CN102225050B - Method for preparing famotidine sodium chloride injection by inclusion method and product prepared by using the same - Google Patents
Method for preparing famotidine sodium chloride injection by inclusion method and product prepared by using the same Download PDFInfo
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- CN102225050B CN102225050B CN2011101758376A CN201110175837A CN102225050B CN 102225050 B CN102225050 B CN 102225050B CN 2011101758376 A CN2011101758376 A CN 2011101758376A CN 201110175837 A CN201110175837 A CN 201110175837A CN 102225050 B CN102225050 B CN 102225050B
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- famotidine
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- sulfobutyl ether
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- sodium chloride
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Abstract
The invention relates to a method for preparing a famotidine sodium chloride injection by an inclusion method and a product prepared by using the same. The method is characterized in that sulfobutyl ether-beta-cyclodextrin is used as an including agent of famotidine, and famotidine is firstly dissolved in glacial acetic acid and then added into a sulfobutyl ether-beta-cyclodextrin saturated solution to allow sulfobutyl ether-beta-cyclodextrin to include famotidine, and the sulfobutyl ether-beta-cyclodextrin including famotidine is dissolved in water; the weight part ratio of famotidine to sulfobutyl ether-beta-cyclodextrin is (1:5)-(1:10); the quantity of glacial acetic acid is 5-7 times of that of famotidine based on weight part; and excessive sterilization at 121 DEG C for 15 minutes is adopted. The method provided by the invention has the following advantages: related substances are controlled within 2%, which is far lower than 5% of domestic like-products, and the sterilization is changed from a residual probability method to an excessive sterilization method, which ensures 100% sterilization, greatly improves product quality and enhances the safety of medicine in clinical applications.
Description
Technical field
The present invention relates to a kind of enclose legal system and be equipped with method of famotidine sodium chloride injection and products thereof, belong to biomedicine field.
Background technology
[[[2-[(diamino methylene)-4-thiazolyl] methyl] sulfo-]-N-sulfonamides third amidine is the crystalline powder of white or off-white color to famotidine chemistry 3-by name; Mildly bitter flavor; Meet photochromic deepening; Slightly soluble in methanol, soluble,very slightly in acetone, almost insoluble in water or chloroform, in glacial acetic acid, be prone to dissolve.Its fusing point is 160～165 ℃, decomposes simultaneously during fusion.The famotidine sodium chloride injection is mainly used in upper gastrointestinal hemorrhage, the Zhuo-Emhorn syndrome due to treatment peptic ulcer, acute stress ulcer and the hemorrhagic gastritis; The upper gastrointestinal hemorrhage that prevention aggressive stress (various major operations, as: cerebrovascular disorders, injury of head, multiple organs failure, large-area burns etc.) causes.Prior art be with glacial acetic acid as cosolvent, directly soluble in water, sterilising conditions adopts remaining probabilistic method; I.e. 115 degree sterilization in 30 minutes is met thermally labile because of famotidine, and related substance reaches 5%; And can not sterilize with the method for excessively killing, can not guarantee the gentle product quality of product sterilized water.
Make inclusion agents with sulfobutyl ether-β-Cyclodextrin in the present technique, make the famotidine sodium chloride injection.Sulfobutyl ether-β-Cyclodextrin is the novel ionizable cyclodextrin derivative of nineties listing, and animal toxicity research shows similar (the malicious LD50 of the oral urgency of rat＞2g/kg) with present widely used hydroxypropyl cyclodextrin of sulfobutyl ether-beta-schardinger dextrin-oral administration safety; But adjuvant as the vascular drug delivery preparation; SBE-β-CD does not have significant cytotoxicity, renal function is not had influence; And have higher water solublity, an advantage such as enclose performance preferably; Be widely used in injecting, different route of administration such as oral, eye and nasal cavity, have broad application prospects at field of medicaments.
Summary of the invention
One of the object of the invention provides the method that a kind of enclose legal system is equipped with the famotidine sodium chloride injection.
Two of the object of the invention provides a kind of famotidine sodium chloride injection of enclose method preparation.
One of the object of the invention is achieved in that employing sulfobutyl ether-beta-schardinger dextrin-is the inclusion agents of famotidine; Be dissolved in famotidine in the glacial acetic acid earlier; Add again that sulfobutyl ether-beta-schardinger dextrin-is full to be closed in the solution, by sulfobutyl ether-beta-schardinger dextrin-with the famotidine enclose after, soluble in water again.
The scope that preferably is the weight part ratio of famotidine and sulfobutyl ether-beta-schardinger dextrin-is 1:5～1:10;
Earlier sulfobutyl ether-beta-schardinger dextrin-is dissolved in the water for injection of 1～2 times of weight portion, processes that sulfobutyl ether-beta-schardinger dextrin-is full to close solution, subsequent use; After being dissolved in famotidine in 5～7 times of weight portion glacial acetic acid earlier, add again that described sulfobutyl ether-beta-schardinger dextrin-is full to be closed in the solution, get into next step technology again.
