CN102512367A - Formula of novel docosahexaenoic acid (DHA) fat emulsion preparation and preparation method thereof - Google Patents
Formula of novel docosahexaenoic acid (DHA) fat emulsion preparation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a formula of a novel docosahexaenoic acid (DHA) fat emulsion preparation and a preparation method thereof. The novel preparation main comprises DHA, an emulsion, soybean oil or other refined oil as an oil-soluble diluent, oleic acid or oleate as auxiliary emulsification, vitamin E or a vitamin E derivative as antioxidation, an ion chelating agent and glycerol or micromolecule sugar as an isotonic adjusting agent. A variety of methods are used alone or are used together to prepare the DHA fat emulsion preparation.
Description
Technical field
The invention belongs to pharmaceutical field, relate to a kind of fat emulsion formulation and preparation method thereof, be specifically related to a kind of new DHA fat emulsion formulation and method for preparing.
Background technology
DHA, docosahexenoic acid is commonly called as NAOHUANGJIN, is a kind of to the very important polyunsaturated fatty acid of human body, belongs to the important member in the Omega-3 unsaturated fatty acid family.
DHA is the necessary composition of brain, accounts for 10% of human brain fat, and is very favourable to the growth promoter of cranial nerve conduction and synapse.The cognitive competence deficiency relevant (1) with DHA that descends.Severe depression patient's cerebral cortex does not almost have DHA (2).DHA can stop the deposition of cholesterol on blood vessel wall, thus prevention or alleviate generations such as atherosclerosis and coronary heart disease.Concerning the hebetic teenager of entering into, DHA can assist to promote intelligence, strengthens memory and improve learning capacity.Current research shows that DHA significantly improves old people's hypophrenia, memory reinforcing.DHA is to large intestine and tumor of prostate effective (3,4,5).
At present, the DHA that sells on the market is the oral soft capsule preparation.We are through discovering that there is poor stability in existing preparation, and the shelf-life is short, and active constituent content is low, absorption difference, problem such as bioavailability is low.In addition, owing to DHA is damaged in digestive tract easily, so we, have researched and developed out a kind of new DHA fat emulsion formulation in order to address the above problem.This Emulsion is intravenous injection, thereby has solved the unstability of DHA in digestive tract.
Summary of the invention
The object of the present invention is to provide a kind of good stability, long shelf-life, the DHA fat emulsion formulation of instant effect.
Preparation of the present invention is mainly by DHA, the oil-soluble diluent, and emulsifying agent, antioxidant, isoosmotic adjusting agent, ionic complexing agent and water for injection are formed.
Preparation of the present invention, most important index is that to account for the preparation ratio be more than the 0.1-50% (weight ratio) for the consumption sum of consumption and the DHA of control refined plant oil in its active component prescription.
DHA fat emulsion formulation of the present invention, mainly be processed into by the composition that following unit is weight percentage:
All the other are water for injection.
Preferably, DHA fat emulsion formulation of the present invention, mainly be processed into by following composition:
All the other are water for injection.
Preferably, DHA fat emulsion formulation of the present invention, mainly be processed into by following composition:
All the other are water for injection.
Fat emulsion formulation of the present invention also comprises an amount of stabilizing agent, and said stabilizing agent is oleic acid or enuatrol.
In the fat emulsion formulation of the present invention:
Said DHA is a docosahexenoic acid.
Said oil-soluble diluent is a vegetable oil; Be preferably: the mixture of the fatty glyceride of any natural, artificial or half artificial preparation of refined soybean oil, refined maize oil, refining Oleum Helianthi, refining Oleum Arachidis hypogaeae semen, refining Oleum sesami, refining rapeseed oil or other or any or several kinds in other oils and fats.
Said emulsifying agent is a phospholipid, one or both in the polyethyleneglycol derivative; Wherein, said phospholipid is selected from Ovum Gallus domesticus Flavus lecithin, soybean lecithin, sphingomyelins, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline or synthetic lecithin; Wherein, said polyethyleneglycol derivative is selected from: Polyethylene Glycol phospholipid derivative, Polyethylene Glycol cholesterol derivative, polyethylene glycol fatty acid derivant, polyethylene glycol fatty 01 derivatives, polyethylene glycol fatty amine derivative, Polyethylene Glycol or other fat-soluble high molecular derivants;
Said antioxidant is a vitamin E.
