CN110302154A - A kind of 2,4- dinitrophenol Fat Emulsion and its preparation method and application - Google Patents
A kind of 2,4- dinitrophenol Fat Emulsion and its preparation method and application Download PDFInfo
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Abstract
The present invention provides a kind of 2,4-DNP Fat Emulsion, every 1L 2,2, 4-dinitrophenol Fat Emulsion is made of the raw material of following weight: 2,4-DNP or its salt 0.1~20g, 50~500g of oil for injection, 1~100g of emulsifier, 5~100g of isotonic regulator, surplus are water for injection.The Fat Emulsion stability is good, can save the long period without there is lamination, drug precipitation is not also precipitated, and ensure that drug effect and safety when Fat Emulsion uses.In addition, the Fat Emulsion is added without organic reagent during the preparation process, the residual of finished product organic reagent and the stimulation of surfactant are avoided, increases Product Safety and patient's compliance；Meanwhile the application of organic reagent in production process is avoided, preparation section can be reduced, production efficiency and safety are improved.The Fat Emulsion is administered by intravenous drip, haemoconcentration can be made steady, to increase safety.In addition, Fat Emulsion has certain hepatic targeting, it can be improved in the distribution of liver, to improve its curative effect to hepatic disease.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of 2,4-DNP Fat Emulsion and preparation method thereof and use
On the way.
Background technique
2,4-DNP (2,4-DNP) is a kind of yellow compound, in history always for manufacture dyestuff, explosive and
Fungicide.Since it can decouple Mitochondria, in eighties of last century early stage used also as antiadipositas drug object.The change
It closes object to be disabled in 1938 by food and drug administration, because it has potential fatal side effect, including cause high
Temperature, cataract, agranulocytosis, hepatotoxicity wind agitation, renal toxicity and cardiac toxic.More and more evidences show 2,4- dinitro at present
Base phenol is protecting neuron from neurodegeneration and enhancing neural plasticity important role, 2, the 4- dinitro of suitable dosage
Base phenol can be with the slight uncoupling of inducing mitochondrial, and promotes neuronal survival.In addition, the uncoupling oxygen of 2,4-DNP
Change and phosphorylation is proved to effective to nonalcoholic fatty liver (NAFLD).Therefore, the clinical application of 2,4-DNP
It is again gradually of interest by people.
The existing 2,4-DNP pharmaceutical dosage form of China market mainly has tablet, capsule, particle etc. at present, these agent
Type action is slower, and single-dose blood concentration is often lower, it is difficult to reach clinical effectiveness.In order to maintain effective blood drug concentration, this
A little dosage forms need repeatedly to be administered mostly, but are repeated as many times administration and be easy to cause blood concentration higher.Due to 2,4- dinitro
For base phenol toxicity compared with strong, therapeutic window is narrow, metabolism individual difference is significant, blood concentration is higher often to will appear aforementioned fatal secondary work
With.Therefore, the clinical application of 2,4-DNP is restricted very much.
2,4-DNP is prepared into sustained-release oral preparation by patent 201480059363.0, and slow release drug can
It is easy to use with stable maintenance effective blood drug concentration in a longer period of time, avoid the occurrence of peak valley phenomenon；Reduce 2,4- dinitro
The adverse reaction of base phenol, improves curative effect.But clinically there is also some disadvantages for the sustained release agent: (1) clinically dosage is adjusted
Flexibility it is lower, encounter occur larger side effect when, cannot stop treating in time；(2) production technology of sustained release preparation is more multiple
It is miscellaneous, it is at high cost.
Summary of the invention
To solve the above-mentioned problems, the present invention provides a kind of 2,4-DNP Fat Emulsions and preparation method thereof and use
On the way.
Present invention firstly provides a kind of 2,4-DNP Fat Emulsion, every 1L 2,4-DNP Fat Emulsion by
The raw material of following weight is made:
2,4-DNP or its salt 0.1~20g, 50~500g of oil for injection, 1~100g of emulsifier, isotonic adjusting
5~100g of agent, surplus are water for injection.
