A kind of Aprepitant intravenous injection emulsion and its preparation method and applicationTechnical field
The present invention relates to a kind of Aprepitant intravenous injection emulsions and its preparation method and application, belong to pharmacy technology neckDomain.
Background technique
World Health Organization 2017 is newest announce statistics indicate that, the whole world has 8,800,000 people to die of cancer every year, and it is dead every year to account for the whole worldDie nearly 1/6th of total number of persons.There are ten thousand new cancer cases more than 1400 every year, it is contemplated that this number will be added to the year two thousand thirtyMore than 21000 ten thousand.
Currently, chemotherapy is considered as one of main mode for the treatment of of cancer.But chemotherapy is referred to, allow the discoloration of people's newsIt is its strong nausea and vomiting side effect (Chemotherapy Induced Nausea and Vomiting, CINV).According to investigations, about 75% chemotherapeutics will lead to symptom as Nausea and vomiting, and about 70%~80% patients undergoing chemotherapy hasThe experience of nausea and vomiting, distress level not only allow patient to endure the pain on body to the fullest extent, therefore many people also hope successive treatmentAnd step back.Therefore, vomiting, which has become, one of needs to consider the problems of emphatically in cancer treatment procedure.
With deepening continuously for the nausea and vomiting Mechanism Study caused to chemotherapy, market has developed a plurality of types of antiemeticsDrug.Currently, the antiemetic of clinical application have dopamine-receptor antagonist, cortical steroid, 5-HT3 receptor antagonist,The other drugs such as neurokinin nk 1 receptor antagonist, the antiemetic Olanzapine of multiple target point and cannabis.By more than 30 yearsClinical practice, there are about 70% CINV to be effectively controlled, and especially nk 1 receptor antagonistic is in clinical application, so that acuteThe control rate of CINV improves 20%, and the control rate of Delayed onset CINV improves 30%.Nevertheless, in the process for the treatment of CINVIn there are still some problems, although nk 1 receptor antagonistic curative effect is prominent, there is also adverse reactions expensive, at a specified future date still notThe problems such as understanding.
Aprepitant is the first high selectivity nk 1 receptor antagonist in the whole world, and oral preparation (Emend) is by the U.S.Mo Shadong drugmaker developed granted listing, a countries and regions of product more than covering the whole world 90 in 2003.The said firm was in last yearAprepitant intravenous injection emulsion is developed, it is clinically complementary using formation with Aprepitant capsule preparations.Original is ground at productSolubilizer of a large amount of phosphatide as emulsifier and ethyl alcohol as phosphatide has been used in side.Clinical vein injects ethyl alcohol mayIt will lead to injection site pain, the adverse reactions such as neuritis.Therefore, inventor passes through to emulsifier in prescription and stabilizer progressOptimization, to avoid the use of ethyl alcohol, improves the safety of clinical use.Meanwhile it is clinically to need dilute production matched that original, which grinds product,Product, the present invention are the intravenous injection emulsions that a specification is 1000mL, and clinic can directly be transfused patient, not need diluteMatch, substantially increases the portability clinically used.
Summary of the invention
A kind of Aprepitant intravenous injection is provided it is an object of the invention to overcome above-mentioned the deficiencies in the prior art placeEmulsion and its preparation method and application, intravenous injection emulsion of the invention greatly improve A Rui without containing low carbon chains alcohol such as ethyl alcoholThe clinical use safety of smooth intravenous injection emulsion.
To achieve the above object, the technical scheme adopted by the invention is as follows: a kind of Aprepitant intravenous injection emulsion, the notePenetrate emulsion include following mass percent component: Aprepitant 0.05~3%, oil phase solvent 5~30%, emulsifier 1.2~18%, stabilizer 0.03~0.6%, isotonic regulator 1~5%, the emulsion for injection also include pH adjusting agent, and surplus is injectionWith water, the pH value of the emulsion for injection is 5.5~8.0.
Aprepitant intravenous injection emulsion of the invention, when clinical use, can directly be injected intravenously, and not need to be diluted.Aprepitant intravenous injection emulsion appearance of the invention is translucent or milky, and mobility is good, no wall built-up phenomenon, before sterilizingRear stability is good；Particle size range is 50~300nm, and latex pH is that 5.5~8.0, ZETA current potential absolute value is 25~40mV.
