CN110237359A - A kind of pre- encapsulating ejection preparation of emulsion injection and preparation method thereof - Google Patents
A kind of pre- encapsulating ejection preparation of emulsion injection and preparation method thereof Download PDFInfo
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- CN110237359A CN110237359A CN201910584076.6A CN201910584076A CN110237359A CN 110237359 A CN110237359 A CN 110237359A CN 201910584076 A CN201910584076 A CN 201910584076A CN 110237359 A CN110237359 A CN 110237359A
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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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M2005/3117—Means preventing contamination of the medicament compartment of a syringe
- A61M2005/3121—Means preventing contamination of the medicament compartment of a syringe via the proximal end of a syringe, i.e. syringe end opposite to needle cannula mounting end
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Abstract
The invention discloses pre- encapsulating ejection preparations of a kind of emulsion injection and preparation method thereof, the pre- encapsulating ejection preparation of emulsion injection includes inoculated envelope sealing container and encapsulating in emulsion injection therein, it includes injection tube, piston, push rod, seal cap, sleeve that inoculated, which seals sealing container, sleeve interior surface is concordant with the injection tube inner surface that it is threadedly engaged, paraffin is filled between sleeve and push rod, injection tube is equipped with containing mark scale, and emulsion injection includes feedstock emulsion and water for injection.Emulsion injection of the invention uses pre- encapsulation technology, emulsion injection is potted in sealing container in advance, it can solve the bad problem of the sealing effect of existing syringe injection tube tail portion, and secondary pollution can be reduced, this design structure is simple, reasonable, sealed reliable is connected, and emulsion injection formulation stability of the invention is good.
Description
Technical field
The present invention relates to the pre- encapsulating ejection preparation of drug preparation technical field more particularly to a kind of emulsion injection and its
Preparation method.
Background technique
Pre- encapsulating preparation is the injection novel form occurred in recent years, i.e., drug is directly filling in syringe, makes to infuse
Emitter has had both the function of packing container, direct injection when use.Its possess dosage it is more acurrate, it is easy to use, without intersection
The advantages of pollution.But the sealing structure of pre-encapsulated injector injection tube tail portion is as built-in medical fluid Sterility Assurance barrier, the knot
The leakproofness of structure is just particularly important.If the sealing effect of this part is bad, the injection of pre- encapsulating cannot be carried out
It seals well, causes injection that can not save for a long time；And currently, not yet there is disclosure that pre- encapsulation technology is applied to cream
The research of agent injection, also without disclosing corresponding preparation process and product.On the other hand, the stability of emulsion is also pre- encapsulating
The big problem of the one of preparation, while the sealing structure of pre-encapsulated injector injection tube tail portion is as built-in medical fluid Sterility Assurance barrier,
The leakproofness of the structure is just particularly important.It, cannot be to the injection of pre- encapsulating if the sealing effect of this part is bad
It is sealed well, leads to that injection can not save for a long time and leakproofness equally influences the stability of emulsion injection.
Summary of the invention
The present invention is to solve existing technological deficiency, provide a kind of good airproof performance, injection is stable, dose is accurate, at
A kind of this cheap pre- encapsulating ejection preparation of emulsion injection and preparation method thereof.Its specific technical solution is as follows:
A kind of pre- encapsulating ejection preparation of emulsion injection, the pre- encapsulating ejection preparation of the emulsion injection includes inoculated
Syringe and encapsulating are sealed in injection therein, the pre-encapsulated injector stack shell is in boss-shaped, the injection tube front end setting
There are injection nozzle, the form of the tapered necking down of injection nozzle, the seal cap is removably connect with the injection nozzle, the work
Liquid is close is assemblied in inside the injection tube for plug, and it further includes sleeve that the push rod is detachably connected with the piston, the sleeve
It is arranged at the injection tube aft end interior surface, the sleeve interior surface and the injection tube inner surface that it is threadedly engaged are flat
Together, paraffin is filled between the sleeve and the push rod, injection tube outer surface is equipped with containing mark scale；It is described
Injection is emulsion injection, and the emulsion injection includes feedstock emulsion and water for injection.By being designed in injection tube tail portion
Sleeve is filled with paraffin between sleeve and push rod, can solve the sealing effect of existing syringe injection tube tail portion
Bad problem, the containing mark scale being arranged on injection tube outer surface can intuitively observe the liquid volume that metering uses, this
Kind design structure is simple, reasonable, connects sealed reliable.Emulsion injection of the invention uses pre- encapsulation technology, and emulsion is injected
Liquid is potted in sealing container in advance, can solve the bad problem of the sealing effect of existing syringe injection tube tail portion,
And secondary pollution can be reduced, this design structure is simple, reasonable, connects sealed reliable, and emulsion of the invention injects formula of liquid
Stability is good.
