CN1830446A - Phenoduopan methanesulphonate medicinal composition and its preparation - Google Patents
Phenoduopan methanesulphonate medicinal composition and its preparation Download PDFInfo
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- CN1830446A CN1830446A CNA2006100395177A CN200610039517A CN1830446A CN 1830446 A CN1830446 A CN 1830446A CN A2006100395177 A CNA2006100395177 A CN A2006100395177A CN 200610039517 A CN200610039517 A CN 200610039517A CN 1830446 A CN1830446 A CN 1830446A
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- fenoldopam mesylate
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Abstract
A freeze-dried powder injection of fenoldopam methylsulfonate as the D1-type dopamine receptor excitomotor is prepared from fenoldopam methylsulfonate, the pharmacologically acceptable acidic substance through preparing clear solution and freeze drying.
Description
Technical field
The present invention relates to a kind of novel pharmaceutical formulation of D1 class dopamine-receptor stimulant, be specifically related to Fenoldopam Mesylate lyophilized injectable powder and preparation method.
Background technology
Fenoldopam Mesylate (Fenoldopam Mesylate) is a kind of D1 class dopamine-receptor stimulant, is the vasodilation of a snap action, chemistry 6-chloro-2 by name, 3,4,5-tetrahydrochysene-1-(4-hydroxyphenyl)-[1H]-3-benzazepine-7,8-glycol mesylate.
Fenoldopam Mesylate has clear and definite vasodilative effect, is used for hypertensive emergency treatment clinically, and the short-term (in 4 hours) that also can be used for pediatric hospital patient blood pressure reduces.Clinical usage instils for the fenoldopam solution posterior vein that adopts 0.9% sodium chloride injection or 5% glucose injection to be diluted to 40 mcg/ml.
At present, the fenoldopam mesylate injection of Abbott company (trade name: Corlopam, concentration is 10 mg/ml) goes on the market, and product is the low capacity liquid injection solution of 1ml or 2ml.China does not still have any Fenoldopam Mesylate launch at present.Because Fenoldopam Mesylate is slightly soluble in water and ethanol, dissolubility is bigger in propylene glycol, therefore contain the propylene glycol that concentration is 518 mg/ml in the fenoldopam mesylate injection of clinical practice, making the concentration of Fenoldopam Mesylate in injection is 10 mg/ml.
Still the development report that does not have the Fenoldopam Mesylate powder ampoule agent for injection both at home and abroad.
Propylene glycol is a kind of colourless heavy-gravity liquid organic solvent.Studies show that some side effect relevant with the central nervous system take place in regular meeting behind the injection propylene glycol, particularly to baby and child.The side reaction of other reports comprises: ototoxicity, cardiovascular effect, serum hyperosmosis and lactic acidosis.These side reactions especially easily betide baby and the child below 4 years old, anemia of pregnant woman and liver failure or renal failure patient.The preparation that contains 35% propylene glycol can cause haemolysis.
Therefore, a kind of Fenoldopam Mesylate injection that does not contain propylene glycol of preparation has the important clinical meaning.
Summary of the invention
The object of the present invention is to provide a kind of Fenoldopam Mesylate lyophilized injectable powder that contains the acidic materials of pharmacology permission, can effectively solve Fenoldopam Mesylate insoluble problem in water, prepare and do not contain propylene glycol, be suitable for intravenous injection, the Fenoldopam Mesylate injection that safety is higher.
We are by a large amount of experimental studies have found that, the acidic materials that add the pharmacology permission can improve the dissolubility of Fenoldopam Mesylate in aqueous solution, thereby make the concentration of Fenoldopam Mesylate can reach clinical needed drug level.And preparation-obtained solution also can keep clear and bright state at low temperatures.In addition, because Fenoldopam Mesylate is in aqueous solution, less stable in hot water particularly, therefore, we improve the stability of Fenoldopam Mesylate in preparation process by cryodesiccated method.
Phenoduopan methanesulphonate medicinal composition of the present invention mainly contains the acidic materials of Fenoldopam Mesylate and pharmacology permission, and the amount of its middle acid substance can make the Fenoldopam Mesylate dissolving reach clinical desired drug level.
Acidic materials used in the present invention can be the acid of a kind of acidic amino acid or one of organic acid or said two devices and the mixture of mineral acid.Wherein acidic amino acid is preferably acetylcysteine, cysteine hydrochloride, L-aspartic acid, glutamic acid; Organic acid is preferably tartaric acid, malic acid, citric acid, fumaric acid, maleic acid, lactic acid.Mineral acid is preferably hydrochloric acid, phosphoric acid.
In the Fenoldopam Mesylate lyophilized injectable powder of the present invention, the agent of pH dash adjustment be can also contain, sodium dihydrogen phosphate, sodium citrate are preferably.
In the Fenoldopam Mesylate lyophilized injectable powder of the present invention, antioxidant be can also contain, vitamin C, sodium pyrosulfite, sodium sulfite, nitrogen are preferably.
