CN102512367B - 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 preparation method.
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 Omega-3 unsaturated fatty acid family.
DHA is the composition of brain necessity, accounts for 10% of human brain fat, very favourable to the growth promoter of cranial nerve conduction and synapse.Cognitive competence decline relevant to the deficiency of DHA (1).Severe depression patient's cerebral cortex does not almost have DHA (2).DHA can stop the deposition of cholesterol in blood vessel wall, thus prevention or alleviate the 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 selling on market is oral soft capsule preparation.We find through research, and existing preparation existence and stability is poor, and the shelf-life is short, and active constituent content is low, absorption difference, the problem such as bioavailability is low.In addition, because DHA is easily damaged in digestive tract, so we in order to address the above problem, have researched and developed a kind of new DHA fat emulsion formulation.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, oil-soluble diluent, and emulsifying agent, antioxidant, isoosmotic adjusting agent, ionic complexing agent and water for injection form.
Preparation of the present invention, in its active component formula, most important index is to control the consumption of refined plant oil and the consumption sum of DHA to account for preparation ratio be 0.1-50% above (weight ratio).
DHA fat emulsion formulation of the present invention, the composition being mainly weight percentage by following unit is processed into:
All the other are water for injection.
Preferably, DHA fat emulsion formulation of the present invention, mainly by following composition, be processed into:
All the other are water for injection.
Preferably, DHA fat emulsion formulation of the present invention, mainly by following composition, be processed into:
All the other are water for injection.
Fat emulsion formulation of the present invention also comprises appropriate stabilizing agent, and described stabilizing agent is oleic acid or enuatrol.
In fat emulsion formulation of the present invention:
Described DHA is docosahexenoic acid.
Described oil-soluble diluent is vegetable oil; Be preferably: the fatty glyceride of refined soybean oil, refined maize oil, refining Oleum Helianthi, refining Oleum Arachidis hypogaeae semen, refining Oleum sesami, refining rapeseed oil or other any natural, artificial or semi-artificial preparation or any or several mixture in other oils and fats.
Described emulsifying agent is phospholipid, one or both in polyethyleneglycol derivative; Wherein, described phospholipid is selected from Ovum Gallus domesticus Flavus lecithin, soybean lecithin, sphingomyelins, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline or synthetic lecithin; Wherein, described 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;
Described antioxidant is vitamin E.
Described isoosmotic adjusting agent is glycerol or sugar compounds; Sugar compounds is selected from: one or several mixing in lactose, Raffinose or xylitol.
Another object of the present invention is to provide the preparation method of fat emulsion formulation.
The preparation method of fat emulsion formulation of the present invention, comprises the following steps:
(1) get the DHA of recipe quantity, oil-soluble diluent, antioxidant and emulsifying agent heated and stirred, make it to dissolve completely,
(2) separately get appropriate water for injection, add isoosmotic adjusting agent,
(3) DHA solution step 1 being obtained joins in the solution of step 2 slowly, stirs, and obtains colostrum solution,
(4) colostrum solution, through high pressure homogenizer homogenizing, regulates pH, filters, and packing, passes into nitrogen, sealing, and sterilizing.
The whole preparation process of fat emulsion formulation of the present invention is to carry out under nitrogen protection.
Preferably, the preparation method of fat emulsion formulation of the present invention, comprises the following steps:
(1) getting DHA, vegetable oil, oleic acid, vitamin E and phospholipid heated and stirred 10-20min makes it to dissolve completely;
(2) separately get appropriate water for injection, 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 by cutter high-speed stirred slowly, under the condition of nitrogen protection, continue to stir 30min, obtain 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing, and 115 ℃ of sterilizing 30min.
Further preferred, preparation method of the present invention, comprises the following steps:
Whole production process is carried out under nitrogen protection.
Getting recipe quantity DHA, vegetable oil, oleic acid, vitamin E and phospholipid heated and stirred 10-20min left and right makes it to dissolve completely.Separately get appropriate water for injection, add glycerol.Under the condition of nitrogen protection, phospholipid DHA vegetable oil solution is added in the glycerine water solution by cutter high-speed stirred (3000r/min) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, to particle size range, at 180-300nm, regulates pH 7.0-8.0, filter, packing, passes into nitrogen, sealing, 115 ℃ of sterilizing 30min, final products should be uniform milky solutions, there is no precipitation, layering and oil spill phenomenon.After lamp inspection is qualified, packing.25 ℃ of following storages.