Preferably, the push rod is that cylindrical and criss-cross two parts form by section, and the push rod is close to the work
Fill in end be it is cylindric, the length of the push rod circular cylinder shaped portion is identical with the length sleeve, the push rod section be cross
Rear end face be provided with pushing disk.
Preferably, it is internally provided with diaphragm seal in the seal cap, the diaphragm seal is planar structure on one side, and another side leans on
The nearly injection nozzle is bulge-structure.
Preferably, the outer surface of piston is provided with sealing ring, there are three the sealing ring design quantities.
Preferably, the handrail of oval ring-type, the handrail court are provided with to vertical direction in the injection tube rear end periphery
It is provided with protrusion on one side to the injection nozzle.
Preferably, the piston, diaphragm seal, sealing ring are made of chlorinated scoline.
Preferably, the emulsion injection includes the raw material of following mass percent: active medicine 0.1%~10%, in
Chain triglyceride, the mixture of long chain triglycerides composition or long chain triglycerides 10%~20%, phospholipid mixing
Object 1%~5%, glycerol 1%~5%, pH adjusting agent 0.05%~0.1% and surplus water for injection.Wherein, medium chain triglyceride three
Acid esters and the w/v of long chain triglycerides are 4: 1~1:4.
Preferably, the phospholipid mixture includes the ingredient of following weight percent: phosphatidyl choline 75%-85%,
Phosphatidyl-ethanolamine 12%-18%, lysophosphatidyl ethanolamine 0.5%-2%, sphingomyelins 0.5%-2%, phosphatidylinositols
0.5%-1.5%, synthesis lecithin PC class 0.2~1.5%, phosphatidyl glycerol PG class 0.2~1.5% and phosphatidylserine PS
Class 0.1~1.5%.
Preferably, the active medicine is flurbiprofen axetil or Propofol.
Preferably, the pH adjusting agent is one or both of sodium dihydrogen phosphate, citric acid, sodium hydroxide.
Preferably, the synthetic phospholipid PC class is dioleyl lecithin DOPC, two myristoyl lecithin DMPC, two
Stearoyl phosphatidyl choline DSPC, two mustard acyl group lecithin DEPC, dipalmitoyl lecithin DPPC, hydrogenated soy phosphatidyl choline
One of HSPC；The phosphatidyl glycerol PG class be dioleoylphosphatidylglycerol DOPG, dipalmitoylphosphatidylglycerol DPPG,
It is a kind of in yolk phosphatidylglycerol EPG, distearoylphosphatidylglycerol DSPG；Phosphatidylserine PS class is two palmityl phosphorus
Acyl serine DPPS.
The present invention also provides a kind of preparation methods of the pre- encapsulating ejection preparation of emulsion injection, which is characterized in that packet
Include following preparation step:
1) mixture or length formed the active medicine of said ratio, median chain triglyceride oil, long chain triglycerides
Chain triglyceride, phospholipid the mixture high-speed stirred at 40 DEG C~75 DEG C are mixed to form solution；
2) solution and glycerol, oil for injection, the aqueous solution for injection obtained step 1) stirs mixed at 20 DEG C~40 DEG C
It closes, and adjusting PH with pH adjusting agent is 8~9, then forms colostrum by homogenizer；
3) colostrum for obtaining step 2) is 500kg/cm in pressure2~600kg/cm2Obtain cream lower continuous homogenizing 5~7 times
Agent；
4) the emulsion injection encapsulating for obtaining step 3) sterilizes into the pre-encapsulated injector, then at 115 DEG C
30min。
Beneficial effects of the present invention: the pre- encapsulating ejection preparation of emulsion injection include inoculated envelope sealing container and encapsulating in
Emulsion injection therein, inoculated envelope sealing container includes injection tube, piston, push rod, seal cap, sleeve, sleeve interior surface with
The injection tube inner surface that it is threadedly engaged is concordant, and paraffin is filled between sleeve and push rod, and injection tube is equipped with containing mark
Scale, emulsion injection include feedstock emulsion and water for injection.Emulsion injection of the invention uses pre- encapsulation technology, emulsion
Injection is potted in sealing container in advance, can reduce secondary pollution, and this design structure is simple, reasonable, connects sealed reliable, and
Emulsion injection formulation stability of the invention is good.
