CN104523715B - Injection containing nervonic acid and phospholipids compounds and its preparation method and application - Google Patents

Injection containing nervonic acid and phospholipids compounds and its preparation method and application Download PDF

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Publication number
CN104523715B
CN104523715B CN201410755321.2A CN201410755321A CN104523715B CN 104523715 B CN104523715 B CN 104523715B CN 201410755321 A CN201410755321 A CN 201410755321A CN 104523715 B CN104523715 B CN 104523715B
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injection
water
lecithin
nervonic acid
homogeneous
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CN104523715A (en
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张耿元
王保红
白东跃
唐湘成
俞世宏
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Harbin Yida pharmaceutical Limited by Share Ltd
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FUZHOU QIANZHENG PHARMACEUTICAL Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles

Abstract

The present invention provides the fat emulsion injection containing phosphatide, nervonic acid and water for injection, the content of water for injection is more than 70% with weight ratio meter in the parenteral solution, fat globule particle diameter in parenteral solution is less than 1 μm, described phosphatide includes lecithin, phosphatidyl-ethanolamine, phosphatidylinositols, and wherein phosphatide and nervonic acid is using weight ratio as 1:The ratio combination of (0.005~1), invention further provides the preparation method of the fat emulsion injection, and the application in the medicine of injection supplement nervonic acid, phosphatide and the disease such as unrighted acid and the retrogression pathological changes of preventing and treating cranial nerve, brain damage, brain disorder.

Description

Injection containing nervonic acid and phospholipids compounds and its preparation method and application
Technical field
The present invention relates to pharmaceutical technology field, the injection medicine specifically containing nervonic acid and phospholipids compounds, with And its preparation method and application.
Background technology
Nervonic acid, NA, it is a kind of monounsaturated fatty acids of long-chain, is biological in nerve fiber The important composition composition of film, the significant composition of brain glucoside medullary substance, the core natural component of cranial nerve fiber and nerve cell, and Nerve cell particularly brain cell, optic cell, peripheral nerve growth, develop again and function maintain required nutrient, Mainly it is present in the form of glycosyl sphingolipid and sphingomyelins in human body brain tissue, is played an important role in the biosynthesis of myelin, it is right Important adjustment effect is played to complete information transmission and Information procession by the ion channel on neuron membrane and acceptor；Grind Study carefully and show, nervonic acid has protective effect to cardiovascular and cerebrovascular, brain tissue, and nervonic acid is also in the world first that scientists from all over the world generally acknowledge It is individual, and only one can repair dredging injured brain nerve pathway ----nerve fibre, and it is double to promote nerve cell to regenerate Imitate magical material；Higher blood plasma nervonic acid level can reduce the occurrence risk of acute ischemic cerebral apoplexy, and nervonic acid lacks It is weary will cause brain function decline, brain disorder, cerebral apoplexy sequela, senile dementia, brain paralysis, encephalatrophy, failure of memory, The cerebral diseases such as insomnia forgetfulness；Nervonic acid is hardly produced in human body itself, it is necessary to be supplemented by absorbing in vitro.
Phosphatide, it is the lipids containing phosphatide root, is the main component for forming biomembrane, phosphatide of the invention includes Lecithin (phosphatidyl choline), phosphatidyl-ethanolamine, phosphatidylinositols etc., there is nutrition cranial nerve, activating brain cell, remain new Too high blood fat and too high cholesterol, protection vascular circulation are smooth in old metabolism and basic metabolism, decomposer, alleviate heart and brain blood Pressure of tube wall etc. acts on, and with advancing age, the lecithin in human body can gradually decrease, and supplements phosphatide, especially lecithin Fat is particularly significant for health.
The common name phosphatidyl choline of lecithin, it is described as " the 3rd nutrient " arranged side by side with protein, vitamin, previous generation Since discipline the nineties, phosphatide research has been achieved for significant effect in life science and brain science field, and lecithin is to people The nutrition of body has the effect of good with health, shows：1st, human nutrition needs：The exogenous choline 90% of needed by human body is There is provided by lecithin, lecithin, which provides choline, there are two big benefits：First, unlike free choline can because of microbial action in enteron aisle and It is degraded into methylamine；Secondly, it is by cephalin in liver and other fibr tissues（PE continuous methylate) obtains choline, and This building-up process needs certain time, therefore when meals choline deficiency, lecithin is remained in vivo（PC）Endogenous resource Supplementing human body needs；2nd, to the adjustment effect of serum lipids：Regulation serum lipid level means that cholesterol levels can be reduced, protected Protect liver is dirty, can also improve memory, booster immunization power and lipotropic vigor；3rd, healthy heart：In the 1960s, Scientists find that lecithin may have the function that cardioprotection, in further research, confirm lecithin pair finally Health of heart has positive role, because it can adjust content of the cholesterol in human body, effectively reduce cholesterol, high fat of blood And the incidence of disease of coronary heart disease；4th, beneficial to brain：The content of lecithin accounts for the 17%~20% of its quality in cranial nerve cell, " courage Alkali " is the basis of lecithin, and the ample supply of lecithin ensures that sufficiently " choline " synthesizes with " acetyl " in human body " acetylcholine ", " acetylcholine " are a kind of IC Information Conduction materials, so as to improve the activation degree of brain cell, are carried Height memory and intellectual level；5th, arteriosclerosis is prevented and treated：Lecithin has the function that emulsification, cut grease, and can promote Blood circulation, improve serum lipids, remove peroxide, reduce Blood Cholesterol and neutral fat content, reduce fat The holdup time of wall in the blood vessels, promote the dissipation of atherosis spot, prevent the blood vessel internal membrane damage as caused by cholesterol.Take Lecithin has the effect of notable to high fat of blood and high cholesterol, thus can prevent and treat arteriosclerosis（Hypertension, cardiac muscle Infraction, cerebral hemorrhage）；6th, Palmitoleic Acid：Lecithin is the indispensable material of each cell of human body, if lacked, will be dropped The power of regeneration of low Skin Cell, cause pachylosis, have wrinkle, if suitably absorbing lecithin, skin regeneration vigor can To ensure, along with lecithin good hydrophily and lipophile, skin is certainly just glossy.In addition, contained by lecithin The main nutrient of inositol or hair, alopecia can be suppressed, make white hair slowly blackening；7th, anti-aging：People with age, Memory can decline, and its reason has certain relation, the neurotransmitter of brain with acetyl choline content deficiency（Acetylcholine） Reduction is acetylcholine required compound when being nervous system information transmission the main reason for causing senile dementia, and " courage Alkali " is the basis of lecithin, and the ample supply of lecithin will ensure the acetyl for having in enough choline and human body in body " acetylcholine " is combined into, so as to provide sufficient Information Conduction material as brain, big brain-capacity directly absorbs ovum from blood Phosphatide and choline, and be converted into acetylcholine quickly, the long-term lecithin that supplements can slow down the process of memory loss, prevention or Postpone the generation of senile dementia；8th, adjust psychological：Social competition is growing more intense, and people are in the environment of anxiety and a variety of pressures for a long time Under power, often with the diseases such as anxiety, irritability, irritability, insomnia, tinnitus, i.e. vegetative nervous disorder, commonly known as neurasthenia, warp Often supplement lecithin, can make cerebral nerve obtain nutritional supplementation in time, the working condition kept fit, and beneficial to dispelling fatigue, swash Change brain cell, improve the disease such as irritability, irritability, insomnia because caused by nervous；9th, PFT is activated：Alveolar is intake in vivo On the contrary the cell of oxygen, alveolar moistening, the oxygen of suction easily dissolves, then cause body anoxic, and lecithin has close well It is water-based, alveolar can be made to keep moistening, it is weaker or smoker's alveolar is done for PFT so as to improve the intake of body oxygen It is dry, take the photograph hypoxgia, and move, be more easy to tired because of anoxic after work, lecithin should be supplemented more.