Sterilization is adopted and is excessively killed method, selects the sterilization in 15 minutes of 121 degree for use.
Further be preferably: earlier sulfobutyl ether-beta-schardinger dextrin-is dissolved in the water for injection of 1.5 times of weight portions, processes that sulfobutyl ether-beta-schardinger dextrin-is full to close solution, subsequent use; After being dissolved in famotidine in 6 times of weight portion glacial acetic acid earlier, add again that described sulfobutyl ether-beta-schardinger dextrin-is full to be closed in the solution, get into next step technology again.
Sulfobutyl ether-beta-schardinger dextrin-s of 1000～2000 parts are dissolved in the water for injection of 1.5 times of weight portions, process that sulfobutyl ether-beta-schardinger dextrin-is full to close solution, subsequent use; After being dissolved in 200 parts of famotidines in 1200 parts of glacial acetic acid, add again that described sulfobutyl ether-beta-schardinger dextrin-is full to be closed in the solution, stirred 30 minutes, add 600000 parts of waters for injection; Stir, add 9000 parts of sodium chloride again and be stirred to dissolving, add water for injection again, to the total amount of water for injection be 1000000 parts; Stir, add 200 parts of pins and use charcoal, stir 30 minutes after-filtration; The filtrating embedding, the method for excessively killing is adopted in sterilization, the sterilization in 15 minutes of 121 degree; The content of said famotidine raw material is more than 99%, and related substance is below 1%, and the related substance of the famotidine sodium chloride injection of preparation is below 2%.
Two of the object of the invention is achieved in that it is made up of following substances in parts by weight: 200 parts of famotidines, 1000～1400 parts in glacial acetic acid, 1000～2000 parts of sulfobutyl ether-beta-schardinger dextrin-s, 9000 parts in sodium chloride, 1000000 parts of waters for injection; The content of said famotidine raw material is more than 99%, and related substance is below 1%, and the related substance of famotidine sodium chloride injection is below 2%.
The present invention has obvious improvement at this aspect two, select for use sulfobutyl ether-beta-schardinger dextrin-with the medicinal liquid enclose after, soluble in water again; The dissolubility of famotidine is improved greatly, and stability is better, and is more stable to heat especially; Select the sterilization in 15 minutes of 121 degree for use, will have the related substance of famotidine sodium chloride injection can be controlled in 2%, be far superior to 5% of domestic like product; Significantly reduced related substance, sterilising conditions has become the method for excessively killing by remaining probabilistic method, guarantees that product 100% is aseptic; Improve product quality greatly, increased clinical application safety.
The specific embodiment
The present invention can do further description to the present invention through following embodiment, yet scope of the present invention is not limited to following embodiment.
Embodiment 1:
Material by following weight portion constitutes prescription:
Famotidine 200g
Glacial acetic acid 1200g
Sulfobutyl ether-beta-schardinger dextrin-1000g
Sodium chloride 9000g
Water for injection 1000000g
Make 10000 bottles altogether
Its preparation process is:
Feedstock production by following weight portion forms, and sulfobutyl ether-beta-schardinger dextrin-of 1000g is dissolved in the 1500g water for injection, processing fullly to close solution, and is subsequent use; The 200g famotidine is dissolved in the 1200g glacial acetic acid, and adds in the full sulfobutyl ether-beta-schardinger dextrin-solution that closes, stirred 30 minutes, add 600000g water for injection; Stir, add 9000g sodium chloride again and be stirred to dissolving, add 398500g water for injection at present; Stir, add the 200g pin and use charcoal, stir 30 minutes after-filtration; 10000 bottles of filtrating embeddings, the method for excessively killing is adopted in sterilization, the sterilization in 15 minutes of 121 degree.
The content of said famotidine raw material is more than 99%, and related substance is below 1%, and the related substance of the famotidine sodium chloride injection of preparation is below 2%.
Embodiment 2:
Material by following weight portion constitutes prescription:
Famotidine 200g
Glacial acetic acid 1200g
Sulfobutyl ether-beta-schardinger dextrin-1500g
Sodium chloride 9000g
Water for injection 1000000g
Make 10000 bottles altogether
Its preparation process is:
Feedstock production by following weight portion forms, and sulfobutyl ether-beta-schardinger dextrin-of 1500g is dissolved in the 2250g water for injection, processing fullly to close solution, and is subsequent use; The 200g famotidine is dissolved in the 1200g glacial acetic acid, and adds in the full sulfobutyl ether-beta-schardinger dextrin-solution that closes, stirred 30 minutes, add 600000 parts of waters for injection; Stir, add 9000g sodium chloride again and be stirred to dissolving, add 397750 waters for injection at present; Stir, add the 200g pin and use charcoal, stir 30 minutes after-filtration; The filtrating embedding, the method for excessively killing is adopted in sterilization, the sterilization in 15 minutes of 121 degree.
