CN101766614A - Omeprazole sodium combined medicament and preparation method thereof - Google Patents
Omeprazole sodium combined medicament and preparation method thereof Download PDFInfo
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- CN101766614A CN101766614A CN201010000490A CN201010000490A CN101766614A CN 101766614 A CN101766614 A CN 101766614A CN 201010000490 A CN201010000490 A CN 201010000490A CN 201010000490 A CN201010000490 A CN 201010000490A CN 101766614 A CN101766614 A CN 101766614A
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Abstract
The invention discloses an omeprazole sodium combined medicament and a preparation method thereof. The omeprazole sodium combined medicament comprises the following medicinal effect compositions in part by weight: 17.3 to 34.8 parts of the omeprazole sodium, 8.7 to 13.0 parts of reduced glutathione and 43.5 to 52.2 parts of sodium glutamate. The omeprazole sodium combined medicament provided by the invention has the effect of resisting drug allergy and can lighten the damage effect and the adverse reaction of the omeprazole sodium on liver; the medicament has high quality; and the preparation method is energy-saving and environment-friendly.
Description
Technical field
The present invention relates to a kind of composite medicament of omeprazole sodium and preparation method thereof.
Background technology
Harmonization of the stomach duodenum mucosa has natural gastric acid and the erosive perfect mechanism of pepsin resisted, but when helicobacter pylori and nonsteroidal anti-inflammatory drug damage it, causes peptic ulcer disease to take place.Australia scholar Warren and Marshall disclose this cause of disease, and use H
2The receptor antagonist medicine has carried out treatment effectively, and after 22 years, therefore two people obtain Nobel Prize in medicine in 2005.Have research again with proton pump inhibitor Drug therapy peptic ulcer disease the eighties in last century, compares H
2The inhibitor for treating effect is more powerful and lasting.Omeprazole Sodium is exactly typically to represent medicine, is one of choice drug for the treatment of at present peptic ulcer disease.But, all adopt the former technology of active carbon desuperheating in the omeprazole sodium freeze-dried injection of prior art, the production of preparation, cause active carbon fine particle, heavy metal ion to remain in the medicinal liquid, bring blood of human body during intravenous drip into, the infringement that brings to health, and the pyrogen in the activated carbon adsorption medicinal liquid is not thorough.The membrane ultrafiltration isolation technics of the isolated molecule amount 10000D of efficient energy-saving is adopted in the pharmaceutical factory that has, and still, molecular weight also has pyrogen reaction in the heat source substance segment of 2000D.The omeprazole sodium freeze-dried injection excipient of prior art for preparing adopts low molecular dextran-40, human body has anaphylaxis to this material, the somebody is after having dripped several low molecular dextrans-40 transfusion, just produce anaphylaxis, low molecular dextran-40 amount that is used as the excipient of Omeprazole Sodium has reached minimum hypersensitive.Prior art generally adopts mannitol to make the skeleton of excipient, and mannitol has the zest untoward reaction to blood vessel.In addition; have in the omeprazole sodium molecule-group of NH-base and sulfur atom-containing; do not contain the composition of protecting above-mentioned group in the existing Omeprazole Sodium medicine; make medicine make, store transportation, use and enter easily oxidation, peroxidating and photooxidation in the intravital process, thus the untoward reaction of this medicine that causes.
Summary of the invention
Easily cause allergic reaction after existing omeprazol sodium preparation is taken in order to overcome, untoward reaction and to problems such as liver injury reactions, the invention provides a kind of composite medicament of omeprazole sodium.
Composite medicament of omeprazole sodium provided by the invention comprises the active ingredient of following parts by weight:
Omeprazole Sodium 17.3～34.8
Reduced glutathion 8.7～13.0
Sodium glutamate 43.5～52.2.
The present invention also provides a kind of method for preparing above-mentioned composition of medicine, and step is as follows:
(1). getting weight is the water for injection of 50～125 times of described Omeprazole Sodium weight, stirs down, the Omeprazole Sodium of described amount, reduced glutathion and sodium glutamate dissolving fully, obtains the solution of medicine respectively.