Nervonic acid or phosphatide have been machined on various health foods, such as soft capsule, tablet, it has not been found that phosphatide and The compound of nervonic acid.
Detrimental effect is that the oral absorption availability of nervonic acid is simultaneously bad, about 30% or so, therefore, by nervonic acid Injection is prepared as, is advantageous to its biological utilisation and Clinical practice.
The content of the invention
It is an object of the invention to provide a kind of fat emulsion injection containing phosphatide, nervonic acid and water for injection, the note The content for penetrating water for injection in liquid is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in parenteral solution is 2 μm, 1 μm, 0.5 μm, 0.2 μm etc.；
Preferably, the present invention provides a kind of fat emulsion injection containing phosphatide, nervonic acid and water for injection, the injection The content of water for injection is more than 75% with weight ratio meter in liquid, and the fat globule particle diameter in parenteral solution is less than 1 μm, such as makes note The fat globule particle diameter penetrated in liquid is 0.7 μm, 0.5 μm, 0.3 μm etc..
Phosphatide of the present invention includes lecithin, phosphatidyl-ethanolamine, phosphatidylinositols；Special, it is of the present invention Phosphatide especially lecithin.
Another aspect of the present invention provides phosphatide with nervonic acid with the combination of arbitrary proportion, preferably with the dosage of synergy Ratio existing for present invention combination, or can preferably be protected existing for stable sex rate of the nervonic acid in parenteral solution with phosphatide Present invention combination, such as phosphatide and nervonic acid are using weight ratio as 1:The ratio combination of (0.005~1),
It is preferred that phosphatide and nervonic acid are using weight ratio as 1:The ratio combination of (0.006~0.8),
It is preferred that phosphatide and nervonic acid are using weight ratio as 1:The ratio combination of (0.008~0.6),
It is preferred that phosphatide and nervonic acid are using weight ratio as 1:The ratio combination of (0.01~0.5),
It is preferred that phosphatide and nervonic acid are using weight ratio as 1:The ratio combination of (0.02~0.3),
It is preferred that phosphatide and nervonic acid are using weight ratio as 1:The ratio combination of (0.03~0.2),
It is preferred that phosphatide and nervonic acid are using weight ratio as 1:The ratio combination of (0.05~0.1),
It is preferred that phosphatide and nervonic acid are using weight ratio as 1:The ratio combination of (0.06~0.1),
Specifically, for example preferred phosphatide and nervonic acid are using weight ratio as 1:0.01、1:0.02、1:0.04、1:0.05、1: 0.06、1:0.08、1:0.09、1:0.1、1:0.2、1:0.3、1:0.4、1:0.5、1:0.6、1:0.7、1:0.8、1:0.9、1:1 Deng ratio combination.
Further, present invention offer one kind contains nervonic acid, lecithin, water for injection and following one or more compositions Fat emulsion injection：DHA (docosahexaenoic acid), arachidonic acid, leukotrienes (including alpha-linolenic acid or γ-flax Acid), linoleic acid, CLA, conjugated linoleic acid glyceride, phosphatidylserine, Polyene Phosphatidylcholine, phosphatidyl ethanol Amine, phosphatidylinositols, phosphatidyl glycerol, phytosterol, phytosterin ester, plant stanol ester, soybean oil, the acid of medium chain triglyceride three Ester, structured triglyceride；Wherein the content of water for injection is more than 70% with weight ratio meter, lecithin and nervonic acid using weight ratio as 1:The ratio combination of (0.005~1), and the fat globule particle diameter in parenteral solution is less than 2 μm, the preferably fat spherule in parenteral solution Footpath is less than 1 μm, and the fat globule particle diameter most preferably in parenteral solution is less than 0.5 μm, such as make the fat globule particle diameter in parenteral solution be 1 μ M, 0.5 μm, 0.3 μm etc..
It should illustrate and it will be appreciated by persons skilled in the art that DHA of the present invention, arachidonic acid, leukotrienes （Including alpha-linolenic acid or gamma-Linolenic acid）, it is linoleic acid, CLA, conjugated linoleic acid glyceride, phosphatidylserine, more Alkene phosphatidyl choline, phosphatidyl-ethanolamine, phosphatidylinositols, phosphatidyl glycerol, phytosterol, phytosterin ester, phytostanyl Alcohol ester, soybean oil, median chain triglyceride oil, structured triglyceride etc. are all fats or liposoluble substance, and the present invention will be above-mentioned Fats or liposoluble substance in addition to lecithin, nervonic acid are referred to as " other liposoluble substances ", typically from vegetable oil or Extracted in yolk, or compound further synthesized again after being extracted from vegetable oil, for example, lecithin be from soybean oil or Extracted in yolk, phosphatidylserine is using lecithin and Serine as raw material, after phosphatide enzymatic conversion reaction, is purified After be made；For another example phytosterol includes the β-paddy extracted from soybean oil, rapeseed oil, corn oil, sunflower oil, Tall oil Sterol, campesterol, stigmasterol etc.；
On the other hand, phosphatide of the present invention, nervonic acid, DHA, arachidonic acid, leukotrienes, alpha-linolenic acid, γ-flax Acid, linoleic acid, CLA, conjugated linoleic acid glyceride, phosphatidylserine, Polyene Phosphatidylcholine, phosphatidyl ethanol Amine, phosphatidylinositols, phosphatidyl glycerol, phytosterol, phytosterin ester, plant stanol ester, soybean oil, the acid of medium chain triglyceride three These fats such as ester, structured triglyceride or liposoluble substance, it will usually which vegetable fat is present in the ratio of certain content In, special, above-mentioned liposoluble substance of the present invention also includes the vegetable oil containing these liposoluble substances, for example, ovum Phosphatide is present in soybean oil extract or oleic acid with 40~60% content, lecithin, phosphatidyl-ethanolamine, phosphatidylinositols It is present in phosphatidyl glycerol with ratio of the total phospholipids content more than 35% in krill oil, nervonic acid exists with the content more than 5% In acer truncatum seed oil or Malania Oleifera Oil, DHA be present in the content more than 35% split kettle algae (my Ken Shi kettles algae or Kou Shi it is hidden Dinoflagellate) algae oil in, leukotrienes is present in peony seed oil or eucommia ulmoides seed oil with the content more than 40%, linoleic acid with 20%~ 40% content be present in silybum marianum seed oil, safflower seed oil, Suaeda salsa seed oil or tea seed oil in, etc..
It should illustrate and understand, lecithin of the present invention, nervonic acid, DHA, arachidonic acid, leukotrienes, α- Leukotrienes, gamma-Linolenic acid, linoleic acid, CLA, conjugated linoleic acid glyceride, phosphatidylserine, polyene phosphatidyl courage Alkali, phosphatidyl-ethanolamine, phosphatidylinositols, phosphatidyl glycerol, phytosterol, phytosterin ester, plant stanol ester, middle chain are sweet Oily three acid esters or structured triglyceride etc. both can be that sterling or the material closest to sterling are applied to the present invention or contained Have nervonic acid, lecithin, DHA, arachidonic acid, leukotrienes, alpha-linolenic acid, gamma-Linolenic acid, linoleic acid, CLA, altogether Conjugated linoleic acid glyceride, phosphatidylserine, Polyene Phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidylinositols, phosphatidyl are sweet The non-sterling application of oil, phytosterol, phytosterin ester, plant stanol ester, median chain triglyceride oil or structured triglyceride In the present invention, the present invention is e.g. applied to Vegetable oil or plant extracts oil, for example, neural acid content is more than 5% Acer truncatum seed oil or donor of the Malania Oleifera Oil as nervonic acid, directly apply to the present invention, linolenic acid content be more than 40% in Peony seed oil or eucommia ulmoides seed oil directly apply to the present invention, water of the linoleic acid content 20%~55% as linolenic donor Fly Ji seed oil, safflower seed oil, Suaeda salsa seed oil or tea seed oil as linoleic donor, directly apply to the present invention.
