CN111973562A - Esomeprazole sodium for injection and preparation method thereof - Google Patents
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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Abstract
The invention discloses esomeprazole sodium for injection and a preparation method thereof, wherein the prescription of the esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 1.0g of edetate disodium, 0.3-0.5g of disodium hydrogen phosphate and 0.3-0.5g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 11.0-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared. According to the invention, a small amount of chelating agent disodium edetate is added, and the disodium hydrogen phosphate and the vitamin E are matched, so that the stability of the preparation can be obviously improved by compounding the disodium edetate, the disodium hydrogen phosphate and the vitamin E.
Description
Technical Field
The invention relates to the field of medicine preparation, and in particular relates to esomeprazole sodium for injection and a preparation method thereof.
Background
The esomeprazole sodium for injection is an aseptic freeze-dried product, and the main component of the esomeprazole sodium is esomeprazole sodium. The esomeprazole serving as an anti-peptic ulcer drug can directly act on a proton pump in a stomach wall and specifically inhibit H + + K + + ATP enzyme, so that gastric acid secretion is effectively inhibited, and the esomeprazole has the advantages of rapid effect, strong effect and few adverse reactions. At present, the esomeprazole sodium for clinical injection is widely applied to treating acute upper gastrointestinal hemorrhage caused by duodenal ulcer, gastric ulcer, acute internal mucous membrane lesion, compound ulcer and the like.
Esomeprazole is poor in stability, unstable to light, heat, oxygen and the like, and the stability in an aqueous solution is seriously dependent on the pH value and can be degraded along with the reduction of the pH value of the solution. Therefore, the selection of the auxiliary materials and the process of the esomeprazole lyophilized powder is very important, the process realizability in the production process is ensured, and the stable pH value of the lyophilized powder needs to be kept after redissolving, so that the safety and the effectiveness of the drug administration of a patient can be ensured.
Disclosure of Invention
The invention aims to provide esomeprazole sodium for injection and a preparation method thereof, so as to improve the stability of the esomeprazole sodium for injection.
The invention is realized by the following technical scheme:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 1.0g of edetate disodium, 0.3-0.5g of disodium hydrogen phosphate and 0.3-0.5g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 11.0-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
In the prior art, pH adjustment is performed only through sodium hydroxide, the pH value changes with the extension of storage time, so that the preparation is unstable, and disodium hydrogen phosphate is independently adopted to be matched with the sodium hydroxide, wherein the sodium hydroxide is used for adjusting the pH value, the disodium hydrogen phosphate plays a role in buffering protection, the pH value basically does not change with the extension of the storage time, but factors influencing the stability of the preparation, such as the pH value, oxidation and the like, also exist.
According to the invention, the edetate disodium, the disodium hydrogen phosphate and the vitamin E are used as auxiliary materials according to a certain proportion and added into the esomeprazole sodium for injection, and the pH value is adjusted to 11.0-11.8 by using sodium hydroxide, wherein the disodium hydrogen phosphate has a buffering effect and can ensure that the pH value of the preparation is maintained for a long time, and the compounding of the disodium hydrogen phosphate and the vitamin E has a good antioxidation effect.
Tests prove that the stability of the esomeprazole sodium for injection is good, and the content of the esomeprazole sodium is basically unchanged within 24 months; and the contents of the impurity I, the impurity II, the impurity III, the impurity IV and the impurity V are basically unchanged and still in a qualified range.
Further, 0.5g of disodium hydrogen phosphate and 0.5g of vitamin E were added.
A preparation method of esomeprazole sodium for injection comprises the following steps:
s1, preparing liquid: dissolving esomeprazole sodium, edetate disodium and disodium hydrogen phosphate by using water for injection, adjusting the pH value to 11.0-11.8 by using sodium hydroxide with the concentration of 1mol/L, and fixing the volume to 1000mL by using the water for injection to form liquid medicine;
s2, cleaning: respectively cleaning and sterilizing the injection bottle, the rubber plug and the aluminum cover;
s3, filling: filling the liquid medicine into an injection bottle according to the amount by a filling machine, and then performing semi-stoppering treatment;
s4, freeze drying;
and S5, performing full pressure and capping of the rubber plug in sequence.
Further, the specific process of liquid preparation in step S1 is as follows:
filling nitrogen into the liquid preparation tank, adding about 8.0kg of water for injection under the condition of keeping nitrogen introduction, and cooling to below 25 ℃; adding the edetate disodium, the disodium hydrogen phosphate and the vitamin E according to the prescription amount, and adjusting the pH value to 11.0-11.8 by using 1mol/L sodium hydroxide solution; adding prescribed amount of esomeprazole sodium, diluting to constant volume with water for injection, sterilizing, filtering, and storing in a collecting tank.
Further, the sterile filtration was performed by pressing into a collection tank using a 0.2 μm polyethersulfone filter.