2, by designing sleeve in injection tube tail portion, it is filled with paraffin between sleeve and push rod, can solve existing
The bad problem of the sealing effect of some syringe injection tubes tail portion, the containing mark scale being arranged on injection tube outer surface can
The liquid volume that intuitive observation metering uses, this design structure is simple, reasonable, connects sealed reliable.
3, the present invention improves the stability of injection, improves the drug effect of preparation, ensure that the safety of drug.
Detailed description of the invention
Fig. 1 is a kind of schematic cross-sectional view for pre-encapsulated injector that the specific embodiment of the invention provides；
Fig. 2 is a kind of structural schematic diagram for pre-encapsulated injector that the specific embodiment of the invention provides；
Fig. 3 is a kind of seal cap structural schematic diagram for pre-encapsulated injector that the specific embodiment of the invention provides；
Fig. 4 is a kind of pusher structure schematic diagram for pre-encapsulated injector that the specific embodiment of the invention provides；
Fig. 5 is a kind of diaphragm seal structural schematic diagram for pre-encapsulated injector that the specific embodiment of the invention provides；
Fig. 6 is that the structure of a kind of pre-encapsulated injector piston that the specific embodiment of the invention provides and sealing ring cooperation is shown
It is intended to.
In figure:
10, syringe；101, injection tube；1011, injection nozzle；1012, handrail；102, piston；103, push rod；1031, it pushes away
Press disk；104, seal cap；20, injection；30, sleeve；40, paraffin；50, diaphragm seal；60, sealing ring.
Specific embodiment
The present invention is further described in detail with reference to the accompanying drawing, these attached drawings are simplified schematic diagram, only
The basic structure that the invention is illustrated in a schematic way, the direction of this specific implementation is using the direction Fig. 1 as standard.
Embodiment 1
Fig. 1-2 exemplary shows a kind of pre- encapsulating ejection preparation of emulsion injection provided by the invention, as Fig. 1~
Shown in 2, including the emulsion injection 20 filled in pre-encapsulated injector 10 and syringe, the syringe 10 includes injection tube
101, piston 102, push rod 103, seal cap 104, the injection tube 101 are made of high molecular synthetic resin, the injection tube 101
Stack shell is in boss-shaped, and 101 front end of injection tube is provided with injection nozzle 1011, the shape of the tapered necking down of the injection nozzle 1011
Formula, the seal cap 104 are removably connect with the injection nozzle 1011,104 liquid of piston it is close be assemblied in the injection
Inside cylinder 101, it further includes sleeve 30 that the push rod 103 is detachably connected with the piston 104, and the sleeve 30 is arranged in institute
It states at 101 aft end interior surface of injection tube, 101 inner surface of the injection tube that 30 inner surface of sleeve is threadedly engaged with it is flat
Together, paraffin 40 is filled between the sleeve 30 and the push rod 103,101 outer surface of injection tube is carved equipped with capacity
Anale settting scale.
The course of work of the invention: the sleeve 30 is dismountable by screw thread with 101 aft end interior surface of injection tube
It links together, paraffin 40 is filled between the sleeve 30 and the push rod 103, in use process, hold the sleeve
30, the push rod 103 is rotated, the paraffin 40 between them is separated, the pushing disk 1031 is promoted, according to the note
The containing mark scale being arranged on 101 outer surface of shooting cylinder, observes calibrated shot medical fluid, the sleeve 30 and the push rod 103 it
Between rotate after, paraffin between them, which has, clearly opens trace, prevents the secondary use of product.The piston
102 front ends are shape corresponding with 101 front inner surface of injection tube, the prominent injection tube 101 of the sleeve 30
Part can form the push rod feed motion and limit, when the piston 102 moves to 101 front inner surface of injection tube
When, the pushing disk 1031 is contacted close to 101 surface of injection tube with the sleeve 30, and the push rod 103 is prevented to continue
It travels forward.
