CN104490775A - Anacetrapib fat emulsion and preparation method thereof - Google Patents
Anacetrapib fat emulsion and preparation method thereof Download PDFInfo
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- CN104490775A CN104490775A CN201410793432.2A CN201410793432A CN104490775A CN 104490775 A CN104490775 A CN 104490775A CN 201410793432 A CN201410793432 A CN 201410793432A CN 104490775 A CN104490775 A CN 104490775A
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Abstract
The invention provides an anacetrapib fat emulsion and a preparation method thereof. The anacetrapib fat emulsion is characterized by comprising the following components in percentage by weight: 1%-15% of anacetrapib, 8%-30% of oil for injection, 0.5%-10% of lecithin for injection, 1%-5% of an isoosmotic adjusting agent and a proper amount of a pH regulating agent; water for injection is added until the anacetrapib fat emulsion is 1000ml. According to the anacetrapib fat emulsion, the in-vivo release of drugs is accelerated, the dose of the drugs can be reduced, the toxicity is reduced, and the bioavailability is improved. The preparation method of the anacetrapib fat emulsion has the advantages that the preparation steps are simple, and technological parameters are easily controllable; the preparation method is suitable for industrial production.
Description
Technical field
The invention belongs to field of medicine preparations, be specifically related to fat milk of bent of a kind of Ansai and preparation method thereof.
Background technology
Cardiovascular and cerebrovascular disease has become one of underlying cause of death of current developed country and China's rural and urban population, atherosclerosis is then the main pathological basis of cardiovascular and cerebrovascular disease, system Study of Etiology shows that atherosclerosis is a pathological development process, and wherein main pathogenic has hyperlipemia and Lipoprotein Disorders etc.Cetp (Cholesterol ester transfer protein, CETP) promotes lipid exchange between plasma lipoprotein and transhipment in blood plasma.The result of CETP high expressed is that the cholesteryl ester amount (HDL-C) of high density lipoprotein is declined, C-VLDL ester and low-density lipoprotein cholesterol ester amount (VLDL-C, LDL-C) rise, its variation tendency and atherosclerosis correlation, be considered to an atherosclerotic target of control.
Bent (Anacetrapib) is the orally active micromolecule (oxazolidinon-5-yl-methyl)-2-thiophene-carboxamides selectivity CETP inhibitor researched and developed by Merck company in Ansai, is used for the treatment of atherosclerosis, coronary heart disease etc.Show with the clinical research that healthy volunteer and hyperlipemic patients are object, the lipid level of bent of Ansai (Anacetrapib) energy safety, effectively adjustment coronary heart disease and coronary heart disease high-risk patient, and to untoward reaction patient tolerance.And domestic relevant report and the patent having no the bent preparation in Ansai.
Fat milk is development in recent years novel pharmaceutical formulation faster, has very high clinical and economic worth.Fat milk is the stable o/w type Emulsion made with vegetable oil, phospholipid emulsifier, isotonic agent and water for injection, can injection for intravenous, completely by organism metabolism and utilization, also can have application in other dosage form simultaneously.The safety of fat milk is good, non-stimulated to vein, can be not only patient's Quick for high-energy, infuse with the therapeutic such as aminoacid, vitamin, electrolyte and also has well compatibility, can be with the use of, become the important preparation research direction of improving curative effect of medication.
The bent dissolubility in Ansai is lower, and the half-life is longer, is applicable to being prepared into o/w type fat emulsion injection, accelerates medicine release in vivo, reduces drug dose, reduces toxicity, improves bioavailability.This research is intended to utilize the advantage of fat milk to carry out modified form to bent of medicine Ansai, take fat milk as pharmaceutical carrier, with bent of Ansai for model drug, develop bioavailability high, the bent fat milk in stay-in-grade Ansai, therefore, develop novel form, to its clinical application, there is important reference significance.Summary of the invention
The present invention aims to provide a kind of safety, and stable, effectively, bioavailability is high, the bent fat emulsion injection in the simple Ansai of preparation technology.
Another object of the present invention is to provide a kind of method preparing the bent fat emulsion injection in Ansai.