Further, the freeze-drying in step S4 includes the following steps:
s41, pre-freezing and cooling: the temperature of the plate layer is controlled to be-35 ℃ and the time is 0.5 hour;
s42, first heat preservation: the temperature of the plate layer is controlled to be-35 ℃ and the time is 2.5 hours;
s43, second heat preservation: controlling the temperature of the plate layer to be-35 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s45, first heating and drying: controlling the temperature of the plate layer to be 3 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s46, third heat preservation: controlling the temperature of the plate layer to be 3 ℃, the time to be 5 hours and setting the vacuum degree to be 200 mu bar;
s47, second heating and drying: controlling the temperature of the plate layer to be 35 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s48, fourth heat preservation: the temperature of the plate layer is controlled to be 35 ℃, the time is 3 hours, and the vacuum degree is set to be 200 mu bar.
The freeze-drying parameter setting is set according to the prescription components, and the content of the prepared preparation can be ensured to be in a standard range and the stability can be maintained in the later period.
Further, 0.5g of disodium hydrogen phosphate and 0.5g of vitamin E were added.
Further, the injection bottle was washed as follows:
ultrasonic cleaning, purified water washing and injection water washing are sequentially carried out, and then compressed air is used for blow-drying.
Further, the cleaning process of the rubber plug is as follows:
rinsing for multiple times by using a rubber plug cleaning machine, and then sequentially sterilizing, vacuum drying, hot air drying and naturally cooling.
Further, the cleaning process of the aluminum cover is as follows:
cleaning with an aluminum cover cleaning machine, sequentially performing steam sterilization, vacuum drying, hot air drying, and naturally cooling.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1. according to the invention, the edetate disodium, the disodium hydrogen phosphate and the vitamin E are used as auxiliary materials according to a certain proportion and added into the esomeprazole sodium for injection, and the pH value is adjusted to 11.0-11.8 by using sodium hydroxide, wherein the disodium hydrogen phosphate has a buffering effect and can ensure that the pH value of the preparation is maintained for a long time, and the compounding of the disodium hydrogen phosphate and the vitamin E has a good antioxidation effect.
2. The stability of the esomeprazole sodium for injection is good, and the marked amount of the esomeprazole sodium contained in the injection is basically unchanged within 24 months; and the contents of the impurity I, the impurity II, the impurity III, the impurity IV and the impurity V are basically unchanged and still in a qualified range.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not used as limitations of the present invention.
Example 1:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 1.0g of edetate disodium, 0.3g of disodium hydrogen phosphate and 0.5g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 11.0-11.3 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Example 2:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 1.0g of edetate disodium, 0.5g of disodium hydrogen phosphate and 0.3g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 11.4-11.5 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Example 3:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 1.0g of edetate disodium, 0.5g of disodium hydrogen phosphate and 0.5g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 11.5-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
A process for the preparation of esomeprazole sodium for injection as described in examples 1-3, comprising the steps of:
s1, preparing liquid: filling nitrogen into the liquid preparation tank, adding about 8.0kg of water for injection under the condition of keeping nitrogen introduction, and cooling to below 25 ℃; adding the prescribed dose of edetate disodium, disodium hydrogen phosphate and vitamin E, and adjusting the pH value by using 1mol/L sodium hydroxide solution; adding prescribed amount of esomeprazole sodium, fixing the volume with injection water, sterilizing and filtering the dissolved liquid medicine, and storing in a collecting tank; the sterilization filtration adopts a polyether sulfone filter of 0.2 mu m to press the filter into a collection tank;
s2, cleaning: respectively cleaning and sterilizing the injection bottle, the rubber plug and the aluminum cover, and specifically:
the injection bottle cleaning process is as follows:
sequentially carrying out ultrasonic cleaning, purified water flushing and injection water flushing, and then blowing by using compressed air;
the cleaning process of the rubber plug is as follows:
rinsing for multiple times by using a rubber plug cleaning machine, then sequentially sterilizing, vacuum drying, hot air drying and naturally cooling;
the cleaning process of the aluminum cover is as follows:
cleaning by using an aluminum cover cleaning machine, then sequentially performing steam sterilization, vacuum drying and hot air drying, and then naturally cooling;
s3, filling: filling the liquid medicine into an injection bottle according to the amount by a filling machine, and then performing semi-stoppering treatment;
s4, freeze drying, which comprises the following steps:
s41, pre-freezing and cooling: the temperature of the plate layer is controlled to be-35 ℃ and the time is 0.5 hour;
s42, first heat preservation: the temperature of the plate layer is controlled to be-35 ℃ and the time is 2.5 hours;
s43, second heat preservation: controlling the temperature of the plate layer to be-35 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s45, first heating and drying: controlling the temperature of the plate layer to be 3 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s46, third heat preservation: controlling the temperature of the plate layer to be 3 ℃, the time to be 5 hours and setting the vacuum degree to be 200 mu bar;
s47, second heating and drying: controlling the temperature of the plate layer to be 35 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s48, fourth heat preservation: controlling the temperature of the plate layer to be 35 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
and S5, sequentially carrying out full pressure, capping, sterilization and lamp inspection on the rubber plug.