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 fully oil phase and be wrapped in 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 DHA fat milk.3), in emulsifiers formula, add Polyethylene Glycol phospholipid derivative or other amphoteric macromolecule polymers.Polyethylene Glycol phospholipid derivative both can strengthen emulsifying effectiveness, guaranteed that DHA can effectively be wrapped in fat milk oil droplet.4), adopt disaccharide or polysaccharide as the isoosmotic adjusting agent of preparation, improve the parcel efficiency of DHA in fat milk.
New DHA fat milk ejection preparation of the present invention, for intravenous injection, has solved the unstability of DHA in digestive tract, has very important clinical meaning.In addition, fat milk ejection preparation of the present invention has not only effectively solved the problem existing in existing DHA preparation, also has following good performance: good stability, extended the shelf-life, and improved bioavailability, strengthened therapeutic effect, safety has no side effect.
The specific embodiment
By following specific embodiment, to fat emulsion formulation of the present invention, and therapeutic effect is further described.
(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 and condition of the present invention, keep the constant rate of other adjuvant, the usage ratio scope of the listed DHA of the claims in the present invention and flux oil is in 0.03-0.07 (weight ratio).Arbitrary consumption within the scope of weight content all guarantees to make 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 of heated and stirred mixes.Separately get water for injection 700ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
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 of heated and stirred mixes.Separately get water for injection 700ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
(2), flux oil amount ranges is investigated
Under the prerequisite not changing in the ratio that guarantees DHA and flux oil, the present invention verifies the amount ranges of listed refining diluent oil.The arbitrary consumption of the consumption of listed refining diluent oil under basic technology condition of the present invention (take soybean oil as example) within the scope of 5-33% weight content all guarantees to make stable DHA fat emulsion formulation.Still take 1%DHA as example:
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 of heated and stirred mixes.Separately get water for injection 600ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
(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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
(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 12.5g soybean lecithin, the about 10-20min of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
Embodiment 10: different phospholipid use amount increases 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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
Embodiment 11: different phospholipid use amount increases 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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
Embodiment 12: the DHA fat emulsion formulation that adds 1% polyethyleneglycol derivative (with 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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, and than conventional fat emulsion formulation, its particle diameter reduces to some extent, to particle size range, at 160nm-280nm, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
Embodiment 13: the DHA fat emulsion formulation that adds 15% polyethyleneglycol derivative (with 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 of heated and stirred mixes.Separately get water for injection 800ml, add glycerol 22.0g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in glycerine water solution, regulate total amount to 1000ml.Through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, and than conventional fat emulsion formulation, its particle diameter has obviously and reduces, and to particle size range, at 130nm-250nm, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
Embodiment 14: the DHA fat emulsion formulation that the disaccharide that employing lactose is representative is isotonic agent
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g lecithin, the about 10-20min of heated and stirred mixes.Separately get water for injection 800ml, add lactose 100g.Under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing, 25 ℃ of following storages.
Embodiment 15: the DHA fat emulsion formulation that the oligosaccharide that employing Raffinose is representative is isotonic agent
Prescription:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g lecithin, the about 10-20min of heated and stirred mixes.Separately get water for injection 800ml, add 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 phosphatide oil solution is added in 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, regulates pH 7.0-8.0, filters, and packing, passes into nitrogen, sealing.115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing.25 ℃ of following storages.
Embodiment 16, the impact of DHA fat emulsion formulation of the present invention on animal learning memory
1. materials and methods
1.1 animals are selected and grouping
30 of SD female mices, body weight 18～22g (being provided by The Fourth Military Medical University's Experimental Animal Center).Before experiment, 3 water maze tests of Morris water maze tester (institute of Materia Medica,Chinese Academy of Medical Sciences, Beijing) row for mice, reject and have 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, continuously 15d every day.
1.2 instrument
Morris water maze labyrinth is comprised of round pool and automatic picture recording and recording system two parts, pool diameter 60cm, the dark 30cm in pond, depth of water 25cm, 26 ± 1 ℃ of water temperatures, in water, be added with prepared Chinese ink, on pool wall, four equidistant points are divided into four quadrants by pond, and an optional quadrant is at central placement platform, and platform is black, on peripheral pool wall, stick some objects of reference, in experimentation, remain unchanged always.Video recording and recording system consist of videocorder, video camera, television set, computer and data processing software.