Further, fat emulsion injection of the present invention also includes other water-soluble substanceses, " other water-soluble substanceses " Including glycerine, sodium chloride, glucose, fructose, inverted sugar, amino acid, water soluble vitamin etc., for adjusting Fat Emulsion of the present invention The osmotic pressure of parenteral solution, or favourable, the beneficial compositions such as sugar needed for patient, electrolyte, amino acid can be provided.
Special, it will be appreciated by those skilled in the art that all the components or thing used in fat emulsion injection of the present invention Matter, it may be that refined, degree of purity highest level, preferably injection stage.
Further, the above-mentioned fat emulsion injection of the present invention, can also optionally contain pH value regulator, by the present invention Injection-used fat emulsion is adjusted to required pH value, generally by the pH value regulation of injection of the present invention 5.5~8.5, preferably by this 6~8, preferable pH value regulator is typically alkalescence, preferably sodium hydroxide, hydroxide for the pH value regulation of invention injection Potassium, arginine, lysine etc., it can also optionally contain antioxidant, such as vitamin C, vitamin E, Cys.
It is special and it is further preferred that the present invention provide it is a kind of containing nervonic acid, lecithin, other water-soluble substanceses, its The content of the fat emulsion injection of its liposoluble substance and water for injection, wherein water for injection is more than 70% with weight ratio meter, lecithin The weight of fat and nervonic acid ratio is 1:(0.005~1), and the fat globule particle diameter in parenteral solution is less than 2 μm, in preferred emulsion Fat globule particle diameter is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm, and other water-soluble substanceses include glycerine, sodium chloride, grape Sugar, fructose, inverted sugar, amino acid or water soluble vitamin, other liposoluble substances include it is following it is one or more into Point：The sub- oil of DHA, arachidonic acid, leukotrienes (including alpha-linolenic acid or gamma-Linolenic acid), linoleic acid, CLA, conjugation Acid glyceride, phosphatidylserine, Polyene Phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidylinositols, phosphatidyl glycerol, plant Sterol, phytosterin ester, plant stanol ester, soybean oil, median chain triglyceride oil, structured triglyceride.
Specifically, the present invention provides a kind of fat emulsion injection containing nervonic acid, lecithin and water for injection, wherein noting Penetrate and be more than 70% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make in liquid Fat globule particle diameter is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion injection containing nervonic acid, lecithin, soybean oil and water for injection The content of liquid, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion containing nervonic acid, lecithin, soybean oil, glycerine and water for injection The content of parenteral solution, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, example The fat globule particle diameter in liquid is such as set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm；
Specifically, the present invention, which provides one kind, contains nervonic acid, lecithin, soybean oil, median chain triglyceride oil, glycerine and note The fat emulsion injection with water is penetrated, the wherein content of water for injection is more than 70%, and the fat globule in parenteral solution with weight ratio meter Particle diameter is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion containing nervonic acid, lecithin, structured triglyceride and water for injection The content of parenteral solution, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, example The fat globule particle diameter in liquid is such as set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm；
Specifically, the present invention provides a kind of Fat Emulsion injection containing nervonic acid, lecithin, glucose and water for injection The content of liquid, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion injection containing nervonic acid, lecithin, sodium chloride and water for injection The content of liquid, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of fat emulsion injection containing nervonic acid, lecithin, fructose and water for injection, Wherein the content of water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes liquid Fat globule particle diameter in body is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion injection containing nervonic acid, lecithin, inverted sugar and water for injection The content of liquid, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion injection containing nervonic acid, lecithin, amino acid and water for injection The content of liquid, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of fat emulsion injection containing nervonic acid, lecithin, DHA and water for injection, its The content of middle water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes liquid In fat globule particle diameter be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion note containing nervonic acid, lecithin, arachidonic acid and water for injection Penetrate liquid, wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as The fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion injection containing nervonic acid, lecithin, alpha-linolenic acid and water for injection The content of liquid, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion note containing nervonic acid, lecithin, gamma-Linolenic acid and water for injection Penetrate liquid, wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as The fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion injection containing nervonic acid, lecithin, linoleic acid and water for injection The content of liquid, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, CLA（Or conjugated linoleic acid glyceride） With the fat emulsion injection of water for injection, the wherein content of water for injection is more than 75%, and the fat in parenteral solution with weight ratio meter Fat spherolite footpath is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion containing nervonic acid, lecithin, phosphatidylserine and water for injection The content of parenteral solution, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, example The fat globule particle diameter in liquid is such as set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm；
Specifically, the present invention provides a kind of fat containing nervonic acid, lecithin, Polyene Phosphatidylcholine and water for injection The content of emulsion injection, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, Such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion containing nervonic acid, lecithin, phosphatidyl-ethanolamine and water for injection The content of parenteral solution, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, example The fat globule particle diameter in liquid is such as set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm；
Specifically, the present invention provides a kind of Fat Emulsion note containing nervonic acid, lecithin, phosphatidylinositols and water for injection Penetrate liquid, wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as The fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides a kind of Fat Emulsion note containing nervonic acid, lecithin, phosphatidyl glycerol and water for injection Penetrate liquid, wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as The fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, phytosterol（Or phytosterin ester, or plant Stanol ester）With the fat emulsion injection of water for injection, wherein the content of water for injection is more than 75% with weight ratio meter, and notes The fat globule particle diameter penetrated in liquid is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm Deng；
Specifically, the present invention provides a kind of fat containing nervonic acid, lecithin, median chain triglyceride oil and water for injection The content of emulsion injection, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, Such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention, which provides one kind, contains nervonic acid, lecithin, DHA, arachidonic acid, CLA and note The fat emulsion injection with water is penetrated, the wherein content of water for injection is more than 75%, and the fat globule in parenteral solution with weight ratio meter Particle diameter is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention, which provides one kind, contains nervonic acid, lecithin, linoleic acid, median chain triglyceride oil and injection The content of the fat emulsion injection of water, wherein water for injection is more than 75%, and the fat globule particle diameter in parenteral solution with weight ratio meter Less than 2 μm, such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provide it is a kind of containing nervonic acid, lecithin, CLA, leukotrienes and water for injection The content of fat emulsion injection, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, CLA, α-flax Acid, phytosterol（Or phytosterin ester, or plant stanol ester）With the fat emulsion injection of water for injection, wherein injection The content of water is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat in liquid Spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, alpha-linolenic acid, medium chain triglyceride three The content of the fat emulsion injection of acid esters and water for injection, wherein water for injection is more than 75% with weight ratio meter, and in parenteral solution Fat globule particle diameter be less than 2 μm, such as fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, CLA, α-flax The fat emulsion injection of acid, median chain triglyceride oil and water for injection, the content of wherein water for injection are more than with weight ratio meter 75%, and the fat globule particle diameter in parenteral solution is less than 2 μm, for example, make fat globule particle diameter in liquid be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, linoleic acid, phosphatidyl silk ammonia Acid, phytosterol（Or phytosterin ester, or plant stanol ester）With the fat emulsion injection of water for injection, wherein injection The content of water is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat in liquid Spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention, which provides one kind, contains nervonic acid, lecithin, arachidonic acid, CLA and injection The content of the fat emulsion injection of water, wherein water for injection is more than 75%, and the fat globule particle diameter in parenteral solution with weight ratio meter Less than 2 μm, such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention, which provides one kind, contains nervonic acid, lecithin, Polyene Phosphatidylcholine, CLA and note The fat emulsion injection with water is penetrated, the wherein content of water for injection is more than 75%, and the fat globule in parenteral solution with weight ratio meter Particle diameter is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, Polyene Phosphatidylcholine, sub- oil The fat emulsion injection of acid and water for injection, the wherein content of water for injection are more than 75% with weight ratio meter, and in parenteral solution Fat globule particle diameter is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, present invention offer is a kind of sub- containing nervonic acid, lecithin, arachidonic acid, phosphatidyl-ethanolamine, conjugation The content of the fat emulsion injection of oleic acid and water for injection, wherein water for injection is more than 75% with weight ratio meter, and in parenteral solution Fat globule particle diameter be less than 2 μm, such as fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, phosphatidylinositols, the sub- oil of conjugation The fat emulsion injection of acid and water for injection, the wherein content of water for injection are more than 75% with weight ratio meter, and in parenteral solution Fat globule particle diameter is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, phosphatidyl glycerol, the sub- oil of conjugation The fat emulsion injection of acid and water for injection, the wherein content of water for injection are more than 75% with weight ratio meter, and in parenteral solution Fat globule particle diameter is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, CLA, medium chain triglyceride The content of the fat emulsion injection of three acid esters and water for injection, wherein water for injection is more than 75%, and parenteral solution with weight ratio meter In fat globule particle diameter be less than 2 μm, such as fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention, which provides one kind, contains nervonic acid, lecithin, gamma-Linolenic acid, median chain triglyceride oil and injection With the fat emulsion injection of water, the wherein content of water for injection is more than 75%, and the fat spherule in parenteral solution with weight ratio meter Footpath is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, CLA, phytosterol （Or phytosterin ester, or plant stanol ester）, median chain triglyceride oil and water for injection fat emulsion injection, wherein noting Penetrate and be more than 75% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make in liquid Fat globule particle diameter is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, CLA, α-flax The fat emulsion injection of acid, median chain triglyceride oil and water for injection, the content of wherein water for injection are more than with weight ratio meter 75%, and the fat globule particle diameter in parenteral solution is less than 2 μm, for example, make fat globule particle diameter in liquid be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the present invention provides one kind containing nervonic acid, lecithin, arachidonic acid, gamma-Linolenic acid, the sub- oil of conjugation Acid, phosphatidylserine, phytosterol（Or phytosterin ester, or plant stanol ester）Injected with the Fat Emulsion of water for injection The content of liquid, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes Fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc..