Fig. 3 exemplary shows a kind of seal cap structural schematic diagram of pre-encapsulated injector provided by the invention, in institute
It states and is formed with spiral helicine groove inside seal cap 104, screw thread can be divided with the 101 front end twist tabs of injection tube
Cooperation, 104 outer surface of seal cap are machined with netted indentation, to increase contact friction.
Preferably, the push rod 103 is that cylindrical and criss-cross two parts form by section, and the push rod 103 is close
102 end of piston be it is cylindric, the columned partial-length of the push rod 103 is identical as 30 length of sleeve, described to push away
103 section of bar is that criss-cross rear end face is provided with pushing disk 1031, and the push rod 103 is designed close to 102 end of piston
At it is cylindric be in order to when in use be convenient for rotating separation described in paraffin 40.
Preferably, 102 outer surface of piston being provided with sealing ring 60, there are three 60 design quantities of sealing ring,
It is permeable from 102 outer surface of piston to prevent injection, while preventing the injection 20 from contacting with the paraffin 40, increases
The leakproofness of feeder apparatus.
Preferably, circumferential vertical direction is provided with the handrail 1012 of oval ring-type outside 101 rear end of injection tube, described
Handrail is provided with protrusion towards injection nozzle on one side, and setting protrusion is to be more easier to operate for increasing friction force.
Preferably, the injection tube 101 is prepared by transparent material, preferably clear high molecular synthetic resin, can be PP,
The synthetic resin such as PE, PS, PA, PC, PVC, ABS, PET.
Preferably, the piston 102, the diaphragm seal 50, the sealing ring 60 are made of chlorinated scoline, because
Injection can generally stablize preservation in the aqueous solution of pH=4.5 or so, be exposed to for a long time using piston prepared by General Purpose Rubber
It is easily deformed under this acid condition, and the piston of selective chlorination butyl rubber preparation is less likely to occur to deform, the note stored
Penetrating liquid can save steadily in the long term.
The emulsion injection of the present embodiment includes the raw material of following quality volume fraction: flurbiprofen axetil 1%, medium chain triglyceride
Three acid esters 5%, long chain triglycerides 5%, phospholipid mixture 2.5%, glycerol 2.25%, disodium hydrogen phosphate 0.05% and remaining
The water for injection of amount.
The phospholipid mixture includes the ingredient of following weight percent: phosphatidyl choline 80%, phosphatidyl-ethanolamine
14%, lysophosphatidyl ethanolamine 1%, sphingomyelins 1%, phosphatidylinositols 1%, dioleyl lecithin 1%, dioleoyl phospholipid
Acyl glycerol DOPG 1%, dipalmitoylphosphatidylserine DPPS1%.
A kind of preparation method of the pre- encapsulating ejection preparation of emulsion injection of the invention, comprising the following steps:
1) by the flurbiprofen axetil of said ratio, median chain triglyceride oil, long chain triglycerides, phosphatidyl choline, phosphorus
Acyl ethanol amine, lysophosphatidyl ethanolamine, sphingomyelins, phosphatidylinositols, dioleyl lecithin, dioleoylphosphatidylglycerol
DOPG, dipalmitoylphosphatidylserine DPPS are blended in 40 DEG C~75 DEG C high-speed stirreds and form solution；
2) solution, glycerol, aqueous solution for injection that step 1) obtains are stirred at 20 DEG C~40 DEG C, and use phosphoric acid
It is 8 that sodium dihydrogen, which adjusts PH, then forms colostrum by homogenizer；
3) colostrum for obtaining step 2) (keeps pressure 500kg/cm under high pressure2~600kg/cm2) continuous homogenizing 5 times；
4) resulting emulsion encapsulating is sterilized into above-mentioned sealing container, then at 115 DEG C by what step 3) obtained
30min。
Embodiment 2
A kind of embodiment of pre- encapsulating ejection preparation as emulsion injection of the present invention, difference from Example 1 is only
It is, the difference of emulsion injection；
The emulsion injection of the present embodiment includes the raw material of following quality volume fraction: Propofol 0.1%, medium chain triglyceride three
The injection of acid esters 16%, long chain triglycerides 4%, phospholipid mixture 1%, glycerol 1%, sodium hydroxide 0.1% and surplus
Use water.
