CN101347429A - Stable tartaric acid ifenprodil injection and method of preparing the same - Google Patents
Stable tartaric acid ifenprodil injection and method of preparing the same Download PDFInfo
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- CN101347429A CN101347429A CNA2007101301453A CN200710130145A CN101347429A CN 101347429 A CN101347429 A CN 101347429A CN A2007101301453 A CNA2007101301453 A CN A2007101301453A CN 200710130145 A CN200710130145 A CN 200710130145A CN 101347429 A CN101347429 A CN 101347429A
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- ifenprodil tartrate
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Abstract
The invention discloses a stable ifenprodil tartrate injection which contains ifenprodil tartrate, an osmotic pressure regulator, a pH regulator and water for injection. The invention also discloses a preparation method of the stable injection. The stable ifenprodil tartrate injection is obtained by controlling the range of the pH value of the solution and insulating oxygen, thus avoiding use of an antioxidant and possible adverse reactions thereof. Sterility tests, accelerated tests and long duration tests prove the stable ifenprodil tartrate injection.
Description
Technical field
The present invention relates to drug preparation technique, more particularly, relate to a kind of stable Ifenprodil Tartrate injection and preparation method thereof
Background technology
Ifenprodil Tartrate grinds (U.S. Pat 3509164, April 28 1970 day for announcing) by the French Sanofi-Synthelabo head of company.Ifenprodil Tartrate, chemical name: (1RS, 2RS)-2-(4-benzyl piepridine base)-1-(4-hydroxy phenyl)-1-propanol-(2R, 3R)-half tartrate semihydrate, existing relevant patent of its tablet and preparation method thereof and bibliographical information, but Ifenprodil Tartrate injection and preparation method thereof is not seen relevant patent and bibliographical information.Phenolic hydroxy group in the structure of Ifenprodil Tartrate, can with heavy metal ion complexation colour generation, reveal and to put easily oxidation in the air.Do not having on the basis of data of literatures this product to be developed to injection, it is challenging solving its stability problem.
Summary of the invention
By the structural analysis of paratartaric acid ifenprodil, find that this product is oxidized easily.By study tour to sodium pyrosulfite, EDTA, EDTA-2Na, sodium sulfite, thiourea, PG, Vc, methionine etc., the inventor is surprised to find, under the condition that does not contain above-mentioned antioxidant, can obtain the highly stable Ifenprodil Tartrate injection of character by oxygen barrier and control injection pH value scope.
The purpose of this invention is to provide a kind of stable Ifenprodil Tartrate injection.
Another object of the present invention provides the preparation method of above-mentioned injection.
The objective of the invention is to reach by following measure:
The invention provides a kind of stable Ifenprodil Tartrate injection, it contains Ifenprodil Tartrate semihydrate, osmotic pressure regulator, pH regulator agent and water for injection.
Wherein the content of Ifenprodil Tartrate semihydrate is 0.01%-2%W/V, preferred 0.1%-1%W/V, preferred especially 0.25%W/V.
Described osmotic pressure regulator in order to regulate the preparation osmotic pressure, is selected from one or more combination of sodium chloride, glucose, dextran, sodium sulfate, mannitol, is preferably sodium sulfate.Its consumption is 1.1%-1.5%, preferred 1.3-1.5%W/V.
Described pH regulator agent, be used to regulate the pH of preparation, increase preparation stability, be selected from: the combination of one or more of hydrochloric acid, methanesulfonic acid, sulphuric acid, citric acid, tartaric acid, maleic acid, phosphoric acid, sodium hydroxide, sodium bicarbonate, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium citrate, acetic acid, sodium acetate, lactic acid, sodium lactate, malic acid, natrium malicum.Be preferably one or several following combinations: hydrochloric acid, tartaric acid, sodium hydroxide.The pH value of control solution, preferably in 5.5～7.5 scopes, preferred especially pH value is in 6.7～7.2 scopes.