In the Fenoldopam Mesylate lyophilized injectable powder of the present invention, caffolding agent be can also contain, mannitol, sodium chloride, glucose or its combination are preferably.
Fenoldopam Mesylate lyophilized injectable powder of the present invention is realized by following process: under the condition of cleaning, the Fenoldopam Mesylate fine powder is suspended in the water for injection, add the acidic materials that pharmacology allows, after stirring makes medicine dissolution, add the dissolving of other additives and caffolding agent again, decolouring, aseptic filtration, again this pyrogen-free clear and bright filtrate is sub-packed in the aseptic cillin bottle, presses the freeze-dry process lyophilizing and promptly get product.The preparation of gained of the present invention can be dissolved in water and form clear and bright aqueous solution rapidly.
The clinical using method of Fenoldopam Mesylate lyophilized injectable powder of the present invention is: the Fenoldopam Mesylate lyophilized injectable powder is dissolved in the solution that is diluted to 40 mcg/ml fenoldopams in 0.9% sodium chloride injection or 5% glucose injection, intravenous drip.
Present fenoldopam mesylate injection clinically contains the propylene glycol of 518 mg/ml, and lyophilized injectable powder of the present invention is owing to can form the Fenoldopam Mesylate aqueous solution of 2～10 mg/ml after dissolving fast, therefore compared with prior art, the main beneficial effect of lyophilized injectable powder of the present invention is: do not contain organic solvent propylene glycol, intravenous injection is safe.
Fenoldopam Mesylate lyophilized injectable powder of the present invention is owing to be the solid composite of solid forms, and steady quality helps storing and transportation.
Some following concrete examples further describe the preparation process of Fenoldopam Mesylate lyophilized injectable powder of the present invention, but are not limited to following examples.
The specific embodiment
Embodiment 1
Under the condition of cleaning, 6.5 gram Fenoldopam Mesylates are suspended in 800 milliliters of waters for injection, logical nitrogen is full sharp, add 1 gram acetylcysteine, after stirring is dissolved medicine fully, drop into 15.7 gram sodium dihydrogen phosphate and 40 gram mannitol stirring and dissolving, add 0.3% pin with the charcoal absorption pyrogen that stirs, filtering decarbonization, add water to 1000 milliliters, through 0.22 micron filtering with microporous membrane, 2 milliliters of packing promptly get every bottle of Fenoldopam Mesylate lyophilized injectable powder that contains 10 milligrams of fenoldopams by the freeze-dry process preparation in aseptic cillin bottle.
Embodiment 2
Under the condition of cleaning, 3.75 gram Fenoldopam Mesylates are suspended in 800 milliliters of waters for injection, adding 0.4 gram citric acid stirring dissolves medicine fully, drop into 2.7 gram sodium dihydrogen phosphate and 60 gram mannitol stirring and dissolving, add 0.3% pin with the charcoal absorption pyrogen that stirs, filtering decarbonization, add water to 1000 milliliters, through 0.22 micron filtering with microporous membrane, 4 milliliters of packing promptly get every bottle of Fenoldopam Mesylate lyophilized injectable powder that contains 10 milligrams of fenoldopams by the freeze-dry process preparation in aseptic cillin bottle.
Embodiment 3
Under the condition of cleaning, 13 gram Fenoldopam Mesylates are suspended in 800 milliliters of waters for injection, adding 4 gram acetylcysteines stirrings dissolves medicine fully, drop into 67.4 gram sodium dihydrogen phosphate, 0.45 gram sodium pyrosulfite and 40 gram mannitol stirring and dissolving, add 0.3% pin with the charcoal absorption pyrogen that stirs, filtering decarbonization, add water to 1000 milliliters, through 0.22 micron filtering with microporous membrane, 2 milliliters of packing promptly get every bottle of Fenoldopam Mesylate lyophilized injectable powder that contains 20 milligrams of fenoldopams by the freeze-dry process preparation in aseptic cillin bottle.
Embodiment 4
Under the condition of cleaning, 6.5 gram Fenoldopam Mesylates are suspended in 800 milliliters of waters for injection, logical nitrogen is saturated, add 0.5 gram tartaric acid, after stirring is dissolved medicine fully, drop into 12.6 gram sodium dihydrogen phosphate, 50 gram mannitol and 0.5 gram sodium pyrosulfite stirring and dissolving, add 0.3% pin with the charcoal absorption pyrogen that stirs, filtering decarbonization, add water to 1000 milliliters, through 0.22 micron filtering with microporous membrane, 2 milliliters of packing promptly get every bottle of Fenoldopam Mesylate lyophilized injectable powder that contains 10 milligrams of fenoldopams by the freeze-dry process preparation in aseptic cillin bottle.