Further, the above-mentioned fat emulsion injection of the present invention, can also optionally contain pH value regulator, by the present invention Injection-used fat emulsion is adjusted to required pH value, generally by the pH value regulation of injection of the present invention 5.5~8.5, preferably by this 6~8, preferable pH value regulator is typically alkalescence, preferably sodium hydroxide, hydroxide for the pH value regulation of invention injection Potassium, arginine, lysine etc., it can also optionally contain antioxidant, such as vitamin C, vitamin E, Cys.
Fat emulsion injection of the present invention, it is the emulsion that a kind of chyle fat is formed, is a complicated, Thermodynamically stable System, especially different grease types or fat-soluble ingredient, water soluble ingredient, such as sugar, electrolyte, amino acid are mixed into Point, because the fat-water distribution and combination energy state of each component are different, and the phase of liposoluble substance and each composition of water-soluble substances Capacitive, the stability for whole system are vital, the bodies of multi-component fat breast, fat breast-electrolyte or fat breast-sugar System, it is easy to the wild effects such as fat floating, flocculation or layering, production method and technique occur, decide fat in parenteral solution The form and size of fat ball, and the microphenomenons such as aggregation whether can occur, so as to influence the fat of parenteral solution in macroscopic aspect Floating, flocculation or layering etc. are unstable, certainly, also contribute to security of the parenteral solution in human body.
Further, the present invention provides a kind of system of the fat emulsion injection containing nervonic acid, lecithin and water for injection Preparation Method, it includes：By nervonic acid, lecithin mixed, emulsified successively with water for injection, homogeneous and uniform liquid is made The content of body, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in emulsion is less than 2 μm, preferred emulsion In fat globule particle diameter be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm.
Further, the present invention provides a kind of containing nervonic acid, lecithin, other water-soluble substanceses, other fat-soluble things The preparation method of the fat emulsion injection of matter and water for injection, it includes：By lecithin, nervonic acid, other water-soluble substanceses, its Its liposoluble substance is mixed with water for injection, emulsified, homogeneous and uniform liquid is made, wherein the content of water for injection is with weight Be more than 70% than meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, fat globule particle diameter in preferred emulsion be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm, other water-soluble substanceses include glycerine, sodium chloride, glucose, fructose, inverted sugar, amino acid or Person's water soluble vitamin, other liposoluble substances include following one or more compositions：DHA, arachidonic acid, leukotrienes It is (including alpha-linolenic acid or gamma-Linolenic acid), linoleic acid, CLA, conjugated linoleic acid glyceride, phosphatidylserine, more Alkene phosphatidyl choline, phosphatidyl-ethanolamine, phosphatidylinositols, phosphatidyl glycerol, phytosterol, phytosterin ester, phytostanyl Alcohol ester, soybean oil, median chain triglyceride oil, structured triglyceride.
Particularly, the present invention provides a kind of containing nervonic acid, lecithin, other water-soluble substanceses, other liposoluble substances With the preparation method of the fat emulsion injection of water for injection, it includes：
(1) dispensing：Lecithin, nervonic acid, other water-soluble substanceses, other liposoluble substances are weighed by formula, adds note Penetrate with water, be settled to required output, be stirred and be uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, nitrogen or two are continuously passed through from emulsification pot bottom Carbonoxide, under conditions of fluid temperature is 45~85 DEG C, speed of agitator is more than 2000r/min, progress emulsification procedure 5~ 35min, after parenteral solution then is cooled into 25 DEG C in 5min, stops stirring and stop being passed through nitrogen or carbon dioxide, stand；
Preferably, nitrogen or carbon dioxide intake are 10~80L/min, and emulsification speed of agitator is not less than 2800r/min；
(3) homogeneous：By liquid regulation pH value made from step (2) 5.5~8.5, through the filtering of 500~1000 mesh, filtrate It is that 15~58MPa carries out homogeneous in 50~98 DEG C of temperature, pressure, can optionally carries out multiple homogeneous, and make the fat in parenteral solution Fat spherolite footpath is less than 2 μm, the fat globule particle diameter in liquid is less than 1 μm, such as be less than the fat globule particle diameter in liquid 0.7 μm, 0.5 μm, 0.3 μm etc., homogeneous, refer to that the feed liquid of material is extruding, make under the triple role that thump expands with decompression Material refines, and broken is more tiny, so that what material can be evenly is mutually mixed, whole product system is more stable, excellent Choosing, the present invention propose homogenization technology, through multiple homogenization so that lecithin, nervonic acid, other water-soluble substanceses, Other liposoluble substances, water for injection etc. uniformly mix and keep stable homogeneous；
(4) refined filtration, filling, sterilizing：Liquid after homogeneous is subjected to vacuum outgas, it is optimal with 2 μm of filtering with microporous membrane From canned after 1 μm of filtering with microporous membrane, sealing, canned, sealing can be optionally carried out with inflated with nitrogen, and in 85~135 DEG C of bars Sterilized 4 seconds~35 minutes under part；
(5) pack, examine, produce fat emulsion injection of the present invention；
The content of water for injection is more than 70% with weight ratio meter in the fat emulsion injection, the weight of lecithin and nervonic acid Amount is than being 1:(0.005~1), and the fat globule particle diameter in parenteral solution is less than 2 μm, is injected in preferably described fat emulsion injection With the content of water with weight ratio meter more than 75%, the weight ratio of lecithin and nervonic acid is 1:(0.008~0.6), and parenteral solution In fat globule particle diameter be less than 1 μm；
Other water-soluble substanceses include glycerine, sodium chloride, glucose, fructose, inverted sugar, amino acid or water solubility Vitamin, other liposoluble substances include following one or more compositions：DHA, arachidonic acid, leukotrienes (including α- Leukotrienes or gamma-Linolenic acid), linoleic acid, CLA, conjugated linoleic acid glyceride, phosphatidylserine, polyene phosphatidyl Choline, phosphatidyl-ethanolamine, phosphatidylinositols, phosphatidyl glycerol, phytosterol, phytosterin ester, plant stanol ester, soybean Oil, median chain triglyceride oil, structured triglyceride.
