CN103705474A - Lyophilized pharmaceutical composition containing omeprazole sodium and preparation method of pharmaceutical composition - Google Patents

Abstract

The invention relates to the field of drug preparations, and particularly relates to a lyophilized pharmaceutical composition containing omeprazole sodium and a preparation method of the pharmaceutical composition. The lyophilized drug composition provided by the invention comprises the following components: omeprazole sodium, chlorogenic acid, edetate disodium, mannitol and sodium hydroxide.

Description

A kind of freeze-drying medicinal composition that contains Omeprazole Sodium and preparation method

Technical field:

The present invention relates to field of pharmaceutical preparations, particularly a kind of freeze-drying medicinal composition that contains Omeprazole Sodium and preparation thereof.Freeze-drying medicinal composition of the present invention comprises following composition: Omeprazole Sodium, chlorogenic acid, disodium edetate, mannitol, sodium hydroxide.

Background technology:

Omeprazole Sodium, its chemical name is: 5-methoxyl group-2-{ [(4-methoxyl group-3,5-dimethyl-2-pyridine radicals)-methyl]-sulfinyl }-1H-benzimidazole sodium.

Omeprazole Sodium is the racemic mixture of a pair of active optical antimer, is reduced the secretion of gastric acid by the mechanism of action of high targeted, is the specific inhibitor of sour pump in parietal cell.This product effect is rapid, the secretion that dosage once a day can reversible gastric acid inhibitory.

Omeprazole Sodium is a kind of alkalescence material, in parietal cell, in this peracidity environment of tubule, is concentrated and is converted into active substance, suppresses H+, K+-ATP enzyme (proton pump).This inhibitory action to gastric acid formation final step is dosage correlation, and highly suppresses basal gastric acid secretion and zest gastric acid secretion, but irrelevant with stimulus object.

Human vein gives Omeprazole Sodium, is the gastric acid secretion inhibiting of dosage correlation, in order to reach rapidly and the repeatedly effect of oral 20 milligrams of identical reduction Acidity in the stomachs, advises that intravenous gives 40 milligrams of omeprazoles first.40 milligrams of omeprazoles of quiet note reduce rapidly Acidity in the stomach, average decline 90% in 24 hours.The gastric acid secretion inhibiting effect of omeprazole is relevant to area under drug-time curve (AUC), and blood drug level during with administration is irrelevant.

Helicobacter pylori is relevant with sour digestion disease, comprises duodenal ulcer and gastric ulcer, relevant with helicobacter pylori infections with gastric ulcer with 70% duodenal ulcer by 95% respectively.Helicobacter pylori is the principal element that causes gastritis.Helicobacter pylori is the principal element that causes peptic ulcer together with gastric acid.

Omeprazole Sodium and antibiotic share can eradicate helicobacter pylori, this is to rapid relief of symptoms, gastric mucosa repair rate is high and long-term remission peptic ulcer disease is relevant, and therefore reduced the complication such as gastrointestinal hemorrhage, also reduced the anti-needs of secreting sour medicine treatment of long-term use simultaneously.

Any method, comprises that gastric acid reduces due to proton pump inhibitor, all increases the quantity of normal flora in gastrointestinal tract, and with antisecretory treatment, salmonella and campylobacter infect gastrointestinal danger may slightly increase.

Rat, give for a long time in the research of Omeprazole Sodium, observe stomach ECL cell and increase and benign tumor, this is the result that persistence hypergastrinemia suppresses because of gastric acid.With after bisfentidine, proton pump inhibitor therapy and part Bottoming is postoperative also a similar discovery.Obviously these change the not direct effect of said medicine.

Omeprazole Sodium can be used and treat digestive ulcerative bleeding, and stoma ulcer is hemorrhage; Concurrent Acute Gastric Mucosal infringement during stress state, and the acute gastric mucosal injury that causes of nonsteroidal antiinflammatory drug; Also be usually used in preventing after seriously disease (as cerebral hemorrhage, severe trauma etc.) stomach operation prevention hemorrhage etc. again; After general anesthesia or major operation and weak comatose patient prevent that regurgitation of gastric juice from merging aspiration pneumonitis.