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, the emulsion for injection includes as followsThe component of mass percent: Aprepitant 0.13~1.3%, oil phase solvent 10~20%, emulsifier 1.2~12%, stabilizer0.03~0.3%, isotonic regulator 2~3%.
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, the emulsion for injection also includes0.02~0.5% antioxidant.
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, the quality hundred of the antioxidantDivide than being 0.02~0.2%.
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, Aprepitant intravenous injection emulsionComposition in every 1000mL are as follows: 0.5~30g of Aprepitant, oil phase solvent 50g~300g, 12~180g of emulsifier, stabilization0.3~6g of agent, 0.2~5g of antioxidant, isotonic regulator 10g~50g, appropriate pH adjusting agent, water for injection are settled to1000mL。
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, Aprepitant intravenous injection emulsionComposition in every 1000mL are as follows: Aprepitant 1.3g~13g, oil phase solvent 100g~200g, 12~120g of emulsifier, steadyDetermine 0.3~3g of agent, 0.2~2g of antioxidant, 20~30g of isotonic regulator, appropriate pH adjusting agent, water for injection to be settled to1000mL。
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, the emulsion droplet grain of the emulsion for injectionDiameter is 50~300nm.
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, the oil phase solvent is long-chain rougeAt least one of fat acid glycerol three ester, MCT Oil.
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, the long-chain fat acid glycerol threeEster is at least one of soybean oil, olive oil, tea-seed oil, fish oil, castor oil, rilanit special；The medium chain fatty acid is sweetOily three esters are at least one of tricaprylin, decanoin, Glycerin, mixed triester with caprylic acid capric acid, laurin.
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, the emulsifier is yolk lecithinRouge, egg PC, soybean lecithin, phosphatidyl glycerol, synthesis single fat sour component phosphatidyl choline in extremelyFew one kind；The stabilizer is at least one of oleic acid, enuatrol, poloxamer, polyoxyethylene sorbitan monoleate.Using stabilizer, makeThe ZETA current potential absolute value of emulsion maintains 25~40mV.
As the preferred embodiment of Aprepitant intravenous injection emulsion of the present invention, the isotonic regulator is sweetAt least one of oil, mannitol, glucose, sodium chloride；The pH adjusting agent is hydrochloric acid or sodium hydroxide；The antioxidantFor at least one of tocopherol, sodium hydrogensulfite, sodium pyrosulfite, sodium thiosulfate.
Second aspect, the present invention provides the preparation methods of above-mentioned Aprepitant intravenous injection emulsion, comprising the following steps:
(1) oil phase solvent, emulsifier, antioxidant, heating water bath are weighed, to be emulsified dose of all dissolution is added A RuiSmooth stirring and dissolving, as oily phase；
(2) stabilizer, isotonic regulator, pH adjusting agent are weighed, is added in water for injection, heating water bath, as water phase；
(3) oil is mutually slowly added in water phase, under stiring high speed shear, remaining water for injection is added, colostrum is made；
(4) the resulting colostrum of step (3) is subjected to microjet homogeneous, obtains whole cream；
(5) by step (4) it is resulting eventually cream carry out filling, nitrogen charging, sealing, be placed in rotation autoclave in sterilize to get AhAuspicious smooth intravenous injection emulsion.
In preparation method of the invention, the addition of emulsifier can be heating for dissolving in oily phase, can also be and is dispersed with stirringIt in water phase, or is partly dissolved in oil phase solvent, is partially dispersed in water phase；Oil phase and water phase in colostrum preparation processTemperature will be consistent as far as possible.
In preparation method of the invention, colostrum uniform particle diameter is turned to using high-pressure homogeneous or micro jetting technology, to load medicineColostrum carries out uniform particle diameter processing.Carry out high-pressure homogeneous or microjet homogenizing process in, first using lesser pressure intoRow processing, then sample treatment is carried out using higher pressure, avoid the viscosity of sample from causing particle diameter distribution unequal greatly very much.Cream eventuallyDisinfecting action is using high pressure sterilization filtration sterilization.
