CN1596893A - Cimetidine freeze-dried powder-injection and its preparation method - Google Patents
Cimetidine freeze-dried powder-injection and its preparation method Download PDFInfo
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- CN1596893A CN1596893A CN 200410021576 CN200410021576A CN1596893A CN 1596893 A CN1596893 A CN 1596893A CN 200410021576 CN200410021576 CN 200410021576 CN 200410021576 A CN200410021576 A CN 200410021576A CN 1596893 A CN1596893 A CN 1596893A
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Abstract
A freeze-dried powder injection of cimetidine for treating gastric ulcer, duodenal ulcer, stress ulcer, etc is prepared through dissolving cimetidine in diluted hydrochloric acid, adding freeze-drying supporter and isotonic regulator, stirring, regulating pH=4-7, adding water for injection, filter and freeze drying.
Description
Technical field:
The present invention relates to freeze-drying preparation for injection, especially about cimetidine freeze dried preparation and preparation method thereof.
Background technology:
Cimetidine is according to the theoretical excretory H of histamine of first gastric acid inhibitory that develops of receptor
2Receptor antagonist by competitive inhibition mechanism, is used to block histamine at first to parietal cell H
2The effect of receptor.Went on the market in the Britain and the U.S. respectively in 1976 and 1977, because of it has tangible curative effect for duodenal ulcer, more than 100 country is able to extensive use in the world, the existing millions of patient in the whole world obtains satisfied curative effect, also is one of medicine of present most widely used treatment Peptic Ulcers.To nineteen ninety, the sales volume of cimetidine has occupied third in global medicine; Nineteen ninety-five, the global demand amount of this medicine reaches 1.5 ten thousand tons, and becomes in the world that first kind of sales volume breaks through 100,000,000 dollars medicine.China's gastropathy sickness rate occupies prostatitis, the world always, and the trend that rises is year by year arranged at present, so China patient being in great demand to such medicine.In addition, because upper gastrointestinal hemorrhage is a kind of multiple commonly encountered diseases in many developing countries, this also increases share for a large amount of outlets of China's cimetidine preparation.Although H of new generation
2Receptor antagonist such as ranitidine, famotidine and omeprazole etc. go on the market in succession, but cimetidine is low because of its determined curative effect, price, still is widely used.Except digestive system disease such as treatment gastric ulcer, also have effects such as immunomodulating, antiviral, antiandrogen, be the good old medicine of potential applicability in clinical practice.
At present, the dosage form of selling on the domestic and international market has ordinary tablet, capsule, chewable tablet, slow releasing tablet, Orally taken emulsion, cimetidine inj etc.Need after oral formulations such as tablet and capsule is oral to make drug effect slow through processes such as disintegrate, stripping, absorptions; Intravenously administrable is rapid-action, good effect, and freeze-dried formulation has more good stability, is easy to preserve transportation, advantage such as safe and convenient to use.Cimetidine is made freeze-dried powder injection, from increasing medicine stability, improve the multiformity of clinical practice, and adapt to aspect such as great demand and consider all to have certain advantage.
Summary of the invention:
The purpose of this invention is to provide cimetidine freeze dried preparation of a kind of injection and preparation method thereof.This freeze-drying preparation for injection is white powder or loose blocks of solid preparation.The convenient storage and transportation; By drug administration by injection, rapid-action, the bioavailability height, nontoxic, nonirritant, good biocompatibility, the lyophilizing rear stability is better, is easier to storage and transport.This freeze-drying preparation for injection is suitable for treating digestive system disease such as gastric ulcer, duodenal ulcer, stress ulcer, gastrointestinal hemorrhage.This freeze-drying preparation for injection is an active substance with the cimetidine, is aided with frozen-dried supporting agent, isoosmotic adjusting agent, and the pH regulator agent reaches the lyophilized formulations that water makes through lyophilization.
The injection cimetidine is made up of following component:
Constituent content (weight %)
Cimetidine 0.05-0.2
Frozen-dried supporting agent 5-15
Isoosmotic adjusting agent 0.1-0.5
It is 4-7 that the preparation pH value is regulated in the pH regulator agent
Water is an amount of
Active component cimetidine in the freeze-drying preparation for injection of the present invention, cimetidine are the mixture of A crystal formation, AB mixing crystal formation or A crystal formation and AB crystal formation.