Said isoosmotic adjusting agent is glycerol or sugar compounds; Sugar compounds is selected from: one or several mixing in lactose, Raffinose or the xylitol.
Another object of the present invention is to provide the method for preparing of fat emulsion formulation.
The method for preparing of fat emulsion formulation of the present invention may further comprise the steps:
(1) get the DHA of recipe quantity, the oil-soluble diluent, antioxidant and emulsifying agent heated and stirred make it to dissolve fully,
(2) get proper amount of water for injection in addition, add isoosmotic adjusting agent,
(3) the DHA solution that step 1 is obtained joins in the solution of step 2 slowly, stirs, and promptly gets colostrum solution,
(4) colostrum solution is regulated pH through the high pressure homogenizer homogenizing, filters, and packing feeds nitrogen, sealing, and sterilization gets final product.
The whole process of preparation of fat emulsion formulation of the present invention is under nitrogen protection, to carry out.
Preferably, the method for preparing of fat emulsion formulation of the present invention may further comprise the steps:
(1) getting DHA, vegetable oil, oleic acid, vitamin E and phospholipid heated and stirred 10-20min makes it to dissolve fully;
(2) get proper amount of water for injection in addition, add glycerol, obtain glycerine water solution;
(3) under the condition of nitrogen protection, phospholipid DHA vegetable oil solution is added in the glycerine water solution with the cutter high-speed stirred slowly, under the condition of nitrogen protection, continue to stir 30min, promptly get colostrum solution;
(4) colostrum solution is through high pressure homogenizer homogenizing 7-8 time, and pressure is 100MPa, to particle size range at 180-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing, 115 ℃ of sterilization 30min get final product.
Further preferred, method for preparing of the present invention may further comprise the steps:
Whole process of production is carried out under nitrogen protection.
Get about recipe quantity DHA, vegetable oil, oleic acid, vitamin E and phospholipid heated and stirred 10-20min and make it to dissolve fully.Other gets proper amount of water for injection, adds glycerol.Under the condition of nitrogen protection, phospholipid DHA vegetable oil solution is added in the glycerine water solution with cutter high-speed stirred (3000r/min) slowly, under the condition of nitrogen protection, continue to stir 30min, promptly get colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, to particle size range at 180-300nm, regulate pH 7.0-8.0; Filter, packing feeds nitrogen, sealing; 115 ℃ of sterilization 30min, final products should be uniform milky solutions, do not have deposition, layering and oil spill phenomenon.After lamp inspection is qualified, packing.In storage below 25 ℃.
Fat emulsion formulation of the present invention has following beneficial effect, wherein 1), utilize phospholipid to make emulsifying agent, make the DHA can be effectively and be dissolved in oil phase fully and be wrapped in the fat milk emulsion droplet.2), improve emulsifying agent phospholipid ratio, keeping under the prerequisite of DHA and the constant rate of vegetable oil, the consumption of raising phospholipid can improve the stability in the DHA fat milk.3), in emulsifiers formula, add Polyethylene Glycol phospholipid derivative or other amphoteric macromolecule polymers.The Polyethylene Glycol phospholipid derivative both can strengthen emulsifying effectiveness, guaranteed that DHA can effectively be wrapped in the fat milk oil droplet.4), adopt disaccharide or polysaccharide as the isoosmotic adjusting agent of preparation, improve the parcel efficient of DHA in fat milk.
New DHA fat milk ejection preparation of the present invention is used for intravenous injection, has solved the unstability of DHA in digestive tract, and very important clinical meaning is arranged.In addition, fat milk ejection preparation of the present invention has not only effectively solved the problem that exists in the existing DHA preparation, also has following good performance: good stable property, prolonged the shelf-life, and improved bioavailability, strengthened therapeutic effect, safety has no side effect.
The specific embodiment
To fat emulsion formulation of the present invention, and therapeutic effect is further described through following specific embodiment.