Further, every 1L 2,4-DNP Fat Emulsion is made of the raw material of following weight:
2,4-DNP or its salt 0.5~10g, 100~300g of oil for injection, 10~50g of emulsifier, isotonic adjusting
10~90g of agent, surplus are water for injection.
Further, every 1L 2,4-DNP Fat Emulsion is made of the raw material of following weight:
2,4-DNP or its salt 2~10g, 100~300g of oil for injection, 10~30g of emulsifier, isotonic regulator
10~50g, surplus are water for injection.
Further, the oil for injection is one of soybean oil, medium chain triglyceride, peanut oil, olive oil, fish oil
Or it is a variety of；
Preferably, the oil for injection is one of soybean oil, medium chain triglyceride, olive oil, fish oil or a variety of；
It is highly preferred that the oil for injection is soybean oil, or it is made of soybean oil and medium chain triglyceride, or by soybean
Oil, medium chain triglyceride, olive oil and fish oil composition.
Further, the emulsifier be lecithin, hydrogenated phospholipid, enuatrol, Solutol Hs15,
One of poloxamer 188, Emulsifier EL-60, alpha-tocofecol succinic acid macrogol ester are a variety of；
Preferably, the emulsifier is lecithin, poloxamer 188, enuatrol, alpha-tocofecol succinic acid macrogol ester
One of or it is a variety of；
It is highly preferred that the emulsifier is lecithin.
Further, the lecithin is one of soybean lecithin, egg yolk lecithin or a variety of.
Further, the isotonic regulator is one of glucose, sodium chloride, glycerol, xylitol or a variety of；
Preferably, the isotonic regulator is one of glucose, glycerol or a variety of；
It is highly preferred that the isotonic regulator is glycerol.
Further, the pH of the Fat Emulsion is 4~9；Preferably, pH is 5~7；It is highly preferred that pH is 6.5.
The present invention also provides a kind of preparation methods of 2,4-DNP Fat Emulsion above-mentioned, it includes following step
It is rapid:
(1) oil for injection is heated to 60~80 DEG C, by 2,4-DNP and except note is added in the emulsifier of enuatrol
It penetrates in oil, high-speed stirred obtains oily phase；
(2) isotonic regulator and emulsifier enuatrol are added in water for injection, are heated to 60-80 DEG C of dissolution, obtain water phase；
(3) it is mutually mixed oily with water phase, high-speed stirred is even by colostrum high pressure cream at colostrum；
(4) adjust pH, sterilizing to get.
Further, described that oil for injection is heated to 60 DEG C in step (1)；And/or in step (1), the high speed
The speed of stirring is 5000r/min；It is described to be heated to 60 DEG C of dissolutions and/or in step (2)；It is described and/or in step (3)
The speed of high-speed stirred is 10000r/min, time 5min；And/or in step (3), the high pressure cream is even in 800bar
Pressure under, high pressure cream it is even 8 times；And/or in step (4), it is 4~9 that the tune pH, which is with sodium hydroxide solution adjusting pH value,；
Preferably, adjusting pH value is 5~7；It is highly preferred that adjusting pH value is 6.5；And/or in step (4), the sterilizing is 115 DEG C
Pressure sterilizing 30min.
The present invention also provides a kind of 2,4-DNP freeze drying powder injections, it is by 2,4-DNP above-mentioned
Fat Emulsion freeze-drying is prepared.
The present invention also provides 2,4- dinitrophenol Fat Emulsion above-mentioned or 2,4- dinitrophenol freeze-dried powders above-mentioned
Injection is in preparation prevention and/or treatment hepatitis, fatty liver, liver fibrosis, cirrhosis, liver cancer, diabetes B, metabolic syndrome
Drug in purposes.
Further, the fatty liver is nonalcoholic fatty liver；The metabolic syndrome is acquired fat metabolism barrier
Hinder, heredity lipodystrophy.
Water for injection, which refers to, in the present invention meets defined water under Chinese Pharmacopoeia water for injection item, as distilled water or go from
Sub- water is distilled resulting water, therefore also known as double distilled water.