(2). with molecular cut off is the solution that the membrane ultrafiltration step (1) of 8000D obtains, and filtrate is the membrane ultrafiltration of 1500D with molecular cut off, and filtrate is regulated pH value 7.2～7.6 with 8% sodium hydroxide solution.
(3). the solution that step (2) obtains was 121 ℃ of moist heat sterilizations 20 minutes.
(4). the solution after the sterilization, be cooled to 20～22 ℃, the sodium hydroxide solution with 8% is regulated pH to 7.2～7.6, with the membrane filtration of 0.22 μ m, obtains the composition of medicine medicinal liquid.
(5). the content of each active ingredient in the composition of medicine medicinal liquid that determination step (4) obtains.
(6). described composition of medicine medicinal liquid is made acceptable forms on the pharmaceutics:
A, press the Omeprazole Sodium dosage that pharmaceutics allows, the composition of medicine medicinal liquid that above-mentioned steps (4) makes is aseptic subpackaged, make the Omeprazole Sodium composite medicinal injection;
B, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in cillin bottle, put into the freeze drying box of lyophilization unit, lyophilization routinely makes residual moisture in the composition of medicine solid≤2%.Tamponade, roll lid, make the lyophilized injection of omeprazole sodium composite medicine;
C, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in 316L rustless steel pallet, and lyophilization makes moisture in the composition of medicine solid≤2%.The drug form preparation such as oral formulations, spray for preparing composite medicament of omeprazole sodium according to a conventional method.
The present invention can realize following technique effect:
1. composition of medicine provided by the invention is higher than the medicine of omeprazol sodium preparation of the prior art and other treatment gastric ulcer to the therapeutic effect of gastric ulcer.
2. replace the low molecular dextran-40 of prior art to make excipient with sodium glutamate, avoided the anaphylaxis of low molecular dextran-40, sodium glutamate and reduced glutathion compound action also can alleviate the effect of Omeprazole Sodium to hepar damnification.
With reduced glutathion as Reducing agent, have protective effect, can eliminate the untoward reaction that Omeprazole Sodium brings owing to photooxidation, oxidation, peroxidating in external and body.
4. adopt molecular cut off 8000D and twice membrane ultrafiltration technology of molecular cut off 1500D depyrogenation, replace traditional active carbon depyrogenation technology, greatly improved the interior quality of medicine, and energy-conserving and environment-protective.
5. the composition of medicine medicinal liquid of above-mentioned steps (4) preparation, the solid after the lyophilization is the dispersed system that is molecularity, makes corresponding preparation, the uniformity of dosage units of each composition mix than traditional coating and high-speed stirred wet mixing technology high more than 20%.
The specific embodiment
The invention will be further described with specific embodiment below, can be implemented so that those skilled in the art can better understand the present invention also, but illustrated embodiment is not as a limitation of the invention.
Embodiment 1
The omeprazole sodium composite medicine that present embodiment provides comprises the active ingredient of following parts by weight:
Omeprazole Sodium: 17.3
Reduced glutathion 8.7
Sodium glutamate 43.5
The preparation method of combinations thereof medicine is as follows:
(1). getting weight is the water for injection of 50～125 times of described Omeprazole Sodium weight, stirs down, the Omeprazole Sodium of described amount, reduced glutathion and sodium glutamate dissolving fully, obtains the solution of medicine respectively.
(2). with molecular cut off is the solution that the membrane ultrafiltration step (1) of 8000D obtains, and filtrate is the membrane ultrafiltration of 1500D with molecular cut off, and filtrate is regulated pH value 7.2～7.6 with 8% sodium hydroxide solution.
(3). the solution that step (2) obtains was 121 ℃ of moist heat sterilizations 20 minutes.
(4). the solution after the sterilization, be cooled to 20～22 ℃, the sodium hydroxide solution with 8% is regulated pH to 7.2～7.6, with the membrane filtration of 0.22 μ m, obtains the composition of medicine medicinal liquid.
(5). the content of each active ingredient in the composition of medicine medicinal liquid that determination step (4) obtains.
