CN105663042A - Stable narcotic drug fat emulsion and preparation method thereof - Google Patents
Stable narcotic drug fat emulsion and preparation method thereof Download PDFInfo
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- CN105663042A CN105663042A CN201610075243.0A CN201610075243A CN105663042A CN 105663042 A CN105663042 A CN 105663042A CN 201610075243 A CN201610075243 A CN 201610075243A CN 105663042 A CN105663042 A CN 105663042A
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
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- 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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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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Abstract
The invention provides stable cyclopropyl MOC-metomidate fat emulsion. The fat emulsion comprises, by weight to volume percentage, 0.02-1% of cyclopropyl MOC-metomidate, 5-30.0% of oil for injection, 0.5-1.8% of phosphatidylcholine and 0.005-0.25% of phosphatidylinositol. The fat emulsion is high in stability and safety and suitable for being used clinically.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of anaesthetic cyclopropyl MOC-metomidate Fat Emulsion andIts preparation method.
Background technology
Etomidate [R (+)-1-(1-phenethyl)-1 hydrogen-imidazole-5] is that a kind of general anesthesia of uniqueness luresLead agent and sedative, its security is apparently higher than barbiturates. The therapeutic index of R type Etomidate is significantly higher than other whole bodiesArcotic. Preclinical zooscopy also shows that injection Etomidate only causes that atomic weak haemodynamics changes and breathes and press downSystem. Etomidate safety margin is large, clear-headed rapid safety, and to breathing without obviously suppressing, to memoryless in art, cardiovascular system is steadyFixed, be specially adapted to old age, weak, blood volume is lower and have the patient of angiocardiopathy. Nineteen eighty-three Ledingham grindsStudy carefully and find that Etomidate can suppress adrenal cortex function. Etomidate suppresses the synthetic 11-β hydroxylase of adrenal cortex, large agentAmount suppresses β-desmolase, and single dose uses Etomidate can make adrenal cortex to the reaction 4-6 hour that slows down stimulating. Due to itVery potent and the time is long to the synthetic inhibitory action of adrenocorticotro, its clinical practice is restricted.
MOC-Etomidate has retained the important favourable pharmacological property of Etomidate, comprises quick acting, and hypnosis effect is high,Hemodynamic stability. It is connected with an ester bond end on the original ester ring of Etomidate, and it can be rapidly by blood and groupNonspecific esterase metabolism in knitting. In zoopery, the anesthetic effect of MOC-Etomidate only continues a few minutes, and it is to kidneyThe inhibition of upper gland continues 30min, than the obvious shortening of Etomidate. But its usefulness is low, degraded is fast, and metabolite can be at brainMiddle accumulation, recovery from anesthesia postpones.
For slowing down the degradation rate of MOC-Etomidate, its structure is redesigned, obtain the U.S. holder of cyclopropyl MOC-Miaow ester (CPMM), the result of testing in different genera shows, compared with MOC-Etomidate, its anesthetic effect time isIts 4 times, anesthesia effect is its 8 times, and required dosage is little, and the accumulation of metabolin greatly reduces, and anesthesia recovery (is about 5 points rapidlyClock), adrenal gland effect recovers (being less than 30 minutes) rapidly. Do not have at present the report about cyclopropyl MOC-metomidate preparationRoad.
Patent CN201210415043 discloses a kind of injection Etomidate composition, adds polyethylene glycol-12-hydroxylThe composition particle diameter that stearate forms is less, appearance transparent. Patent CN201310027567 provides a kind of stable supportMiaow ester fat emulsion, it adopts lower pH4.5-7.0 to prevent that the impurity of Etomidate from relying on the increase of miaow acid content. PatentCN201510096942 discloses a kind of stable Etomidate fat emulsion, by adjusting PC, PE, PG in emulsifying agent phosphatideRatio obtains a kind of stability and the higher preparation of security.
For cyclopropyl MOC-metomidate (CPMM), in its structure, there are two ester bonds, compared with Etomidate, moreEasily hydrolysis. For the ease of CPMM use clinically, be necessary to provide stability and the security of a kind of CPMM of being more suitable forHigher fat emulsion.