Alpha-tocofecol succinic acid macrogol ester is water soluble vitamin E in the present invention, is also abbreviated as α-fertility in the present invention
Phenol.
2,4-DNP is prepared into Fat Emulsion, blood circulation can be injected by way of intravenous drip, is absorbed fast
Fast and rapid-action, bioavilability 100%, dosage is more accurate, and blood concentration is easier to control, and stable blood medicine can be maintained dense
Degree reduces the toxic side effect of 2,4-DNP, improves curative effect.Meanwhile Fat Emulsion has certain hepatic targeting, can be improved
It improves its curative effect to hepatic disease in the distribution of liver.
2,4-DNP Fat Emulsion stability of the present invention is good, can save longer time without being layered
Drug precipitation is not also precipitated in phenomenon, ensure that drug effect and safety when Fat Emulsion uses.In addition, the present invention 2,4- dinitro
Phenol Fat Emulsion is added without organic reagent and surfactant during the preparation process, avoids the residual of final products organic reagent
With the stimulation of surfactant, increase Product Safety and patient's compliance；Meanwhile avoiding organic reagent in production process
Application, can also reduce preparation section, improve production efficiency and safety.2,4- dinitrophenol Fat Emulsion of the present invention passes through quiet
Arteries and veins dropleting medicine-feeding can make haemoconcentration steady, to increase safety.In addition, Fat Emulsion has certain hepatic targeting, it can
It is improved in the distribution of liver, to improve its curative effect to hepatic disease.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples remakes further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention
The technology realized all belongs to the scope of the present invention.
Specific embodiment
Raw material, equipment used in the specific embodiment of the invention are known product, are obtained by purchase commercial product.
The preparation of embodiment 1,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 100g and is placed in a beaker, be heated to 60 DEG C, by 12g
Lecithin and 3g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.Note is added in 22.5g glycerol
It penetrates with 60 DEG C of dissolutions in water, are heated to, obtains water phase.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 2,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 200g and is placed in a beaker, be heated to 60 DEG C, by 12g
Lecithin and 3g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.Note is added in 22.5g glycerol
It penetrates with 60 DEG C of dissolutions in water, are heated to, obtains water phase.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 3,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 300g and is placed in a beaker, be heated to 60 DEG C, by 12g
Lecithin and 3g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.Note is added in 22.5g glycerol
It penetrates with 60 DEG C of dissolutions in water, are heated to, obtains water phase.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 4,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 200g and is placed in a beaker, be heated to 60 DEG C, by 10g
Lecithin and 3g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.Note is added in 22.5g glycerol
It penetrates with 60 DEG C of dissolutions in water, are heated to, obtains water phase.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 5,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 200g and is placed in a beaker, be heated to 60 DEG C, by 30g
Lecithin and 3g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.Note is added in 22.5g glycerol
It penetrates with 60 DEG C of dissolutions in water, are heated to, obtains water phase.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 6,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 300g and is placed in a beaker, be heated to 60 DEG C, by 20g
Lecithin and 3g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.Note is added in 22.5g glycerol
It penetrates with 60 DEG C of dissolutions in water, are heated to, obtains water phase.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 7,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 200g and is placed in a beaker, be heated to 60 DEG C, by 12g
Lecithin, 2g poloxamer 188 and 5g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.
22.5g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.It is added in blender when water phase is identical with oil,
10000r/min stirs 5min, stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then is adjusted with sodium hydroxide solution
PH value dispenses, 115 DEG C of pressure sterilizing 30min to 6.5.
The preparation of embodiment 8,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 200g and is placed in a beaker, be heated to 60 DEG C, by 20g
Lecithin, 4g poloxamer 188 and 10g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.
10g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.It is added in blender when water phase is identical with oil,
10000r/min stirs 5min, stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then is adjusted with sodium hydroxide solution
PH value dispenses, 115 DEG C of pressure sterilizing 30min to 6.5.
The preparation of embodiment 9,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 200g and is placed in a beaker, be heated to 60 DEG C, by 20g
Lecithin, 4g poloxamer 188 and 4g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.