Connected outdoor platform, transformator and the timer in ,Yu darkroom, darkroom that light and shade avoidance conditioning case experimental provision is covered with copper grid by bottom forms.Darkroom has a hole to communicate with outdoor platform (5 * 8cm), there is a 40W incandescent source top, darkroom, darkroom and platform are divided into light and shade twoth district, darkroom is 13cm * 5cm * 11cm, bottom, darkroom paving is with copper grid, spacing 0.5cm is connected with power supply, and voltage strength is connected with timer by transformator control, darkroom, and record immerses incubation period and the errors number in darkroom automatically.
1.3 detect index
The performance testing of Morris water maze is tested by Morris water maze, measure mice and enter water to the time (being incubation period) and the total swimming stroke (i.e. swimming distance) that find platform, after drug withdrawal, 1d tests, continuously 3d, respectively test every day 4 times, average.
Darkness avoidance test test is first put into darkroom animal and is adapted to 3min.During test, mice is started to timer after being placed on platform in hole dorsad immediately, and switch on power, mice enters darkroom by hole and is shocked by electricity, timing stops automatically, take out mice, mice is incubation period, recast test after 24h from putting into platform to entering the darkroom chance 36V voltage electric shock time, record the errors number (with the every contact copper rod of two forelimbs of mice for once wrong) of latency change and 5min, using this index as learning and memory.
1.4 statistical analysis
Adopt SPSS 10.0 statistical softwares to carry out statistical analysis, measurement data with
represent, relatively adopt one factor analysis of variance between group, P < 0.05 has statistical significance for difference.
2. result
2.1 Mice water maze performance testing results
The 3rd day incubation period of 3 groups of mices and swimming distance all shortened (P < 0.05) compared with the 1st day; T
1organize 3 day incubation period and swimming apart from there is no marked difference (P > 0.05) compared with C group; T
2group incubation period and swimming distance significantly reduce (P < 0.05) compared with C group, compared with T
1group also significantly reduces (P < 0.05) (in Table 1).
Table 1 is respectively organized the comparison of Mice water maze test incubation period and swimming distance
With 1d comparison,
*p < 0.05; Compare with C group,
△p < 0.05; With T
1group compares,
☆p < 0.05
2.2 mice light and shade avoidance response test results
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) (in Table 2).
Table 2 is respectively organized the comparison of mice light and shade avoidance response test incubation period and errors number
Compare with C group,
*p < 0.05; With T
1relatively,
△p < 0.05
3. conclusion
This experiment is tested by mice being carried out to the test of Morris water maze and light and shade avoidance response, to evaluate the cognitive competence of mice.Found that the mice group of intravenous injection embodiment of the present invention 5DHA fat milk sample, water maze laboratory Middle latency and swimming distance significantly reduce; Light and shade avoidance response test significant prolongation incubation period, errors number significantly reduces, but blank fat milk has no significant effect these indexs, this DHA fat milk sample that just shows prepared by the present invention can improve mice spatial memory and light and shade reaction well, and learning and memory of little mouse is had to facilitation significantly.
Claims (1)
1. a DHA fat emulsion formulation, by following composition, be processed into:
DHA 10.0g
Injection soybean oil 200.0g
Lecithin 12.5g
DSPE-PEG 150 g
Vitamin E 3.0g
Glycerol 22.0g
Water for injection adds to 1000ml
Its preparation method is as follows:
Get DHA 10.0g, vitamin E 3.0g, refined soybean oil 200.0g, add 12.5g lecithin and 150g DSPE-PEG, heated and stirred 10-20min mixes, separately get water for injection 800ml, add glycerol 22.0g, under nitrogen protection and stirring condition, DHA phosphatide oil solution is added in glycerine water solution, regulate total amount to 1000ml, through high pressure homogenizer homogenizing 7-8 time, homogenization pressure is 100MPa, than conventional fat emulsion formulation, its particle diameter has obviously and reduces, to particle size range at 130nm-250nm, regulate pH 7.0-8.0, filter, packing, pass into nitrogen, sealing, 115 ℃ of sterilizing 30min, after lamp inspection is qualified, packing, 25 ℃ of following storages.
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| WO2015113986A1 (en) * | 2014-01-28 | 2015-08-06 | Fresenius Kabi Deutschland Gmbh | Composition comprising epa and dha ethylester for parenteral administration |
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| 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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| CN102512367A (en) | 2012-06-27 |
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