CN1470238A - Levosimendan formulation and its preparing method - Google Patents
Levosimendan formulation and its preparing method Download PDFInfo
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- CN1470238A CN1470238A CNA031124275A CN03112427A CN1470238A CN 1470238 A CN1470238 A CN 1470238A CN A031124275 A CNA031124275 A CN A031124275A CN 03112427 A CN03112427 A CN 03112427A CN 1470238 A CN1470238 A CN 1470238A
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- levosimendan
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Abstract
The invention is a levosimendan preparation and the preparing method, largely improving its water solubility. Place hydroxypropyl-beta-cyclodextrin in injection water for mixing and dissolving, and then add levosimendan for mixing, grinding or ultrasonic processing, so as to obtain the levosimendan inclusion complex solution. The solution can be used to prepare levosimendan injection, transfusion, injection powder, drop, oral solution and spray, so as to realize making levosimendan preparation using water as solvent and avoid using organic solvents like alcohol.
Description
Technical field:
The present invention relates to medical technical field, more precisely it is levosimendan preparation and preparation method thereof.
Technical background:
Levosimendan, chemical name ((4-(1,4,5,6-tetrahydrochysene-4-methyl-6-oxo-3-pyridazinyl) phenyl) hydrazono-) Cyanoacetyl-Cyacetazid, represent with following formula:
Levosimendan is used for the treatment of short distance decompensated heart failure as positive inotropic medicament.The levosimendan selectivity combines with the N-of cardiac troponin C is terminal, stablizes myocardium calcium key, strengthens the sensitivity of cardiac troponin C (heart My) to calcium ion, strengthens myocardial contraction, does not influence heart rate, does not increase myocardial oxygen consumption.The better tolerance of levosimendan, very valuable to the short term therapy of decompensation DHF.
Levosimendan is Finland Ou Liang company research and development, and in 2000 in Sweden's Initial Public Offering, U.S. Abbott company obtains the permission listing in the U.S..Levosimendan listing dosage form is an injection, two kinds of specifications of 12.5mg/5ml and 25mg/10ml.
Levosimendan listing injection is alcoholic acid solution, and needs cryopreservation.The invention reside in water is that solvent is made injection or drop, oral administration solution, spray, avoids ethanol with an organic solvent, and its preparation is safer, more stable, zest is little.
Summary of the invention:
The purpose of this invention is to provide levosimendan preparation and preparation method thereof, it has solved the water solublity problem of levosimendan, and it is the preparation of solvent that levosimendan be can be made into water.
It has following scheme to realize: HP-is put in the water for injection, after the stirring and dissolving, add levosimendan again, stirring or grinding or ultrasonic get the levosimendan inclusion complex in solution.This solution can be used to prepare levosimendan injection, transfusion, powder pin, drop, oral administration solution, spray.Wherein the mol ratio of levosimendan and HP-is 1: 1～1: 40, and optimum range is 1: 10～1: 30.With the levosimendan inclusion complex in solution, add pharmaceutically known suitable adjuvant, directly prepare the levosimendan preparation; Or the levosimendan inclusion complex in solution, get levosimendan clathrate powder through vacuum drying or lyophilization or spray drying, be used further to prepare the levosimendan preparation.
Suitable adjuvant has the PH regulator, is the known bronsted lowry acids and bases bronsted lowry of acceptable pharmaceutically; Chelating agent be can complexation of metal ions the material disodiumedetate; Isoosmotic adjusting agent is glucose, sodium chloride; Proppant is the used adjuvant mannitol of injectable powder, lactose, glucose and dextran.
Advantage of the present invention is: use the high HP-of water solublity, to levosimendan wrap and, make the levosimendan can be soluble in water, make injection, transfusion, powder pin, drop, oral administration solution, spray.HP-can be used for intravenously administrable, and nontoxic, nonirritant.Do not use ethanol, overcome inconvenience and the side effect of using ethanol to bring.
The specific embodiment:
Embodiment 1: HP-1.4g, be dissolved in the 4ml water for injection, and add levosimendan 12.5mg, ultrasonic 30 minutes, add the injection water to 5ml, get the levosimendan solution of 2.5mg/ml.
Embodiment 2: HP-0.8g, be dissolved in the 4ml water for injection, and add levosimendan 12.5mg, ultrasonic 30 minutes, add the injection water to 5ml, get the levosimendan solution of 2.5mg/ml.
Embodiment 3: HP-2.0g, be dissolved in the 4ml water for injection, and add levosimendan 12.5mg, ultrasonic 30 minutes, add the injection water to 5ml, get the levosimendan solution of 2.5mg/ml.
Embodiment 4: with the levosimendan solution of embodiment 1,2,3, and the 0.22um filtration sterilization, fill is sealed.Make injection.
Embodiment 5: get sodium chloride 9g, add the injection water and dissolve in right amount; Merge with the levosimendan solution 5ml of embodiment 1,2,3, add the injection water to 100ml, the 0.22um filtration sterilization, fill is sealed.Make transfusion.
Embodiment 6: with the levosimendan solution 5ml of embodiment 1,2,3, add 0.4g mannitol, and dissolving, the 0.22um filtration sterilization, fill, lyophilization is jumped a queue, Zha Gai.Make the powder pin.