The phospholipid mixture includes the ingredient of following weight percent: phosphatidyl choline 75%, phosphatidyl-ethanolamine
15%, lysophosphatidyl ethanolamine 2%, sphingomyelins 2%, phosphatidylinositols 1.5%, hydrogenated soy phosphatidyl choline HSPC1.5%, two
Palmityl phosphatidyl glycerol DPPG 1.5%, dipalmitoylphosphatidylserine DPPS 1.5%.
The preparation method of the pre- encapsulating ejection preparation of the emulsion injection of the present embodiment, comprising the following steps:
1) by the Propofol of said ratio, median chain triglyceride oil, long chain triglycerides, phosphatidyl choline, phosphatidyl
Ethanol amine, lysophosphatidyl ethanolamine, sphingomyelins, phosphatidylinositols, hydrogenated soy phosphatidyl choline HSPC, two palmityl phosphatidyls are sweet
Oily DPPG, dipalmitoylphosphatidylserine DPPS are blended in 40 DEG C~75 DEG C high-speed stirreds and form solution；
2) solution and glycerol that step 1) obtains, aqueous solution for injection are stirred at 20 DEG C~40 DEG C, and use hydrogen
It is 9 that sodium oxide molybdena, which adjusts PH, then forms colostrum by homogenizer；
3) colostrum for obtaining step 2) (keeps pressure 500kg/cm under high pressure2~600kg/cm2) continuous homogenizing 5 times；
4) by the resulting emulsion encapsulating of step 3) into above-mentioned sealing container, then the 30min that sterilizes at 115 DEG C.
Embodiment 3
A kind of embodiment of pre- encapsulating ejection preparation as emulsion injection of the present invention, difference from Example 1 is only
It is, the difference of emulsion injection；
The emulsion injection of the present embodiment includes the raw material of following quality volume fraction: flurbiprofen axetil 2%, long-chain glycerol
The injection of three acid esters 10%, phospholipid mixture 3%, glycerol 3%, disodium hydrogen phosphate 0.04%, citric acid 0.02% and surplus
Use water.
The phospholipid mixture includes the ingredient of following weight percent: phosphatidyl choline 78%, phosphatidyl-ethanolamine
18%, lysophosphatidyl ethanolamine 1.5%, sphingomyelins 0.5%, phosphatidylinositols 0.5%, distearoyl phosphatidylcholine
DSPC0.5%, yolk phosphatidylglycerol EPG 0.5%, dipalmitoylphosphatidylserine DPPS 0.5%.
The preparation method of the pre- encapsulating ejection preparation of the emulsion injection of the present embodiment, comprising the following steps:
1) by the flurbiprofen axetil of said ratio, long chain triglycerides, phosphatidyl choline, phosphatidyl-ethanolamine, haemolysis
Phosphatidyl-ethanolamine, sphingomyelins, phosphatidylinositols, distearoyl phosphatidylcholine DSPC, yolk phosphatidylglycerol EPG, two
Palmityl phosphatidylserine DPPS is blended in 40 DEG C~75 DEG C high-speed stirreds and forms solution；
2) solution and sodium dihydrogen phosphate, glycerol, aqueous solution for injection that step 1) obtains are stirred at 20 DEG C~40 DEG C
Mixing, and adjusting PH with citric acid is 8, then forms colostrum by homogenizer；
3) colostrum for obtaining step 2) (keeps pressure 500kg/cm under high pressure2~600kg/cm2) continuous homogenizing 7 times；
4) by the resulting emulsion injection of step 3) into above-mentioned sealing container, then the 30min that sterilizes at 115 DEG C.
Embodiment 4
A kind of embodiment of pre- encapsulating ejection preparation as emulsion injection of the present invention, difference from Example 1 is only
It is, the difference of emulsion injection；
The emulsion injection of the present embodiment includes the raw material of following quality volume fraction: Propofol 6%, three acid of medium chain triglyceride
Ester 3%, long chain triglycerides 12%, phospholipid mixture 4%, glycerol 2.5%, disodium hydrogen phosphate 0.08% and surplus note
It penetrates and uses water.
The lecithin includes the ingredient of following weight percent: phosphatidyl choline 80%, phosphatidyl-ethanolamine 18%, molten
Serium inorganic phosphorus acyl ethanol amine 0.5%, sphingomyelins 0.5%, phosphatidylinositols 0.5%, two mustard acyl group lecithin DEPC 0.2%, two are hard
Acyl phosphatidyl glycerol DSPG 0.2%, dipalmitoylphosphatidylserine DPPS 0.1%.