(1), the proportion of flux oil and DHA is investigated
The present invention has carried out checking to the usage ratio scope of listed DHA and flux oil and has investigated.Under technology of the present invention and condition, keep the constant rate of other adjuvant, the usage ratio scope of listed DHA of claim of the present invention and flux oil is in 0.03-0.07 (weight ratio).Arbitrary consumption in the weight content scope all guarantees to process stable fat milk medicinal plant oil ejection preparation.
The ratio of embodiment 1:DHA and flux oil (DHA: the weight ratio of soybean oil is 1: 1)
Prescription:
Get DHA 70.0g, vitamin E 3.0g, refined soybean oil 70.0g, add 12.5g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 700ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
The ratio of embodiment 2:DHA and flux oil (DHA: the weight ratio of soybean oil is 0.03)
Prescription:
Get DHA10.0g, vitamin E 3.0g, refined soybean oil 330.0g, add 12.5g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 700ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
(2), the flux oil amount ranges is investigated
Under the prerequisite that the ratio that guarantees DHA and flux oil does not change, the present invention verifies the amount ranges of listed refining diluent oil.The arbitrary consumption of consumption in 5-33% weight content scope in listed refining diluent oil under the basic technology condition of the present invention (is example with the soybean oil) all guarantees to process stable DHA fat emulsion formulation.Still be example with 1%DHA:
Embodiment 3: the DHA fat emulsion formulation of minimum soybean oil content (flux oil content 5%, weight content)
Prescription:
Get DHA10.0g, vitamin E 3.0g, refined soybean oil 300.0g, add 12.5g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 600ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 4: the DHA fat emulsion formulation of the highest soybean oil content (flux oil content 33%, weight content)
Prescription:
Get DHA10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
(3), use the suitability of different flux oils to investigate
Embodiment 5: soybean oil DHA fat emulsion formulation (25%, weight content)
Prescription:
Get DHA10.0g, vitamin E 3.0g, refined soybean oil 250.0g, add 12.5g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 6: Petiolus Trachycarpi oil new DHA fat emulsion formulation (25%, weight content)
Prescription:
Get DHA10.0g, vitamin E 3.0g, refining Petiolus Trachycarpi oil 250.0g, add 12.5g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
(4), use the suitability of different phospholipid to investigate
Embodiment 7: the DHA fat emulsion formulation (25%, weight content) that adopts soybean lecithin
Prescription:
Get DHA10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add the 12.5g soybean lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 8: the DHA fat emulsion formulation (25%, weight content) that adopts synthetic lecithin
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g synthetic lecithin (DPPC), the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 9: the DHA fat emulsion formulation (25%, weight content) that adopts mixed phosphatide
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 6g sphingomyelins and 6.5g lecithin,, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 10: different phospholipid use amount increases the 50%DHA fat emulsion formulation
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refining Petiolus Trachycarpi oil 250.0g, add 18.75g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 11: different phospholipid use amount increases the 100%DHA fat emulsion formulation
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refining Petiolus Trachycarpi oil 250.0g, add 25g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 12: the DHA fat emulsion formulation that adds 1% polyethyleneglycol derivative (with the weight note)
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g lecithin and 10g (polyethyleneglycol derivative) DSPE-PEG, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, and than the fat emulsion formulation of routine, its particle diameter reduces to some extent, to particle size range at 160nm-280nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 13: the DHA fat emulsion formulation that adds 15% polyethyleneglycol derivative (with the weight note)
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g lecithin and 150g (polyethyleneglycol derivative) DSPE-PEG, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, and than the fat emulsion formulation of routine, its particle diameter has obviously and reduces, to particle size range at 130nm-250nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
Embodiment 14: the employing lactose is that the disaccharide of representative is the DHA fat emulsion formulation of isotonic agent
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds lactose 100g.Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the lactose aqueous solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection was qualified, packing was in storage below 25 ℃.