50g glucose is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.It is added in blender when water phase is identical with oil,
10000r/min stirs 5min, stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then is adjusted with sodium hydroxide solution
PH value dispenses, 115 DEG C of pressure sterilizing 30min to 6.5.
The preparation of embodiment 10,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: weighing soybean oil 50g and medium chain triglyceride 50g in beaker, uses
It is uniformly mixed, is heated to 60 DEG C, 12g lecithin is added and 5g2,2, 4-dinitrophenol, 5000r/min high-speed stirred obtain
Oily phase.22.5g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.Blender is added when water phase is identical with oil
In, 10000r/min stirs 5min, stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then use sodium hydroxide solution
PH value is adjusted to 6.5, is dispensed, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 11,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: weighing soybean oil 100g and medium chain triglyceride 100g in beaker,
With being uniformly mixed, it is heated to 60 DEG C, is added 12g lecithin and 8g2,2, 4-dinitrophenol, 5000r/min high-speed stirred,
Obtain oily phase.22.5g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.Stirring is added when water phase is identical with oil
In device, 10000r/min stirs 5min, stirs into colostrum, colostrum high pressure cream is even (800bar, 8 times) then molten with sodium hydroxide
Liquid adjusts pH value to 6.5, dispenses, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 12,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: weighing soybean oil 150g and medium chain triglyceride 150g in beaker,
With being uniformly mixed, it is heated to 60 DEG C, is added 12g lecithin and 8g2,2, 4-dinitrophenol, 5000r/min high-speed stirred,
Obtain oily phase.22.5g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.Stirring is added when water phase is identical with oil
In device, 10000r/min stirs 5min, stirs into colostrum, colostrum high pressure cream is even (800bar, 8 times) then molten with sodium hydroxide
Liquid adjusts pH value to 6.5, dispenses, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 13,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4-DNP Fat Emulsion: weighing soybean oil 75g and medium chain triglyceride 25g in beaker, uses
It is uniformly mixed, is heated to 60 DEG C, 12g lecithin is added and 5g2,2, 4-dinitrophenol, 5000r/min high-speed stirred obtain
Oily phase.22.5g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.Blender is added when water phase is identical with oil
In, 10000r/min stirs 5min, stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then use sodium hydroxide solution
PH value is adjusted to 6.5, is dispensed, 115 DEG C of pressure sterilizing 30min.
The preparation of embodiment 14,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4- dinitrophenol Fat Emulsion: soybean oil 60g, medium chain triglyceride 60g, fish oil 30g, olive are weighed
Olive oil 50g is in beaker, with being uniformly mixed, is heated to 60 DEG C, 0.135g alpha-tocopherol, 12g lecithin and 5g2 is added,
2, 4-dinitrophenol, 5000r/min high-speed stirred obtain oily phase to being completely dissolved.Take 0.3g enuatrol, 25g glycerol that injection is added
With 60 DEG C of dissolutions in water, are heated to, water phase is obtained.It being added in blender when water phase is identical with oil, 10000r/min stirs 5min,
Colostrum is stirred into, colostrum high pressure cream is even (800bar, 8 times), then pH value is adjusted to 6.5 with sodium hydroxide solution, it dispenses, 115
DEG C pressure sterilizing 30min.
The preparation of embodiment 15,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4- dinitrophenol Fat Emulsion: soybean oil 30g, medium chain triglyceride 30g, fish oil 15g, olive are weighed
Olive oil 25g is in beaker, with being uniformly mixed, is heated to 60 DEG C, 0.135g alpha-tocopherol, 12g lecithin and 3g2 is added,
2, 4-dinitrophenol, 5000r/min high-speed stirred obtain oily phase to being completely dissolved.Take 0.3g enuatrol, 25g glycerol that injection is added
With 60 DEG C of dissolutions in water, are heated to, water phase is obtained.It being added in blender when water phase is identical with oil, 10000r/min stirs 5min,
Colostrum is stirred into, colostrum high pressure cream is even (800bar, 8 times), then pH value is adjusted to 6.5 with sodium hydroxide solution, it dispenses, 115
DEG C pressure sterilizing 30min.