The preparation method of the pre- encapsulating ejection preparation of the emulsion injection of the present embodiment, comprising the following steps:
1) by the Propofol of said ratio, median chain triglyceride oil, long chain triglycerides, phosphatidyl choline, phosphatidyl
Ethanol amine, lysophosphatidyl ethanolamine, sphingomyelins, phosphatidylinositols, two mustard acyl group lecithin DEPC, distearoylphosphatidyl are sweet
Oily DSPG, dipalmitoylphosphatidylserine DPPS are blended in 40 DEG C~75 DEG C high-speed stirreds and form solution；
2) solution, glycerol, aqueous solution for injection that step 1) obtains are stirred at 20 DEG C~40 DEG C, and use phosphoric acid
It is 8.5 that sodium dihydrogen, which adjusts PH, then forms colostrum by homogenizer；
3) colostrum for obtaining step 2) (keeps pressure 500kg/cm under high pressure2~600kg/cm2) continuous homogenizing 7 times；
4) it by step 3) again by resulting emulsion injection into above-mentioned sealing container, then sterilizes at 115 DEG C
30min。
Embodiment 5
A kind of embodiment of ejection preparation as emulsion injection of the present invention, difference from Example 1 be only that,
The difference of preparation method；
The emulsion injection of the present embodiment includes the raw material of following quality volume fraction: flurbiprofen axetil 10%, long-chain are sweet
Oily three acid esters 20%, phospholipid mixture 5%, glycerol 5%, sodium hydroxide 0.08% and surplus water for injection；
The phospholipid mixture includes the ingredient of following weight percent: phosphatidyl choline 85%, phosphatidyl-ethanolamine
12%, lysophosphatidyl ethanolamine 0.5%, sphingomyelins 0.5%, phosphatidylinositols 0.5%, dioleyl lecithin
DOPC0.5%, dioleoylphosphatidylglycerol DOPG 0.5%, dipalmitoylphosphatidylserine DPPS0.5%.
The precharging preparation of the emulsion injection of the present embodiment, comprising the following steps:
1) by the flurbiprofen axetil of said ratio, long chain triglycerides, phosphatidyl choline, phosphatidyl-ethanolamine, haemolysis
Phosphatidyl-ethanolamine, sphingomyelins, phosphatidylinositols, dioleyl lecithin DOPC, dioleoylphosphatidylglycerol DOPG, two palms
Acyl phospholipids acyl serine DPPS is blended in 40 DEG C~75 DEG C high-speed stirreds and forms solution；
2) solution, glycerol, aqueous solution for injection that step 1) obtains are stirred at 20 DEG C~40 DEG C, and use hydrogen-oxygen
Changing sodium to adjust PH is 8.5, then forms colostrum by homogenizer；
3) colostrum for obtaining step 2) (keeps pressure 500kg/cm under high pressure2~600kg/cm2) continuous homogenizing 7 times；
4) by the resulting emulsion encapsulating of step 3) into above-mentioned sealing container, then the 30min that sterilizes at 115 DEG C.
Comparative example 1
The difference of this comparative example and embodiment 1 is only that used pre-encapsulated injector is common inoculated on the market
Seal syringe.
Comparative example 2
The difference of this comparative example and embodiment 1 is only that the phospholipid mixture in emulsion injection is common on the market
Lecithin.
Comparative example 3
The difference of this comparative example and embodiment 1 is only that, the content of the phospholipid mixture in the emulsion injection
It is 0.6%.
Comparative example 4
The difference of this comparative example and embodiment 1 is only that, the content of the phospholipid mixture in the emulsion injection
It is 5.5%.
Comparative example 5
The difference of this comparative example and embodiment 1 is only that the phosphatide constituents in the emulsion injection are phosphatidyl gallbladder
Alkali.
Comparative example 6
The difference of this comparative example and embodiment 1 is only that the phosphatide constituents in the emulsion injection are phosphatidyl second
Hydramine.
Comparative example 7
The difference of this comparative example and embodiment 1 is only that the phosphatide constituents in the emulsion injection are phosphatidyl second
Hydramine 85%, phosphatidyl-ethanolamine 15%.
