent CN101687848B discloses A, B, E, F, the I crystal of ilaprazole compound.Wherein racemic ilaprazole crystal form A is that in all crystal formations, in aqueous solvent, dissolubility is minimum, but a kind of crystal formation that thermokinetics is the most stable; Other four kinds of crystal formations are derived by diverse ways by crystal form A and obtain.Crystal formation F, compared with crystal form A, is more soluble in aqueous solvent, and the biology of crystal form B and crystal formation F is acceptable poor, and it can be used to prepare depot drug product composition.Which describe the preparation method of crystal form A: 3%NH4OH/ acetonitrile (MeCN) (6.00kg, 15.0 parts) load in flask, adjust the temperature to 5 DEG C (2-8 DEG C), add ilaprazole (0.400kg), stir 1 hour, elimination filtrate, filter cake 3%NH4OH/ acetonitrile (MeCN) (2 × 0.400kg, 2 × 1.00 parts) rinsing.Filter cake load flask, add 0.5%NH4OH/EtOH (0.200kg, 0.500 part) and at 20-25 DEG C concentrating under reduced pressure, until there is no distillation.0.5%NH4OH/EtOH (1.00kg, 2.50 parts) is added again in flask, and dichloromethane (2.40kg, 6.00 parts).The solution obtained is evaporated to ca.1.2L (3.00 amount) at 20-25 DEG C.Add 0.5%NH4OH/EtOH (0.200kg, 0.500 part) again, be adjusted to 5 DEG C (2-8 DEG C), stir 45 minutes.With 0.5%NH4OH/EtOH (0.200kg, 0.500 part) after elimination filtrate, EtOH (0.200kg, 0.500 part) and MTBE (2 × 0.200kg, 2 × 0.500 parts) rinsing.Filtration cakes torrefaction 2 hours, then under maximum temperature is 53 DEG C of conditions vacuum drying 92 hours, obtain racemic ilaprazole crystal form A.
Patent CN103172618A discloses Ilaprazole crystal form X, which describe the preparation method of crystal form X: be dissolved in by ilaprazole in the mixed solvent of halogenated alkane and absolute methanol, again above-mentioned solvent is slowly added in ether solvent, stir until crystallize out, crystal Precipitation Temperature is 25 DEG C, wherein said halogenated alkane is the one in dichloromethane, chloroform, and the volume ratio of halogenated alkane and ether is 1:25-10, and the volume ratio of halogenated alkane and absolute methanol is 1:1.
Patent CN104370886A discloses Ilaprazole crystal form M, which describes the preparation method of M crystal formation: 1) be dissolved in 5-20mL chloroform by 1-2g ilaprazole; 2) by above-mentioned solution evaporated under reduced pressure below 30 DEG C, after evaporate to dryness, add 5-40mL ethyl acetate, dissolve, stir, crystallize at least 20 minutes; 3) filtered by crystal, filter cake ethyl acetate is washed, 20-35 DEG C of drying, obtains ilaprazole M crystal formation.
But it is lower still to there is drug effect in above-mentioned crystal formation, the problem of less stable etc., the present inventor starts with from the research of Ilaprazole Sodium solid chemical material existence, a kind of Ilaprazole Sodium compound crystal has been prepared through a large amount of tests, find through overtesting, this crystal compound purity is high, good fluidity, good stability, impurity content is low, not easily moisture absorption, clinical practice is safe and reliable, the injectable powder drug effect utilizing this crystal compound obtained and bioavailability high, good stability, good with solvent compatibility rear stability, particulate matter content is extremely low, be very suitable for clinical practice.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of medicine ilaprazole composition of sodium for the treatment of gastric ulcer.
In order to complete object of the present invention, the technical scheme of employing is:
Treat a medicine ilaprazole composition of sodium for gastric ulcer, consisting of of described compositions: Ilaprazole Sodium 1 weight portion, arginine 0.001-0.003 weight portion; Described Ilaprazole Sodium is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
Preferably, consisting of of described ilaprazole composition of sodium: Ilaprazole Sodium 1 weight portion, arginine 0.002 weight portion.
Preferably, the dosage form of described ilaprazole composition of sodium is injection, and the preparation method of described injection comprises the following steps:
(1) take ilaprazole sodium crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
Preferably, the preparation method of the ilaprazole sodium crystal in the present composition comprises the following steps:
The saturated butanol solution of preparation Ilaprazole Sodium crude product, then the chloroform that volume is 8 times of saturated butanol solution volume is added, after stirring, cooling limit, limit is stirred, and cooling rate is 8 DEG C/h, mixing speed is 125 revs/min, add the chloroform that volume is chloroform volume 2 times simultaneously, stop after being cooled to-5 DEG C stirring, leave standstill growing the grain 4 hours, filter, after drying under reduced pressure, obtain Ilaprazole Sodium crystalline compounds.