The preparation of embodiment 16,2,4- dinitrophenol Fat Emulsion of the present invention
Preparation 1L 2,4- dinitrophenol Fat Emulsion: soybean oil 90g, medium chain triglyceride 90g, fish oil 45g, olive are weighed
Olive oil 75g is in beaker, with being uniformly mixed, is heated to 60 DEG C, 0.135g alpha-tocopherol, 12g lecithin and 3g2 is added,
2, 4-dinitrophenol, 5000r/min high-speed stirred obtain oily phase to being completely dissolved.Take 0.3g enuatrol, 25g glycerol that injection is added
With 60 DEG C of dissolutions in water, are heated to, water phase is obtained.It being added in blender when water phase is identical with oil, 10000r/min stirs 5min,
Colostrum is stirred into, colostrum high pressure cream is even (800bar, 8 times), then pH value is adjusted to 6.5 with sodium hydroxide solution, it dispenses, 115
DEG C pressure sterilizing 30min.
The preparation of embodiment 17,2,4- dinitrophenol freeze drying powder injection of the present invention
The 2,4-DNP Fat Emulsion of any one embodiment of Example 1~16 preparation, it is freeze-dried to get 2,
2, 4-dinitrophenol freeze drying powder injection.
The preparation of comparative example 1,2,4- dinitrophenol Fat Emulsion
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 700g and is placed in a beaker, be heated to 60 DEG C, by 12g
Lecithin and 3g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.Note is added in 22.5g glycerol
It penetrates with 60 DEG C of dissolutions in water, are heated to, obtains water phase.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of comparative example 2,2,4- dinitrophenol Fat Emulsion
Preparation 1L 2,4-DNP Fat Emulsion: weighing soybean oil 300g and medium chain triglyceride 300g in beaker,
With being uniformly mixed, it is heated to 60 DEG C, is added 12g lecithin and 3g2,2, 4-dinitrophenol, 5000r/min high-speed stirred,
Obtain oily phase.22.5g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.Stirring is added when water phase is identical with oil
In device, 10000r/min stirs 5min, stirs into colostrum, colostrum high pressure cream is even (800bar, 8 times) then molten with sodium hydroxide
Liquid adjusts pH value to 6.5, dispenses, 115 DEG C of pressure sterilizing 30min.
The preparation of comparative example 3,2,4- dinitrophenol Fat Emulsion
Preparation 1L 2,4- dinitrophenol Fat Emulsion: weigh soybean oil 180g, medium chain triglyceride 180g, fish oil 90g,
Olive oil 150g is in beaker, with being uniformly mixed, is heated to 60 DEG C, be added 0.135g alpha-tocopherol, 6g lecithin and
5g2,2, 4-dinitrophenol, 5000r/min high-speed stirred obtain oily phase to being completely dissolved.0.3g enuatrol, 25g glycerol is taken to be added
In water for injection, 60 DEG C of dissolutions are heated to, water phase is obtained.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of comparative example 4,2,4- dinitrophenol Fat Emulsion
Preparation 1L 2,4-DNP Fat Emulsion: it weighs soybean oil 200g and is placed in a beaker, be heated to 60 DEG C, by 12g
Lecithin and 80g2,2, 4-dinitrophenol are added in soybean oil, and 5000r/min high-speed stirred obtains oily phase.22.5g glycerol is added
In water for injection, 60 DEG C of dissolutions are heated to, water phase is obtained.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
The preparation of comparative example 5,2,4- dinitrophenol Fat Emulsion
Preparation 1L 2,4-DNP Fat Emulsion: weighing soybean oil 75g and medium chain triglyceride 75g in beaker, uses
It is uniformly mixed, is heated to 60 DEG C, 12g lecithin is added and 80g2,2, 4-dinitrophenol, 5000r/min high-speed stirred obtain
Oily phase.22.5g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.Blender is added when water phase is identical with oil
In, 10000r/min stirs 5min, stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then use sodium hydroxide solution
PH value is adjusted to 6.5, is dispensed, 115 DEG C of pressure sterilizing 30min.