Summary of the invention
The invention provides a kind of stable anaesthetic cyclopropyl MOC-metomidate Fat Emulsion and preparation method thereof.
Described cyclopropyl MOC-metomidate Fat Emulsion Fat Emulsion comprises cyclopropyl MOC-metomidate, oil for injection, phosphorusAcyl choline, phosphatidylinositols, wherein the heavily appearance percentage of each component is as follows:
In above-mentioned cyclopropyl MOC-metomidate Fat Emulsion, the heavily appearance percentage of cyclopropyl MOC-metomidate is preferably0.05-0.5％w/v。
Above-mentioned cyclopropyl MOC-metomidate fat also contains phosphatidyl-ethanolamine, and the heavily appearance percentage of phosphatidyl-ethanolamineThan being less than or equal to 0.18%w/v, more preferably 0.06～0.18%w/v.
Described phosphatid ylcholine is phosphatid ylcholine and the salt thereof of natural origin, synthetic phosphatid ylcholine and salt thereof or itAny combination; Described synthetic phosphatid ylcholine is selected from DSPC, dioleyl phosphatidyl choline,Dioctonoyl pnosphotidyl choline, L-Dimyristoylphosphatidylcholine, DDPC, two bay acyl phospholipidsPhatidylcholine, two mustard acyl phospholipids phatidylcholines, 1-stearyl-2-oleoyl phosphatid ylcholine, 1-palmityl-2-oleoyl phosphorusAcyl choline, 1-myristoyl-2-oleoyl phosphatid ylcholine, 1-stearyl-2-palmityl phosphatid ylcholine, 1-is hardFatty acyl group-2-myristoyl phosphatid ylcholine, 1-palmityl-2-stearyl phosphatid ylcholine, 1-palmityl-2-meatCardamom acyl group phosphatid ylcholine, 1-myristoyl-2-stearyl phosphatid ylcholine, 1-myristoyl-2-palmitylPhosphatid ylcholine or its combination.
Described phosphatidylinositols is the phosphatidylinositols of natural origin and salt thereof, synthetic phosphatidylinositols and salt thereof or itAny combination; Described synthetic phosphatidylinositols is selected from distearyl acyl group phosphatidylinositols, dioleoyl phosphatidylinositols,Two palmityl phosphatidylinositols, two myristoyl phosphatidylinositols, 1-palmityl-2-oleoyl phosphatidylinositols, twoMustard acyl phosphatidylinositols, two lauroyl phosphatidylinositols or its combination.
Described phosphatidyl-ethanolamine is phosphatidyl-ethanolamine and the salt thereof of natural origin, synthetic phosphatidyl-ethanolamine andSalt or their any combination; Described synthetic phosphatidyl-ethanolamine is selected from DSPE, dioleoylPhosphatidyl-ethanolamine, DPPE, two myristoyl phosphatidyl-ethanolamines, two mustard acyl phosphatidyl ethanolAmine, two lauroyl phosphatidyl-ethanolamines or its combination.
Described oil for injection be selected from refined soybean oil, safflower oil, cottonseed oil, olive oil, coconut oil, castor oil, fish oil, inChain monoglyceride, medium chain glycerine dibasic acid esters, medium chain triglyceride, ethyl oleate, acetylated monoglyceride, propane diols dibasic acid esters, sub-oilAcid glyceride, polyethylene glycol glyceryl laurate ester or its combination; Be preferably olive oil and medium chain triglyceride, both weight ratios are1:1。
In described cyclopropyl MOC-metomidate Fat Emulsion, also comprise pH adjusting agent, described pH adjusting agent is selected from hydroxideSodium, hydrochloric acid, phosphoric acid, phosphate, citric acid, citrate, acetic acid, acetate or its combination.
In described cyclopropyl MOC-metomidate Fat Emulsion, also comprise isotonic regulator, described isotonic regulator is selected from sweetOil, glucose, mannitol, propane diols or its combination.