Comparative example 1:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium and 1.0g of edetate disodium; the formulation is dissolved by water for injection, the pH value is adjusted to 11.5-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Comparative example 2:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium and 2.0g of edetate disodium; the formulation is dissolved by water for injection, the pH value is adjusted to 11.5-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Comparative example 3:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium and 0.5g of disodium hydrogen phosphate; the formulation is dissolved by water for injection, the pH value is adjusted to 11.5-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Comparative example 4:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium and 0.8g of disodium hydrogen phosphate; the formulation is dissolved by water for injection, the pH value is adjusted to 11.5-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Comparative example 5:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 0.5g of disodium hydrogen phosphate and 0.5g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 11.5-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Comparative example 6:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 1.0g of edetate disodium and 0.5g of disodium hydrogen phosphate; the formulation is dissolved by water for injection, the pH value is adjusted to 11.5-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Comparative example 7:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 1.0g of edetate disodium and 0.5g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 11.5-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
Comparative example 8:
the prescription of esomeprazole sodium for injection is as follows: 42.6g of esomeprazole sodium, 1.0g of edetate disodium, 0.3g of disodium hydrogen phosphate and 0.5g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 10.5 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
The detection is carried out according to (Chinese pharmacopoeia) 2015 edition, and the detection results are shown in tables 1 and 2:
TABLE 1 alkalinity test results
TABLE 2 measurement results of effective content (%, wherein the standard content is 97.0% to 109.0% of the labeled amount)
Wherein, the impurity contents of the examples 1 to 3 and the comparative examples 1 to 7 are all in accordance with the standard along with the time, and the appearance shape is white freeze-dried block, and the table comparison is not listed.
As can be seen from the data in tables 1 and 2:
1) through the compounding of the edetate disodium, the disodium hydrogen phosphate and the vitamin E, the stability effect of the preparation is obviously superior to that of the preparation added with one or two of the edetate disodium, the disodium hydrogen phosphate and the vitamin E.
2) The pH of the formulation to which disodium hydrogen phosphate was added was substantially unchanged over time, and the pH of the formulation to which disodium hydrogen phosphate was not added was changed over time.
3) According to the invention, by adding disodium hydrogen phosphate and vitamin E, the dosage of edetate disodium can be reduced, the stability of the preparation can be improved, and excessive chelating agents are avoided.
4) The initial pH of the formulation has some effect on the stability of the formulation.
In conclusion, the stability of the preparation can be obviously improved by adding a small amount of chelating agent disodium edetate and compounding the disodium hydrogen phosphate and the vitamin E.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (10)
1. The esomeprazole sodium for injection is characterized by comprising the following components in parts by weight: 42.6g of esomeprazole sodium, 1.0g of edetate disodium, 0.3-0.5g of disodium hydrogen phosphate and 0.3-0.5g of vitamin E; the formulation is dissolved by water for injection, the pH value is adjusted to 11.0-11.8 by sodium hydroxide with the concentration of 1mol/L, the volume is fixed to 1000mL by the water for injection, and 1000 bottles of injection preparations are prepared.
2. The esomeprazole sodium for injection according to claim 1, wherein the disodium hydrogen phosphate is 0.5g and the vitamin E is 0.5 g.
3. A process for the preparation of esomeprazole sodium for injection according to claim 1 or 2, comprising the steps of:
s1, preparing liquid: dissolving esomeprazole sodium, edetate disodium and disodium hydrogen phosphate by using water for injection, adjusting the pH value to 11.0-11.8 by using sodium hydroxide with the concentration of 1mol/L, and fixing the volume to 1000mL by using the water for injection to form liquid medicine;
s2, cleaning: respectively cleaning and sterilizing the injection bottle, the rubber plug and the aluminum cover;
s3, filling: filling the liquid medicine into an injection bottle according to the amount by a filling machine, and then performing semi-stoppering treatment;
s4, freeze drying;
and S5, performing full pressure and capping of the rubber plug in sequence.
4. The preparation method of esomeprazole sodium for injection according to claim 3, wherein the specific process of preparing the solution in step S1 is as follows:
filling nitrogen into the liquid preparation tank, adding about 8.0kg of water for injection under the condition of keeping nitrogen introduction, and cooling to below 25 ℃; adding the edetate disodium, the disodium hydrogen phosphate and the vitamin E according to the prescription amount, and adjusting the pH value to 11.0-11.8 by using 1mol/L sodium hydroxide solution; adding prescribed amount of esomeprazole sodium, diluting to constant volume with water for injection, sterilizing, filtering, and storing in a collecting tank.
