CN102525918A - Clevidipine butyrate fat emulsion injection and preparation process thereof - Google Patents
Clevidipine butyrate fat emulsion injection and preparation process thereof Download PDFInfo
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- CN102525918A CN102525918A CN2010106143246A CN201010614324A CN102525918A CN 102525918 A CN102525918 A CN 102525918A CN 2010106143246 A CN2010106143246 A CN 2010106143246A CN 201010614324 A CN201010614324 A CN 201010614324A CN 102525918 A CN102525918 A CN 102525918A
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Abstract
The invention provides a clevidipine butyrate fat emulsion injection for intravenous injection. The clevidipine butyrate fat emulsion injection is prepared from an active ingredient, namely clevidipine butyrate and excipients, namely oil for injection, an emulsifier, an isoosmotic adjusting agent, a pH value regulator and water for injection. The fat emulsion injection for the intravenous injection is developed by taking the clevidipine butyrate as the active ingredient and adding some specific kinds of excipients in a specific proportion by the preparation process; and each milliliter of clevidipine butyrate fat emulsion injection contains 0.5 or 1.0mg of the clevidipine butyrate.
Description
Technical field
The invention belongs to technical field of medicine, relate to a kind of fat emulsion injection and preparation technology thereof of butyrate clevidipine.
Background technology
Butyrate clevidipine is a dihydrogen pyridine derivative, is a kind of ultra fugitive used for intravenous injection calcium channel blocker, has the blood vessel and the myocardium selectivity of height, and metabolism is an inert matter rapidly in vivo.Butyrate clevidipine has the activity of very strong reduction pulse frequency, and whole body blood vessel and lung blood vessel are also had expansion effect.Butyrate clevidipine is rapid-action, and effect is eliminated also fast, but ascending-dose controlling blood pressure accurately.With present many intravenous injections through kidney with (or) antihypertensive of hepatic metabolism is different, its blood with organize in metabolism, thereby do not accumulate in vivo.
The butyrate clevidipine injection obtains FDA approval listing in August, 2008, it is the long chain fat emulsion injection that butyrate clevidipine concentration is 0.5mg/mL that contains by pH6.0～8.0 of 20% soybean oil, 1.2% refine yolk lecithin, 2.25% glycerol, an amount of sodium hydroxide and water for injection preparation.
Medium and long chain fat emulsion injection has had the characteristics of medium chain triglyceride and LCT, compares with long chain fat emulsion injection to have the further nitrogen balance of improving, and promotes advantages such as albumen synthesizes, and does not influence lipid metabolism, influences less to liver, renal function.At present, medium and long chain fat emulsion injection has been widely used in clinical.
There is a patent of invention ZL 94194111.6 to disclose the method for dihydropyridines medicine butyrate clevidipine being processed intravenous injection emulsion at present; In this patent in preparation preferred mutually triglyceride of lipid during Emulsion; Mentioned and used a kind of in the listed oil phase or their a kind of mixture; But do not point out it is what kind of mixture, be appreciated that mixture, be appreciated that mixture yet into the arbitrary proportion of all listed oil phases into the arbitrary proportion of any several kinds of oil phases.Although in embodiment 2-6, used midchain oil and olive oil, all used soybean oil in other embodiments, do not occur two kinds of oil are mixed the embodiment that uses, more there are not midchain oil and soybean oil to mix the embodiment that uses.
Also have a patent of invention, application number is 200810246824.1, and the patent of invention name is called " a kind of Emulsion and preparation technology and purposes that contains clevidipine "; Be active component with clevidipine and pharmaceutically acceptable salt thereof or hydrate in the literary composition; Active component is mentioned when preparation Emulsion all in clevidipine when calculating content, and oil phase uses the mixture of one or more esters in the listed oils and fats; Do not point out it is what kind of mixture yet; And the oil phase of using in an embodiment is single oils and fats, do not occur two kinds of oils and fatss are mixed the embodiment that uses, and more do not have midchain oil and soybean oil to mix the embodiment of use.