The preparation method of Ifenprodil Tartrate injection of the present invention comprises the following steps:
(1) osmotic pressure regulator is dissolved in the water for injection;
(2) with the Ifenprodil Tartrate hemihydrate dissolves in the isosmotic solution that step (1) obtains;
(3) with the pH value of pH regulator agent regulator solution, pH value of solution is in 5.5～7.5 scopes, and preferred pH is 6.7～7.2;
(4) the Ifenprodil Tartrate injection takes the one or more combination of following formula method to carry out oxygen barrier in preparation process:
A, logical carbon dioxide oxygen barrier.
B, logical nitrogen oxygen barrier.
C, logical argon oxygen barrier.
D, evacuation oxygen barrier.
Stable Ifenprodil Tartrate injection provided by the present invention, its beneficial technical effects is embodied in:
1. avoided in injection, adding antioxidant, thereby reduced the cost of product, also reduced the risk of product generation untoward reaction simultaneously.
2. through sterile test, accelerated test, long term test, proved that further Ifenprodil Tartrate injection of the present invention is stable (the results are shown in Table one, two, three)
The specific embodiment
By embodiment preferred the present invention is described now.Provide these embodiment and be in order to help better to understand the present invention, rather than as limit, for a person skilled in the art, under instruction of the present invention, the modification that the specific embodiment is carried out still belongs to protection scope of the present invention.
Embodiment 1
Ifenprodil Tartrate 5g,
Sodium sulfate 30g,
Tartaric acid or sodium hydroxide are regulated pH6.7～7.2,
Water for injection 2000ml
A. by above-mentioned preparation prescription, take by weighing sodium sulfate 30g, add 40 ℃～80 ℃ water for injection 2000mL dissolving.
B. adopt tartaric acid or sodium hydrate regulator solution pH6.7～7.2, add Ifenprodil Tartrate 5g, dissolving.
C. filter with the microporous filter membrane of 0.8um, detect pH, clarity and the content of filtrate, be sub-packed in the clean ampoule after qualified, loading amount is not less than 2.15ml.
D. logical nitrogen sealing by fusing gets semi-finished product.
Adopted 100 ℃ of water-bath sterilizations 40 minutes and leak detection.
Embodiment 2
Ifenprodil Tartrate 20g,
Sodium sulfate 22g,
Hydrochloric acid or sodium hydroxide are regulated pH6.7～7.2,
Water for injection 2000ml
A. by above-mentioned preparation prescription, take by weighing sodium sulfate 22g, add 40 ℃～80 ℃ water for injection 2000mL dissolving.
B. adopt hydrochloric acid or sodium hydrate regulator solution pH6.7～7.2, add Ifenprodil Tartrate 20g, dissolving.
C. filter with the microporous filter membrane of 0.8um, detect pH, clarity and the content of filtrate, be sub-packed in the clean ampoule after qualified, loading amount must not be less than 2.15ml.
D. logical argon sealing by fusing gets semi-finished product.
Adopted 100 ℃ of water-bath sterilizations 40 minutes and leak detection.
Embodiment 3
Ifenprodil Tartrate 20g,
Sodium sulfate 139g,
Tartaric acid or sodium hydroxide are regulated pH6.7～7.2,
Water for injection 10000ml
A. by above-mentioned preparation prescription, take by weighing sodium sulfate 139g, add 40 ℃～80 ℃ water for injection 10000mL dissolving.
B. adopt tartaric acid or sodium hydrate regulator solution pH6.7～7.2, add Ifenprodil Tartrate 20g, dissolving.
C. filter with the microporous filter membrane of 0.8um, detect pH, clarity and the content of filtrate, be sub-packed in the clean ampoule after qualified, loading amount is not less than 2.15ml.
D. logical nitrogen sealing by fusing gets semi-finished product.
Adopted 100 ℃ of water-bath sterilizations 40 minutes and leak detection.
Embodiment 4
Injection of the present invention is carried out sterile test, accelerated test and long term test respectively investigate, investigate result such as table one to three.Investigate through sterilization, the injection pH value is stable in 5.5 to 7.5 scopes; Further accelerated test, long term test investigation result show that the product stability that feeds noble gas in pH value 6.7 to 7.2 scopes is more excellent.Below test is the product of embodiment 1.