The content of said famotidine raw material is more than 99%, and related substance is below 1%, and the related substance of the famotidine sodium chloride injection of preparation is below 2%.
Embodiment 3:
Material by following weight portion constitutes prescription:
Famotidine 200g
Glacial acetic acid 1200g
Sulfobutyl ether-beta-schardinger dextrin-2000g
Sodium chloride 9000g
Water for injection 1000000g
Make 10000 bottles altogether
Its preparation process is:
Feedstock production by following weight portion forms, and sulfobutyl ether-beta-schardinger dextrin-of 2000g is dissolved in the 3000g water for injection, processing fullly to close solution, and is subsequent use; The 200g famotidine is dissolved in the 1200g glacial acetic acid, and adds in the full sulfobutyl ether-beta-schardinger dextrin-solution that closes, stirred 30 minutes, add 600000g water for injection; Stir, add 9000g sodium chloride again and be stirred to dissolving, add 397000g water for injection at present; Stir, add the 200g pin and use charcoal, stir 30 minutes after-filtration; The filtrating embedding, the method for excessively killing is adopted in sterilization, the sterilization in 15 minutes of 121 degree.
The content of said famotidine raw material is more than 99%, and related substance is below 1%, and the related substance of the famotidine sodium chloride injection of preparation is below 2%.
Claims (1)
1. an enclose legal system is equipped with the method for famotidine sodium chloride injection; Adopting sulfobutyl ether-beta-schardinger dextrin-is the inclusion agents of famotidine; Famotidine is dissolved in earlier in the glacial acetic acid, adds again that sulfobutyl ether-beta-schardinger dextrin-is full to be closed in the solution, by sulfobutyl ether-beta-schardinger dextrin-with the famotidine enclose after; Soluble in water again, it is characterized in that:
(1) sulfobutyl ether-beta-schardinger dextrin-of 1000～2000 parts is dissolved in the water for injection of 1.5 times of weight portions, processes that sulfobutyl ether-beta-schardinger dextrin-is full to close solution, subsequent use;
(2) after being dissolved in 200 parts of famotidines in 1200 parts of glacial acetic acid, add again that described sulfobutyl ether-beta-schardinger dextrin-is full to be closed in the solution, stirred 30 minutes, add 600000 parts of waters for injection, stir;
(3) add 9000 parts of sodium chloride again and be stirred to dissolving, add water for injection again, to the total amount of water for injection be 1000000 parts, stir;
(4) add 200 parts of pins and use charcoal, stir 30 minutes after-filtration, the filtrating embedding, the method for excessively killing is adopted in sterilization, the sterilization in 15 minutes of 121 degree;
The content of said famotidine raw material is more than 99%, and related substance is below 1%, and the related substance of the famotidine sodium chloride injection of preparation is below 2%.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011101758376A CN102225050B (en) | 2011-06-28 | 2011-06-28 | Method for preparing famotidine sodium chloride injection by inclusion method and product prepared by using the same |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011101758376A CN102225050B (en) | 2011-06-28 | 2011-06-28 | Method for preparing famotidine sodium chloride injection by inclusion method and product prepared by using the same |
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| CN102225050B true CN102225050B (en) | 2012-06-20 |
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| CN103446048A (en) * | 2013-09-12 | 2013-12-18 | 南京正宽医药科技有限公司 | Famotidine injection and preparation method thereof |
| CN114767626A (en) * | 2022-03-31 | 2022-07-22 | 天津金耀集团湖北天药药业股份有限公司 | Famotidine injection and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101380313A (en) * | 2008-10-16 | 2009-03-11 | 沈阳药科大学 | Famotidine high density type gastric retention osmotic pump controlled release preparation and preparation method thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101380313A (en) * | 2008-10-16 | 2009-03-11 | 沈阳药科大学 | Famotidine high density type gastric retention osmotic pump controlled release preparation and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| FATMA M. MADY等.Enhancement of the Aqueous Solubility and Masking the Bitter.《JOURNAL OF PHARMACEUTICAL SCIENCES》.2010,第99卷(第10期),4285-4294. * |
| 文爱东等.法莫替丁氯化钠注射液的稳定性研究.《解放军药学学报》.2002,第18卷(第2期),83. * |
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Address after: 331800 No. 6, Dongshan Industrial Park, Dongxiang Economic Development Zone, Fuzhou, Jiangxi. Patentee after: Hui Yin group Jiangxi East Asia Pharmaceutical Co., Ltd. Address before: 331800 Dongxiang Province Economic Development Zone, Dongshan Industrial Park, Fuzhou, Hui Road, No. 6, No. Patentee before: Huiyinbi Group (Jiangxi) Dongya Pharmaceutical Co., Ltd. |
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