The present invention surprisingly has found, obtained containing nervonic acid, lecithin, other liposoluble substances and water for injection Parenteral solution, fat globule particle diameter distributed effect is good, so-called particle diameter distribution effect, refers to particle size homogeneity, difference in size rate, shape State regularity etc., it is the most critical factor for reflecting fat globule particle diameter and parenteral solution stability.Lead to especially in emulsification procedure Enter gas（Nitrogen or carbon dioxide）, blending and stirring and cavitation that gas and liquid are formed when high-speed stirred is sheared are sheared, made The fat globule that various fat-soluble ingredient energy rapid dispersions are emulsified into uniform particle diameter is obtained, fat globule particle diameter is small and particle diameter distribution is narrow, and And parenteral solution being quickly cooled to 25 DEG C using in 5min so that homogeneous, regular spherical shape is presented in the form of fat globule, Prevent fat globule drop regroup, for parenteral solution stability have significantly improve, also have for safety in utilization significantly Improve, such as the security with other medicines in compatible use, and injecting security after entering in human body etc. Significantly improve.
Further, the present invention provide it is a kind of containing nervonic acid, it is lecithin, other water-soluble substanceses, other fat-soluble The fat emulsion injection of material and water for injection, the content of water for injection is more than with weight ratio meter in the fat emulsion injection 70%, the weight ratio of lecithin and nervonic acid is 1:(0.005~1), and the fat globule particle diameter in parenteral solution is less than 2 μm, preferably For the content of water for injection with weight ratio meter more than 75%, the weight ratio of lecithin and nervonic acid is 1 in the fat emulsion injection: (0.008~0.6), and the fat globule particle diameter in parenteral solution is less than 1 μm；Other water-soluble substanceses include glycerine, chlorination Sodium, glucose, fructose, inverted sugar, amino acid or water soluble vitamin, other liposoluble substances include it is following a kind of or Multiple components：DHA, arachidonic acid, leukotrienes (including alpha-linolenic acid or gamma-Linolenic acid), linoleic acid, CLA, altogether Conjugated linoleic acid glyceride, phosphatidylserine, Polyene Phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidylinositols, phosphatidyl are sweet Oil, phytosterol, phytosterin ester, plant stanol ester, soybean oil, median chain triglyceride oil, structured triglyceride；Wherein, The preparation method of the fat emulsion injection includes：
(1) dispensing：Lecithin, nervonic acid, other water-soluble substanceses, other liposoluble substances are weighed by formula, adds note Penetrate with water, be settled to required output, be stirred and be uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, nitrogen or two are continuously passed through from emulsification pot bottom Carbonoxide, under conditions of fluid temperature is 45~85 DEG C, speed of agitator is more than 2000r/min, progress emulsification procedure 5~ 35min, after parenteral solution then is cooled into 25 DEG C in 5min, stops stirring and stop being passed through nitrogen or carbon dioxide, stand；
Preferably, nitrogen or carbon dioxide intake are 10~80L/min, and emulsification speed of agitator is not less than 2800r/min；
(3) homogeneous：By liquid regulation pH value made from step (2) 5.5~8.5, through the filtering of 500~1000 mesh, filtrate It is that 15~58MPa carries out homogeneous in 50~98 DEG C of temperature, pressure, can optionally carries out multiple homogeneous, and make the fat in parenteral solution Fat spherolite footpath is less than 2 μm, the fat globule particle diameter in liquid is less than 1 μm, such as be less than the fat globule particle diameter in liquid 0.7 μm, 0.5 μm, 0.3 μm etc., homogeneous, refer to that the feed liquid of material is extruding, make under the triple role that thump expands with decompression Material refines, and broken is more tiny, so that what material can be evenly is mutually mixed, whole product system is more stable, excellent Choosing, the present invention propose homogenization technology, through multiple homogenization so that lecithin, nervonic acid, other water-soluble substanceses, Other liposoluble substances, water for injection etc. uniformly mix and keep stable homogeneous；
(4) refined filtration, filling, sterilizing：Liquid after homogeneous is subjected to vacuum outgas, it is optimal with 2 μm of filtering with microporous membrane From canned after 1 μm of filtering with microporous membrane, sealing, canned, sealing can be optionally carried out with inflated with nitrogen, and in 85~135 DEG C of bars Sterilized 4 seconds~35 minutes under part；
(5) pack, examine, produce fat emulsion injection of the present invention；
The content of water for injection is more than 70% with weight ratio meter in the fat emulsion injection, the weight of lecithin and nervonic acid Amount is than being 1:(0.005~1), and the fat globule particle diameter in parenteral solution is less than 2 μm, is injected in preferably described fat emulsion injection With the content of water with weight ratio meter more than 75%, the weight ratio of lecithin and nervonic acid is 1:(0.008~0.6), and parenteral solution In fat globule particle diameter be less than 1 μm；
Specifically, the fat emulsion injection contains the content of nervonic acid, lecithin and water for injection, wherein water for injection It is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make the fat globule particle diameter in liquid small In 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, soybean oil and water for injection, wherein injection The content of water is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat in liquid Spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, soybean oil, glycerine and water for injection, wherein noting Penetrate and be more than 70% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make in liquid Fat globule particle diameter is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contain nervonic acid, lecithin, soybean oil, median chain triglyceride oil, glycerine and The content of water for injection, wherein water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, Such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, structured triglyceride and water for injection, wherein The content of water for injection is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes in liquid Fat globule particle diameter be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, glucose and water for injection, wherein injection The content of water is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat in liquid Spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, sodium chloride and water for injection, wherein injection The content of water is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat in liquid Spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, fructose and water for injection, wherein water for injection Content be more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat globule in liquid Particle diameter is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, inverted sugar and water for injection, wherein injection The content of water is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat in liquid Spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, amino acid and water for injection, wherein injection The content of water is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat in liquid Spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, DHA and water for injection, wherein water for injection Content is more than 70% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat spherule in liquid Footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid and water for injection, wherein noting Penetrate and be more than 75% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make in liquid Fat globule particle diameter is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, alpha-linolenic acid and water for injection, wherein injecting It is more than 75% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make the fat in liquid Fat spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, gamma-Linolenic acid and water for injection, wherein injecting It is more than 75% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make the fat in liquid Fat spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, linoleic acid and water for injection, wherein injection The content of water is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes the fat in liquid Spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, CLA（Or CLA glycerine Ester）And water for injection, wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is small In 2 μm, such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, phosphatidylserine and water for injection, wherein The content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes in liquid Fat globule particle diameter be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, Polyene Phosphatidylcholine and water for injection, its The content of middle water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes liquid In fat globule particle diameter be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, phosphatidyl-ethanolamine and water for injection, wherein The content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes in liquid Fat globule particle diameter be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, phosphatidylinositols and water for injection, wherein noting Penetrate and be more than 75% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make in liquid Fat globule particle diameter is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, phosphatidyl glycerol and water for injection, wherein noting Penetrate and be more than 75% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make in liquid Fat globule particle diameter is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, phytosterol（Or phytosterin ester, Huo Zhezhi Thing stanol ester）And water for injection, the wherein content of water for injection are more than 75%, and the fat in parenteral solution with weight ratio meter Spherolite footpath is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, median chain triglyceride oil and water for injection, its The content of middle