Special needs to be pointed out is the ratio of butyrate clevidipine, emulsifying agent and oil for injection, this is very important for the medicine carrying fat emulsion injection that preparation meets the drug administration by injection requirement.If the butyrate clevidipine proportion is excessive, mixed with water when carrying out emulsifying after then crude drug dissolves in oil for injection, have the risk that medicine is separated out again; If the oil for injection proportion is excessive, then in the administration process, can increase the greasy input of patient virtually, influence patient's lipid metabolism to a certain extent; If the emulsifying agent proportion is excessive, hydrolysis discharges choline in the lecithin entering brain, under enzyme catalysis, generates acetylcholine, makes the interior acetyl choline content rising of brain cause the probability of central nervous system function abnormal response (like delirium convulsions, auditory hallucination photis etc.) to become big.
Summary of the invention
The present invention is directed to the butyrate clevidipine poorly water-soluble, fat-soluble characteristics preferably are prepared into medium and long chain fat emulsion injection with it, so that a kind of butyrate clevidipine injection that supplies clinical use and preparation method thereof to be provided.We are active component with the butyrate clevidipine; Mix at 1: 1 as oil for injection according to weight ratio with medium chain triglyceride and soybean oil; Under the prerequisite that guarantees same medicine concentration, reduced the consumption of oil for injection, also reduced the consumption of emulsifying agent accordingly; Can reduce because the oil for injection of high consumption and the toxic and side effects that emulsifying agent produced of high consumption have guaranteed safety of clinical administration.
For realizing the purpose of foregoing invention, realize through following technical proposals:
Butyrate clevidipine lipid fat emulsion injection of the present invention is processed through certain preparation technology by butyrate clevidipine, oil for injection, emulsifying agent, isoosmotic adjusting agent, pH value regulator and water for injection.Contain butyrate clevidipine 0.1～3mg in every milliliter of fat emulsion injection, be preferably 0.5～2mg.Its used accessory package is drawn together oil for injection, emulsifying agent, isoosmotic adjusting agent, pH value regulator and water for injection.Oil for injection content is 5～15g in wherein every 100ml injection, and emulsifier content is 0.2～1.2g, and water for injection content is 85～95mL.
Oil for injection of the present invention is the mixture of soybean oil and medium chain triglyceride, and its weight ratio is 1: 1.Find that under study for action butyrate clevidipine has good dissolubility in medium chain triglyceride, the mixture through using medium chain triglyceride and soybean oil, can significantly reduce the ratio of oil for injection under the situation of same medicine concentration as oil for injection.
Emulsifying agent of the present invention is one or both the mixture in refine yolk lecithin and the soybean lecithin, preferred refine yolk lecithin.
Isoosmotic adjusting agent of the present invention is one or both the mixture in glycerol and the xylitol, preferably glycerine.
Butyrate clevidipine lipid fat emulsion injection specification provided by the invention is 50mL and 100mL, and every kind of specification injection butyrate clevidipine content is 0.5 and 1.0mg/mL.
The used butyrate clevidipine raw material of the present invention is the self-control of this laboratory, and through the HPLC detection, the content of butyrate clevidipine is more than 99%.
The method for preparing of butyrate clevidipine lipid fat emulsion injection of the present invention is characterized in that this method carries out according to the following steps:
1) under inert gas shielding, take by weighing the recipe quantity oil for injection, be heated to 40～90 ℃; Recipe quantity emulsifying agent and recipe quantity butyrate clevidipine are added in the oil for injection; High speed shear stirs emulsifying agent and butyrate clevidipine is dissolved fully, and as oil phase, insulation is at 50～80 ℃;
2) the recipe quantity isoosmotic adjusting agent is dissolved in the proper amount of water for injection, regulates pH value 8.0～11.0 with the pH value regulator, through the membrane filtration of 0.2～0.5 μ m as water, with water heating and insulation at 50～80 ℃;
3) stir down in high speed shear, oil phase slowly added aqueous phase, and continue high speed shear and stir and process colostrum, mend add to the full amount of water for injection after, through the high pressure homogenize breast spare to the emulsion droplet particle diameter at 50～500nm;
4) regulate pH value to 6.0～10.0, jump a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly get butyrate clevidipine lipid fat emulsion injection after the cooling through filtration, fill, filling with inert gas.