(6). described composition of medicine medicinal liquid is made acceptable forms on the pharmaceutics:
A, press the Omeprazole Sodium dosage that pharmaceutics allows, the aseptic subpackaged Omeprazole Sodium composite medicinal injection of making of composition of medicine medicinal liquid that above-mentioned steps (4) is made;
B, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in cillin bottle, put into the freeze drying box of lyophilization unit, lyophilization routinely makes residual moisture in the composition of medicine solid≤2%.Tamponade, roll lid, make the lyophilized injection of omeprazole sodium composite medicine;
C, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in 316L rustless steel pallet, and lyophilization makes moisture in the composition of medicine solid≤2%.The drug form preparation such as oral formulations, spray for preparing composite medicament of omeprazole sodium according to a conventional method.
The pharmacodynamics demonstration test:
1. animal is selected:
Rat commonly used, 10 every group, body weight 200-250g, health, male or female is indicated kind system and the quality certification number of animal.
2. model and method:
2.1. acetic acid burns the type gastric ulcer model
Experimental animal rat, the male and female dual-purpose, random packet, fasting is 24 hours before the experiment, freely drinks water, and under etherization opens the abdominal cavity, the glass tubing of internal diameter 5mm, long 30mm vertically is positioned on the body of stomach serosal surface, ice acetic acid 0.2ml in tube chamber dipped in out glacial acetic acid with cotton swab after 1.5 minutes, the suture operation otch.Postoperative rat normal diet was set up matched group and administration group in second day at random.Successive administration 15 days.Dissect and take out stomach, measure the ulcer area, compare between each group.
2.2. pyloric ligation ulcers gastric ulcer model (making negative control)
Rat, male and female dual-purpose, random packet, the experiment before fasting 36-72 hour, freely drink water, with ether with Animal Anesthesia, open the abdominal cavity, the ligation pylorus, postoperative was dissected and is got stomach in 18 hours, injected 1% formalin 8ml in gastral cavity, stomach is immersed in 1% formalin solution, after 10 minutes, cut off stomach along greater gastric curvature, the preceding stomach ulcer surface of counting is long-pending to be 43～47mm
2
The result is as follows:
| Selected medicine/medication | Rat quantity/only | 2.1 every rat gastric ulcer area average/mm of method 2 | Uniformity of dosage units raising rate/% | Pyrogen reaction rate/% | Untoward reaction rate/% |
| Famotidine 20mg/kg is oral | ??10 | ??39 | ??- | ??10％ | ??10％ |
| Injection omeprazole sodium 20mg/kg injection | ??10 | ??36 | ??- | ??10％ | ??10％ |
| Selected medicine/medication | Rat quantity/only | 2.1 every rat gastric ulcer area average/mm of method 2 | Uniformity of dosage units raising rate/% | Pyrogen reaction rate/% | Untoward reaction rate/% |
| 20mg/kg is oral for the present embodiment composition of medicine | ??10 | ??21 | ??26％ | ??0 | ??0 |
| Present embodiment composition of medicine lyophilized injection 20mg/kg injection | ??10 | ??18 | ??- | ??0 | ??0 |
Embodiment 2:
The omeprazole sodium composite medicine that present embodiment provides, the active ingredient that comprises following parts by weight becomes:
Omeprazole Sodium: 34.8
Reduced glutathion 13.0
Sodium glutamate 52.2
The preparation method of above-mentioned omeprazole sodium composite medicine is:
(1). getting weight is the water for injection of 50～125 times of described Omeprazole Sodium weight, stirs down, the Omeprazole Sodium of described amount, reduced glutathion and sodium glutamate dissolving fully, obtains the solution of medicine respectively.
(2). with molecular cut off is the solution that the membrane ultrafiltration step (1) of 8000D obtains, and filtrate is the membrane ultrafiltration of 1500D with molecular cut off, and filtrate is regulated pH value to 7.2～7.6 with 8% sodium hydroxide solution.
(3). the solution that step (2) obtains was 121 ℃ of moist heat sterilizations 20 minutes.
(4). the solution after the sterilization, be cooled to 20～22 ℃, the sodium hydroxide solution with 8% is regulated pH to 7.2～7.6, with the membrane filtration of 0.22 μ m, obtains the composition of medicine medicinal liquid.