The preparation of comparative example 6,2,4- dinitrophenol Fat Emulsion
Preparation 1L 2,4-DNP Fat Emulsion: weighing soybean oil 75g and medium chain triglyceride 75g in beaker, uses
It is uniformly mixed, is heated to 60 DEG C, 2g lecithin is added and 80g2,2, 4-dinitrophenol, 5000r/min high-speed stirred obtain
Oily phase.22.5g glycerol is added in water for injection, is heated to 60 DEG C of dissolutions, obtains water phase.Blender is added when water phase is identical with oil
In, 10000r/min stirs 5min, stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then use sodium hydroxide solution
PH value is adjusted to 6.5, is dispensed, 115 DEG C of pressure sterilizing 30min.
The preparation of comparative example 7,2,4- dinitrophenol Fat Emulsion
Preparation 1L 2,4- dinitrophenol Fat Emulsion: weigh soybean oil 180g, medium chain triglyceride 180g, fish oil 90g,
Olive oil 150g is in beaker, with being uniformly mixed, is heated to 60 DEG C, be added 0.135g alpha-tocopherol, 3g lecithin and
80g2,2, 4-dinitrophenol, 5000r/min high-speed stirred obtain oily phase to being completely dissolved.0.3g enuatrol, 25g glycerol is taken to be added
In water for injection, 60 DEG C of dissolutions are heated to, water phase is obtained.It is added in blender when water phase is identical with oil, 10000r/min stirring
5min stirs into colostrum, and colostrum high pressure cream is even (800bar, 8 times), then adjusts pH value to 6.5 with sodium hydroxide solution, divides
Dress, 115 DEG C of pressure sterilizing 30min.
Beneficial effects of the present invention are proved below by way of specific test example.
The research of test example 1,2,4- dinitrophenol Fat Emulsion stability
2,4-DNP Fat Emulsion room temperature preservation prepared by embodiment 1~16 and comparative example 1~7, takes after 1 month
Out, observe whether each Fat Emulsion is layered or has Precipitation.Test result is as shown in table 1.
The test result of 1 2,4- dinitrophenol Fat Emulsion stability of table
Test result shows: 2,4-DNP Fat Emulsion prepared by the present invention has good stability, after placing 1 month
It is not layered, is also precipitated without drug precipitation.And the 2,4- dinitrophenol Fat Emulsion other than the scope of the present invention is placed 1 week
After there is lamination, and/or have drug precipitation precipitation, stability is poor.
To sum up, 2,4-DNP Fat Emulsion stability of the present invention is good, can save longer time without going out
Existing lamination, is not also precipitated drug precipitation, ensure that drug effect and safety when Fat Emulsion uses.In addition, the present invention 2,4-
Dinitrophenol Fat Emulsion is added without organic reagent and surfactant during the preparation process, avoids final products organic reagent
Residual and surfactant stimulation, increase Product Safety and patient's compliance；Meanwhile it avoiding having in production process
The application of machine reagent can also reduce preparation section, improve production efficiency and safety.2,4- dinitrophenol Fat Emulsion of the present invention
It is administered by intravenous drip, haemoconcentration can be made steady, to increase safety.In addition, Fat Emulsion has certain liver target
It can be improved in the distribution of liver in tropism, to improve its curative effect to hepatic disease.
Claims (13)
1. a kind of 2,4-DNP Fat Emulsion, it is characterised in that: every 1L2,2, 4-dinitrophenol Fat Emulsion is by following weight
Raw material be made:
2,4-DNP or its salt 0.1~20g, 50~500g of oil for injection, 1~100g of emulsifier, isotonic regulator 5~
100g, surplus are water for injection.
2. 2,4-DNP Fat Emulsion according to claim 1, it is characterised in that: every 1L2,2, 4-dinitrophenol rouge
Fat cream is made of the raw material of following weight:
2,4-DNP or its salt 0.5~10g, 100~300g of oil for injection, 10~50g of emulsifier, isotonic regulator 10
~90g, surplus are water for injection.
3. 2,4-DNP Fat Emulsion according to claim 1, it is characterised in that: every 1L2,2, 4-dinitrophenol rouge
Fat cream is made of the raw material of following weight:
2,4-DNP or its salt 2~10g, 100~300g of oil for injection, 10~30g of emulsifier, isotonic regulator 10~
50g, surplus are water for injection.