The polymorphism of solid chemical is the natural phenomena that a kind of general material exists, this phenomenon refers to that a kind of solid chemical can exist 2 kinds or two or more crystal form state, be also called the polymorphic state of material, the polymorphic state of material is also referred to as " allomorphism " phenomenon.Although its chemical nature of allomorphous solid matter is identical, its physicochemical property may be different.For " allomorphism medicine " that physicochemical property is different, also can show the curative effect of different disease preventing and treating clinically, directly affect application and the clinical effectiveness of medicine.
The present invention is by the precise controlling to crystallization condition, and prepared a kind of ilaprazole sodium novel crystal form unlike the prior art, the X-ray powder diffraction pattern of this ilaprazole sodium crystal unlike the prior art.Simultaneously due to the ins and outs of this crystal formation, find through test, this crystal compound purity is high, good fluidity, good stability, impurity content is low, not easily moisture absorption, clinical practice is safe and reliable, the injectable powder drug effect utilizing this crystal compound obtained and bioavailability high, good stability, good with solvent compatibility rear stability, particulate matter content is extremely low, is very suitable for clinical practice.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the ilaprazole sodium crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
Detailed description of the invention
Below by specific embodiment, summary of the invention of the present invention is described in further detail, but does not therefore limit content of the present invention.
embodiment 1:the preparation of ilaprazole sodium crystal
The saturated butanol solution of preparation Ilaprazole Sodium crude product, then the chloroform that volume is 8 times of saturated butanol solution volume is added, after stirring, cooling limit, limit is stirred, and cooling rate is 8 DEG C/h, mixing speed is 125 revs/min, add the chloroform that volume is chloroform volume 2 times simultaneously, stop after being cooled to-5 DEG C stirring, leave standstill growing the grain 4 hours, filter, after drying under reduced pressure, obtain Ilaprazole Sodium crystalline compounds.
The X-ray powder diffraction pattern that the ilaprazole sodium crystal prepared uses the measurement of Cu-K alpha ray to obtain as shown in Figure 1.
embodiment 2:the preparation of ilaprazole composition of sodium
Consist of: ilaprazole sodium crystal 1 weight portion prepared by the present invention, arginine 0.001 weight portion.
Preparation method is:
(1) take ilaprazole sodium crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 3:the preparation of ilaprazole composition of sodium
Consist of: ilaprazole sodium crystal 1 weight portion prepared by the present invention, arginine 0.002 weight portion.
Preparation method is:
(1) take ilaprazole sodium crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 4:the preparation of ilaprazole composition of sodium
Consist of: ilaprazole sodium crystal 1 weight portion prepared by the present invention, arginine 0.003 weight portion.
Preparation method is:
(1) take ilaprazole sodium crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
comparative example 1:the preparation (with reference to patent WO2011071314A2) of Ilaprazole crystal form A
10g Ilaprazole Sodium is dissolved in 200mL dehydrated alcohol, neutralizes, stirring at normal temperature 2h with the alcoholic solution containing acetic acid 10%, and filter, with the washing with alcohol filter cake of 40mL50%, 40 DEG C of dry 12h, obtain off-white color solid 8.5g, yield 85%.
comparative example 2:the preparation (with reference to patent WO2011071314A2) of Ilaprazole crystal form B
10g ilaprazole is dissolved in the methanol of 50mL and the mixed solvent of dichloromethane, slowly drips 250mL ether, stirring at normal temperature 45min, filters, filter cake washed with diethylether, and 30 DEG C are dried 12h, off-white color solid 8.5g, yield 85%.
comparative example 3:the preparation (referenced patent US20110082174) of Ilaprazole crystal form E
10g ilaprazole crystal form A is dissolved in 700mL methanol drip in the solution of a triethylamine.Solid supersound process is dissolved.Membrane filtration is in vial, and bottle covers mouth with the aluminium foil having 5 apertures and then at room temperature evaporates.Obtain dark green solid after 6 days, obtain Ilaprazole crystal form E.
comparative example 4:the preparation (referenced patent US20110082174) of Ilaprazole crystal form F
Getting 10g ilaprazole crystal form A is dissolved in 200mL dichloromethane, drips a triethylamine.Solution evaporates with under room temperature after membrane filtration with 0.2.Obtaining slight colored solid after about 1 day, is Ilaprazole crystal form F.