For achieving the above object, the present invention takes following technical scheme:
Bent fat emulsion injection in a kind of Ansai of the present invention and preparation method thereof, it is characterized in that said preparation prescription is made up of bent of Ansai, oil for injection, injection lecithin, isoosmotic adjusting agent, pH adjusting agent and water for injection, its formula following (percentage by weight):
The bent 1-15% in Ansai; Oil for injection 8-30%; Injection lecithin 0.5-10%; Isoosmotic adjusting agent 1-5%; PH adjusting agent regulates pH to 4.5-8.5; Water for injection adds to 1000ml.
Bent fat emulsion injection in a kind of Ansai of the present invention and preparation method thereof, is characterized in that described oil for injection is wherein one or more combinations in soybean oil, Oleum Arachidis hypogaeae semen, Semen Maydis oil, olive oil, safflower oil, Oleum Gossypii semen, Oleum Camelliae or midchain oil.
Bent fat emulsion injection in a kind of Ansai of the present invention and preparation method thereof, is characterized in that described injection lecithin is wherein one or more combinations in natural yolk lecithin, native soy lecithin, hydrogenation egg yolk lecithin, hydrogenated soy phosphatidyl choline.
Bent fat emulsion injection in a kind of Ansai of the present invention and preparation method thereof, is characterized in that described isoosmotic adjusting agent is wherein one or more combinations in glycerol, glucose, xylitol or sorbitol.
Bent fat emulsion injection in a kind of Ansai of the present invention and preparation method thereof, it is characterized in that described pH adjusting agent be potassium hydroxide, sodium hydroxide, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium citrate, hydrochloric acid, citric acid, acetic acid, in wherein one or more combinations.
Bent fat emulsion injection in a kind of Ansai of the present invention and preparation method thereof, is characterized in that described preparation method:
1) take recipe quantity oil for injection, the mixing of injection lecithin, add bent of Ansai, in 40 ~ 80 DEG C of stirring in water bath to clear, as oil phase;
2) add the isoosmotic adjusting agent of recipe quantity in water for injection, stirring and evenly mixing, and be incubated as aqueous phase under 40 ~ 80 DEG C of water bath condition;
3) 40 ~ 80 DEG C of water-baths, under 6000 ~ 25000r/min speed conditions, oil phase is slowly joined in aqueous phase, continue after adding to keep rotating speed to stir 5-30min, then let cool to room temperature, obtain colostrum.
4) add the water for injection of surplus in first Ruzhong, mixing, is placed in high pressure homogenizer, circulate 5-20 time under homogenizing gross pressure is 300bar ~ 1800bar pressure condition, regulate pH value to 4.5-8.5 after homogenizing completes, and fill is in ampoule bottle, sealing by fusing, 121 DEG C of sterilizing 15 min, to obtain final product.
Advantage of the present invention has: 1. the oil for injection that the present invention uses is soybean oil, Oleum Arachidis hypogaeae semen, Semen Maydis wet goods safety, easily absorb, and avoids with an organic solvent the shortcomings such as the stimulation to skin that (as ethanol) bring and toxic and side effects.
2. the injection lecithin that uses of the present invention is good for the safeties such as natural yolk lecithin, native soy lecithin and biocompatibility, has been applied to multiple injection through intravenously administrable abroad.
3. bent for a medicine Ansai bag is loaded in emulsion droplet by the present invention, and improve the stability of preparation, this fat milk is all stable in moist heat sterilization and stability test process, is beneficial to suitability for industrialized production and clinical practice.
Beneficial effect of the present invention: the bent fat emulsion injection in Ansai of the present invention accelerates drug releasing rate, can play drug effect at short notice, improve drug bioavailability.It is o/w type Emulsion that the present invention prepares the bent hard fat emulsion injection in Ansai, safety, and stable, effectively, bioavailability is high, and preparation technology is simple, is beneficial to suitability for industrialized production and clinical practice.
Accompanying drawing illustrates:
Fig. 1: embodiment of the present invention 1-4 in every Experimental comparison's data;
Fig. 2: the embodiment of the present invention 1 stability experiment data.