Preferred manufacturing procedure is following:
1) under nitrogen protection; Take by weighing recipe quantity soybean oil and medium chain triglyceride (mixing) by weight 1: 1; Be heated to 60～80 ℃, recipe quantity emulsifying agent and recipe quantity butyrate clevidipine are added in the oil for injection, high speed shear stirs emulsifying agent and butyrate clevidipine is dissolved fully; As oil phase, insulation is at 55～75 ℃;
2) recipe quantity glycerol is dissolved in the proper amount of water for injection, regulates pH value 8.0～10.5 with sodium hydroxide solution, through the membrane filtration of 0.2～0.5 μ m as water, with water heating and insulation at 55～75 ℃;
3) stir down in high speed shear, oil phase slowly added aqueous phase, and continue high speed shear and stir and process colostrum, mend add to the full amount of water for injection after, through the high pressure homogenize breast spare to the emulsion droplet particle diameter at 50～500nm;
4) regulate pH value to 7.0～9.0, jump a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly get butyrate clevidipine lipid fat emulsion injection after the cooling through 1 μ m filter filtration, fill, inflated with nitrogen.
The specific embodiment
Following examples can help those skilled in the art more comprehensively to understand the present invention, but do not limit the present invention in any way.
Embodiment 1
Under nitrogen protection, take by weighing injection soybean oil 250g and medium chain triglyceride 250g mixing, be heated to 80 ℃, add refine yolk lecithin 30g, butyrate clevidipine 2.5g, high speed shear is stirred to dissolving fully, and as oil phase, and insulation is at 70 ℃; Injection xylitol 250g is added in the 2500mL water for injection, regulate pH value to 8.5 with the 1mol/L sodium hydroxide solution behind the mixing, the membrane filtration of warp 0.22 μ m is as water, and heating also is incubated at 70 ℃; Under high speed shear stirs, oil phase is slowly added aqueous phase, and continue the high speed shear stirring and process colostrum, add water for injection to 5L; With high pressure dispersing emulsification machine homogenized milk under 600bar pressure even to the emulsion droplet particle diameter at 50～500nm; Regulate pH value to 8.0, through 1 μ m filter, be filled in the 50mL glass infusion bottle, inflated with nitrogen is jumped a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly getting butyrate clevidipine concentration after the cooling is the butyrate clevidipine lipid fat emulsion injection of 0.5mg/mL.
With Ma Erwen Zetasizer Nano ZS90 particle size determination appearance, measuring butyrate clevidipine lipid fat emulsion injection mean diameter is 286nm, and polydispersity coefficient is 0.016.
Embodiment 2
Under nitrogen protection, take by weighing injection soybean oil 250g and medium chain triglyceride 250g mixing, be heated to 75 ℃, add refine yolk lecithin 30g, butyrate clevidipine 5.0g, high speed shear is stirred to dissolving fully, and as oil phase, and insulation is at 60 ℃; Glycerol for injection 125g is added in the 3000mL water for injection, regulate pH value to 10.0 with the 1mol/L sodium hydroxide solution behind the mixing, the membrane filtration of warp 0.22 μ m is as water, and heating also is incubated at 60 ℃; Under high speed shear stirs, oil phase is slowly added aqueous phase, and continue the high speed shear stirring and process colostrum, add water for injection to 5L; With high pressure dispersing emulsification machine homogenized milk under 800bar pressure even to the emulsion droplet particle diameter at 50～500nm; Regulate pH value to 8.5, through 1 μ m filter, be filled in the 100mL glass infusion bottle, inflated with nitrogen is jumped a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly getting butyrate clevidipine concentration after the cooling is the butyrate clevidipine lipid fat emulsion injection of 1.0mg/mL.
With Ma Erwen Zetasizer Nano ZS90 particle size determination appearance, measuring butyrate clevidipine lipid fat emulsion injection mean diameter is 261nm, and polydispersity coefficient is 0.021.
Embodiment 3
Under nitrogen protection, take by weighing injection soybean oil 125g and medium chain triglyceride 125g mixing, be heated to 65 ℃, add refine yolk lecithin 15g, butyrate clevidipine 2.5g, high speed shear is stirred to dissolving fully, and as oil phase, and insulation is at 65 ℃; Glycerol for injection 100g, xylitol 50g are added in the 3500mL water for injection, regulate pH value to 9.5 with the 1mol/L sodium hydroxide solution behind the mixing, the membrane filtration of warp 0.22 μ m is as water, and heating also is incubated at 65 ℃; Under high speed shear stirs, oil phase is slowly added aqueous phase, and continue the high speed shear stirring and process colostrum, add water for injection to 5L; With microjet appearance homogenized milk under 80MPa pressure even to the emulsion droplet particle diameter at 50～500nm; Regulate pH value to 9.0, through 1 μ m filter, be filled in the 100mL glass infusion bottle, inflated with nitrogen is jumped a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly getting butyrate clevidipine concentration after the cooling is the butyrate clevidipine lipid fat emulsion injection of 0.5mg/mL.