1. sterile test
Show the investigation result contrast of a pair of injection sterile test front and back
| PH value before the sterilization | Sterilization back pH value | Character before the sterilization | Sterilization back character | Related substance before the sterilization | Sterilization back related substance |
| 3 | 3.2 | Colourless clear liquid | Colourless clear liquid | 0.38 | 1.73 |
| 3.5 | 3.6 | Colourless clear liquid | Colourless clear liquid | 0.40 | 1.26 |
| 4.0 | 4.1 | Colourless clear liquid | Colourless clear liquid | 0.41 | 1.10 |
| 4.5 | 4.5 | Colourless clear liquid | Colourless clear liquid | 0.40 | 1.03 |
| 5.0 | 5.0 | Colourless clear liquid | Colourless clear liquid | 0.41 | 0.78 |
| 5.5 | 5.5 | Colourless clear liquid | Colourless clear liquid | 0.40 | 0.56 |
| 6.0 | 6.1 | Colourless clear liquid | Colourless clear liquid | 0.40 | 0.52 |
| 6.5 | 6.5 | Colourless clear liquid | Colourless clear liquid | 0.42 | 0.47 |
| 7.0 | 7.0 | Colourless clear liquid | Colourless clear liquid | 0.41 | 0.44 |
| 7.5 | 7.5 | Colourless clear liquid | Colourless clear liquid | 0.40 | 0.49 |
| 8.0 | 8.0 | Colourless clear liquid | Colourless clear liquid | 0.47 | 2.34 |
Result of the test shows: investigate through sterilization, the prescription pH value is basicly stable in 5.5 to 7.5 scopes.
2. accelerated test
Table two accelerated test is investigated the result
Remarks: "+" expression is connected with protective gas; "-" illogical protective gas.
Result of the test shows: in stable p H scope, solution is highly stable in the condition accelerated test that is connected with protective gas.
3. long term test
Table three long term test is investigated the result
Remarks: "+" expression is connected with protective gas; "-" illogical protective gas.
Long-term test results shows: solution-stabilized.
Claims (10)
1. a stable Ifenprodil Tartrate injection is characterized in that this injection contains Ifenprodil Tartrate, osmotic pressure regulator, pH regulator agent and water for injection.
2. injection according to claim 1 wherein contains the Ifenprodil Tartrate semihydrate of 0.1%-1%W/V, the osmotic pressure regulator of 1.1%-1.5%W/V.
3. injection according to claim 1 and 2, the pH value scope of described injection is 5.5-7.5
4. injection according to claim 3, the pH scope of wherein said solution is preferably at 6.7-7.2.
5. injection according to claim 1 and 2, wherein the pH regulator agent is selected from one or more combination of hydrochloric acid, methanesulfonic acid, sulphuric acid, citric acid, tartaric acid, maleic acid, phosphoric acid, sodium hydroxide, sodium bicarbonate, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium citrate, acetic acid, sodium acetate, lactic acid, sodium lactate, malic acid, natrium malicum.
6. injection according to claim 5, wherein said pH regulator agent are the combination of following one or several:
Hydrochloric acid, tartaric acid, sodium hydroxide.
7. injection according to claim 1 and 2, wherein said osmotic pressure regulator are one or more combination of sodium chloride, glucose, dextran, sodium sulfate, mannitol.
8. injection according to claim 7, wherein said osmotic pressure regulator are sodium sulfate.
9. injection according to claim 1 and 2, it comprises that further described injection preserved by oxygen barrier.
10. the preparation method of a stable Ifenprodil Tartrate injection, it comprises the steps:
(1) osmotic pressure regulator is dissolved in the water for injection;
(2) with the Ifenprodil Tartrate hemihydrate dissolves in the isosmotic solution that step (1) obtains;
(3) with the pH value of pH regulator agent regulator solution, pH value of solution is in 5.5～7.5 scopes;
(4) the Ifenprodil Tartrate injection takes the one or more combination of following formula method to carry out oxygen barrier in preparation process:
A, logical carbon dioxide oxygen barrier.
B, logical nitrogen oxygen barrier.
C, logical argon oxygen barrier.