Frozen-dried supporting agent is one or more the mixture that is selected from glucose, lactose, dextran, mannitol, sorbitol, arginine, glycine, the gelatin hydrolysate;
Isoosmotic adjusting agent is the material that is selected from sodium chloride, glucose, mannitol, sorbitol and the like;
The pH regulator agent is to adopt hydrochloric acid, sodium hydroxide, sodium bicarbonate, citric acid, sodium citrate, glacial acetic acid, triethanolamine.
The preparation method of freeze-drying preparation for injection of the present invention, step is as follows:
The preparation of medicinal liquid by above-mentioned prescription weighing, is dissolved in dilute hydrochloric acid solution with cimetidine, adds frozen-dried supporting agent, isoosmotic adjusting agent stirring and dissolving again, and regulating pH with the pH regulator agent is 4-7, adds sterile water for injection to total amount; Medicinal liquid removes thermal source with active carbon, will add active carbon in the above-mentioned medicinal liquid solution, and consumption is 0.05-1.0% (w/v), 80 ℃ of heating 15-60 minute, while hot or cooled and filtered; The above-mentioned medicinal liquid that removes thermal source is the microporous filter membrane of 0.22 μ m by the aperture; Solidify through lyophilization, method is will be through the medicinal liquid of degerming/sterilization in-30--80 ℃ pre-freeze 20-180 minute under the aseptic condition, in vacuum is 5-50Pa, temperature is-and 10--30 ℃ following vacuum lyophilization 8-24 hour, then at temperature 5-30 ℃ of following vacuum drying 2-12 hour; Quality Identification is carried out in sampling, qualified after, packing is promptly.
The physicochemical character of formulation products of the present invention: this product is white powder or loose blocks of solid.
Freeze-dried preparation of the present invention is applicable to treatment gastric ulcer, duodenal ulcer, stress ulcer, digestive system disease such as gastrointestinal hemorrhage.Dissolve with sterile water for injection during use, but intravenous injection or with 5% glucose injection or 0.9% sodium chloride injection dilution back intramuscular injection or intravenous drip.
Advantage of the present invention is: this freeze-drying preparation for injection is white powder or loose blocks of solid preparation.The convenient storage and transportation; By drug administration by injection, rapid-action, the bioavailability height, nontoxic, nonirritant, good biocompatibility, the lyophilizing rear stability is better, is easier to storage and transport.This freeze-drying preparation for injection is suitable for treating digestive system disease such as gastric ulcer, duodenal ulcer, stress ulcer, gastrointestinal hemorrhage.
The specific embodiment:
Embodiment 1
Get 10% dilute hydrochloric acid 300ml,, stir and make it dissolving, add water for injection 1.5kg, add mannitol 0.2kg again, stirring and dissolving with cimetidine (A crystal formation) 0.2kg.Regulating pH with 10%NaOH solution is 5.0, and adding water for injection to cumulative volume once more is 2L; Add the 2g active carbon in the medicinal liquid, 80 ℃ were heated 20 minutes while stirring, and filtrate is put cold after-filtration de-carbon, and medicinal liquid is the filtering with microporous membrane of 0.22 μ m again through the aperture; Quality Identification is carried out in sampling, qualified back aseptic subpackaged in cillin bottle the 2ml/ bottle, in-40 ℃ of pre-freezes 3 hours, be 20Pa in vacuum, temperature is-20 ℃ of following vacuum lyophilizations 12 hours, then 15 ℃ of following vacuum dryings of temperature 4 hours; Quality Identification is carried out in sampling, qualified after, packing is promptly.