(5). the content of each active ingredient in the composition of medicine medicinal liquid that determination step (4) obtains.
(6). described composition of medicine medicinal liquid is made acceptable forms on the pharmaceutics:
A, press the Omeprazole Sodium dosage that pharmaceutics allows, the aseptic subpackaged Omeprazole Sodium composite medicinal injection of making of composition of medicine medicinal liquid that above-mentioned steps (4) is made;
B, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in cillin bottle, put into the freeze drying box of lyophilization unit, lyophilization routinely makes residual moisture in the composition of medicine solid≤2%.Tamponade, roll lid, make the lyophilized injection of omeprazole sodium composite medicine;
C, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in 316L rustless steel pallet, and lyophilization makes moisture in the composition of medicine solid≤2%.The drug form preparation such as oral formulations, spray for preparing composite medicament of omeprazole sodium according to a conventional method.
The pharmacodynamics demonstration test:
1. animal is selected:
Rat commonly used, 10 every group, body weight 200-250g, health, male or female is indicated kind system and the quality certification number of animal.
2. model and method:
2.1. acetic acid burns the type gastric ulcer model
Experimental animal rat, the male and female dual-purpose, random packet, fasting is 24 hours before the experiment, freely drinks water, and under etherization opens the abdominal cavity, the glass tubing of internal diameter 5mm, long 30mm vertically is positioned on the body of stomach serosal surface, ice acetic acid 0.2ml in tube chamber dipped in out glacial acetic acid with cotton swab after 1.5 minutes, the suture operation otch.Postoperative rat normal diet was set up matched group and administration group in second day at random.Successive administration 15 days.Dissect and take out stomach, measure the ulcer area, compare between each group.
2.2. pyloric ligation ulcers gastric ulcer model (making negative control)
Rat, male and female dual-purpose, random packet, the experiment before fasting 36-72 hour, freely drink water, with ether with Animal Anesthesia, open the abdominal cavity, the ligation pylorus, postoperative was dissected and is got stomach in 18 hours, injected 1% formalin 8ml in gastral cavity, stomach is immersed in 1% formalin solution, after 10 minutes, cut off stomach along greater gastric curvature, the preceding stomach ulcer surface of counting is long-pending to be 43～47mm
2
The result is as follows:
| Selected medicine/medication | Rat quantity/only | 2.1 every rat gastric ulcer area average/mm of method 2 | Uniformity of dosage units raising rate/% | Pyrogen reaction rate/% | Untoward reaction rate/% |
| Famotidine 20mg/kg is oral | ??10 | ??38 | ??- | ??10％ | ??10％ |
| Injection omeprazole sodium 20mg/kg injection | ??10 | ??35 | ??- | ??10％ | ??10％ |
| 20mg/kg is oral for the present embodiment composition of medicine | ??10 | ??22 | ??26％ | ??0 | ??0 |
| Present embodiment composition of medicine lyophilized injection 20mg/kg injection | ??10 | ??17 | ??- | ??0 | ??0 |
Embodiment 3:
The omeprazole sodium composite medicine that present embodiment provides comprises the active ingredient of following parts by weight:
Omeprazole Sodium: 29.1
Reduced glutathion 10.2
Sodium glutamate 46.3
The preparation method of above-mentioned omeprazole sodium composite medicine is:
(1). getting weight is the water for injection of 50～125 times of described Omeprazole Sodium weight, stirs down, the Omeprazole Sodium of described amount, reduced glutathion and sodium glutamate dissolving fully, obtains the solution of medicine respectively.
(2). with molecular cut off is the solution that the membrane ultrafiltration step (1) of 8000D obtains, and filtrate is the membrane ultrafiltration of 1500D with molecular cut off, and filtrate is regulated pH value 7.2～7.6 with 8% sodium hydroxide solution.
(3). the solution that step (2) obtains was 121 ℃ of moist heat sterilizations 20 minutes.