5. The process for preparing esomeprazole sodium for injection according to claim 4, wherein the sterilizing filtration is performed using a 0.2 μm polyethersulfone filter pressed into a collection tank.
6. The method for preparing esomeprazole sodium for injection according to claim 3, wherein the freeze-drying in step S4 comprises the following specific steps:
s41, pre-freezing and cooling: the temperature of the plate layer is controlled to be-35 ℃ and the time is 0.5 hour;
s42, first heat preservation: the temperature of the plate layer is controlled to be-35 ℃ and the time is 2.5 hours;
s43, second heat preservation: controlling the temperature of the plate layer to be-35 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s45, first heating and drying: controlling the temperature of the plate layer to be 3 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s46, third heat preservation: controlling the temperature of the plate layer to be 3 ℃, the time to be 5 hours and setting the vacuum degree to be 200 mu bar;
s47, second heating and drying: controlling the temperature of the plate layer to be 35 ℃, the time to be 3 hours and setting the vacuum degree to be 200 mu bar;
s48, fourth heat preservation: the temperature of the plate layer is controlled to be 35 ℃, the time is 3 hours, and the vacuum degree is set to be 200 mu bar.
7. The process for preparing esomeprazole sodium for injection according to claim 3, wherein the disodium hydrogen phosphate is 0.5g and the vitamin E is 0.5 g.
8. The process for preparing esomeprazole sodium for injection according to claim 3, wherein the cleaning process of the injection bottle is as follows:
ultrasonic cleaning, purified water washing and injection water washing are sequentially carried out, and then compressed air is used for blow-drying.
9. The preparation method of esomeprazole sodium for injection according to claim 3, wherein the cleaning process of the rubber plug is as follows:
rinsing for multiple times by using a rubber plug cleaning machine, and then sequentially sterilizing, vacuum drying, hot air drying and naturally cooling.
10. The process for preparing esomeprazole sodium for injection according to claim 3, wherein the cleaning process of the aluminum cap is as follows:
cleaning with an aluminum cover cleaning machine, sequentially performing steam sterilization, vacuum drying, hot air drying, and naturally cooling.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101283986A (en) * | 2008-06-03 | 2008-10-15 | 海南瑞基药物研究有限公司 | Omeprazole freeze-dried powder injection and preparation method thereof |
| CN101632667A (en) * | 2009-06-03 | 2010-01-27 | 邓菊娟 | New application of injection omeprazole sodium for treating gastric mucosa-associated lymphoid tissue lymphoma |
| CN102657622A (en) * | 2012-05-17 | 2012-09-12 | 康普药业股份有限公司 | Preparation process of freeze-dry powder injection containing esomeprazole sodium |
| CN104161732A (en) * | 2013-05-17 | 2014-11-26 | 福建省闽东力捷迅药业有限公司 | Sodium omeprazole for injection, preparation method and application thereof |
| CN107982261A (en) * | 2017-11-30 | 2018-05-04 | 乐普药业股份有限公司 | A kind of esomeprazole sodium freeze dry and preparation method thereof |
| CN108553413A (en) * | 2018-05-25 | 2018-09-21 | 福安药业集团湖北人民制药有限公司 | Injection esomeprazole sodium |
| CN108785259A (en) * | 2017-12-27 | 2018-11-13 | 成都国为生物医药有限公司 | A kind of pharmaceutical composition and preparation method thereof containing esomeprazole sodium |
-
2020
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Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101283986A (en) * | 2008-06-03 | 2008-10-15 | 海南瑞基药物研究有限公司 | Omeprazole freeze-dried powder injection and preparation method thereof |
| CN101632667A (en) * | 2009-06-03 | 2010-01-27 | 邓菊娟 | New application of injection omeprazole sodium for treating gastric mucosa-associated lymphoid tissue lymphoma |
| CN102657622A (en) * | 2012-05-17 | 2012-09-12 | 康普药业股份有限公司 | Preparation process of freeze-dry powder injection containing esomeprazole sodium |
| CN104161732A (en) * | 2013-05-17 | 2014-11-26 | 福建省闽东力捷迅药业有限公司 | Sodium omeprazole for injection, preparation method and application thereof |
| CN107982261A (en) * | 2017-11-30 | 2018-05-04 | 乐普药业股份有限公司 | A kind of esomeprazole sodium freeze dry and preparation method thereof |
| CN108785259A (en) * | 2017-12-27 | 2018-11-13 | 成都国为生物医药有限公司 | A kind of pharmaceutical composition and preparation method thereof containing esomeprazole sodium |
| CN108553413A (en) * | 2018-05-25 | 2018-09-21 | 福安药业集团湖北人民制药有限公司 | Injection esomeprazole sodium |
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