Embodiment 15: the employing Raffinose is that the oligosaccharide of representative is the DHA fat emulsion formulation of isotonic agent
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g lecithin, the about 10-20min mixing of heated and stirred.Other gets water for injection 800ml, adds Raffinose 150g (Raffinose called after O-α-D-galactose pyranose-(1 → 6)-α-D-glucose pyranose-β-D-fructose furan glycosides).Under nitrogen protection and stirring condition, DHA phospholipid oil solution is added in the Raffinose aqueous solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, to particle size range at 180nm-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing.115 ℃ of sterilization 30min, after lamp inspection is qualified, packing.In storage below 25 ℃.
The influence that embodiment 16, DHA fat emulsion formulation of the present invention are remembered animal learning
1. material and method
1.1 animal is selected and divides into groups
30 of SD female mices, body weight 18～22g (providing) by The Fourth Military Medical University's Experimental Animal Center.Mice is with 3 water maze tests of Morris water maze tester (institute of Materia Medica,Chinese Academy of Medical Sciences, Beijing) row before the experiment, and rejecting has obvious dyskinetic mice.Mice is divided into 3 groups at random, and matched group (C, n=10) every day is by body weight tail vein injection saline (NS); Blank fat milk (T
1, n=10) organize every day by the blank fat milk of body weight tail vein injection; DHA fat milk group (T
2, n=10) press body weight tail vein injection embodiment 5 sample DHA content 100mg/kg, 15d continuously every day.
1.2 instrument
Pool diameter 60cm, the dark 30cm in pond are formed by round pool and automatic picture recording and recording system two parts in Morris water maze labyrinth; Depth of water 25cm, 26 ± 1 ℃ of water temperatures are added with prepared Chinese ink in the water; Four equidistant points are divided into four quadrants with the pond on the pool wall, and an optional quadrant is at central placement platform, and platform is a black; Stick some objects of reference on the peripheral pool wall, in experimentation, remain unchanged always.Video recording and recording system are made up of videocorder, video camera, television set, computer and data processing software.
Light and shade avoidance conditioning case experimental provision is covered with the darkroom of copper grid, the outdoor platform that links to each other with the darkroom, transformator and timer by the bottom and forms.There is a hole in the darkroom, and (5 * 8cm) communicate with outdoor platform; There is a 40W incandescent source top, darkroom, and darkroom and platform are divided into light and shade two districts, and the darkroom is 13cm * 5cm * 11cm; Shop, bottom, darkroom is with the copper grid; Spacing 0.5cm links to each other with power supply, and voltage strength is linked to each other with timer by transformator control, darkroom, and record immerses the incubation period and the errors number in darkroom automatically.
1.3 detection index
The performance testing of Morris water maze is measured mice entry to the time of finding platform (being incubation period) and total swimming stroke (i.e. swimming distance) through the test of Morris water maze, and 1d tests after drug withdrawal, and 3d respectively tests 4 every day continuously, averages.
The darkness avoidance test test is put into the darkroom to animal earlier and is adapted to 3min.During test mice is started timer after being placed on platform in the hole dorsad immediately, and energized, mice gets into the darkroom through the hole and is promptly shocked by electricity; Timing stops automatically; Take out mice, mice is incubation period, recast test behind the 24h from putting into platform to getting into the darkroom chance 36V voltage electric shock time; Record changes incubation period and the errors number of 5min (being mistake once with the every contact copper rod of two forelimbs of mice), with this index as learning and memory.
1.4 statistical analysis
Adopt SPSS 10.0 statistical softwares to carry out statistical analysis; Measurement data is represented with
; Relatively adopt one factor analysis of variance between group, there is statistical significance P＜0.05 for difference.
2. result
2.1 mice water maze performance testing result
The 3rd day incubation period of 3 groups of mices and swimming distance all shortened (P＜0.05) than the 1st day; T
1Organize 3 day incubation period and swimming apart from not having marked difference (P＞0.05) than the C group; T
2Group incubation period and swimming distance significantly reduce (P＜0.05) than the C group, than T
1Group also significantly reduces (P＜0.05) (seeing table 1).