water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes liquid In fat globule particle diameter be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contain nervonic acid, lecithin, DHA, arachidonic acid, CLA and The content of water for injection, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, Such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, linoleic acid, median chain triglyceride oil and injection With water, wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as The fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, CLA, leukotrienes and water for injection, Wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as makes liquid Fat globule particle diameter in body is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, CLA, α-flax Acid, phytosterol（Or phytosterin ester, or plant stanol ester）And water for injection, wherein the content of water for injection is with weight Be more than 75% than meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, for example, make fat globule particle diameter in liquid be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, alpha-linolenic acid, medium chain triglyceride The content of three acid esters and water for injection, wherein water for injection is more than 75%, and the fat globule particle diameter in parenteral solution with weight ratio meter Less than 2 μm, such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, CLA, α-flax Acid, median chain triglyceride oil and water for injection, the wherein content of water for injection are more than 75% with weight ratio meter, and in parenteral solution Fat globule particle diameter be less than 2 μm, such as fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, linoleic acid, phosphatidyl silk ammonia Acid, phytosterol（Or phytosterin ester, or plant stanol ester）And water for injection, wherein the content of water for injection is with weight Be more than 75% than meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, for example, make fat globule particle diameter in liquid be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, CLA and injection With water, wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as The fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contain nervonic acid, lecithin, Polyene Phosphatidylcholine, CLA and The content of water for injection, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, Such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, Polyene Phosphatidylcholine, Asia The content of oleic acid and water for injection, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is small In 2 μm, such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, phosphatidyl-ethanolamine, conjugation The content of linoleic acid and water for injection, wherein water for injection is more than 75%, and the fat globule particle diameter in parenteral solution with weight ratio meter Less than 2 μm, such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, phosphatidylinositols, conjugation Asia The content of oleic acid and water for injection, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is small In 2 μm, such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, phosphatidyl glycerol, conjugation Asia The content of oleic acid and water for injection, wherein water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is small In 2 μm, such as the fat globule particle diameter in liquid is set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, to contain nervonic acid, lecithin, arachidonic acid, CLA, middle chain sweet for the fat emulsion injection Oily three acid esters and water for injection, the wherein content of water for injection are more than 75%, and the fat spherule in parenteral solution with weight ratio meter Footpath is less than 2 μm, such as the fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, gamma-Linolenic acid, median chain triglyceride oil and note Penetrate and use water, wherein the content of water for injection is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, example The fat globule particle diameter in liquid is such as set to be less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, CLA, plant steroid Alcohol（Or phytosterin ester, or plant stanol ester）, median chain triglyceride oil and water for injection, wherein water for injection content It is more than 75% with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make the fat globule particle diameter in liquid small In 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, CLA, α-flax Acid, median chain triglyceride oil and water for injection, the wherein content of water for injection are more than 75% with weight ratio meter, and in parenteral solution Fat globule particle diameter be less than 2 μm, such as fat globule particle diameter in liquid is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc.；
Specifically, the fat emulsion injection contains nervonic acid, lecithin, arachidonic acid, gamma-Linolenic acid, conjugation Asia Oleic acid, phosphatidylserine, phytosterol（Or phytosterin ester, or plant stanol ester）And water for injection, wherein injecting It is more than 75% with the content of water with weight ratio meter, and the fat globule particle diameter in parenteral solution is less than 2 μm, such as make the fat in liquid Fat spherolite footpath is less than 1 μm, 0.7 μm, 0.5 μm or 0.3 μm etc..
It should illustrate, the present invention contains nervonic acid, lecithin, other water-soluble substanceses, other liposoluble substances and note The fat emulsion injection with water is penetrated, special, 35~85 DEG C of the heating temperature of preferred feed, preferably homogenization pressure are 25- 58Mpa, preferably vacuum outgas vacuum are 0.04~0.09Mpa, preferably sterilising conditions be 115~121 DEG C 25 minutes.
Further, lecithin of the present invention, nervonic acid, other water-soluble substanceses and other liposoluble substances have well Pharmacology acts synergistically, and for health, is especially mended in injection supplement nervonic acid, phosphatide and unrighted acid, parenteral nutrition Fill, prevent and treat cranial nerve retrogression pathological changes, brain damage, atelencephalia or brain disorder disease, protection cardiovascular and cerebrovascular, drop blood In terms of fat, hypotensive, the treatment effect such as fatty liver, there is good synergy, present invention also offers it is above-mentioned containing containing Nervonic acid, the fat emulsion injection of lecithin are used to prepare injection supplement nervonic acid, phosphatide and unrighted acid, preventing and treating brain god Through retrogression pathological changes, brain damage, atelencephalia or brain disorder disease, protection cardiovascular and cerebrovascular, reducing blood lipid, hypotensive, control Treat the application in the medicine of fatty liver.
It is of the invention surprisingly to find, the fat emulsion injection containing nervonic acid, lecithin obtained by the present invention, fat globule Particle diameter distribution effect is good, and gas is especially passed through in emulsification procedure（Nitrogen or carbon dioxide）, the shape when high-speed stirred is sheared Sheared into the blending and stirring and cavitation of gas and liquid so that various fat-soluble ingredient energy rapid dispersions are emulsified into uniform particle diameter Fat globule, particle diameter is small and particle diameter distribution is narrow, moreover, parenteral solution is quickly cooled into 25 DEG C using in 5min so that fat globule Form homogeneous, regular spherical shape is presented, fat globule drop can be prevented to regroup well, significantly improve parenteral solution Stability；
In addition, the present invention contains the fat emulsion injection containing nervonic acid, lecithin, fat globule particle diameter is small and particle diameter distribution Narrow, fat globule particle size distribution is generally at 0.2~0.5 μm in obtained parenteral solution, close to nano-scale, for injection The stability of liquid, which has, to be significantly improved, and is also significantly increased for safety in utilization, such as with other medicines in compatible use Security, and significantly improved in the security etc. injected after entering in human body.
For embodiment in the implementation process of the present invention, those of ordinary skill in the art are not departing from the present invention's Caused various embodiments and modification are obvious and are easy to perform on the basis of scope and spirits.It is logical Cross the following examples to be further elaborated with come application to the present invention etc., it is not intended that limit of the embodiment to the present invention System.
Embodiment 1, lecithin nervonic acid fat emulsion injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 1%~5%, preferably 1.5%,
Nervonic acid 0.03%~1.5%, preferably 0.1%,
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid are weighed by formula, adds in water for injection, is settled to required output, It is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 65~80 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 2, acer truncatum seed oil nervonic acid Fat Emulsion penetrate liquid and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 1%~10%, preferably 2%,
Acer truncatum seed oil (neural acid content >=4.0%) 0.05%~2%, preferably 0.15%（With nervonic acid content meter）,
Water for injection adds to 100%；
Prepare：Acer truncatum seed oil is subjected to degumming in advance, depickling, decolouring, absorption, deodorization, filtering and high temperature go out mattress, make it Color and luster, acid value, peroxide value, unsaponifiable matter and moisture meet the quality standard of pharmacopeia refined plant oil, and nervonic acid Content >=4.0%, the refined acer truncatum seed oil are applied to the present embodiment as the donor of nervonic acid；
(1) dispensing：Lecithin, acer truncatum seed oil are weighed by formula, adds in water for injection, is settled to required output, It is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 65~80 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 3, nervonic acid fat emulsion injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 1.2%,
Nervonic acid 0.03%~1.5%, preferably 0.2%,
Soybean oil 3%~15%, preferably 10%,
Water for injection adds to 100%；
Prepare：Soybean oil is subjected to degumming in advance, depickling, decolouring, absorption, deodorization, filtering and high temperature go out mattress, make its color Pool, acid value, peroxide value, unsaponifiable matter and moisture meet the quality standard of pharmacopeia refined plant oil, or medicine purchased in market The soybean oil of injection stage is applied to the present embodiment；