Detailed description of the invention
Embodiment is only for further illustrating the present invention below, does not limit the present invention in any form.Embodiment 1:
Prescription (making 1000ml):
Bent 3.0%, Ansai; Soybean oil 15.0%; Native soy lecithin 2%; Glycerol 2.5%; Sodium hydrogen phosphate regulates pH to 7.5; Water for injection adds to 1000ml.
Preparation method:
1) take recipe quantity oil for injection, the mixing of injection lecithin, add bent of Ansai, in 40 ~ 80 DEG C of stirring in water bath to clear, as oil phase;
2) add the isoosmotic adjusting agent of recipe quantity in water for injection, stirring and evenly mixing, and be incubated as aqueous phase under 40 ~ 80 DEG C of water bath condition;
3) 40 ~ 80 DEG C of water-baths, under 6000 ~ 25000r/min speed conditions, oil phase is slowly joined in aqueous phase, continue after adding to keep rotating speed to stir 5-30min, then let cool to room temperature, obtain colostrum.
4) add the water for injection of surplus in first Ruzhong, mixing, is placed in high pressure homogenizer, circulate 5-20 time under homogenizing gross pressure is 300bar ~ 1800bar pressure condition, regulate pH value to 4.5-8.5 after homogenizing completes, and fill is in ampoule bottle, sealing by fusing, 121 DEG C of sterilizing 15 min, to obtain final product.
Embodiment 2:
Prescription (making 1000ml):
Bent 3.0%, Ansai; Soybean oil 10.0%; Natural yolk lecithin 1.8%; Glycerol 2.5%; Sodium hydroxide regulates pH to 8; Water for injection adds to 1000ml.
Preparation method:
1) take recipe quantity oil for injection, the mixing of injection lecithin, add bent of Ansai, in 40 ~ 80 DEG C of stirring in water bath to clear, as oil phase;
2) add the isoosmotic adjusting agent of recipe quantity in water for injection, stirring and evenly mixing, and be incubated as aqueous phase under 40 ~ 80 DEG C of water bath condition;
3) 40 ~ 80 DEG C of water-baths, under 6000 ~ 25000r/min speed conditions, oil phase is slowly joined in aqueous phase, continue after adding to keep rotating speed to stir 5-30min, then let cool to room temperature, obtain colostrum.
4) add the water for injection of surplus in first Ruzhong, mixing, is placed in high pressure homogenizer, circulate 5-20 time under homogenizing gross pressure is 300bar ~ 1800bar pressure condition, regulate pH value to 4.5-8.5 after homogenizing completes, and fill is in ampoule bottle, sealing by fusing, 121 DEG C of sterilizing 15 min, to obtain final product.
Embodiment 3:
Prescription (making 1000ml):
Bent 3.0%, Ansai; Semen Maydis oil 12.0%; Hydrogenation egg yolk lecithin 2.2%; Glucose 5%; Sodium dihydrogen phosphate regulates pH to 6.5; Water for injection adds to 1000ml.
Preparation method:
1) take recipe quantity oil for injection, the mixing of injection lecithin, add bent of Ansai, in 40 ~ 80 DEG C of stirring in water bath to clear, as oil phase;
2) add the isoosmotic adjusting agent of recipe quantity in water for injection, stirring and evenly mixing, and be incubated as aqueous phase under 40 ~ 80 DEG C of water bath condition;
3) 40 ~ 80 DEG C of water-baths, under 6000 ~ 25000r/min speed conditions, oil phase is slowly joined in aqueous phase, continue after adding to keep rotating speed to stir 5-30min, then let cool to room temperature, obtain colostrum.
4) add the water for injection of surplus in first Ruzhong, mixing, is placed in high pressure homogenizer, circulate 5-20 time under homogenizing gross pressure is 300bar ~ 1800bar pressure condition, regulate pH value to 4.5-8.5 after homogenizing completes, and fill is in ampoule bottle, sealing by fusing, 121 DEG C of sterilizing 15 min, to obtain final product.