The preferred embodiment of preparation method as Aprepitant intravenous injection emulsion of the present invention, following (a)~At least one of in (e):
(a) in the step (1), heating temperature is 50~80 DEG C；
(b) in the step (2), the volume of water for injection is the 60~80% of emulsion for injection total volume, and heating temperature is50~80 DEG C；
(c) in the step (3), speed of agitator is 5000~20000rpm, and shear time is 5~25min；
(d) in the step (4), homogenizing temperature is 30~50 DEG C, and homogeneous recycles 4~10 at 8000~35000PsiIt is secondary；
(e) in the step (5), sterilising temp is 121 DEG C, sterilization time 15min.
The preferred embodiment of preparation method as Aprepitant intravenous injection emulsion of the present invention, the step(3) in, speed of agitator is 8000~18000rpm, and shear time is 5~15min；In the step (4), homogenization pressure is10000~25000Psi, cycle-index are 6~10 times.
The third aspect, the present invention provides the preparations of above-mentioned Aprepitant intravenous injection emulsion to dislike caused by chemotherapy treatingApplication in the heart and the drug of vomiting.
Inventor has found that original is ground in prescription in the course of the research, and the dosage of ethyl alcohol is for Aprepitant intravenous injection emulsionLast physical stability does not directly affect, and effect of the ethyl alcohol in the prescription only is used to increase the dissolubility of phosphatide.Therefore,The present invention is by avoiding the addition of ethyl alcohol in prescription to improve the safety of emulsion for injection.Original is ground phosphatide dosage in prescription and is up to14.44% or so, it is difficult to be directly dissolved in 9.44% oil-phase solution, it is therefore desirable to which the ethyl alcohol for being added 2.78% carrys out hydrotropy.Result of study shows that phosphatide can be dissolved completely in oil phase solvent when ethanol consumption is 0.5% or so；Lower than 0.5%, phosphorusRouge cannot be completely dissolved, and drug has and can dissolve on a small quantity, but before this sterilizing for prepared Aprepitant intravenous injection creamRear stability does not significantly affect directly, and concrete outcome is as shown in table 1.
Table 1
Compared with prior art, the invention has the benefit that Aprepitant intravenous injection emulsion of the invention does not containThe low carbon chains alcohol such as ethyl alcohol, while being adjusted by process innovation, the quality requirement as commercialized product can be reached, mentioned significantlyThe high clinical use safety of Aprepitant intravenous injection emulsion；It is directly injected intravenously when clinical use, does not need to carry out diluteIt releases；Acute and delayed nausea and vomiting caused by the cisplatin combined high dose sensitization cancer chemotherapy of high dose can be used to treat, subtractedThe nausea and vomiting of few chemotherapy of tumors early period and mid-term.
Specific embodiment
Purposes, technical schemes and advantages in order to better illustrate the present invention, below in conjunction with specific embodiment to the present inventionIt is described further.
Embodiment 1
In the Aprepitant intravenous injection emulsion of the present embodiment, contain in every 1000mL emulsion: Aprepitant 1.3g, purificationSoybean oil 100.0g refines egg yolk lecithin 12g, and oleic acid 2.5g, 0.1N NaOH are appropriate, and glycerol 25g, water for injection is settled to1000mL.Wherein, refined soybean oil is 10% as oily phase proportion.
The present embodiment Aprepitant intravenous injection emulsion the preparation method comprises the following steps:
(1) recipe quantity refined soybean oil, purification egg yolk lecithin and oleic acid are weighed, stirring dissolves emulsifier, at additionThe Aprepitant just measured, it is mutually stand-by that heating water bath to 70 DEG C of conducts carries medicine oil；
(2) it weighs recipe quantity glycerol to be added in 800mL water for injection, heating water bath is to 70 DEG C as water phase；
(3) oil is mutually slowly added into water phase, maintains temperature at 70 DEG C, the high speed shear 10min under 8000rpm, noteIt penetrates and is settled to 1000mL with water and obtains colostrum, adjust colostrum pH to 7.5 with 0.1N NaOH；
(4) colostrum being prepared progress is high-pressure homogeneous, under the homogenization pressure of 800bar, recycle 6 times, homogenizing temperatureIt is 30 DEG C；
(5) after high-pressure homogeneous cream eventually, filling, nitrogen charging gas shielded will be carried out by cream eventually, sealing is placed in rotation autoclaveHigh pressure sterilization 15min obtains finished product at 121 DEG C.