Embodiment 2
Get 10% dilute hydrochloric acid 300ml,, stir and make it dissolving, add water for injection 1.5kg, add mannitol 0.2kg again, stirring and dissolving with cimetidine (AB mixing crystal formation) 0.2kg.Regulating pH with 10%NaOH solution is 5.0, and adding water for injection to cumulative volume once more is 2L; Add the 2g active carbon in the medicinal liquid, 80 ℃ were heated 20 minutes while stirring, and filtrate is put cold after-filtration de-carbon, and medicinal liquid is the filtering with microporous membrane of 0.22 μ m again through the aperture; Quality Identification is carried out in sampling, qualified back aseptic subpackaged in cillin bottle the 2ml/ bottle, in-40 ℃ of pre-freezes 3 hours, be 20Pa in vacuum, temperature is-20 ℃ of following vacuum lyophilizations 12 hours, then 15 ℃ of following vacuum dryings of temperature 4 hours; Quality Identification is carried out in sampling, qualified after, packing is promptly.
Embodiment 3
Get 10% dilute hydrochloric acid 300ml,, stir and make it dissolving, add water for injection 1.5kg, add mannitol 0.16kg and sodium chloride 0.05kg again, stirring and dissolving with cimetidine (A crystal formation) 0.2kg.Regulating pH with 10%NaOH solution is 5.0, and adding water for injection to cumulative volume once more is 2L; Add the 2g active carbon in the medicinal liquid, 80 ℃ were heated 20 minutes while stirring, and filtrate is put cold after-filtration de-carbon, and medicinal liquid is the filtering with microporous membrane of 0.2 μ m again through the aperture; Quality Identification is carried out in sampling, qualified back aseptic subpackaged in cillin bottle the 2ml/ bottle, in-40 ℃ of pre-freezes 3 hours, be 20Pa in vacuum, temperature is-20 ℃ of following vacuum lyophilizations 12 hours, then 15 ℃ of following vacuum dryings of temperature 4 hours; Quality Identification is carried out in sampling, qualified after, packing is promptly.
Embodiment 4
Get 12.5% dilute hydrochloric acid 300ml,, stir and make it dissolving, add water for injection 1.5kg, add lactose 0.2kg and sodium chloride 0.05kg again, stirring and dissolving with cimetidine (A crystal formation) 0.2kg.Regulating pH with 10%NaOH solution is 5.0, and adding water for injection to cumulative volume once more is 2L; Add the 2g active carbon in the medicinal liquid, 80 ℃ were heated 20 minutes while stirring, and filtrate is put cold after-filtration de-carbon, and medicinal liquid is the filtering with microporous membrane of 0.22 μ m again through the aperture; Quality Identification is carried out in sampling, qualified back aseptic subpackaged in cillin bottle the 2ml/ bottle, in-40 ℃ of pre-freezes 3 hours, be 20Pa in vacuum, temperature is-15 ℃ of following vacuum lyophilizations 18 hours, then 10 ℃ of following vacuum dryings of temperature 4 hours; Quality Identification is carried out in sampling, qualified after, packing is promptly.
Claims (5)
1. the cimetidine freeze dried preparation of injection is characterized in that being made up of following component:
Constituent content (weight %)
Cimetidine 0.05-0.2
Frozen-dried supporting agent 5-15
Isoosmotic adjusting agent 0-0.5
It is 4-7 that the preparation pH value is regulated in the pH regulator agent
Water is an amount of
2. freeze-drying preparation for injection according to claim 1 is characterized in that: described cimetidine is the A crystal formation, AB mixing crystal formation, or the mixture of A crystal formation and AB crystal formation.
According to right to require 1 described freeze-drying preparation for injection, it is characterized in that:
Described frozen-dried supporting agent be selected from following: the mixture of one or more in glucose, lactose, dextran, mannitol, sorbitol, arginine, glycine, the gelatin hydrolysate;
Described isoosmotic adjusting agent is to be selected from sodium chloride, glucose, mannitol, sorbitol or suchlike material;
Described pH regulator agent is to adopt hydrochloric acid, sodium hydroxide, sodium bicarbonate, citric acid, sodium citrate, glacial acetic acid.
4. freeze-drying preparation for injection according to claim 1 is characterized in that: said preparation is white powder or loose block preparation.