comparative example 5:the preparation of Ilaprazole crystal form I
Getting 10g ilaprazole crystal form A is dissolved in 200mL methanol, drips a triethylamine, freezing after membrane filtration.About 2 days final vacuum collecting by filtration white solids, this solid is Methanol Solvate.White solid is put into vial, and opening is placed in room temperature under vacuo, and obtaining white solid after about 1 day is crystalline form I.
comparative example 6:the preparation (referenced patent CN103172618A) of Ilaprazole crystal form X
At 25 DEG C, in the single port bottle of 250m1, add l0g ilaprazole, add 100m1 dichloromethane, 100m1 absolute methanol successively, agitating solution dissolves completely to ilaprazole, then is transferred in constant pressure funnel by solution.Slowly be added drop-wise in 250m1 ether by above-mentioned ilaprazole mixed solution, control temperature of reaction system in dropping process in the scope of 25 scholar 2 DEG C, time for adding controls between 25-30min.After dropwising, keep temperature 25 DEG C of agitating solutions 40 minutes crystallizes.Decompress filter, with 150mL ether washing leaching cake, dry 24 hours of ambient temperature in vacuum, obtaining off-white powder, is Ilaprazole crystal form X, and productive rate is 84%.
comparative example 7:the preparation (referenced patent CN104370886A) of Ilaprazole crystal form M
1) 1g ilaprazole is dissolved in 20mL chloroform, lucifuge rapid solution;
2) by above-mentioned solution evaporated under reduced pressure below 30 DEG C, 20mL ethyl acetate is added after evaporate to dryness, lucifuge rapid solution, lucifuge stirring and crystallizing 1h after dissolving;
3) filtered by crystal, filter cake ethyl acetate washes three times, 28 DEG C of dryings.Obtain off-white color crystalline powder 0.789g, productive rate 78.9%.
experimental example 1:stability test
The stability difference of the present invention and Ilaprazole crystal form of the prior art is described below by way of contrast experiment.
1, temperatures involved Factor Experiment
Get comparative example 1-7 (Ilaprazole crystal form A respectively, B, E, F, I.X, M) and the Ilaprazole sodium crystal form of the embodiment of the present invention 1 at temperature 60 C, place 10 days under the condition of relative humidity 75%, respectively the 0th, 5, its outward appearance, color and luster measure impurity content, the results detailed in Table 1 are observed in sampling in 10 days.
Table 1 temperatures involved Factor Experiment result
Result shows, from table 1, and ilaprazole A, B, E, F, the placement under the high temperature conditions of I, X, M crystal formation is after 10 days, from character, see ilaprazole A in appearance, B, E, F, I darken, and ilaprazole X and M does not have change substantially, Ilaprazole sodium crystal form of the present invention is compared with other Ilaprazole crystal form, and the content placing its impurity after 10 days is under the high temperature conditions starkly lower than other Ilaprazole crystal form, and stability is better.
2, high humidity influence factor experiment
Get 1g comparative example 1-7 (Ilaprazole crystal form A, B, E respectively, F, I, X, and the Ilaprazole sodium crystal form of embodiment 1 M), in the exsiccator containing saturated potassium nitrate solution, (25 DEG C, relative humidity 92.5%) are placed 10 days, respectively the 0th, 5, sampling in 10 days, observes its outward appearance, color and luster measure impurity content, the results detailed in Table 2.
Table 2 high humidity influence factor experimental result
Result shows, from table 2, and ilaprazole A, B, E, F, the placement under conditions of high humidity of I, X, M crystal formation is after 10 days, from character, see ilaprazole A in appearance, B, E, F, I darken, and ilaprazole X and M does not have change substantially, Ilaprazole sodium crystal form of the present invention is compared with other Ilaprazole crystal form, and the content placing its impurity after 10 days is under conditions of high humidity starkly lower than other Ilaprazole crystal form, and stability is better.
3, high light influence factor experiment
Get 1g comparative example 1-7 Ilaprazole crystal form A respectively, B, E, F, I, X, M) and embodiment 1 Ilaprazole sodium crystal form, place 10 days in the lighting box that illumination is the daylight lamp of (4500 scholar 500) lx, sampling in 0th, 5,10 days respectively, observe its outward appearance, color and luster measure impurity content, the results detailed in Table 3.