(4). the solution after the sterilization, be cooled to 20～22 ℃, the sodium hydroxide solution with 8% is regulated pH to 7.2～7.6, with the membrane filtration of 0.22 μ m, obtains the composition of medicine medicinal liquid.
(5). the content of each active ingredient in the composition of medicine medicinal liquid that determination step (4) obtains.
(6). described composition of medicine medicinal liquid is made acceptable forms on the pharmaceutics:
A, press the Omeprazole Sodium dosage that pharmaceutics allows, the aseptic subpackaged Omeprazole Sodium composite medicinal injection of making of composition of medicine medicinal liquid that above-mentioned steps (4) is made;
B, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in cillin bottle, put into the freeze drying box of lyophilization unit, lyophilization routinely makes residual moisture in the composition of medicine solid≤2%.Tamponade, roll lid, make the lyophilized injection of omeprazole sodium composite medicine;
C, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in 316L rustless steel pallet, and lyophilization makes moisture in the composition of medicine solid≤2%.The drug form preparation such as oral formulations, spray for preparing composite medicament of omeprazole sodium according to a conventional method.
The pharmacodynamics demonstration test:
1. animal is selected:
Rat commonly used, 10 every group, body weight 200-250g, health, male or female is indicated kind system and the quality certification number of animal.
2. model and method:
2.1. acetic acid burns the type gastric ulcer model
Experimental animal rat, the male and female dual-purpose, random packet, fasting is 24 hours before the experiment, freely drinks water, and under etherization opens the abdominal cavity, the glass tubing of internal diameter 5mm, long 30mm vertically is positioned on the body of stomach serosal surface, ice acetic acid 0.2ml in tube chamber dipped in out glacial acetic acid with cotton swab after 1.5 minutes, the suture operation otch.The postoperative normal diet was set up matched group and administration group in second day at random.Successive administration 15 days.Dissect and take out stomach, measure the ulcer area, compare between each group.
2.2. pyloric ligation ulcers gastric ulcer model (making negative control)
Rat, male and female dual-purpose, random packet, the experiment before fasting 36-72 hour, freely drink water, with ether with Animal Anesthesia, open the abdominal cavity, the ligation pylorus, postoperative was dissected and is got stomach in 18 hours, injected 1% formalin 8ml in gastral cavity, stomach is immersed in 1% formalin solution, after 10 minutes, cut off stomach along greater gastric curvature, the preceding stomach ulcer surface of counting is long-pending to be 43～47mm
2
The result is as follows:
| Selected medicine/medication | Rat quantity/only | 2.1 every rat gastric ulcer area average/mm of method 2 | Uniformity of dosage units raising rate/% | Pyrogen reaction rate/% | Untoward reaction rate/% |
| Famotidine 20mg/kg is oral | ??10 | ??35 | ??- | ??10％ | ??10％ |
| Selected medicine/medication | Rat quantity/only | 2.1 every rat gastric ulcer area average/mm of method 2 | Uniformity of dosage units raising rate/% | Pyrogen reaction rate/% | Untoward reaction rate/% |
| Injection omeprazole sodium 20mg/kg injection | ??10 | ??34 | ??- | ??10％ | ??10％ |
| 20mg/kg is oral for the present embodiment composition of medicine | ??10 | ??20 | ??26％ | ??0 | ??0 |
| Present embodiment composition of medicine lyophilized injection 20mg/kg injection | ??10 | ??14 | ??- | ??0 | ??0 |
Embodiment 4:
The omeprazole sodium composite medicine that present embodiment provides comprises the active ingredient of following parts by weight:
Omeprazole Sodium: 34.8
Reduced glutathion 8.7
Sodium glutamate 52.2
The preparation method of above-mentioned omeprazole sodium composite medicine is:
(1). getting weight is the water for injection of 50～125 times of described Omeprazole Sodium weight, stirs down, the Omeprazole Sodium of described amount, reduced glutathion and sodium glutamate dissolving fully, obtains the solution of medicine respectively.
(2). with molecular cut off is the solution that the membrane ultrafiltration step (1) of 8000D obtains, and filtrate is the membrane ultrafiltration of 1500D with molecular cut off, gets filtrate and regulates pH value to 7.2～7.6 with 8% sodium hydroxide solution.