Embodiment 7: with the levosimendan solution 5ml of embodiment 1,2,3, it is an amount of to add antiseptic, and tween 80 is an amount of, adds water to 10ml, filters, and fill is jumped a queue, Zha Gai.Make oral liquid.
Embodiment 8: with the levosimendan solution 5ml of embodiment 1,2,3, the adding antiseptic is an amount of, and tween 80 is an amount of, adds water to 10ml, filters, and fill is made drop in drop bottle.
Embodiment 9: with the levosimendan solution of embodiment 1,2,3, the adding antiseptic is an amount of, and tween 80 is an amount of, filters, and fill is made spray in the bottle of band sprayer unit.
Claims (5)
1, levosimendan preparation and preparation method thereof is characterized in that HP-is put in the water for injection, after the stirring and dissolving, adds levosimendan again, and stirring or grinding or ultrasonic get the levosimendan inclusion complex in solution.This solution can be used to prepare the levosimendan preparation.Wherein the mol ratio of levosimendan and HP-is 1: 1～1: 40.
2, levosimendan preparation according to claim 1 and preparation method thereof is characterized in that: the optimum range of levosimendan and HP-mol ratio is 1: 10～1: 30.
3, levosimendan preparation according to claim 1 and preparation method thereof is characterized in that: said levosimendan preparation comprises injection, transfusion, powder pin, drop, oral administration solution, spray.
4, levosimendan preparation according to claim 1 and preparation method thereof is characterized in that: the levosimendan inclusion complex in solution, add suitable adjuvant, and make the levosimendan preparation; Or the levosimendan inclusion complex in solution, get levosimendan clathrate powder through vacuum drying or lyophilization or spray drying, be used further to prepare the levosimendan preparation.
5, levosimendan preparation according to claim 4 and preparation method thereof, it is characterized in that: said suitable adjuvant is meant injection, transfusion, powder pin, drop, oral administration solution, the common used adjuvant of each dosage form of spray, PH regulator, chelating agent, isoosmotic adjusting agent, proppant, antiseptic, correctives, antioxidant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031124275A CN1470238A (en) | 2003-06-18 | 2003-06-18 | Levosimendan formulation and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031124275A CN1470238A (en) | 2003-06-18 | 2003-06-18 | Levosimendan formulation and its preparing method |
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| Publication Number | Publication Date |
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| CN1470238A true CN1470238A (en) | 2004-01-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031124275A Pending CN1470238A (en) | 2003-06-18 | 2003-06-18 | Levosimendan formulation and its preparing method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100367964C (en) * | 2004-04-29 | 2008-02-13 | 王思清 | Inclusion preparation of levosimendan and beta cyclodextrin |
| CN101411708B (en) * | 2007-10-17 | 2010-12-22 | 齐鲁制药有限公司 | Stable Levosimendan pharmaceutical composition and preparation method thereof |
| WO2017077032A1 (en) * | 2015-11-06 | 2017-05-11 | Carinopharm Gmbh | Improved formulations of levosimendan for intravenous administration as infusion or injection and of infusion concentrate |
| CN108261398A (en) * | 2016-12-30 | 2018-07-10 | 齐鲁制药有限公司 | A kind of injection pharmaceutical preparation containing Levosimendan and preparation method thereof |
-
2003
- 2003-06-18 CN CNA031124275A patent/CN1470238A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100367964C (en) * | 2004-04-29 | 2008-02-13 | 王思清 | Inclusion preparation of levosimendan and beta cyclodextrin |
| CN101411708B (en) * | 2007-10-17 | 2010-12-22 | 齐鲁制药有限公司 | Stable Levosimendan pharmaceutical composition and preparation method thereof |
| WO2017077032A1 (en) * | 2015-11-06 | 2017-05-11 | Carinopharm Gmbh | Improved formulations of levosimendan for intravenous administration as infusion or injection and of infusion concentrate |
| CN108289832A (en) * | 2015-11-06 | 2018-07-17 | 卡利努法姆股份有限公司 | For carrying out the Levosimendan of intravenously administrable with infusion or injection form and being transfused the improvement formula of concentrate |
| US10507179B2 (en) | 2015-11-06 | 2019-12-17 | Carinopharm Gmbh | Formulations of levosimendan for intravenous administration as infusion or injection and of infusion concentrate |
| EA034565B1 (en) * | 2015-11-06 | 2020-02-20 | Каринофарм Гмбх | Compositions of levosimendan for intravenous administration as infusion or injection and of infusion concentrate |
| AU2016349408B2 (en) * | 2015-11-06 | 2021-06-03 | Carinopharm Gmbh | Improved formulations of Levosimendan for intravenous administration as infusion or injection and of infusion concentrate |
| CN108289832B (en) * | 2015-11-06 | 2021-08-31 | 卡利努法姆股份有限公司 | Improved formulations of levosimendan and infusion concentrates for intravenous administration in infusion or injection form |
| CN108261398A (en) * | 2016-12-30 | 2018-07-10 | 齐鲁制药有限公司 | A kind of injection pharmaceutical preparation containing Levosimendan and preparation method thereof |
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