Table 3 high light influence factor experimental result
Result shows, from table 3, and ilaprazole A, B, E, F, the placement of I, X, M crystal formation under intense light conditions is after 10 days, from character, see ilaprazole A in appearance, B, E, F, I darken, and ilaprazole X and M does not have change substantially, Ilaprazole sodium crystal form of the present invention is compared with other Ilaprazole crystal form, and the content placing its impurity after 10 days under intense light conditions is starkly lower than other Ilaprazole crystal form, and stability is better.
experimental example 2:ilaprazole crystal form pharmacodynamic experiment
To the pharmacodynamic experiment of the mouse gastric ulcer caused by aspirin
Get male and female half and half mice 90, body weight 18-22g, be divided into 9 groups at random, group is divided into: group 1: blank group; Group 2: Ilaprazole crystal form A3mg/kg dosage group; Group 3: Ilaprazole crystal form B3mg/kg dosage group; Group 4: Ilaprazole crystal form E3mg/kg dosage group; Group 5: Ilaprazole crystal form F3mg/kg dosage group; Group 6: Ilaprazole crystal form I3mg/kg dosage group; Group 7: Ilaprazole crystal form X3mg/kg dosage group, group 8: Ilaprazole crystal form M3mg/kg dosage group, group 9: Ilaprazole sodium crystal form 3mg/kg dosage group of the present invention, after water 24h is can't help in mice fasting, group 2-6 presses the corresponding medicine of 0.2ml/10g body weight gavage respectively, and the blank group of group 1 presses the body weight gavage distilled water of 0.2ml/10g.The equal gavage aspirin 150mg/kg of each group after mice administration 30min, mice is put to death after 4h, open mouse peritoneal, ligation cardia and pylorus and inject in gastral cavity through coat of the stomach 1% formalin 2ml, stomach is taken out in immersion 1% formalin, 30min tailing edge greater gastric curvature is cut open, and a situation arises to observe stomach ulcer under anatomic microscope, calculates ulcer area and ulcer inhibition rate.Concrete outcome is as shown in table 4:
Ulcer inhibition rate account form:
Table 4 Ilaprazole crystal form is on the impact of the gastric ulcer caused by aspirin in mouse
Result shows: from table 4, and the group 9 i.e. ulcer average area of Ilaprazole sodium crystal form 3mg/kg dosage group of the present invention is 0.41mm
2, ulcer inhibition rate is 92.38%, and compared with other Ilaprazole crystal form, the ulcer area of Ilaprazole sodium crystal form of the present invention reduces obviously, and ulcer inhibition rate obviously raises.
experimental example 3:bioavailability study
This experimental example has investigated the bioavailability of ilaprazole sodium compound by pharmacokinetic.
Trial drug: commercially available Ilaprazole Sodium, ilaprazole sodium compound of the present invention are made injectable powder respectively.
Experimental animal: Beagle dog.
Dosage and mode: dosage is respectively 10mg, morning injection administration after animal fasting, each cleaning intersects administration after one week.
Sample collecting: respectively at before animals administer and administration after different time (0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,8,12h) get blood by dog forelimb, get blood at every turn and be about 2ml, add and use in the centrifuge tube of anticoagulant heparin in advance, the insulating foam box being built-in with ice bag is put at once interior standing 20 minutes after blood specimen collection, 3000rpm low-temperature centrifugation is separated plasma after 10 minutes,-40 DEG C of preservations, to be checked.
The pretreatment of sample: plasma sample thawed at room temperature, the blood plasma getting 0.2ml joins in 1.5ml centrifuge tube, then adds 100 μ L50mM ammonium formate solution, mark liquid in the omeprazole of 50mL280ng/ml, vortex mixed 30s, then the t-butyl methyl ether adding 0.6ml, vortex shakes 2 minutes, centrifugal (13,000 rev/min) after 10min, get supernatant 30 DEG C of heating in water bath N2 and volatilize, residue 200 μ l mobile phases dissolve, get 10 μ l and carry out LC/MS/MS analysis, record chromatogram.
The oral pharmacokinetic studies data of the commercially available ilaprazole of table 5
The oral medicine of table 6 ilaprazole sodium compound of the present invention is for dynamic experiment data
Pharmacokinetic results is in table 5 and table 6.From table 5 and table 6, the blood drug level of ilaprazole sodium compound of the present invention is significantly higher than the blood drug level of commercially available ilaprazole, shows that Ilaprazole Sodium crystalline compound of the present invention makes effective ingredient bioavailability in vivo be significantly improved.