With Ma Erwen Zetasizer Nano ZS90 particle size determination appearance, measuring butyrate clevidipine lipid fat emulsion injection mean diameter is 229nm, and polydispersity coefficient is 0.015.
Embodiment 4
Under nitrogen protection, take by weighing injection soybean oil 250g and medium chain triglyceride 250g mixing, be heated to 60 ℃; Add refine yolk lecithin 15g, soybean lecithin 15g, butyrate clevidipine 5.0g; High speed shear is stirred to dissolving fully, and as oil phase, and insulation is at 75 ℃; Glycerol for injection 125g is added in the 2500mL water for injection, regulate pH value to 9.0 with the 1mol/L sodium hydroxide solution behind the mixing, the membrane filtration of warp 0.22 μ m is as water, and heating also is incubated at 75 ℃; Under high speed shear stirs, oil phase is slowly added aqueous phase, and continue the high speed shear stirring and process colostrum, add water for injection to 5L; With high pressure dispersing emulsification machine homogenized milk under 1000bar pressure even to the emulsion droplet particle diameter at 50～500nm; Regulate pH value to 7.5, through 1 μ m filter, be filled in the 100mL glass infusion bottle, inflated with nitrogen is jumped a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly getting butyrate clevidipine concentration after the cooling is the butyrate clevidipine lipid fat emulsion injection of 1.0mg/mL.
With Ma Erwen Zetasizer Nano ZS90 particle size determination appearance, measuring butyrate clevidipine lipid fat emulsion injection mean diameter is 235nm, and polydispersity coefficient is 0.019.
Embodiment 5
Under nitrogen protection, take by weighing injection soybean oil 250g and medium chain triglyceride 250g mixing, be heated to 80 ℃, add soybean lecithin 30g, butyrate clevidipine 2.5g, high speed shear is stirred to dissolving fully, and as oil phase, and insulation is at 80 ℃; Glycerol for injection 125g is added in the 2500mL water for injection, regulate pH value to 10.5 with the 1mol/L sodium hydroxide solution behind the mixing, the membrane filtration of warp 0.22 μ m is as water, and heating also is incubated at 80 ℃; Under high speed shear stirs, oil phase is slowly added aqueous phase, and continue the high speed shear stirring and process colostrum, add water for injection to 5L; With high pressure dispersing emulsification machine homogenized milk under 800bar pressure even to the emulsion droplet particle diameter at 50～500nm; Regulate pH value to 8.0, through 1 μ m filter, be filled in the 50mL glass infusion bottle, inflated with nitrogen is jumped a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly getting butyrate clevidipine concentration after the cooling is the butyrate clevidipine lipid fat emulsion injection of 0.5mg/mL.
With Ma Erwen Zetasizer Nano ZS90 particle size determination appearance, measuring butyrate clevidipine lipid fat emulsion injection mean diameter is 254nm, and polydispersity coefficient is 0.026.
Embodiment 6
Under nitrogen protection, take by weighing injection soybean oil 250g and medium chain triglyceride 250g mixing, be heated to 55 ℃, add refine yolk lecithin 30g, butyrate clevidipine 5.0g, high speed shear is stirred to dissolving fully, and as oil phase, and insulation is at 60 ℃; Injection xylitol 250g is added in the 3000mL water for injection, regulate pH value to 11.0 with the 1mol/L sodium hydroxide solution behind the mixing, the membrane filtration of warp 0.22 μ m is as water, and heating also is incubated at 55 ℃; Under high speed shear stirs, oil phase is slowly added aqueous phase, and continue the high speed shear stirring and process colostrum, add water for injection to 5L; With high pressure dispersing emulsification machine homogenized milk under 700bar pressure even to the emulsion droplet particle diameter at 50～500nm; Regulate pH value to 9.0, through 1 μ m filter, be filled in the 100mL glass infusion bottle, inflated with nitrogen is jumped a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly getting butyrate clevidipine concentration after the cooling is the butyrate clevidipine lipid fat emulsion injection of 1.0mg/mL.