Table 1 is respectively organized the comparison
of mice water maze test incubation period and swimming distance
Compare with 1d,
*P＜0.05; Compare with the C group,
△P＜0.05; With T
1Group compares,
☆P＜0.05
2.2 mice light and shade avoidance response test result
The DHA fat milk has obvious facilitation to normal mouse light and shade avoidance response, shows as T
2Group and C group, T
1Group is significant prolongation incubation period (P＜0.05) relatively, and errors number significantly reduces (P＜0.05); C group and T
1Group compares incubation period and errors number does not have significant difference (P＞0.05) (seeing table 2).
Table 2 is respectively organized the comparison
of mice light and shade avoidance response test incubation period and errors number
Compare with the C group,
*P＜0.05; With T
1Relatively,
△P＜0.05
3. conclusion
This experiment is through mice being carried out test of Morris water maze and the test of light and shade avoidance response, to estimate the cognitive competence of mice.The result finds the mice group of intravenous injection embodiment of the invention 5DHA fat milk sample, and significantly reduce with the swimming distance incubation period in the water maze laboratory; Light and shade avoidance response test significant prolongation incubation period; Errors number significantly reduces; But blank fat milk does not have appreciable impact to these indexs; This DHA fat milk sample that just shows that the present invention prepares can improve mice spatial memory and light and shade reaction well, and learning and memory of little mouse is had facilitation significantly.
Claims (10)
1. DHA fat emulsion formulation, mainly be processed into by the composition that following unit is weight percentage:
All the other are water for injection.
2. preparation according to claim 1 is characterized in that, the composition that mainly is weight percentage by following unit is processed into:
All the other are water for injection.
3. preparation according to claim 1 is characterized in that, the composition that mainly is weight percentage by following unit is processed into:
All the other are water for injection.
4. according to described any one preparation of claim 1-3, it is characterized in that also comprise an amount of stabilizing agent, said stabilizing agent is oleic acid or enuatrol.
5. according to described any one preparation of claim 1-3, it is characterized in that said DHA is a docosahexenoic acid; Said oil-soluble diluent is a vegetable oil; Said emulsifying agent is a phospholipid, one or both in the polyethyleneglycol derivative; Said antioxidant is a vitamin E; Said isoosmotic adjusting agent is glycerol or sugar compounds.
6. according to described any one preparation of claim 1-3, it is characterized in that said DHA is a docosahexenoic acid; Said oil-soluble diluent is selected from: the mixture of the fatty glyceride of any natural, artificial or half artificial preparation of refined soybean oil, refined maize oil, refining Oleum Helianthi, refining Oleum Arachidis hypogaeae semen, refining Oleum sesami, refining rapeseed oil or other or any or several kinds in other oils and fats; Said phospholipid is selected from Ovum Gallus domesticus Flavus lecithin, soybean lecithin, sphingomyelins, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline or synthetic lecithin; Said polyethyleneglycol derivative is selected from: Polyethylene Glycol phospholipid derivative, Polyethylene Glycol cholesterol derivative, polyethylene glycol fatty acid derivant, polyethylene glycol fatty 01 derivatives, polyethylene glycol fatty amine derivative, Polyethylene Glycol or other fat-soluble high molecular derivants; Said antioxidant is a vitamin E; Said isoosmotic adjusting agent is selected from: glycerol, lactose, Raffinose or xylitol.
7. according to described any one preparation of claim 1-3, it is characterized in that said phospholipid shared weight ratio in preparation is 0.1-10%, said polyethyleneglycol derivative shared weight ratio in preparation is 0-1.5%.
8. according to the method for preparing of described any one preparation of claim 1-3, may further comprise the steps:
(1) get DHA, the oil-soluble diluent, stabilizing agent, antioxidant and emulsifying agent heated and stirred make it to dissolve fully,
(2) get proper amount of water for injection in addition, add isoosmotic adjusting agent,
(3) the DHA solution that step 1 is obtained joins in the solution of step 2 slowly, stirs, and promptly gets colostrum solution,
(4) through the high pressure homogenizer homogenizing, regulate pH, filter, packing feeds nitrogen, sealing, and sterilization gets final product.