Embodiment 5
Under the condition of cleaning, 6.5 gram Fenoldopam Mesylates are suspended in the 800ml water for injection, logical nitrogen is saturated, add 0.5 gram cysteine hydrochloride, after stirring is dissolved medicine fully, drop into 12.9 gram sodium dihydrogen phosphate and 45 gram mannitol stirring and dissolving, add 0.25% pin with the charcoal absorption pyrogen that stirs, filtering decarbonization, add water to 1000 milliliters, through 0.22 micron filtering with microporous membrane, 2 milliliters of packing promptly get every bottle of Fenoldopam Mesylate lyophilized injectable powder that contains 10 milligrams of fenoldopams by the freeze-dry process preparation in aseptic cillin bottle.
Embodiment 6
Under the condition of cleaning, 13 gram Fenoldopam Mesylates are suspended in 800 milliliters of waters for injection, adding 1.5 gram glutamic acid stirrings dissolves about thing fully, drop into 10.6 gram sodium dihydrogen phosphate and 40 gram mannitol stirring and dissolving, add 0.3% pin with the charcoal absorption pyrogen that stirs, filtering decarbonization, add water to 1000 milliliters, through 0.22 micron filtering with microporous membrane, 2 milliliters of packing promptly get every bottle of Fenoldopam Mesylate lyophilized injectable powder that contains 20 milligrams of fenoldopams by the freeze-dry process preparation in aseptic cillin bottle.
Claims (12)
1 one kinds is the pharmaceutical composition of active substance with the Fenoldopam Mesylate, it is characterized in that, said composition comprises Fenoldopam Mesylate and the pharmacology goes up the acidic materials that allow, and the amount of its middle acid substance can make the Fenoldopam Mesylate meltage reach clinical desired drug level.
2 Fenoldopam Mesylate compositionss according to claim 1 is characterized in that, described acidic materials are the acid of acidic amino acid or one of organic acid or said two devices and the mixture of mineral acid.
3 Fenoldopam Mesylate compositionss according to claim 2, wherein acidic amino acid is acetylcysteine, cysteine hydrochloride, L-aspartic acid, glutamic acid or its combination.
4 Fenoldopam Mesylate compositionss according to claim 2, wherein organic acid is tartaric acid, malic acid, citric acid, fumaric acid, maleic acid, lactic acid or its combination.
5 Fenoldopam Mesylate compositionss according to claim 2, wherein mineral acid is hydrochloric acid, phosphoric acid or its combination.
6 Fenoldopam Mesylate compositionss according to claim 1 is characterized in that, also contain the agent of pH dash adjustment.
7 Fenoldopam Mesylate compositionss according to claim 6, wherein the agent of pH dash adjustment is sodium dihydrogen phosphate, sodium citrate or its combination.
8 Fenoldopam Mesylate compositionss according to claim 1 is characterized in that, also contain antioxidant.
9 Fenoldopam Mesylate compositionss according to claim 8, wherein antioxidant is vitamin C, sodium pyrosulfite, sodium sulfite, nitrogen or its combination.
10 Fenoldopam Mesylate compositionss according to claim 1 is characterized in that, also contain caffolding agent.
11 Fenoldopam Mesylate compositionss according to claim 10, wherein caffolding agent is mannitol, sodium chloride, glucose or its combination.
12 Fenoldopam Mesylate preparation of compositions methods according to claim 1, it is characterized in that, the Fenoldopam Mesylate fine powder is suspended in the water for injection, add the acidic materials that pharmacology allows, after stirring makes medicine dissolution, add the dissolving of other additives and caffolding agent again, decolouring, aseptic filtration is sub-packed in this pyrogen-free clear and bright filtrate in the aseptic cillin bottle, presses the freeze-dry process lyophilizing and promptly gets product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100395177A CN100356924C (en) | 2006-04-14 | 2006-04-14 | Phenoduopan methanesulphonate medicinal composition and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100395177A CN100356924C (en) | 2006-04-14 | 2006-04-14 | Phenoduopan methanesulphonate medicinal composition and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1830446A true CN1830446A (en) | 2006-09-13 |
| CN100356924C CN100356924C (en) | 2007-12-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2006100395177A Expired - Fee Related CN100356924C (en) | 2006-04-14 | 2006-04-14 | Phenoduopan methanesulphonate medicinal composition and its preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104971040A (en) * | 2015-07-15 | 2015-10-14 | 扬子江药业集团广州海瑞药业有限公司 | Fenoldopam methylsulfonate injection and preparation method thereof |
-
2006
- 2006-04-14 CN CNB2006100395177A patent/CN100356924C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104971040A (en) * | 2015-07-15 | 2015-10-14 | 扬子江药业集团广州海瑞药业有限公司 | Fenoldopam methylsulfonate injection and preparation method thereof |
| CN104971040B (en) * | 2015-07-15 | 2018-01-19 | 扬子江药业集团广州海瑞药业有限公司 | A kind of fenoldopam mesylate injection and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN100356924C (en) | 2007-12-26 |
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Granted publication date: 20071226 Termination date: 20100414 |