With Ma Erwen Zetasizer Nano ZS90 particle size determination appearance, measuring butyrate clevidipine lipid fat emulsion injection mean diameter is 269nm, and polydispersity coefficient is 0.017.
Claims (10)
1. butyrate clevidipine lipid fat emulsion injection; It is characterized in that; With the butyrate clevidipine is active component; The mixture of forming by certain weight ratio with injection soybean oil and injection medium chain triglyceride is as oil for injection, with pharmaceutically acceptable other adjuvants through the resulting fat emulsion injection of certain preparation technology.
2. butyrate clevidipine lipid fat emulsion injection according to claim 1 is characterized in that, oil for injection content is 5～15g in per 100 milliliters of injection,, butyrate clevidipine content is 50～200mg.
3. butyrate clevidipine lipid fat emulsion injection according to claim 1 is characterized in that, describedly by certain weight ratio is: injection soybean oil and injection medium chain triglyceride are by weight being 1: 1.
4. butyrate clevidipine lipid fat emulsion injection according to claim 1 is characterized in that other adjuvants comprise emulsifying agent, isoosmotic adjusting agent, pH value regulator and water for injection.Emulsifier content is 0.2～1.2g in wherein per 100 milliliters of injection, and water for injection content is 85～95mL.
5. butyrate clevidipine lipid fat emulsion injection according to claim 4 is characterized in that, said emulsifying agent is one or both the mixture in refine yolk lecithin and the soybean lecithin, preferred refine yolk lecithin.
6. butyrate clevidipine lipid fat emulsion injection according to claim 4 is characterized in that, said isoosmotic adjusting agent is one or both the mixture in glycerol and the xylitol, preferably glycerine.
7. butyrate clevidipine lipid fat emulsion injection according to claim 4 is characterized in that said pH value regulator is sodium hydroxide solution or hydrochloric acid solution.
8. butyrate clevidipine lipid fat emulsion injection according to claim 1 is characterized in that said fat emulsion injection particle size distribution is 50～1000nm, preferred 50～500nm, and particle diameter is Unimodal Distribution.
9. butyrate clevidipine lipid fat emulsion injection according to claim 1 is characterized in that this preparation technology comprises the steps:
1) under inert gas shielding, take by weighing the recipe quantity oil for injection, be heated to 40～90 ℃; Recipe quantity emulsifying agent and recipe quantity butyrate clevidipine are added in the oil for injection; High speed shear stirs emulsifying agent and butyrate clevidipine is dissolved fully, and as oil phase, insulation is at 50～80 ℃;
2) the recipe quantity isoosmotic adjusting agent is dissolved in the proper amount of water for injection, regulates pH value 8.0～11.0 with the pH value regulator, through the membrane filtration of 0.2～0.5 μ m as water, with water heating and insulation at 50～80 ℃;
3) stir down in high speed shear, oil phase slowly added aqueous phase, and continue high speed shear and stir and process colostrum, add water for injection to recipe quantity, through the high pressure homogenize breast spare to the emulsion droplet particle diameter at 50～500nm;
4) regulate pH value to 6.0～10.0, jump a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly get butyrate clevidipine lipid fat emulsion injection after the cooling through filtration, fill, filling with inert gas.