Embodiment 6
The emulsion injection prepared to embodiment 1 to 5 and comparative example 1 is according to " Chinese Pharmacopoeia is version in 2015 " about close
The guideline of envelope property experiment is sealed oxygen barrier test.Sample is put into climatic chamber, 40 DEG C of relative humidity of temperature
Under conditions of 25%, is measured respectively at 0,1,2,3 and 6 months, the results are shown in Table 1:
The emulsion injection performing leak test of the present invention of table 1
As can be seen from Table 1, accelerate anisidine value, the partial size of the embodiment of the present invention in June 1~5 opposite with related substance
Change in comparative example 1 unobvious.Illustrate the pre- encapsulating preparation better tightness of the present invention.Anisidine value is measured, it can be indirect
Understand oxidization condition of the above-mentioned supplementary material in production, storage and production process, will also realize that from changing value therein, oxygen barrier
It is good.
Embodiment 7
Injection prepared by Examples 1 to 5 and comparative example 1,2 is saved 10 months under conditions of refrigeration is protected from light, in
It samples within 0th, 1,2,3,6,8,10 month, is detected, investigate its Zeta potential during storage.Test result is shown in Table 3.
3 stability test of table
As can be seen from Table 3, the embodiment of the present invention 1~5 has more preferable relative to emulsion injection prepared by comparative example 1~2
Stability, save 10 months after, still good stability, the leakproofness of comparative example 1 further influence the stabilization of emulsion injection
Property, it is seen then that leakproofness of the invention, good stability.
The content of the phospholipid mixture of comparative example 3~4 outside the scope of the present invention, when its phospholipid mixture is less than
When 1%, stability is bad, and as the content of phospholipid mixture increases, stability increases, when containing for phospholipid mixture
Amount be greater than 5% when, stability tends to be steady, and slightly declines, therefore, phospholipid mixture content of the invention be 1~
5%.
The phospholipid mixture of comparative example 5~7 contains only phosphatidyl-ethanolamine, phosphatidyl-ethanolamine relative to embodiment 1,
Poor lysophosphatidyl ethanolamine, sphingomyelins, phosphatidylinositols, dioleyl lecithin DOPC, dioleoyl phosphorus are lacked
Phosphatidyl glycerol DOPG, dipalmitoylphosphatidylserine DPPS, but as can be known from the results, stability has relative to embodiment 1
Obvious decline shows even if poor lysophosphatidyl ethanolamine, sphingomyelins, phosphatidylinositols, dioleoyl ovum
Phosphatide DOPC, dioleoylphosphatidylglycerol DOPG, dipalmitoylphosphatidylserine DPPS be also it is indispensable, with phosphatide
Acyl ethanol amine, phosphatidyl-ethanolamine compounding, can have the function of significantly improving emulsion injection stability.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Within mind and principle, any modification, equivalent substitution, improvement and etc. done be should be included within the scope of the present invention.
Claims (10)
1. a kind of pre- encapsulating ejection preparation of emulsion injection, which is characterized in that system is injected in the pre- encapsulating of the emulsion injection
Agent includes pre-encapsulated injector and encapsulating in injection therein, and the pre-encapsulated injector stack shell is in boss-shaped, the injection
Cylinder front end is provided with injection nozzle, the form of the tapered necking down of injection nozzle, the seal cap removably with the injection nozzle
Connection, the piston liquid is close to be assemblied in inside the injection tube, and the push rod is detachably connected with the piston, and feature exists
In further including sleeve, the sleeve is arranged at the injection tube aft end interior surface, and the sleeve interior surface is threadedly engaged with it
The injection tube inner surface it is concordant, paraffin is filled between the sleeve and the push rod, on injection tube outer surface
Equipped with containing mark scale；The injection is emulsion injection, and the emulsion injection includes feedstock emulsion and water for injection.
2. pre- encapsulating ejection preparation according to claim 1, it is characterised in that: the push rod is cylinder and ten by section
Two parts of font form, and the push rod is cylindric, the length of the push rod circular cylinder shaped portion and institute close to the piston end
It is identical to state length sleeve, the push rod section is that criss-cross rear end face is provided with pushing disk.