After high-pressure homogeneous, appearance is creamy white Aprepitant intravenous injection emulsion manufactured in the present embodiment, flowingProperty is good, does not have wall built-up phenomenon, and with apparent blue-opalescent.It is 0.027 that it, which is centrifuged stability constant, after measured, average grain diameterFor 142.22 ± 31.22nm, zeta potential absolute value is 30.22mV.Aprepitant intravenous injection emulsion manufactured in the present embodiment, goes outBacterium fore-and-aft stability is good, and placing 3 months its partial sizes is 149.54 ± 28.61nm, illustrates Aprepitant manufactured in the present embodimentIntravenous injection emulsion has good stability.
Embodiment 2
In the Aprepitant intravenous injection emulsion of the present embodiment, contain in every 1000mL emulsion: Aprepitant 13g, purificationOlive oil 150g refines egg yolk lecithin 50g, and oleic acid 2.5g, 0.1N NaOH are appropriate, and glycerol 25g, water for injection is settled to1000mL.Wherein, purification olive oil is 15% as oily phase proportion.
The present embodiment Aprepitant intravenous injection emulsion the preparation method comprises the following steps:
(1) recipe quantity purification olive oil, purification egg yolk lecithin and oleic acid are weighed, stirring dissolves emulsifier, at additionSide's amount Aprepitant, heating water bath is to 75 DEG C as load medicine oil phase；
(2) it weighs recipe quantity glycerol to be added in 700mL water for injection, heating water bath is to 75 DEG C as water phase；
(3) oil is mutually slowly added into water phase, maintains temperature at 75 DEG C, the high speed shear 5min under 15000rpm, noteIt penetrates and is settled to 1000mL with water and obtains colostrum, adjust colostrum pH to 7.5 with 0.1N NaOH；
(4) colostrum being prepared progress is high-pressure homogeneous, under the homogenization pressure of 8000psi, recycle 6 times, homogeneous temperatureDegree is 40 DEG C；
(5) after high-pressure homogeneous cream eventually, filling, nitrogen charging gas shielded will be carried out by cream eventually, sealing is placed in rotation autoclaveHigh pressure sterilization 15min obtains finished product at 121 DEG C.
Aprepitant intravenous injection emulsion manufactured in the present embodiment is after high-pressure homogeneous, and appearance is in shallow white, flowingProperty it is good, there is no a wall built-up phenomenon, and with apparent blue-opalescent, the fore-and-aft stability that sterilizes is good.After measured, sterilize front and backAprepitant intravenous injection emulsion average grain diameter is respectively 112.35 ± 24.36nm and 116.82 ± 17.68nm, illustrates this realityApply having good stability for an Aprepitant intravenous injection cream sterilizing front and back.
Embodiment 3
In the Aprepitant intravenous injection emulsion of the present embodiment, contain in every 1000mL emulsion: Aprepitant 20g, purificationSoybean oil 100g refines olive oil 100g, and egg PC 100g, enuatrol 5g, 0.1N NaOH are appropriate, glycerol 25g,Water for injection is settled to 1000mL.Wherein, it is 20% that refined soybean oil and purification olive oil, which are used as oily phase proportion,.
The present embodiment Aprepitant intravenous injection emulsion the preparation method comprises the following steps:
(1) recipe quantity purification olive oil, refined soybean oil, egg PC are weighed, stirring is dissolved emulsifier, addedEnter the Aprepitant of recipe quantity, heating water bath is to 75 DEG C as load medicine oil phase；
(2) recipe quantity glycerol, enuatrol are weighed, is added in 800mL water for injection, heating water bath is to 75 DEG C as water phase；
(3) oil is mutually slowly added into water phase, maintains temperature at 75 DEG C, the high speed shear 15min under 18000rpm is obtainedTo colostrum, colostrum pH to 7.5 is adjusted with 0.1N NaOH；
(4) colostrum being prepared progress is high-pressure homogeneous, under the homogenization pressure of 15000psi, recycle 6 times, homogeneous temperatureDegree is 40 DEG C；
(5) after high-pressure homogeneous cream eventually, filling, nitrogen charging gas shielded will be carried out by cream eventually, sealing is placed in rotation autoclaveHigh pressure sterilization 15min obtains finished product at 121 DEG C.