10. the preparation technology of butyrate clevidipine lipid fat emulsion injection according to claim 9 is characterized in that comprising the steps:
1) under nitrogen protection, take by weighing recipe quantity soybean oil and medium chain triglyceride, be heated to 60～80 ℃; Recipe quantity emulsifying agent and recipe quantity butyrate clevidipine are added in the oil for injection; High speed shear stirs emulsifying agent and butyrate clevidipine is dissolved fully, and as oil phase, insulation is at 55～75 ℃;
2) recipe quantity glycerol is dissolved in the proper amount of water for injection, regulates pH value 8.0～10.5 with sodium hydroxide solution, through the membrane filtration of 0.2～0.5 μ m as water, with water heating and insulation at 55～75 ℃;
3) stir down in high speed shear, oil phase slowly added aqueous phase, and continue high speed shear and stir and process colostrum, mend add to the full amount of water for injection after, through the high pressure homogenize breast spare to the emulsion droplet particle diameter at 50～500nm;
4) regulate pH value to 7.0～9.0, jump a queue, gland, put in the rotary water-bath sterilization cabinet and sterilize, promptly get butyrate clevidipine lipid fat emulsion injection after the cooling through 1 μ m filter filtration, fill, inflated with nitrogen.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103110580A (en) * | 2013-02-20 | 2013-05-22 | 北京德立福瑞医药科技有限公司 | Clevidipine butyrate injection |
| CN103169672A (en) * | 2012-12-26 | 2013-06-26 | 辰欣药业股份有限公司 | Clevidipine butyrate freeze-dried emulsion |
| CN103520104A (en) * | 2013-10-25 | 2014-01-22 | 北京蓝丹医药科技有限公司 | Clevidipine butyrate fat emulsion injection and preparation method thereof |
| CN104490777A (en) * | 2014-12-26 | 2015-04-08 | 北京蓝丹医药科技有限公司 | Clevidipine butyrate fat emulsion and preparation method thereof |
| CN105853353A (en) * | 2015-01-20 | 2016-08-17 | 江苏正大丰海制药有限公司 | Method for preparing clevidipine fat emulsion injection |
| WO2020151444A1 (en) * | 2019-01-23 | 2020-07-30 | 广东嘉博制药有限公司 | Clevidipine butyrate fat emulsion injection and preparation process therefor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1136774A (en) * | 1993-11-12 | 1996-11-27 | 阿斯特拉公司 | Pharmaceutical emulsion |
| CN101766568A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Emulsion containing clevidipine and preparation process and application thereof |
| CN101791311A (en) * | 2009-12-31 | 2010-08-04 | 广州中大创新药物研究与开发中心有限公司 | Pharmaceutical composition with short pressure-reducing function |
| CN102000027A (en) * | 2010-11-23 | 2011-04-06 | 北京中海康医药科技发展有限公司 | Clevidipine butyrate medium-length chain fat emulsion and preparation method thereof |
-
2010
- 2010-12-30 CN CN2010106143246A patent/CN102525918A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1136774A (en) * | 1993-11-12 | 1996-11-27 | 阿斯特拉公司 | Pharmaceutical emulsion |
| CN101766568A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Emulsion containing clevidipine and preparation process and application thereof |
| CN101791311A (en) * | 2009-12-31 | 2010-08-04 | 广州中大创新药物研究与开发中心有限公司 | Pharmaceutical composition with short pressure-reducing function |
| CN102000027A (en) * | 2010-11-23 | 2011-04-06 | 北京中海康医药科技发展有限公司 | Clevidipine butyrate medium-length chain fat emulsion and preparation method thereof |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103169672A (en) * | 2012-12-26 | 2013-06-26 | 辰欣药业股份有限公司 | Clevidipine butyrate freeze-dried emulsion |
| CN103110580A (en) * | 2013-02-20 | 2013-05-22 | 北京德立福瑞医药科技有限公司 | Clevidipine butyrate injection |
| CN103110580B (en) * | 2013-02-20 | 2014-09-17 | 北京德立福瑞医药科技有限公司 | Clevidipine butyrate injection |
| CN103520104A (en) * | 2013-10-25 | 2014-01-22 | 北京蓝丹医药科技有限公司 | Clevidipine butyrate fat emulsion injection and preparation method thereof |
| CN103520104B (en) * | 2013-10-25 | 2015-08-26 | 北京蓝丹医药科技有限公司 | Clevidipine butyrate fat emulsion injection and preparation method thereof |
| CN104490777A (en) * | 2014-12-26 | 2015-04-08 | 北京蓝丹医药科技有限公司 | Clevidipine butyrate fat emulsion and preparation method thereof |
| CN104490777B (en) * | 2014-12-26 | 2019-07-23 | 北京蓝丹医药科技有限公司 | A kind of butyrate clevidipine lipid fat cream and preparation method thereof |
| CN105853353A (en) * | 2015-01-20 | 2016-08-17 | 江苏正大丰海制药有限公司 | Method for preparing clevidipine fat emulsion injection |
| WO2020151444A1 (en) * | 2019-01-23 | 2020-07-30 | 广东嘉博制药有限公司 | Clevidipine butyrate fat emulsion injection and preparation process therefor |
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Application publication date: 20120704 |