Embodiment 4:
Prescription (making 1000ml):
Bent 3.0%, Ansai; Olive oil 8%; Native soy lecithin 1.6%; Glucose 5%; Sodium citrate regulates pH to 7.5; Water for injection adds to 1000ml.
Preparation method:
1) take recipe quantity oil for injection, the mixing of injection lecithin, add bent of Ansai, in 40 ~ 80 DEG C of stirring in water bath to clear, as oil phase;
2) add the isoosmotic adjusting agent of recipe quantity in water for injection, stirring and evenly mixing, and be incubated as aqueous phase under 40 ~ 80 DEG C of water bath condition;
3) 40 ~ 80 DEG C of water-baths, under 6000 ~ 25000r/min speed conditions, oil phase is slowly joined in aqueous phase, continue after adding to keep rotating speed to stir 5-30min, then let cool to room temperature, obtain colostrum.
4) add the water for injection of surplus in first Ruzhong, mixing, is placed in high pressure homogenizer, circulate 5-20 time under homogenizing gross pressure is 300bar ~ 1800bar pressure condition, regulate pH value to 4.5-8.5 after homogenizing completes, and fill is in ampoule bottle, sealing by fusing, 121 DEG C of sterilizing 15 min, to obtain final product.
Embodiment of the present invention 1-4 is shown in Fig. 1 in every experimental data contrast:
See that the fat milk of embodiment 1-4 formula preparation is basically identical in outward appearance, particle diameter, current potential index by result of the test, but the bent fat emulsion injection content in the Ansai of embodiment 2 formula preparation is the highest.
The stability experiment data that the embodiment of the present invention 1 is stored 0,1,2,3,6 month are at different temperatures shown in Fig. 2:
Seen by result, in Ansai, a bent fat emulsion injection is stored all stable under 4 DEG C, 25 DEG C, 40 DEG C conditions.
Claims (6)
1. bent fat milk in Ansai and preparation method thereof, it is characterized in that, the weight percentages of components of fat emulsion injection is: the bent 1-15% in Ansai; Oil for injection 8-30%; Injection lecithin 0.5-10%; Isoosmotic adjusting agent 1-5%; PH adjusting agent is appropriate; Water for injection adds to 1000ml.
2. the bent fat emulsion injection in Ansai as claimed in claim 1, is characterized in that, described oil for injection is wherein one or more combinations in soybean oil, Oleum Arachidis hypogaeae semen, Semen Maydis oil, olive oil, safflower oil, Oleum Gossypii semen, Oleum Camelliae or midchain oil.
3. the bent fat emulsion injection in Ansai as claimed in claim 1, is characterized in that, described injection lecithin is wherein one or more combinations in natural yolk lecithin, native soy lecithin, hydrogenation egg yolk lecithin, hydrogenated soy phosphatidyl choline.
4. the bent fat emulsion injection in Ansai as claimed in claim 1, is characterized in that, described isoosmotic adjusting agent is wherein one or more combinations in glycerol, glucose, xylitol or sorbitol.
5. the bent fat emulsion injection in Ansai as claimed in claim 1, it is characterized in that, described pH adjusting agent is wherein one or more combinations in potassium hydroxide, sodium hydroxide, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium citrate, hydrochloric acid, citric acid, acetic acid.