The present invention also provides a kind of preparation method of described cyclopropyl MOC-metomidate Fat Emulsion, comprises the following steps:
(1) preparation of oil phase: to cyclopropyl MOC-metomidate in oil for injection, phosphatid ylcholine, phosphatidylinositols, stirsMix it is dissolved, as oil phase;
(2) preparation of colostrum: step (1) oil phase is added in water for injection, and high speed shear is disperseed, and forms colostrum;
(3) high pressure homogenize: the homogenize of step (2) colostrum high pressure, obtains smart breast;
(4) filter, embedding, sterilizing, to obtain final product.
CPMM is different from Etomidate, and it contains two ester bonds, and more easily hydrolysis, adopts the technical scheme of Etomidate alsoNot can solve its stability problem. The side that the present invention adopts phosphatid ylcholine (PC) and phosphatidylinositols (PI) to combineFormula, can improve its stability significantly, secondly, the amount of phosphatidyl-ethanolamine (PE) is limited in to certain limit, can more enterOne step improve its stability.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, so that those of ordinary skill in the art can be more clearlyUnderstand and enforcement the present invention. But, should be understood that, the present invention is not limited to these embodiment. Made for the present inventionWhy not deviate from spirit and scope of the invention change, revise and be equal to replacement, all fall within the scope of the present invention.
Comparative example 1
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine and phosphatidyl ethanolAmine, stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 6.0 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Comparative example 2
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidyl ethanolAmine, phosphatidyl glycerol, stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.5 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Embodiment 1
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidylinositols,Stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 6.0 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Embodiment 2
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidyl ethanolAmine, phosphatidylinositols, stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.5 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Embodiment 3
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidylinositols,Stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.0 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Embodiment 4
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidylinositols,Stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.0 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Embodiment 5
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidylinositols,Stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.0, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Embodiment 6
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidyl ethanolAmine, phosphatidylinositols, stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.0 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Embodiment 7
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidyl ethanolAmine, phosphatidylinositols, stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.0 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Comparative example 3
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get soybean oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidyl ethanolAmine, phosphatidylinositols, stirring and dissolving, as oil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.0 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Test case 1
The sample of embodiment 1～7 and comparative example 1～3 is positioned over respectively to lower 0 day of 60 DEG C of conditions, 5 days, within 10 days, measuresThe content of breast grain particle diameter and hydrolysis impurity. Average grain diameter requires to be less than 400nm conventionally, comes for the emulsion of 10%w/v oil phaseSay, average grain diameter should be controlled at 150～250nm conventionally, and for the emulsion of 20%w/v oil phase, average grain diameter should be controlled conventionallyBuilt in 250～350nm.
Affect result of the test as shown in table 1:
The comparison of table 1 influence factor result of the test
Comparative example 1 and embodiment 1 are contrasted, and comparative example 2 and embodiment 2 contrast, and can find with respect to existingThere is the Fat Emulsion auxiliary material combination that in technology, Etomidate adopts, the phosphatid ylcholine that the present invention adopts and the combination of phosphatidylinositolsThe fat emulsion average grain diameter obtaining is more stable, and hydrolysis impurity amount is lower, has higher stability and security. Adopt phosphorusAcyl choline (PC) is better than phosphatid ylcholine (PC) and phosphatidyl-ethanolamine (PE) with phosphatidylinositols (PI). Adopt phosphatidyl courageAlkali (PC), phosphatidylinositols (PI) and phosphatidyl-ethanolamine (PE) are significantly better than adopting phosphatid ylcholine (PC), phosphatidyl glycerolAnd phosphatidyl-ethanolamine (PE) (PG).
Can find according to the measurement result of embodiment 1-7, within the scope of the invention prepared CPMM fat emulsionParticle diameter is stable, and the hydrolysis impurity content of gained is lower.
Although phosphatidyl-ethanolamine (PE) is conducive to the particle diameter of stabilization formulations, according to embodiment 6-7 and comparative example 3Measurement result can find, when its content exceed a certain amount of after, the increase of PE can cause the hydrolysis impurity content of CPMM to increase.