Aprepitant intravenous injection cream manufactured in the present embodiment is after high-pressure homogeneous, and appearance is translucent, mobilityWell, there is no wall built-up phenomenon, and with apparent blue-opalescent.After measured, the Aprepitant intravenous injection emulsion before and after sterilizingAverage grain diameter is 85.34 ± 12.43nm and 90.22 ± 16.28nm, before illustrating the intravenous injection cream sterilizing of the present embodiment AprepitantHaving good stability afterwards.
Embodiment 4
In the Aprepitant intravenous injection emulsion of the present embodiment, contain in every 1000mL emulsion: Aprepitant 20g, middle chainTriglycerides 150g, refined soybean oil 150g refine egg yolk lecithin 180g, and enuatrol 2.0g, 0.1N NaOH are appropriate, glycerol25g, vitamin E 5g, water for injection are settled to 1000mL.Wherein, medium chain triglyceride and refined soybean oil are as shared by oily phaseRatio is 30%.
The present embodiment Aprepitant intravenous injection emulsion the preparation method comprises the following steps:
(1) recipe quantity medium chain triglyceride, refined soybean oil, purification egg yolk lecithin, oleic acid and vitamin E are weighed, is stirredDissolution is mixed, the dissolution of Aprepitant bulk pharmaceutical chemicals is added, heating water bath is to 75 DEG C as load medicine oil phase；
(2) it weighs recipe quantity glycerol to be added in 800mL water for injection, heating water bath is to 75 DEG C as water phase；
(3) oil is mutually slowly added into water phase, maintains temperature at 75 DEG C, the high speed shear 10min under 15000rpm is obtainedTo colostrum, colostrum pH to 7.5 is adjusted with 0.1N NaOH；
(4) colostrum being prepared is subjected to microjet homogeneous, under the homogenization pressure of 15000psi, recycled 6 times, homogeneousTemperature is 30 DEG C；
(5) after high-pressure homogeneous cream eventually, filling, nitrogen charging gas shielded will be carried out by cream eventually, sealing is placed in rotation autoclaveHigh pressure sterilization 15min obtains finished product at 121 DEG C.
After microjet homogeneous, appearance is translucent Aprepitant intravenous injection emulsion manufactured in the present embodiment, streamDynamic property is good, does not have wall built-up phenomenon, and with apparent blue-opalescent.After measured, the Aprepitant after sterilizing is injected intravenously creamThe average grain diameter of agent sterilizing front and back is 101.26 ± 26.81nm and 106.37 ± 30.48nm, and the front and back that sterilizes has good stability.
Embodiment 5
In the Aprepitant intravenous injection emulsion of the present embodiment, contain in every 1000mL emulsion: Aprepitant 1.3g, purificationSoybean oil 100g refines olive oil 100g, median chain triglyceride oil 100g, egg PC 150g, enuatrol 5g, 0.1NAppropriate NaOH, glycerol 25g, water for injection are settled to 1000mL.Wherein, refined soybean oil, purification olive oil, three acid of medium chain triglycerideEster is 30% as oily phase proportion.
The present embodiment Aprepitant intravenous injection emulsion the preparation method comprises the following steps:
(1) recipe quantity refined soybean oil, purification olive oil, median chain triglyceride oil, egg PC, stirring are weighedRecipe quantity Aprepitant is added in dissolution, and heating water bath is to 75 DEG C as load medicine oil phase；
(2) recipe quantity glycerol, enuatrol are weighed, surplus egg PC is added in 800mL water for injection, water-bath70 DEG C are heated to as water phase；
(3) oil is mutually slowly added into water phase, maintains temperature at 70 DEG C, the high speed shear 10min under 20000rpm is obtainedTo colostrum, colostrum pH to 7.5 is adjusted with 0.1N NaOH；
(4) colostrum being prepared is subjected to microjet homogeneous, under the homogenization pressure of 25000psi, recycled 6 times, homogeneousTemperature is 50 DEG C；
(5) after high-pressure homogeneous cream eventually, cream passes through 0.22 μm of membrane filtration degerming, nitrogen charging gas shielded, the finished product of sealing eventually.