(3). the solution that step (2) obtains was 121 ℃ of moist heat sterilizations 20 minutes.
(4). the solution after the sterilization, be cooled to 20～22 ℃, the sodium hydroxide solution with 8% is regulated pH to 7.2～7.6, with the membrane filtration of 0.22 μ m, obtains the composition of medicine medicinal liquid.
(5). the content of each active ingredient in the composition of medicine medicinal liquid that determination step (4) obtains.
(6). described composition of medicine medicinal liquid is made acceptable forms on the pharmaceutics:
A, press the Omeprazole Sodium dosage that pharmaceutics allows, the aseptic subpackaged Omeprazole Sodium composite medicinal injection of making of composition of medicine medicinal liquid that above-mentioned steps (4) is made;
B, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in cillin bottle, put into the freeze drying box of lyophilization unit, lyophilization routinely makes residual moisture in the composition of medicine solid≤2%.Tamponade, roll lid, make the lyophilized injection of omeprazole sodium composite medicine;
C, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in 316L rustless steel pallet, and lyophilization makes moisture in the composition of medicine solid≤2%.The drug form preparation such as oral formulations, spray for preparing composite medicament of omeprazole sodium according to a conventional method.
The pharmacodynamics demonstration test:
1. animal is selected:
Rat commonly used, 10 every group, body weight 200-250g, health, male or female is indicated kind system and the quality certification number of animal.
2. model and method:
2.1. acetic acid burns the type gastric ulcer model
Experimental animal rat, the male and female dual-purpose, random packet, fasting is 24 hours before the experiment, freely drinks water, and under etherization opens the abdominal cavity, the glass tubing of internal diameter 5mm, long 30mm vertically is positioned on the body of stomach serosal surface, ice acetic acid 0.2ml in tube chamber dipped in out glacial acetic acid with cotton swab after 1.5 minutes, the suture operation otch.The postoperative normal diet was set up matched group and administration group in second day at random.Successive administration 15 days.Dissect and take out stomach, measure the ulcer area, compare between each group.
2.2. pyloric ligation ulcers gastric ulcer model (making negative control)
Rat, male and female dual-purpose, random packet, the experiment before fasting 36-72 hour, freely drink water, with ether with Animal Anesthesia, open the abdominal cavity, the ligation pylorus, postoperative was dissected and is got stomach in 18 hours, injected 1% formalin 8ml in gastral cavity, stomach is immersed in 1% formalin solution, after 10 minutes, cut off stomach along greater gastric curvature, the preceding stomach ulcer surface of counting is long-pending to be 43～47mm
2
The result is as follows:
| Selected medicine/medication | Rat quantity/only | 2.1 every rat gastric ulcer area average/mm of method 2 | Uniformity of dosage units raising rate/% | Pyrogen reaction rate/% | Untoward reaction rate/% |
| Famotidine 20mg/kg is oral | ??10 | ??37 | ??- | ??10％ | ??10％ |
| Injection omeprazole sodium 20mg/kg injection | ??10 | ??33 | ??- | ??10％ | ??10％ |
| 20mg/kg is oral for the present embodiment composition of medicine | ??10 | ??23 | ??24％ | ??0 | ??0 |
| Present embodiment composition of medicine lyophilized injection 20mg/kg injection | ??10 | ??16 | ?- | ??0 | ??0 |
Embodiment 5:
The omeprazole sodium composite medicine that present embodiment provides comprises the active ingredient of following parts by weight:
Omeprazole Sodium: 17.3
Reduced glutathion 13.0
Sodium glutamate 43.5
The preparation method of above-mentioned omeprazole sodium composite medicine is:
(1). getting weight is the water for injection of 50～125 times of described Omeprazole Sodium weight, stirs down, the Omeprazole Sodium of described amount, reduced glutathion and sodium glutamate dissolving fully, obtains the solution of medicine respectively.
(2). with molecular cut off is the solution that the membrane ultrafiltration step (1) of 8000D obtains, and filtrate is the membrane ultrafiltration of 1500D with molecular cut off, gets filtrate and regulates pH value to 7.2～7.6 with 8% sodium hydroxide solution.