9. according to the method for preparing of described any one preparation of claim 1-3, may further comprise the steps:
(1) getting DHA, vegetable oil, oleic acid, vitamin E and phospholipid heated and stirred 10-20min makes it to dissolve fully;
(2) get proper amount of water for injection in addition, add glycerol, obtain glycerine water solution;
(3) under the condition of nitrogen protection, phospholipid DHA vegetable oil solution is added in the glycerine water solution with the cutter high-speed stirred slowly, under the condition of nitrogen protection, continue to stir 30min, promptly get colostrum solution;
(4) colostrum solution is through high pressure homogenizer homogenizing 7-8 time, and pressure is 100MPa, to particle size range at 180-300nm, regulate pH 7.0-8.0, filter, packing feeds nitrogen, sealing, 115 ℃ of sterilization 30min get final product.
10. method for preparing according to claim 9 is characterized in that, said preparation process is carried out under nitrogen protection.
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| CN201110447957.7A CN102512367B (en) | 2011-12-26 | 2011-12-26 | Formula of novel docosahexaenoic acid (DHA) fat emulsion preparation and preparation method thereof |
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| CN201110447957.7A CN102512367B (en) | 2011-12-26 | 2011-12-26 | Formula of novel docosahexaenoic acid (DHA) fat emulsion preparation and preparation method thereof |
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| CN102512367B CN102512367B (en) | 2014-02-12 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015113987A1 (en) * | 2014-01-28 | 2015-08-06 | Fresenius Kabi Deutschland Gmbh | Composition comprising epa and dha triglycerides for parenteral administration |
| CN105939706A (en) * | 2014-01-28 | 2016-09-14 | 费森尤斯卡比德国有限公司 | Composition comprising EPA and DHA ethylester for parenteral administration |
| CN109223712A (en) * | 2018-10-10 | 2019-01-18 | 武汉大安制药有限公司 | Flurbiprofen axetil emulsion for injection and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1432367A (en) * | 2003-02-26 | 2003-07-30 | 刘威 | Seal oil cream and its prepn process and appplication in preparing intravenous injection |
| CN1757396A (en) * | 2004-10-09 | 2006-04-12 | 中国药品生物制品检定所 | Ursine fat injection emulsion, and its prepn. method |
| CN101991535A (en) * | 2010-11-16 | 2011-03-30 | 王京南 | Docosahexaenoic acid (DHA) ester fat emulsion intravenous injection and manufacturing method thereof |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1432367A (en) * | 2003-02-26 | 2003-07-30 | 刘威 | Seal oil cream and its prepn process and appplication in preparing intravenous injection |
| CN1757396A (en) * | 2004-10-09 | 2006-04-12 | 中国药品生物制品检定所 | Ursine fat injection emulsion, and its prepn. method |
| CN101991535A (en) * | 2010-11-16 | 2011-03-30 | 王京南 | Docosahexaenoic acid (DHA) ester fat emulsion intravenous injection and manufacturing method thereof |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015113987A1 (en) * | 2014-01-28 | 2015-08-06 | Fresenius Kabi Deutschland Gmbh | Composition comprising epa and dha triglycerides for parenteral administration |
| CN105939705A (en) * | 2014-01-28 | 2016-09-14 | 费森尤斯卡比德国有限公司 | Composition comprising EPA and DHA triglycerides for parenteral administration |
| CN105939706A (en) * | 2014-01-28 | 2016-09-14 | 费森尤斯卡比德国有限公司 | Composition comprising EPA and DHA ethylester for parenteral administration |
| US10143674B2 (en) | 2014-01-28 | 2018-12-04 | Fresenius Kabi Deutschland Gmbh | Composition comprising EPA and DHA triglycerides for parenteral administration |
| CN105939705B (en) * | 2014-01-28 | 2020-03-17 | 费森尤斯卡比德国有限公司 | Composition comprising triglycerides of EPA and DHA for parenteral administration |
| CN109223712A (en) * | 2018-10-10 | 2019-01-18 | 武汉大安制药有限公司 | Flurbiprofen axetil emulsion for injection and preparation method thereof |
| CN109223712B (en) * | 2018-10-10 | 2020-06-02 | 武汉大安制药有限公司 | Emulsion for injection of flurbiprofen axetil and preparation method thereof |
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| Publication number | Publication date |
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| CN102512367B (en) | 2014-02-12 |
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