Aprepitant intravenous injection emulsion manufactured in the present embodiment its translucent appearance, mobility after microjet homogeneousWell, there is no wall built-up phenomenon, and with apparent blue-opalescent.After measured, front and back Aprepitant intravenous injection emulsion after sterilizingAverage grain diameter be 82.41 ± 27.18nm and 90.11 ± 20.66nm, illustrate the present embodiment Aprepitant intravenous injection cream sterilizingFront and back has good stability.
Embodiment 6
In the Aprepitant intravenous injection emulsion of the present embodiment, contain in every 1000mL emulsion: Aprepitant 13g, purificationSoybean oil 100g refines egg yolk lecithin 120g, and oleic acid 2.5g, 0.1N NaOH are appropriate, glycerol 25g, vitamin E 0.2g, noteIt penetrates and is settled to 1000mL with water.Wherein, refined soybean oil is 10% as oily phase proportion.
The present embodiment Aprepitant intravenous injection emulsion the preparation method comprises the following steps:
(1) purification egg yolk lecithin, oleic acid, the vitamin E of recipe quantity refined soybean oil, 1/5 recipe quantity are weighed, is stirred moltenPrescription Aprepitant is added in solution, and heating water bath is to 65 DEG C as load medicine oil phase；
(2) recipe quantity glycerol is weighed, the purification egg yolk lecithin of remaining recipe quantity is added in 60mL water for injection, and water-bath addsHeat is to 65 DEG C as water phase；
(3) oil is mutually slowly added into water phase, maintains temperature at 70 DEG C, the high speed shear 10min under 15000rpm, noteIt penetrates and is settled to 1000mL with water and obtains colostrum, adjust colostrum pH to 7.5 with 0.1N NaOH；
(4) colostrum being prepared is subjected to high pressure microjet homogeneous, under the pressure of 30000psi, recycled 8 times, homogeneousTemperature is 30 DEG C；
(5) after high-pressure homogeneous cream eventually, filling, nitrogen charging gas shielded will be carried out by cream eventually, sealing is placed in rotation autoclaveHigh pressure sterilization 15min obtains finished product at 121 DEG C.
Aprepitant vein emulsion manufactured in the present embodiment is after microjet homogeneous, and appearance is creamy white, mobilityWell, there is no wall built-up phenomenon, and with apparent blue-opalescent.It is somebody's turn to do through surveying, Aprepitant intravenous injection emulsion sterilizing front and backAverage grain diameter is 104 ± 24.18nm and 105.31 ± 30.52nm, and sterilizing fore-and-aft stability is good.
Embodiment 7
Inventor investigates the dissolution mechanism of phosphatide in Aprepitant intravenous injection emulsion, by partial emulsifier phosphorusRouge is dissolved in the solubilizer in oily phase as drug in oil phase solvent, and rest part emulsifier phosphatide is dispersed in water phase；?It prepares in the high speed processes of colostrum, oil is mutually slowly dropped into water phase and prepares colostrum, then pass through microjet or high-pressure homogeneous to firstCream carries out uniform particle diameter processing.The emulsifier emulsifier evaluation result that in grease prepared by different proportion is as shown in table 2.By table2 it is found that the sterilizing fore-and-aft stability of unsaturated fatty acid fat of triglyceride cream is good.
Table 2
Effect example 1
Inventor investigates the mass ratio of each component in Aprepitant intravenous injection emulsion, and test group and right is arrangedAccording to group, influence of the mass ratio of each component to Aprepitant intravenous injection emulsion stability is investigated.The system of test group and control groupFor Preparation Method with embodiment 1, the quality of each component, entrapment efficiency, average grain diameter, particle diameter distribution and zeta potential are as shown in table 3.
Table 3
As shown in Table 3, when the mass ratio of Aprepitant intravenous injection emulsion each component within the scope of the present invention when, toolThere is preferable stability；When the mass percent of emulsion for injection each component are as follows: Aprepitant 0.13~1.3%, oil phase solvent 10~20%, when emulsifier 1.2~12%, stabilizer 0.03~0.3%, isotonic regulator 2~3%, Aprepitant obtained is quietThe optimal stability of arteries and veins emulsion for injection.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present inventionThe limitation of range is protected, although the invention is described in detail with reference to the preferred embodiments, those skilled in the art shouldUnderstand, it can be with modification or equivalent replacement of the technical solution of the present invention are made, without departing from the essence of technical solution of the present inventionAnd range.