4. described in any item 2,4-DNP Fat Emulsions according to claim 1~3, it is characterised in that: the injection
Oil is one of soybean oil, medium chain triglyceride, peanut oil, olive oil, fish oil or a variety of；
Preferably, the oil for injection is one of soybean oil, medium chain triglyceride, olive oil, fish oil or a variety of；
It is highly preferred that the oil for injection is soybean oil, or be made of soybean oil and medium chain triglyceride, or by soybean oil, in
Chain triglyceride, olive oil and fish oil composition.
5. described in any item 2,4-DNP Fat Emulsions according to claim 1~3, it is characterised in that: the emulsifier
For lecithin, hydrogenated phospholipid, enuatrol, Solutol Hs15, poloxamer 188, Emulsifier EL-60,
One of alpha-tocofecol succinic acid macrogol ester is a variety of；
Preferably, the emulsifier is lecithin, in poloxamer 188, enuatrol, alpha-tocofecol succinic acid macrogol ester
It is one or more；
It is highly preferred that the emulsifier is lecithin.
6. 2,4-DNP Fat Emulsion according to claim 5, it is characterised in that: the lecithin is soybean lecithin
One of rouge, egg yolk lecithin are a variety of.
7. described in any item 2,4-DNP Fat Emulsions according to claim 1~3, it is characterised in that: the isotonic tune
Section agent is one of glucose, sodium chloride, glycerol, xylitol or a variety of；
Preferably, the isotonic regulator is one of glucose, glycerol or a variety of；
It is highly preferred that the isotonic regulator is glycerol.
8. described in any item 2,4-DNP Fat Emulsions according to claim 1~3, it is characterised in that: the Fat Emulsion
PH is 4~9；Preferably, pH is 5~7；It is highly preferred that pH is 6.5.
9. a kind of preparation method of 2,4-DNP Fat Emulsion according to any one of claims 1 to 8, it is characterised in that:
It includes the following steps:
(1) oil for injection is heated to 60~80 DEG C, by 2,4-DNP and except injection is added in the emulsifier of enuatrol
In oil, high-speed stirred obtains oily phase；
(2) isotonic regulator and emulsifier enuatrol are added in water for injection, are heated to 60-80 DEG C of dissolution, obtain water phase；
(3) it is mutually mixed oily with water phase, high-speed stirred is even by colostrum high pressure cream at colostrum；
(4) adjust pH, sterilizing to get.
10. preparation method according to claim 9, it is characterised in that: described to be heated to oil for injection in step (1)
60℃；And/or in step (1), the speed of the high-speed stirred is 5000r/min；It is described to be heated to and/or in step (2)
60 DEG C of dissolutions；And/or in step (3), the speed of the high-speed stirred is 10000r/min, time 5min；And/or step
(3) in, the even high pressure cream is high pressure cream even 8 times under the pressure of 800bar；And/or in step (4), the tune pH is to use
It is 4~9 that sodium hydroxide solution, which adjusts pH value,；Preferably, adjusting pH value is 5~7；It is highly preferred that adjusting pH value is 6.5；With/
Or, the sterilizing is 115 DEG C of pressure sterilizing 30min in step (4).
11. a kind of 2,4-DNP freeze drying powder injection, it is characterised in that: it is by according to any one of claims 1 to 8
The freeze-drying of 2,4- dinitrophenol Fat Emulsion is prepared.
12. 2,4- dinitro described in 2,4- dinitrophenol Fat Emulsion according to any one of claims 1 to 8 or claim 11
Base phenol freeze drying powder injection is in preparation prevention and/or treatment hepatitis, fatty liver, liver fibrosis, cirrhosis, liver cancer, 2 type glycosurias
Purposes in sick, metabolic syndrome drug.
13. purposes according to claim 12, it is characterised in that: the fatty liver is nonalcoholic fatty liver；The generation
Thanking to syndrome is acquired lipodystrophy, heredity lipodystrophy.
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