D, evacuation oxygen barrier.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2007101301453A CN101347429A (en) | 2007-07-20 | 2007-07-20 | Stable tartaric acid ifenprodil injection and method of preparing the same |
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| CNA2007101301453A CN101347429A (en) | 2007-07-20 | 2007-07-20 | Stable tartaric acid ifenprodil injection and method of preparing the same |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102133198A (en) * | 2011-03-09 | 2011-07-27 | 北京四环科宝制药有限公司 | Ifenprodil tartrate freeze-dried powder injection and preparation method thereof |
| CN106109406A (en) * | 2016-08-09 | 2016-11-16 | 成都佳迪璐莎生物科技有限公司 | Improve the medicinal composition for injections of breviscapine drug injection preparation stability |
| CN106176590A (en) * | 2016-08-09 | 2016-12-07 | 成都佳迪璐莎生物科技有限公司 | Improve the preparation method of quinidine sulfate ejection preparation stability composition |
| CN106176588A (en) * | 2016-08-09 | 2016-12-07 | 成都佳迪璐莎生物科技有限公司 | Improve the preparation method of composition of Codeine Hydrochloride ejection preparation stability |
| CN106176589A (en) * | 2016-08-09 | 2016-12-07 | 成都佳迪璐莎生物科技有限公司 | Improve the medicinal composition for injections of quinidine sulfate drug injection preparation stability |
| CN106214629A (en) * | 2016-08-09 | 2016-12-14 | 成都佳迪璐莎生物科技有限公司 | A kind of preparation method of breviscapine drug injection preparation stability compositions |
| CN106214630A (en) * | 2016-08-09 | 2016-12-14 | 成都佳迪璐莎生物科技有限公司 | Improve the preparation method of the pharmaceutical composition of Venenum apis drug injection preparation stability |
| CN106265493A (en) * | 2016-08-09 | 2017-01-04 | 成都佳迪璐莎生物科技有限公司 | Improve the pharmaceutical composition of Codeine Hydrochloride drug injection preparation stability |
| CN108969541A (en) * | 2018-10-23 | 2018-12-11 | 广西中医药大学 | Leech injection preparation process |
-
2007
- 2007-07-20 CN CNA2007101301453A patent/CN101347429A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102133198A (en) * | 2011-03-09 | 2011-07-27 | 北京四环科宝制药有限公司 | Ifenprodil tartrate freeze-dried powder injection and preparation method thereof |
| CN102133198B (en) * | 2011-03-09 | 2012-02-08 | 北京四环科宝制药有限公司 | Ifenprodil tartrate freeze-dried powder injection and preparation method thereof |
| CN106109406A (en) * | 2016-08-09 | 2016-11-16 | 成都佳迪璐莎生物科技有限公司 | Improve the medicinal composition for injections of breviscapine drug injection preparation stability |
| CN106176590A (en) * | 2016-08-09 | 2016-12-07 | 成都佳迪璐莎生物科技有限公司 | Improve the preparation method of quinidine sulfate ejection preparation stability composition |
| CN106176588A (en) * | 2016-08-09 | 2016-12-07 | 成都佳迪璐莎生物科技有限公司 | Improve the preparation method of composition of Codeine Hydrochloride ejection preparation stability |
| CN106176589A (en) * | 2016-08-09 | 2016-12-07 | 成都佳迪璐莎生物科技有限公司 | Improve the medicinal composition for injections of quinidine sulfate drug injection preparation stability |
| CN106214629A (en) * | 2016-08-09 | 2016-12-14 | 成都佳迪璐莎生物科技有限公司 | A kind of preparation method of breviscapine drug injection preparation stability compositions |
| CN106214630A (en) * | 2016-08-09 | 2016-12-14 | 成都佳迪璐莎生物科技有限公司 | Improve the preparation method of the pharmaceutical composition of Venenum apis drug injection preparation stability |
| CN106265493A (en) * | 2016-08-09 | 2017-01-04 | 成都佳迪璐莎生物科技有限公司 | Improve the pharmaceutical composition of Codeine Hydrochloride drug injection preparation stability |
| CN108969541A (en) * | 2018-10-23 | 2018-12-11 | 广西中医药大学 | Leech injection preparation process |
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Application publication date: 20090121 |