In prior art, omeprazole sodium injection is had to multiple report, the present invention finds, existing omeprazole sodium injection has blood vessel irritation when injection, even cause local pain, the present invention injects discovery by Omeprazole Sodium and chlorogenic acid when research chlorogenic acid simultaneously, and blood vessel irritation alleviates greatly.Chlorogenic acid is prepared into together with Omeprazole Sodium to lyophilized formulations simultaneously, can accelerates the redissolution speed of medicine, be conducive to the use of lyophilized formulations, summary of the invention:

The invention provides a kind of freeze-drying medicinal composition of Omeprazole Sodium, it is freeze-dried pharmaceutical formulation form, and every 1000 freeze dried injections are prepared from by following component:

The present invention also provides the preparation method of the freeze-drying medicinal composition of Omeprazole Sodium of the present invention, and preparation process is as follows:

1) get sodium hydroxide, Omeprazole Sodium, chlorogenic acid, disodiumedetate and add in water for injection, be stirred to completely and dissolve,

2) add 2g medicinal carbon, stir 10-30 minute, add mannitol, after dissolving, stir 10-30 minute, with the filter decarbonization filtering of 0.45um.

3) with the sodium hydroxide solution of 1mol/L or the hydrochloric acid of 1mol/L, regulate medicinal liquid pH value to 10.90-11.00, water for injection is settled to ingredients amount, stirring, mix homogeneously;

4) medicinal liquid carries out aseptic filtration through 0.22um microporous filter membrane, fill, lyophilizing, gland, lamp inspection, packing, warehouse-in.

The depside that chlorogenic acid (Chlorogenicacid) is comprised of caffeic acid (Caffeic acid) and quinic acid (Quinic acid), different name chlorogenic acid, chemical name 3-O-caffeoyl Kui acid (3-O-caffeoylquinic acid) molecular formula: C ₁₆h ₁₈o ₉, molecular weight: 354.30, be a kind of benzene-like compounds that plant produces through shikimic acid pathway in aerobic respiration process.Chlorogenic acid is extensively present in high dicotyledon and pteridophyta, main be richly that in Caprifoliaceae Lonicera (Lonicera), Compositae artemisia (Artemisia) plant, the plant that wherein content is higher is mainly the Cortex Eucommiae, Flos Lonicerae, Helianthi, the wood that continues, coffee, cocoa tree etc.Chlorogenic acid has biological activity widely, and to chlorogenic acid, bioactive research has been deep into a plurality of fields such as food, health care, medicine and daily-use chemical industry to modern science.Chlorogenic acid is a kind of important bioactive substance, has antibacterial, antiviral, increases the effects such as leukocyte, hepatic cholagogic, antitumor, blood pressure lowering, blood fat reducing, removing free radical and stimulating central nervous system system.

The present invention finds in research chlorogenic acid injection process, it can reduce blood vessel irritation and local pain, the use amount that the present invention simultaneously finds chlorogenic acid through screening is at 10mg, and this dosage can not produce any side effect, but can play the effect of auxiliary Omeprazole Sodium.

Below data declaration beneficial effect of the present invention by experiment:

Contrast experiment:

Investigate embodiment 1 and do not add the comparative example of chlorogenic acid and the indices of the injection omeprazole sodium sample that gone on the market

1. vascular stimulation test method

9 of white big ear rabbits that select body weight 2.5～3.0kg, male and female half and half, divide four groups, 3 every group at random.The omeprazole sample sets of be made as respectively embodiment 1 sample (adding chlorogenic acid) group, comparative example 1 sample (not adding chlorogenic acid) group, having gone on the market.Respectively at auricular vein, give the sample under clinical working concentration, administration in continuous 7 days, 48～96 hours perusal animals and injection site before administration every day and after administration.After last administration, 48～96 hour observation period finished, and got Some Animals medicine-feeding part tissue slice and carried out pathological examination.The animal staying, according to the feature of tested material and irritative response situation, continues to observe and within 14-21 days, carries out histopathological examination again.