Claims (4)
1. treat a medicine ilaprazole composition of sodium for gastric ulcer, it is characterized in that, consisting of of described compositions: Ilaprazole Sodium 1 weight portion, arginine 0.001-0.003 weight portion; Described Ilaprazole Sodium is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
2. the medicine ilaprazole composition of sodium for the treatment of gastric ulcer according to claim 1, is characterized in that, consisting of of described compositions: Ilaprazole Sodium 1 weight portion, arginine 0.002 weight portion.
3. the medicine ilaprazole composition of sodium for the treatment of gastric ulcer according to claim 2, is characterized in that, the dosage form of described compositions is injection, and the preparation method of described injection comprises the following steps:
(1) take ilaprazole sodium crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
4. the medicine ilaprazole composition of sodium for the treatment of gastric ulcer according to claim 1, is characterized in that, the crystal preparation method of described Ilaprazole Sodium is:
The saturated butanol solution of preparation Ilaprazole Sodium crude product, then the chloroform that volume is 8 times of saturated butanol solution volume is added, after stirring, cooling limit, limit is stirred, and cooling rate is 8 DEG C/h, mixing speed is 125 revs/min, add the chloroform that volume is chloroform volume 2 times simultaneously, stop after being cooled to-5 DEG C stirring, leave standstill growing the grain 4 hours, filter, after drying under reduced pressure, obtain Ilaprazole Sodium crystalline compounds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510629814.6A CN105147682A (en) | 2015-09-29 | 2015-09-29 | Pharmaceutical ilaprazole sodium composition for treating gastric ulcer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510629814.6A CN105147682A (en) | 2015-09-29 | 2015-09-29 | Pharmaceutical ilaprazole sodium composition for treating gastric ulcer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105147682A true CN105147682A (en) | 2015-12-16 |
Family
ID=54788967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510629814.6A Withdrawn CN105147682A (en) | 2015-09-29 | 2015-09-29 | Pharmaceutical ilaprazole sodium composition for treating gastric ulcer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105147682A (en) |
-
2015
- 2015-09-29 CN CN201510629814.6A patent/CN105147682A/en not_active Withdrawn
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105055342A (en) | Sodium ilaprazole medicine composition freeze-dried powder injection for treating peptic ulcer | |
| CN110312705B (en) | Crystal form of GFT-505, preparation method and application thereof | |
| CN102285970B (en) | Esomeprazole compound, preparation method and pharmaceutical compoistion | |
| CN104784146A (en) | Pharmaceutical Ilaprazole sodium composition for treating peptic ulcer | |
| CN102584790B (en) | S-pantoprazole sodium trihydrate, and preparation method and application thereof | |
| CN105030772A (en) | Ilaprazole sodium composition serving as medicine for treating digestive diseases | |
| CN104922080A (en) | Pharmaceutical ilaprazole sodium freeze-dried powder injection composition for treating digestive system diseases | |
| CN102351812B (en) | Methanesulfonic acid cinepazide crystal form III and preparation method thereof | |
| CN105055343A (en) | Ilaprazole sodium composition freeze-dried powder injection serving as medicine for treating stomach diseases | |
| CN105147682A (en) | Pharmaceutical ilaprazole sodium composition for treating gastric ulcer | |
| CN104370886A (en) | Ilaprazole crystal form as well as preparation method and application thereof | |
| CN105213389A (en) | The medicine ilaprazole composition of sodium that a kind of gastric acid inhibitory produces | |
| CN105147680A (en) | Drug ilaprazole sodium composition resisting to gastric acid secretion | |
| CN101250180A (en) | Amorphous S-pantoprazole sodium, preparation method and use thereof | |
| CN108685918B (en) | Pharmaceutical composition containing ilaprazole or salt thereof and preparation method thereof | |
| CN104072482A (en) | Rabeprazole sodium compound and pharmaceutical composition thereof | |
| CN109053685B (en) | Pharmaceutical composition containing ilaprazole sodium and preparation method thereof | |
| CN105106121A (en) | Drug ilaprazole sodium composition dry suspension for treating digestive system diseases | |
| CN105106150A (en) | Drug ilaprazole sodium composition tablets for treating peptic ulcer | |
| CN104761543A (en) | Ilaprazole compound for treating peptic ulcer and preparation method thereof | |
| CN102746272A (en) | Esomeprazole sodium polymorph, preparation method and application thereof | |
| CN102351835B (en) | Mangiferin aglycone crystal forms, and composition, preparation method and application thereof | |
| CN105213320A (en) | A kind of medicine Ilaprazole Sodium composition granule for the treatment of gastric ulcer | |
| CN102675378A (en) | C-glucoside derivative containing cyclopropane structure and method and application of C- glucoside derivative | |
| CN101250181B (en) | S-pantoprazole sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20151216 |