5. the preparation method of a freeze-drying preparation for injection as claimed in claim 1 is characterized in that:
The collocation method of medicinal liquid is, by described prescription weighing, cimetidine is dissolved in 10～12.5% dilute hydrochloric acid, adds frozen-dried supporting agent, isoosmotic adjusting agent stirring and dissolving again, and pH is 4-7 with pH regulator agent adjusting, adds sterile water for injection to total amount;
Medicinal liquid heat extraction source side method is, the activated carbon dosage that adds in the above-mentioned medicinal liquid solution is 0.05-1.0% (w/v), 80 ℃ of heating 15-60 minute, while hot or cooled and filtered;
The medicinal liquid degerming method is that the medicinal liquid that removes thermal source is the microporous filter membrane of 0.22 μ m by the aperture;
The method of freezing dry process is, aseptic condition down will be through the medicinal liquid of sterilization in-30--80 ℃ pre-freeze 20-180 minute, in vacuum is 5-50Pa, temperature is-and 10--30 ℃ following vacuum lyophilization 8-24 hour, then at temperature 5-30 ℃ of following vacuum drying 2-12 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410021576 CN1596893A (en) | 2004-07-29 | 2004-07-29 | Cimetidine freeze-dried powder-injection and its preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410021576 CN1596893A (en) | 2004-07-29 | 2004-07-29 | Cimetidine freeze-dried powder-injection and its preparation method |
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| CN1596893A true CN1596893A (en) | 2005-03-23 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102018677A (en) * | 2010-12-28 | 2011-04-20 | 哈药集团三精制药股份有限公司 | Roxatidine acetate hydrochloride used for injection and preparation method thereof |
| CN102349895A (en) * | 2011-09-28 | 2012-02-15 | 海南良方医药有限公司 | Cimetidine composition for injection and preparation method thereof |
| CN102670496A (en) * | 2012-05-25 | 2012-09-19 | 鼎正动物药业（天津）有限公司 | Cimetidine injection and preparation process |
| CN103385877A (en) * | 2013-08-02 | 2013-11-13 | 海南灵康制药有限公司 | Taxol and cimetidine pharmaceutical composition |
| CN109431982A (en) * | 2018-11-27 | 2019-03-08 | 山西诺成制药有限公司 | A kind of cimetidine in sodium chloride injection production method preventing contaminant overstandard |
| CN110623923A (en) * | 2019-10-22 | 2019-12-31 | 江苏恒丰强生物技术有限公司 | Cimetidine sodium chloride injection for dogs and preparation method thereof |
| CN112353799A (en) * | 2021-01-06 | 2021-02-12 | 福安药业集团湖北人民制药有限公司 | Cimetidine composition for injection and preparation method and application thereof |
-
2004
- 2004-07-29 CN CN 200410021576 patent/CN1596893A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102018677A (en) * | 2010-12-28 | 2011-04-20 | 哈药集团三精制药股份有限公司 | Roxatidine acetate hydrochloride used for injection and preparation method thereof |
| CN102349895A (en) * | 2011-09-28 | 2012-02-15 | 海南良方医药有限公司 | Cimetidine composition for injection and preparation method thereof |
| CN102349895B (en) * | 2011-09-28 | 2013-04-10 | 海南良方医药有限公司 | Cimetidine composition for injection and preparation method thereof |
| CN102670496A (en) * | 2012-05-25 | 2012-09-19 | 鼎正动物药业（天津）有限公司 | Cimetidine injection and preparation process |
| CN103385877A (en) * | 2013-08-02 | 2013-11-13 | 海南灵康制药有限公司 | Taxol and cimetidine pharmaceutical composition |
| CN103385877B (en) * | 2013-08-02 | 2014-04-16 | 海南灵康制药有限公司 | Taxol and cimetidine pharmaceutical composition |
| CN109431982A (en) * | 2018-11-27 | 2019-03-08 | 山西诺成制药有限公司 | A kind of cimetidine in sodium chloride injection production method preventing contaminant overstandard |
| CN110623923A (en) * | 2019-10-22 | 2019-12-31 | 江苏恒丰强生物技术有限公司 | Cimetidine sodium chloride injection for dogs and preparation method thereof |
| CN112353799A (en) * | 2021-01-06 | 2021-02-12 | 福安药业集团湖北人民制药有限公司 | Cimetidine composition for injection and preparation method and application thereof |
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