(1) dispensing：Lecithin, nervonic acid, soybean oil are weighed by formula, first nervonic acid is dissolved completely in soybean oil, Added again together with lecithin in water for injection, be settled to required output, be stirred and be uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 55~65 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 4, nervonic acid fat emulsion injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~3%, preferably 1.2%,
Nervonic acid 0.03%~1.5%, preferably 0.15%,
Soybean oil 3%~15%, preferably 5%,
Glycerine 1.5%~3.5%, preferably 2.5%,
Water for injection adds to 100%；
Prepare：Soybean oil is subjected to degumming in advance, depickling, decolouring, absorption, deodorization, filtering and high temperature go out mattress, make its color Pool, acid value, peroxide value, unsaponifiable matter and moisture meet the quality standard of pharmacopeia refined plant oil, or medicine purchased in market The soybean oil of injection stage is applied to the present embodiment；
(1) dispensing：Lecithin, nervonic acid, soybean oil, glycerine are weighed by formula, nervonic acid is first dissolved completely in soybean In oil, then added together with lecithin, glycerine in water for injection, be settled to required output, be stirred and be uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 75~85 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
In embodiment 5, nervonic acid/long chain fat emulsion injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~3%, preferably 1.5%,
Nervonic acid 0.03%~1.5%, preferably 0.15%,
Soybean oil 3%~15%, preferably 5%,
Median chain triglyceride oil 3%~15%, preferably 5%,
Glycerine 1.5%~3.5%, preferably 2.5%,
Water for injection adds to 100%；
Prepare：Soybean oil is subjected to degumming in advance, depickling, decolouring, absorption, deodorization, filtering and high temperature go out mattress, make its color Pool, acid value, peroxide value, unsaponifiable matter and moisture meet the quality standard of pharmacopeia refined plant oil, or medicine purchased in market The soybean oil of injection stage is applied to the present embodiment；
(1) dispensing：Lecithin, nervonic acid, soybean oil, median chain triglyceride oil, glycerine are weighed by formula, first by nervonic acid It is dissolved completely in soybean oil, then is added together with lecithin, median chain triglyceride oil, glycerine in water for injection, is settled to institute Output is needed, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 75~85 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 6, nervonic acid structural fatty emulsion injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 3%,
Nervonic acid 0.03%~1.5%, preferably 0.15%,
Structured triglyceride 10%~30%, preferably 20%,
Glycerine 1.5%~3.5%, preferably 2.5%,
Sodium hydroxide q. s
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, structured triglyceride, glycerine, which are weighed, by formula sequentially adds injection In water, required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 65~85 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is adjusted into pH value 7.5~8.5 with sodium hydroxide, through 800~1000 mesh Filtering, filtrate is that 35~58MPa carries out homogeneous in 50~98 DEG C of temperature, pressure, and is less than the fat globule particle diameter in parenteral solution 0.5μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 7, nervonic acid Fat Emulsion glucose injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 2%,
Nervonic acid 0.03%~1.5%, preferably 0.2%,
Glucose 4%~10%, preferably 5%,
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, glucose are weighed by formula to sequentially add in water for injection, are settled to Required output, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 65~85 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 8, nervonic acid Fat Emulsion sodium chloride injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 2%,
Nervonic acid 0.03%~1.5%, preferably 0.2%,
Sodium chloride 0.5%~1%, preferably 0.9%,
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, sodium chloride are weighed by formula to sequentially add in water for injection, are settled to Required output, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 65~85 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 9, nervonic acid Fat Emulsion inverted sugar parenteral solution and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 2%,
Nervonic acid 0.03%~1.5%, preferably 0.3%,
Glucose 2.5%,
Fructose 2.5%,
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, glucose, fructose are weighed by formula to sequentially add in water for injection, it is fixed Hold to required output, be stirred and be uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 75~80 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 10, nervonic acid Fat Emulsion amino acid injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 2%,
Nervonic acid 0.03%~1.5%, preferably 0.3%,
Amino Acid Compound Injection（Commercially available acquirement）Add to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, Amino Acid Compound Injection mixing are weighed by formula, is settled to required Output, it is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 55~65 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 11, nervonic acid DHA fat emulsion injections and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 2%,
Nervonic acid 0.03%~1.5%, preferably 0.2%,
DHA algal oil（DHA content >=40%）0.03%~2%, preferably 0.1%（In terms of DHA content）,
Glycerine 1.5%~3.5%, preferably 2.5%,
Water for injection adds to 100%；
Prepare：It will split that kettle algae oil carries out degumming, depickling, decolouring, absorption, deodorization, filtering and high temperature go out mattress in advance, and make its color Pool, acid value, peroxide value, unsaponifiable matter and moisture meet the quality standard of pharmacopeia refined plant oil, and control DHA to contain Amount >=40%, is applied to the present embodiment using the algae oil as DHA donor；
(1) dispensing：Lecithin, nervonic acid, DHA algal oil, glycerine are weighed by formula to sequentially add in water for injection, are settled to Required output, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 55~75 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 12, nervonic acid arachidonic acid fat emulsion injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 1.5%,
Nervonic acid 0.03%~1.5%, preferably 0.15%,
Arachidonic acid 0.03%~2%, preferably 0.3%,
Glycerine 1.5%~3.5%, preferably 2.5%,
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, arachidonic acid, glycerine, which are weighed, by formula sequentially adds water for injection In, required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 45~85 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 13, nervonic acid CLA Medium chain fatty emulsion injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 2%,
Nervonic acid 0.03%~1.5%, preferably 0.2%,
CLA 0.03%~2%, preferably 0.2%,
Median chain triglyceride oil 3%~15%, preferably 5%,
Glycerine 1.5%~3.5%, preferably 2.5%,
Water for injection adds to 100%；
Prepare：(1) dispensing：By formula weigh lecithin, nervonic acid, CLA, median chain triglyceride oil, glycerine according to In secondary addition water for injection, required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 65~80 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure Homogeneous is carried out for 35~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
Embodiment 14, nervonic acid Medium chain fatty emulsion injection and preparation method thereof
Recipe quantity by weight percentage, contains：
Lecithin 0.5%~5%, preferably 1.5%,
Nervonic acid 0.03%~2%, preferably 0.2%,
Median chain triglyceride oil 3%~20%, preferably 5%,
Glycerine 1.5%~3.5%, preferably 2.5%,
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, median chain triglyceride oil, glycerine, which are weighed, by formula sequentially adds injection With required output in water, is settled to, it is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, 20~30L/ is continuously passed through from emulsification pot bottom Min nitrogen or carbon dioxide, under conditions of fluid temperature is 75~85 DEG C, speed of agitator is more than 2500r/min, carry out breast Change 10~20min of operation, then pass to interlayer cooling water, after making parenteral solution be cooled to 25 DEG C in 5min, stop stirring and stopping Nitrogen or carbon dioxide are only passed through, is stood；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 75~85 DEG C of temperature, pressure Homogeneous is carried out for 45~58MPa, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：After liquid after homogeneous is carried out into vacuum outgas, with 1 μm of filtering with microporous membrane, tank Dress, inflated with nitrogen sealing, and sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
Through laser diffraction analyzer, the fat globule particle size distribution of the fat emulsion injection is at 0.2~0.5 μm.
The parenteral solution containing phosphatide and nervonic acid described in embodiment 15, embodiment 1 to embodiment 14 is at following aspects Using：
Answering in the medicine for injecting supplement nervonic acid, phosphatide and unrighted acid and parenteral nutrition supplement is prepared With；
Application in the medicine for preparing preventing and treating cranial nerve retrogression pathological changes；
Application in the medicine for preparing treatment brain damage；
Application in the medicine for the treatment of atelencephalia or brain disorder disease is prepared；
Application in the medicine for preparing protection cardiovascular and cerebrovascular；
Application in the medicine for preparing reducing blood lipid；
Application in the medicine for preparing hypotensive；
Application in the medicine for preparing treatment fatty liver.
The stability study of embodiment 15, the parenteral solution of the invention containing phosphatide and nervonic acid
Fully according to the preferred amounts formula of embodiment 14, routinely the method for injection is prepared into parenteral solution, with embodiment Fat emulsion injection prepared by 14 preferred amounts is centrifuged, heats and boil and thawing 5 times repeatedly respectively, the thing before and after contrast operation State changes, and analyzes and compares its stability.As a result such as table 1 below.