(3). the solution that step (2) obtains was 121 ℃ of moist heat sterilizations 20 minutes.
(4). the solution after the sterilization, be cooled to 20～22 ℃, the sodium hydroxide solution with 8% is regulated pH to 7.2～7.6, with the membrane filtration of 0.22 μ m, obtains the composition of medicine medicinal liquid.
(5). the content of each active ingredient in the composition of medicine medicinal liquid that determination step (4) obtains.
(6). described composition of medicine medicinal liquid is made acceptable forms on the pharmaceutics:
A, press the Omeprazole Sodium dosage that pharmaceutics allows, the aseptic subpackaged Omeprazole Sodium composite medicinal injection of making of composition of medicine medicinal liquid that above-mentioned steps (4) is made;
B, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in cillin bottle, put into the freeze drying box of lyophilization unit, lyophilization routinely makes residual moisture in the composition of medicine solid≤2%.Tamponade, roll lid, make the lyophilized injection of omeprazole sodium composite medicine;
C, by the Omeprazole Sodium dosage that allows on the pharmaceutics, the composition of medicine medicinal liquid of above-mentioned steps (4) preparation is aseptic subpackaged in 316L rustless steel pallet, and lyophilization makes moisture in the composition of medicine solid≤2%.The drug form preparation such as oral formulations, spray for preparing composite medicament of omeprazole sodium according to a conventional method.
The pharmacodynamics demonstration test:
1. animal is selected:
Rat commonly used, 10 every group, body weight 200-250g, health, male or female is indicated kind system and the quality certification number of animal.
2. model and method:
2.1. acetic acid burns the type gastric ulcer model
Experimental animal rat, the male and female dual-purpose, random packet, fasting is 24 hours before the experiment, freely drinks water, and under etherization opens the abdominal cavity, the glass tubing of internal diameter 5mm, long 30mm vertically is positioned on the body of stomach serosal surface, ice acetic acid 0.2ml in tube chamber dipped in out glacial acetic acid with cotton swab after 1.5 minutes, the suture operation otch.Postoperative rat normal diet was set up matched group and administration group in second day at random.Successive administration 15 days.Dissect and take out stomach, measure the ulcer area, compare between each group.
2.2. pyloric ligation ulcers gastric ulcer model (making negative control)
Rat, male and female dual-purpose, random packet, the experiment before fasting 36-72 hour, freely drink water, with ether with Animal Anesthesia, open the abdominal cavity, the ligation pylorus, postoperative was dissected and is got stomach in 18 hours, injected 1% formalin 8ml in gastral cavity, stomach is immersed in 1% formalin solution, after 10 minutes, cut off stomach along greater gastric curvature, the preceding stomach ulcer surface of counting is long-pending to be 43～47mm
2
The result is as follows:
| Selected medicine/medication | Rat quantity/only | 2.1 every rat gastric ulcer area average/mm of method 2 | Uniformity of dosage units raising rate/% | Pyrogen reaction rate/% | Untoward reaction rate/% |
| Famotidine 20mg/kg is oral | ??10 | ??36 | ??- | ??10％ | ??10％ |
| Injection omeprazole sodium 20mg/kg injection | ??10 | ??35 | ??- | ??10％ | ??10％ |
| 20mg/kg is oral for the present embodiment composition of medicine | ??10 | ??21 | ??25％ | ??0 | ??0 |
| Present embodiment composition of medicine lyophilized injection 20mg/kg injection | ??10 | ??15 | ??- | ??0 | ??0 |
The above embodiment is the preferred embodiment that proves absolutely that the present invention lifts, and protection scope of the present invention is not limited thereto.Being equal to that those skilled in the art are done on basis of the present invention substitutes or conversion, all within protection scope of the present invention.Protection scope of the present invention is as the criterion with claims.
Claims (4)
1. a composite medicament of omeprazole sodium is characterized in that, comprises the active ingredient of following parts by weight:
Omeprazole Sodium 17.3～34.8
Reduced glutathion 8.7～13.0
Sodium glutamate 43.5～52.2.