6. the preparation method of the bent fat emulsion injection in Ansai as claimed in claim 1, is characterized in that:
1) take recipe quantity oil for injection, the mixing of injection lecithin, add bent of Ansai, in 40 ~ 80 DEG C of stirring in water bath to clear, as oil phase;
2) add the isoosmotic adjusting agent of recipe quantity in water for injection, stirring and evenly mixing, and be incubated as aqueous phase under 40 ~ 80 DEG C of water bath condition;
3) 40 ~ 80 DEG C of water-baths, under 6000 ~ 25000r/min speed conditions, oil phase is slowly joined in aqueous phase, continue after adding to keep rotating speed to stir 5-30min, then let cool to room temperature, obtain colostrum;
4) add the water for injection of surplus in first Ruzhong, mixing, is placed in high pressure homogenizer, circulate 5-20 time under homogenizing gross pressure is 300bar ~ 1800bar pressure condition, regulate pH value to 4.5-8.5 after homogenizing completes, and fill is in ampoule bottle, sealing by fusing, 121 DEG C of sterilizing 15 min, to obtain final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410793432.2A CN104490775A (en) | 2014-12-20 | 2014-12-20 | Anacetrapib fat emulsion and preparation method thereof |
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| CN201410793432.2A CN104490775A (en) | 2014-12-20 | 2014-12-20 | Anacetrapib fat emulsion and preparation method thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107595863A (en) * | 2017-10-25 | 2018-01-19 | 桂林浩新科技服务有限公司 | It is a kind of to be used to reduce drug compound preparation of blood pressure and blood lipoid and application thereof |
| CN107595844A (en) * | 2017-10-25 | 2018-01-19 | 桂林浩新科技服务有限公司 | A kind of Ansai Qu levamlodipine medicinal composition and application thereof |
| CN107595842A (en) * | 2017-10-25 | 2018-01-19 | 桂林浩新科技服务有限公司 | A kind of drug compound preparation and the purposes in the medicine for preparing treatment hypertensive patients coronary heart disease |
| CN107595853A (en) * | 2017-10-25 | 2018-01-19 | 桂林浩新科技服务有限公司 | A kind of medical composition and its use for being used to treat hypertensive patients coronary heart disease |
| CN107789351A (en) * | 2017-10-25 | 2018-03-13 | 桂林浩新科技服务有限公司 | A kind of Ansai Qu Nilvadipine medical composition and its use |
| CN107789352A (en) * | 2017-10-25 | 2018-03-13 | 桂林浩新科技服务有限公司 | A kind of compound medicinal formulation and prepare treatment hyperglycaemia, high fat of blood medicine in application |
| CN110302154A (en) * | 2019-07-30 | 2019-10-08 | 成都医学院 | A kind of 2,4- dinitrophenol Fat Emulsion and its preparation method and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1376460A (en) * | 2002-04-05 | 2002-10-30 | 华瑞制药有限公司 | Fat emulsion for injection and its preparing process |
| CN1635911A (en) * | 2001-06-21 | 2005-07-06 | 辉瑞产品公司 | Self-emulsifying formulations of cholesteryl ester transfer protein inhibitors |
-
2014
- 2014-12-20 CN CN201410793432.2A patent/CN104490775A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1635911A (en) * | 2001-06-21 | 2005-07-06 | 辉瑞产品公司 | Self-emulsifying formulations of cholesteryl ester transfer protein inhibitors |
| CN1376460A (en) * | 2002-04-05 | 2002-10-30 | 华瑞制药有限公司 | Fat emulsion for injection and its preparing process |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107595863A (en) * | 2017-10-25 | 2018-01-19 | 桂林浩新科技服务有限公司 | It is a kind of to be used to reduce drug compound preparation of blood pressure and blood lipoid and application thereof |
| CN107595844A (en) * | 2017-10-25 | 2018-01-19 | 桂林浩新科技服务有限公司 | A kind of Ansai Qu levamlodipine medicinal composition and application thereof |
| CN107595842A (en) * | 2017-10-25 | 2018-01-19 | 桂林浩新科技服务有限公司 | A kind of drug compound preparation and the purposes in the medicine for preparing treatment hypertensive patients coronary heart disease |
| CN107595853A (en) * | 2017-10-25 | 2018-01-19 | 桂林浩新科技服务有限公司 | A kind of medical composition and its use for being used to treat hypertensive patients coronary heart disease |
| CN107789351A (en) * | 2017-10-25 | 2018-03-13 | 桂林浩新科技服务有限公司 | A kind of Ansai Qu Nilvadipine medical composition and its use |
| CN107789352A (en) * | 2017-10-25 | 2018-03-13 | 桂林浩新科技服务有限公司 | A kind of compound medicinal formulation and prepare treatment hyperglycaemia, high fat of blood medicine in application |
| CN110302154A (en) * | 2019-07-30 | 2019-10-08 | 成都医学院 | A kind of 2,4- dinitrophenol Fat Emulsion and its preparation method and application |
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