3. pre- encapsulating ejection preparation according to claim 1, it is characterised in that: be internally provided with sealing in the seal cap
Piece, the diaphragm seal are planar structure on one side, and another side is bulge-structure close to the injection nozzle.
4. pre- encapsulating ejection preparation according to claim 1, it is characterised in that: the outer surface of piston is provided with sealing
Circle, there are three the sealing ring design quantities, it is preferable that the piston, diaphragm seal, sealing ring are by chlorinated scoline system
At.
5. the pre- encapsulating ejection preparation of emulsion injection according to claim 1, which is characterized in that the emulsion injection
Raw material including following mass percent: active medicine 0.1%~10%, median chain triglyceride oil, long chain triglycerides group
At mixture or long chain triglycerides 10%~20%, phospholipid mixture 1%~5%, glycerol 1%~5%, pH adjust
The water for injection of agent 0.05%~0.1% and surplus.
6. the pre- encapsulating ejection preparation of emulsion injection according to claim 5, which is characterized in that the active medicine is
Flurbiprofen axetil or Propofol.
7. the pre- encapsulating ejection preparation of emulsion injection according to claim 5, which is characterized in that the pH adjusting agent is
One or both of sodium dihydrogen phosphate, citric acid, sodium hydroxide.
8. the pre- encapsulating ejection preparation of emulsion injection according to claim 5, which is characterized in that the phospholipid mixing
Object includes the ingredient of following weight percent: phosphatidyl choline 75%-85%, phosphatidyl-ethanolamine 12%-18%, lysophosphatide
Acyl ethanol amine 0.5%-2%, sphingomyelins 0.5%-2%, phosphatidylinositols 0.5%-1.5%, synthesis lecithin PC class 0.2~
1.5%, phosphatidyl glycerol PG class 0.2~1.5% and phosphatidylserine PS class 0.1~1.5%.
9. the pre- encapsulating ejection preparation of the emulsion injection according to claim 8, which is characterized in that the synthesis
Phosphatide PC class be dioleyl lecithin DOPC, two myristoyl lecithin DMPC, distearoyl phosphatidylcholine DSPC,
One of two mustard acyl group lecithin DEPC, dipalmitoyl lecithin DPPC, hydrogenated soy phosphatidyl choline HSPC；The phosphatidyl
Glycerol PG class is dioleoylphosphatidylglycerol DOPG, dipalmitoylphosphatidylglycerol DPPG, yolk phosphatidylglycerol EPG, two hard
It is a kind of in acyl phosphatidyl glycerol DSPG；Phosphatidylserine PS class is dipalmitoylphosphatidylserine DPPS.
10. a kind of preparation method of the pre- encapsulating ejection preparation of the emulsion injection as described in claim 5~9, feature exist
In, including following preparation step:
1) active medicine of said ratio, median chain triglyceride oil, the mixture of long chain triglycerides composition or long-chain is sweet
Oily three acid esters, phospholipid mixture high-speed stirred at 40 DEG C~75 DEG C are mixed to form solution；
2) solution and glycerol that step 1) obtains, aqueous solution for injection are stirred at 20 DEG C~40 DEG C, and are adjusted with pH
It is 8~9 that agent, which adjusts pH, then forms colostrum by homogenizer；
3) colostrum for obtaining step 2) is 500kg/cm in pressure2~600kg/cm2Obtain emulsion lower continuous homogenizing 5~7 times；
4) the emulsion injection encapsulating for obtaining step 3) sterilizes into the pre-encapsulated injector, then at 115 DEG C
30min。
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| CN201910584076.6A CN110237359A (en) | 2019-06-28 | 2019-06-28 | A kind of pre- encapsulating ejection preparation of emulsion injection and preparation method thereof |
| PCT/CN2019/127779 WO2020258785A1 (en) | 2019-06-28 | 2019-12-24 | Pre-filled injection formulation of emulsion injection solution and preparation method therefor |
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| CN201910584076.6A CN110237359A (en) | 2019-06-28 | 2019-06-28 | A kind of pre- encapsulating ejection preparation of emulsion injection and preparation method thereof |
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| CN110237359A true CN110237359A (en) | 2019-09-17 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020258785A1 (en) * | 2019-06-28 | 2020-12-30 | 广东嘉博制药有限公司 | Pre-filled injection formulation of emulsion injection solution and preparation method therefor |
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| WO2020258785A1 (en) | 2020-12-30 |
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