2. prepare the method for the described composition of medicine of claim 1, it is characterized in that, step is as follows:
(1). getting weight is the water for injection of 50～125 times of described Omeprazole Sodium weight, stirs down, the Omeprazole Sodium of described amount, reduced glutathion and sodium glutamate dissolving fully, obtains the solution of medicine respectively;
(2). with molecular cut off is the solution that the membrane ultrafiltration step (1) of 8000D obtains, and filtrate is the membrane ultrafiltration of 1500D with molecular cut off, and filtrate is regulated pH value 7.2～7.6 with 8% sodium hydroxide solution;
(3). the solution that step (2) obtains was 121 ℃ of moist heat sterilizations 20 minutes;
(4). the solution after the sterilization, be cooled to 20～22 ℃, the sodium hydroxide solution with 8% is regulated pH value to 7.2～7.6, with the membrane filtration of 0.22 μ m, obtains the composition of medicine medicinal liquid;
(5). the content of each active ingredient in the composition of medicine medicinal liquid that determination step (4) obtains;
(6). described composition of medicine medicinal liquid is made acceptable forms on the pharmaceutics.
3. method according to claim 2 is characterized in that, acceptable forms is injection, lyophilized injection, oral formulations, spray on the described pharmaceutics.
4. the medicine of the treatment gastric ulcer of the described composition of medicine of claim 1 preparation.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010000490A CN101766614A (en) | 2010-01-11 | 2010-01-11 | Omeprazole sodium combined medicament and preparation method thereof |
| CN2010102786472A CN101947220A (en) | 2010-01-11 | 2010-09-13 | Combined medicament of omeprazole sodium |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201010000490A CN101766614A (en) | 2010-01-11 | 2010-01-11 | Omeprazole sodium combined medicament and preparation method thereof |
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| Publication Number | Publication Date |
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| CN101766614A true CN101766614A (en) | 2010-07-07 |
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| CN201010000490A Pending CN101766614A (en) | 2010-01-11 | 2010-01-11 | Omeprazole sodium combined medicament and preparation method thereof |
| CN2010102786472A Pending CN101947220A (en) | 2010-01-11 | 2010-09-13 | Combined medicament of omeprazole sodium |
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| CN2010102786472A Pending CN101947220A (en) | 2010-01-11 | 2010-09-13 | Combined medicament of omeprazole sodium |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058593A (en) * | 2010-12-27 | 2011-05-18 | 吴赣英 | Combination medicament of ilaprazole sodium and preparation process thereof |
| CN102091070A (en) * | 2010-12-27 | 2011-06-15 | 吴赣英 | Rabeprazole sodium combined medicament and preparation process thereof |
| CN103059000A (en) * | 2013-01-29 | 2013-04-24 | 黄明芳 | Novel omeprazole compound and pharmaceutical composition thereof |
| CN107773529A (en) * | 2016-08-24 | 2018-03-09 | 华仁药业股份有限公司 | A kind of Esomeprazole sodium sodium chloride injection and preparation method thereof |
-
2010
- 2010-01-11 CN CN201010000490A patent/CN101766614A/en active Pending
- 2010-09-13 CN CN2010102786472A patent/CN101947220A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058593A (en) * | 2010-12-27 | 2011-05-18 | 吴赣英 | Combination medicament of ilaprazole sodium and preparation process thereof |
| CN102091070A (en) * | 2010-12-27 | 2011-06-15 | 吴赣英 | Rabeprazole sodium combined medicament and preparation process thereof |
| CN103059000A (en) * | 2013-01-29 | 2013-04-24 | 黄明芳 | Novel omeprazole compound and pharmaceutical composition thereof |
| CN107773529A (en) * | 2016-08-24 | 2018-03-09 | 华仁药业股份有限公司 | A kind of Esomeprazole sodium sodium chloride injection and preparation method thereof |
| CN107773529B (en) * | 2016-08-24 | 2020-06-16 | 华仁药业股份有限公司 | Esomeprazole sodium and sodium chloride injection and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101947220A (en) | 2011-01-19 |
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