2. local pain experimental technique

From the Healthy People of voluntary participation experimental study, randomly draw 60 examples, men and women half and half, age 25-55 year.Be divided at random 3 groups, every group of 20 people.The omeprazole sample sets of be made as respectively embodiment 1 sample (adding chlorogenic acid) group, comparative example 1 sample (not adding chlorogenic acid) group, having gone on the market.Vein gives after sample, observes experimenter's pain reaction.Adopt Wong-Banker facial expression scale (FPS-R) to assess, indicate the numeral of 0-5 under the types of facial makeup in Beijing operas, numeral is larger, represents that pain intensity is larger.After off-test, adopt SPSS11.5 version software to carry out statistical procedures, the P<0.05 of take has statistical significance as difference.

3. dissolution velocity experimental technique

Get omeprazole sample 40mg, be dissolved in 10ml sterilized water for injection.Observe sample dissolution situation.

4. accelerate 3 months medicine assay experimental techniques

The sample of getting at random 3 batches carries out accelerated test, is placed on and commercially produces in the same or analogous packing container of product, and experimental condition is 40 ℃ ± 2 ℃/RH75% ± 5%, and the investigation time is 3 months.Adopt the content of high effective liquid chromatography for measuring omeprazole.Method And Principle: test sample is made mobile phase solution, enters high performance liquid chromatograph and carries out chromatographic isolation, with ultraviolet absorption detector, detects omeprazole absorption value in wavelength 280nm place, calculates its content.(content acceptability limit: 94.0%～106.0%)

The specific embodiment:

Embodiment 1

Every 1000 freeze dried injections are prepared from by following component:

The present invention also provides the preparation method of the freeze-drying medicinal composition of Omeprazole Sodium of the present invention, and preparation process is as follows:

1) get sodium hydroxide, Omeprazole Sodium, chlorogenic acid, disodiumedetate and add in water for injection, be stirred to completely and dissolve,

2) add 2g medicinal carbon, stir 10-30 minute, add mannitol, after dissolving, stir 10-30 minute, with the filter decarbonization filtering of 0.45um.

3) with the sodium hydroxide solution of 1mol/L or the hydrochloric acid of 1mol/L, regulate medicinal liquid pH value to 10.90-11.00, water for injection is settled to ingredients amount, stirring, mix homogeneously;

4) medicinal liquid carries out aseptic filtration through 0.22um microporous filter membrane, fill, lyophilizing, gland, lamp inspection, packing, warehouse-in.

Comparative example

Every 1000 freeze dried injections are prepared from by following component:

The present invention also provides the preparation method of the freeze-drying medicinal composition of Omeprazole Sodium of the present invention, and preparation process is as follows:

1) get sodium hydroxide, Omeprazole Sodium, disodiumedetate and add in water for injection, be stirred to completely and dissolve,

2) add 2g medicinal carbon, stir 10-30 minute, add mannitol, after dissolving, stir 10-30 minute, with the filter decarbonization filtering of 0.45um.

3) with the sodium hydroxide solution of 1mol/L or the hydrochloric acid of 1mol/L, regulate medicinal liquid pH value to 10.90-11.00, water for injection is settled to ingredients amount, stirring, mix homogeneously;

4) medicinal liquid carries out aseptic filtration through 0.22um microporous filter membrane, fill, lyophilizing, gland, lamp inspection, packing, warehouse-in.

Claims (1)

1. a freeze-drying medicinal composition for Omeprazole Sodium, it is freeze-dried pharmaceutical formulation form, every 1000 freeze dried injections are prepared from by following component:

Its preparation process is as follows:

1) get sodium hydroxide, Omeprazole Sodium, chlorogenic acid, disodiumedetate and add in water for injection, be stirred to completely and dissolve,

2) add 2g medicinal carbon, stir 10-30 minute, add mannitol, after dissolving, stir 10-30 minute, with the filter decarbonization filtering of 0.45um,

3) with the sodium hydroxide solution of 1mol/L or the hydrochloric acid of 1mol/L, regulate medicinal liquid pH value to 10.90-11.00, water for injection is settled to ingredients amount, stirring, mix homogeneously,

4) medicinal liquid carries out aseptic filtration through 0.22um microporous filter membrane, fill, lyophilizing, gland, lamp inspection, packing, warehouse-in.