In sum, CPMM is different from Etomidate, and it contains two ester bonds, more easily hydrolysis, employing EtomidateTechnical scheme not can solve its stability problem. The mode that adopts PC and PI to combine, can improve that it is steady significantlyQualitative, secondly, the amount of PE is limited in to certain limit, can further improve its stability.
Embodiment 8
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get olive oil, be heated to 60 DEG C, add CPMM, phosphatid ylcholine, phosphatidylinositols, stirring and dissolving, as oilPhase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 4.5 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Embodiment 9
Preparation technology:
(1) get water for injection, be heated to 60 DEG C, add glycerine to dissolve, as water;
(2) get olive oil and medium chain triglyceride, be heated to 60 DEG C, add CPMM, DSPC, DSPI, stirring and dissolving, asOil phase;
(3) oil phase is slowly injected to the water of 60 DEG C of insulations under high-speed stirred condition, high speed shear, shear rate10000rpm, shear time 15min, makes to form even colostrum;
(4) regulate colostrum pH value to 7.5 ± 0.1, inject water to 1000ml;
(5) colostrum is transferred in high pressure homogenizer, pressure 1000bar, circulates 3 times;
(6) filter, embedding, high-temperature sterilization (121 DEG C, F0 >=12).
Claims (10)
1. a cyclopropyl MOC-metomidate Fat Emulsion, is characterized in that, this Fat Emulsion comprises cyclopropyl MOC-metomidate,Oil for injection, phosphatid ylcholine, phosphatidylinositols, wherein the heavily appearance percentage of each component is as follows:
Cyclopropyl MOC-metomidate 0.02-1%w/v
Oil for injection 5-30.0%w/v
Phosphatid ylcholine 0.5-1.8%w/v
Phosphatidylinositols 0.005-0.25%w/v.
2. cyclopropyl MOC-metomidate Fat Emulsion according to claim 1, is characterized in that, the U.S. holder of cyclopropyl MOC-miaowThe heavily appearance percentage of ester is 0.05-0.5%w/v.
3. cyclopropyl MOC-metomidate Fat Emulsion according to claim 1 and 2, is characterized in that, this Fat Emulsion containsPhosphatidyl-ethanolamine, and the heavily appearance percentage of phosphatidyl-ethanolamine is less than or equal to 0.18%w/v.
4. cyclopropyl MOC-metomidate Fat Emulsion according to claim 3, is characterized in that the weight of phosphatidyl-ethanolamineAppearance percentage is 0.06 ~ 0.18%w/v.
5. cyclopropyl MOC-metomidate Fat Emulsion according to claim 1, is characterized in that, described phosphatid ylcholine isThe phosphatid ylcholine of natural origin and salt thereof, synthetic phosphatid ylcholine and salt thereof or their any combination; Described syntheticPhosphatid ylcholine is selected from DSPC, dioleyl phosphatidyl choline, Dioctonoyl pnosphotidyl choline, twoMyristoyl phosphatid ylcholine, DDPC, DLPC, two mustard acyl phospholipids acyl couragesAlkali, 1-stearyl-2-oleoyl phosphatid ylcholine, 1-palmityl-2-oleoyl phosphatid ylcholine, 1-myristoyl-2-oleoyl phosphatid ylcholine, 1-stearyl-2-palmityl phosphatid ylcholine, 1-stearyl-2-myristoyl phosphorusAcyl choline, 1-palmityl-2-stearyl phosphatid ylcholine, 1-palmityl-2-myristoyl phosphatid ylcholine, 1-Myristoyl-2-stearyl phosphatid ylcholine, 1-myristoyl-2-palmityl phosphatid ylcholine or its combination.
6. cyclopropyl MOC-metomidate Fat Emulsion according to claim 1, is characterized in that, described phosphatidylinositols isThe phosphatidylinositols of natural origin and salt thereof, synthetic phosphatidylinositols and salt or their any combination; Described syntheticPhosphatidylinositols is selected from distearyl acyl group phosphatidylinositols, dioleoyl phosphatidylinositols, two palmityl phosphatidylinositols, twoMyristoyl phosphatidylinositols, 1-palmityl-2-oleoyl phosphatidylinositols, two mustard acyl phosphatidylinositols, two lauroylPhosphatidylinositols or its combination.