Table 1
Compare content Fat globule particle diameter distribution 1000r/min is centrifuged 2000r/min is centrifuged 20min is boiled in heating Thawing 5 times repeatedly
Fat emulsion injection prepared by embodiment 14 0.2~0.5 μm, particle diameter distribution is narrow Without significant change Without significant change Without significant change Without significant change
Parenteral solution made of conventional method 3.5~8 μm, particle diameter distribution is wide A small amount of oil droplet separates out More oil droplet separates out, liquid layered, and irregular colour is even A small amount of oil droplet separates out More oil droplet separates out, liquid layered, and irregular colour is even
As can be seen from Table 1, the fat globule particle diameter of the parenteral solution containing phosphatide and nervonic acid of the invention is small and particle diameter distribution Narrow, homogeneity is good, and fat globule particle size distribution is at 0.2~0.5 μm in parenteral solution, and close to nano-scale, stability shows Work is higher than conventional oil epoxy-type parenteral solution, is significantly increased for safety in utilization, especially when with other medicines in compatible use Security, and significantly improved in the security etc. injected after entering in human body.

Claims (14)

1. a kind of lecithin nervonic acid fat emulsion injection, its recipe quantity by weight percentage, contain：
Lecithin 1.5%,
Nervonic acid 0.1%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid are weighed by formula, is added in water for injection, is settled to required Output, it is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 65~80 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
2. a kind of acer truncatum seed oil nervonic acid fat emulsion injection, its recipe quantity by weight percentage, contain：
Lecithin 2%,
The acer truncatum seed oil 0.15% of neural acid content >=4.0%, with nervonic acid content meter,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, acer truncatum seed oil are weighed by formula, adds in water for injection, is settled to Required output, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 65~80 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
3. a kind of nervonic acid fat emulsion injection, its recipe quantity by weight percentage, contain：
Lecithin 1.2%,
Nervonic acid 0.2%,
Soybean oil 10%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, soybean oil are weighed by formula, is first completely dissolved nervonic acid In soybean oil, then added together with lecithin in water for injection, be settled to required output, be stirred and be uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 55~65 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
4. a kind of nervonic acid fat emulsion injection, its recipe quantity by weight percentage, contain：
Lecithin 1.2%,
Nervonic acid 0.15%,
Soybean oil 5%,
Glycerine 2.5%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, soybean oil, glycerine are weighed by formula, it is first that nervonic acid is complete It is dissolved in soybean oil, then is added together with lecithin, glycerine in water for injection, be settled to required output, is stirred point Dissipate uniform；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 75~85 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
5. in a kind of nervonic acid/long chain fat emulsion injection, its recipe quantity by weight percentage, contains：
Lecithin 1.5%,
Nervonic acid 0.15%,
Soybean oil 5%,
Median chain triglyceride oil 5%,
Glycerine 2.5%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, soybean oil, median chain triglyceride oil, sweet is weighed by formula Oil, first nervonic acid is dissolved completely in soybean oil, then injection is added together with lecithin, median chain triglyceride oil, glycerine In water, required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 75~85 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
6. a kind of nervonic acid structural fatty emulsion injection, its recipe quantity by weight percentage, contain：
Lecithin 3%,
Nervonic acid 0.15%,
Structured triglyceride 20%,
Glycerine 2.5%,
Sodium hydroxide q. s
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, structured triglyceride, glycerine are weighed by formula to sequentially add In water for injection, required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 65~85 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is adjusted into pH value 7.5~8.5 with sodium hydroxide, through 800~1000 mesh mistakes Filter, filtrate is that 35~58MPa carries out homogeneous in 50~98 DEG C of temperature, pressure, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
7. a kind of nervonic acid Fat Emulsion glucose injection, its recipe quantity by weight percentage, contain：
Lecithin 2%,
Nervonic acid 0.2%,
Glucose 5%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, glucose are weighed by formula to sequentially add in water for injection, Required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 65~85 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
8. a kind of nervonic acid Fat Emulsion sodium chloride injection, its recipe quantity by weight percentage, contain：
Lecithin 2%,
Nervonic acid 0.2%,
Sodium chloride 0.9%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, sodium chloride are weighed by formula to sequentially add in water for injection, Required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 65~85 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
9. a kind of nervonic acid Fat Emulsion inverted sugar parenteral solution, its recipe quantity by weight percentage, contain：
Lecithin 2%,
Nervonic acid 0.3%,
Glucose 2.5%,
Fructose 2.5%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, glucose, fructose, which are weighed, by formula sequentially adds injection In water, required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 75~80 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
10. a kind of nervonic acid Fat Emulsion amino acid injection, its recipe quantity by weight percentage, contain：
Lecithin 2%,
Nervonic acid 0.3%,
Amino Acid Compound Injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, Amino Acid Compound Injection mixing, constant volume are weighed by formula To required output, it is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 55~65 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
11. a kind of nervonic acid DHA fat emulsion injections, its recipe quantity by weight percentage, contain：
Lecithin 2%,
Nervonic acid 0.2%,
The DHA algal oil 0.1% of DHA content >=40%, in terms of DHA content,
Glycerine 2.5%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, DHA algal oil, glycerine, which are weighed, by formula sequentially adds injection In water, required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 55~75 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
12. a kind of nervonic acid arachidonic acid fat emulsion injection, its recipe quantity by weight percentage, contain：
Lecithin 1.5%,
Nervonic acid 0.15%,
Arachidonic acid 0.3%,
Glycerine 2.5%,
Water for injection adds to 100%；
Its preparation method includes：(1) dispensing：Lecithin, nervonic acid, arachidonic acid, glycerine, which are weighed, by formula sequentially adds note Penetrate with water, be settled to required output, be stirred and be uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 45~85 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
13. a kind of nervonic acid CLA Medium chain fatty emulsion injection, its recipe quantity by weight percentage, contain：
Lecithin 2%,
Nervonic acid 0.2%,
CLA 0.2%,
Median chain triglyceride oil 5%,
Glycerine 2.5%,
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, CLA, median chain triglyceride oil, glycerine are weighed by formula successively to add Enter in water for injection, be settled to required output, be stirred and be uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 65~80 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 50~98 DEG C of temperature, pressure 35 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
14. a kind of nervonic acid Medium chain fatty emulsion injection, its recipe quantity by weight percentage, contain：
Lecithin 1.5%,
Nervonic acid 0.2%,
Median chain triglyceride oil 5%,
Glycerine 2.5%,
Water for injection adds to 100%；
Prepare：(1) dispensing：Lecithin, nervonic acid, median chain triglyceride oil, glycerine, which are weighed, by formula sequentially adds water for injection In, required output is settled to, is stirred and is uniformly dispersed；
(2) emulsify：The liquid prepared in (1) is placed in emulsion tank, is continuously passed through 20~30L/min's from emulsification pot bottom Nitrogen or carbon dioxide, under conditions of fluid temperature is 75~85 DEG C, speed of agitator is more than 2500r/min, carry out emulsification behaviour Make 10~20min, then pass to interlayer cooling water, after parenteral solution is cooled to 25 DEG C in 5min, stop stirring and stop leading to Enter nitrogen or carbon dioxide, stand；
(3) homogeneous：Liquid made from step (2) is filtered through 800~1000 mesh, filtrate is in 75~85 DEG C of temperature, pressure 45 ~58MPa carries out homogeneous, and the fat globule particle diameter in parenteral solution is less than 0.5 μm；
(4) refined filtration, filling, sterilizing：It is canned, fill with 1 μm of filtering with microporous membrane after liquid after homogeneous is carried out into vacuum outgas Nitrogen seals, and is sterilized 25 minutes in 115 DEG C of rotations；
(5) pack, examine, produce.
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CN111150706A (en) * 2020-02-28 2020-05-15 深圳市金枫生物医药科技有限公司 Submicron emulsion containing acer truncatum seed oil and preparation method thereof
CN111714529A (en) * 2020-08-14 2020-09-29 宝枫生物科技（北京）有限公司 Application of acer truncatum seed oil in preparing medicine for improving intestinal flora
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CN103285018A (en) * 2013-06-06 2013-09-11 崔晓廷 Compound dual-channel nervonic acid product for preventing and treating encephalopathy as well as preparation method and application thereof

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