7. cyclopropyl MOC-metomidate Fat Emulsion according to claim 1, is characterized in that, described oil for injection is selected fromRefined soybean oil, safflower oil, cottonseed oil, olive oil, coconut oil, castor oil, fish oil, medium chain monoglyceride, medium chain glycerine dibasic acid esters,Medium chain triglyceride, ethyl oleate, acetylated monoglyceride, propane diols dibasic acid esters, glyceryl linoleate, polyethylene glycol laurate are sweetGrease or its combination; Be preferably olive oil and medium chain triglyceride, both weight ratios are 1:1.
8. cyclopropyl MOC-metomidate Fat Emulsion according to claim 1, is characterized in that, also comprises pH adjusting agent,Described pH adjusting agent is selected from NaOH, hydrochloric acid, phosphoric acid, phosphate, citric acid, citrate, acetic acid, acetate or its groupClose.
9. cyclopropyl MOC-metomidate Fat Emulsion according to claim 1, is characterized in that, this Fat Emulsion comprises etc.Ooze conditioning agent, described isotonic regulator is selected from glycerine, glucose, mannitol, propane diols or its combination.
10. a preparation method for the arbitrary described cyclopropyl MOC-metomidate Fat Emulsion of claim 1-2, comprises following stepRapid:
(1) preparation of oil phase: to cyclopropyl MOC-metomidate in oil for injection, phosphatid ylcholine, phosphatidylinositols, stirring makesIt dissolves, as oil phase;
(2) preparation of colostrum: step (1) oil phase is added in water for injection, and high speed shear is disperseed, and forms colostrum;
(3) high pressure homogenize: the homogenize of step (2) colostrum high pressure, obtains smart breast;
(4) filter, embedding, sterilizing, to obtain final product.
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Cited By (4)
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| CN109985003A (en) * | 2017-12-29 | 2019-07-09 | 北京蓝丹医药科技有限公司 | A kind of injection auxotype Fat Emulsion and preparation method thereof |
| CN109985005A (en) * | 2017-12-29 | 2019-07-09 | 北京普德康利医药科技发展有限公司 | Flurbiprofen axetil Fat Emulsion and preparation method thereof |
| WO2019149228A1 (en) * | 2018-01-30 | 2019-08-08 | 成都安诺晨创医药科技有限公司 | Substituted imidazole formate derivative and use thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109985001A (en) * | 2017-12-29 | 2019-07-09 | 北京蓝丹医药科技有限公司 | A kind of injection auxotype Fat Emulsion and preparation method thereof |
| CN109985003A (en) * | 2017-12-29 | 2019-07-09 | 北京蓝丹医药科技有限公司 | A kind of injection auxotype Fat Emulsion and preparation method thereof |
| CN109985005A (en) * | 2017-12-29 | 2019-07-09 | 北京普德康利医药科技发展有限公司 | Flurbiprofen axetil Fat Emulsion and preparation method thereof |
| WO2019149228A1 (en) * | 2018-01-30 | 2019-08-08 | 成都安诺晨创医药科技有限公司 | Substituted imidazole formate derivative and use thereof |
| JP2021512132A (en) * | 2018-01-30 | 2021-05-13 | チェンドゥ・エムエフエス・ファーマ・カンパニー・リミテッド | Substituted imidazole carboxylic acid ester derivative and its use |
| US11434205B2 (en) | 2018-01-30 | 2022-09-06 | Chengdu Mfs Pharma. Co., Ltd. | Substituted imidazole carboxylate derivatives and the use thereof |
| JP7215758B2 (en) | 2018-01-30 | 2023-01-31 | チェンドゥ・エムエフエス・ファーマ・カンパニー・リミテッド | Substituted imidazole carboxylic acid ester derivative and use thereof |
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