CN113712915A - Preparation method of aprepitant emulsion injection - Google Patents
Preparation method of aprepitant emulsion injection Download PDFInfo
- Publication number
- CN113712915A CN113712915A CN202110018100.7A CN202110018100A CN113712915A CN 113712915 A CN113712915 A CN 113712915A CN 202110018100 A CN202110018100 A CN 202110018100A CN 113712915 A CN113712915 A CN 113712915A
- Authority
- CN
- China
- Prior art keywords
- injection
- aprepitant
- emulsion
- oil
- preparing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 title claims abstract description 77
- 229960001372 aprepitant Drugs 0.000 title claims abstract description 77
- 239000000839 emulsion Substances 0.000 title claims abstract description 77
- 238000002347 injection Methods 0.000 title claims abstract description 75
- 239000007924 injection Substances 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims abstract description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 72
- 238000002156 mixing Methods 0.000 claims abstract description 35
- 238000003756 stirring Methods 0.000 claims abstract description 35
- 235000013336 milk Nutrition 0.000 claims abstract description 27
- 239000008267 milk Substances 0.000 claims abstract description 27
- 210000004080 milk Anatomy 0.000 claims abstract description 27
- 238000005303 weighing Methods 0.000 claims abstract description 24
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 23
- 239000008215 water for injection Substances 0.000 claims abstract description 23
- 238000001914 filtration Methods 0.000 claims abstract description 22
- 239000006184 cosolvent Substances 0.000 claims abstract description 16
- 230000003204 osmotic effect Effects 0.000 claims abstract description 16
- 238000010008 shearing Methods 0.000 claims abstract description 15
- 239000012528 membrane Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 12
- 230000001954 sterilising effect Effects 0.000 claims abstract description 12
- 239000000243 solution Substances 0.000 claims abstract description 8
- 239000012071 phase Substances 0.000 claims description 55
- 239000003921 oil Substances 0.000 claims description 41
- 235000019198 oils Nutrition 0.000 claims description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims description 20
- 239000003549 soybean oil Substances 0.000 claims description 20
- 235000012424 soybean oil Nutrition 0.000 claims description 20
- 229930006000 Sucrose Natural products 0.000 claims description 18
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 18
- 239000005720 sucrose Substances 0.000 claims description 18
- JLPULHDHAOZNQI-JLOPVYAASA-N [(2r)-3-hexadecanoyloxy-2-[(9e,12e)-octadeca-9,12-dienoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC JLPULHDHAOZNQI-JLOPVYAASA-N 0.000 claims description 14
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 11
- 239000008346 aqueous phase Substances 0.000 claims description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 4
- 238000004945 emulsification Methods 0.000 claims description 3
- 238000005070 sampling Methods 0.000 claims description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 235000019483 Peanut oil Nutrition 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 239000010513 hydrogenated corn oil Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 239000012982 microporous membrane Substances 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 239000000312 peanut oil Substances 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 239000008159 sesame oil Substances 0.000 claims description 2
- 235000011803 sesame oil Nutrition 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 235000020238 sunflower seed Nutrition 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 230000001804 emulsifying effect Effects 0.000 abstract description 12
- 230000003078 antioxidant effect Effects 0.000 abstract 1
- 239000002245 particle Substances 0.000 description 27
- 239000000523 sample Substances 0.000 description 24
- 238000000265 homogenisation Methods 0.000 description 14
- 239000000126 substance Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 7
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 5
- 239000008347 soybean phospholipid Substances 0.000 description 5
- 150000003904 phospholipids Chemical class 0.000 description 3
- 229940083466 soybean lecithin Drugs 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 1
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- FKCBLVCOSCZFHV-UHFFFAOYSA-N acetonitrile;ethanol Chemical compound CCO.CC#N FKCBLVCOSCZFHV-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 230000000095 emetic effect Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 150000003248 quinolines Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to the technical field of medicinal preparations, in particular to a preparation method of aprepitant emulsion injection, which comprises the following steps: weighing aprepitant, an emulsifier, a cosolvent and oil for injection, and stirring and mixing in a water bath to obtain an oil phase; weighing a pH regulator, an osmotic pressure regulator and water for injection, and stirring and mixing to obtain a water phase; adding the water phase into the oil phase, and shearing and emulsifying at the rotating speed of 15000-20000 rpm to obtain coarse emulsion; and (3) adding the crude milk into a high-pressure homogenizer, homogenizing for 5-6 times at 12000-15000 psi, filtering and sterilizing the fine milk through a microporous filter membrane after homogenizing, wherein the pH value of the solution is 7.5-8.5, and thus obtaining the aprepitant emulsion injection. The aprepitant emulsion injection with good antioxidant property and emulsifying effect is prepared by controlling the content of the emulsifier, and parameters such as shearing speed, homogenizing pressure, homogenizing temperature and the like in the emulsion preparation process, and meanwhile, the operability is ensured in the preparation process, the process is simplified, and the equipment loss is reduced.
Description
Technical Field
The invention relates to the technical field of medicinal preparations, in particular to a preparation method of an aprepitant emulsion injection.
Background
Aprepitant (Aprepitant), namely Aprepitant and acenidazole, is an off-white to light-yellow crystalThe solid chemical of (1). Chemical name 5- [2(R) - [1(R) - [3, 5-bis (trifluoromethyl) phenyl]Ethoxy radical]-3(S) - (4-fluorophenyl) morpholin-4-ylmethyl]-3, 4-dihydro-2H-1, 2, 4-triazol-3-one of formula C23H21F7N4O3The molecular weight is 534.42700, the water-insoluble acetonitrile-slightly soluble acetonitrile-ethanol soluble glass has a melting point of 75-76 ℃. Aprepitant is used clinically mainly to prevent acute and delayed nausea and vomiting during the primary and repeat treatments of highly emetogenic anti-tumor chemotherapy.
In the prior art, in the aprepitant emulsion injection preparation process, an aprepitant raw material is insoluble in water, an oil-in-water preparation process is adopted, high-speed shearing and high-pressure homogenization are adopted, the high-pressure homogenization pressure is 18000psi, homogenization is carried out for 8 times, and the homogenization process is complex and has more times; and the operation is complicated, and the excessive pressure can cause great loss to equipment. Therefore, there is a need for an improved process for preparing an aprepitant emulsion injection.
Disclosure of Invention
Aiming at the problems, the invention provides a preparation method of aprepitant emulsion injection, which ensures the operability of the preparation process, simplifies the process and reduces the equipment loss.
The invention adopts the following technical scheme:
a preparation method of aprepitant emulsion injection comprises the following steps:
(1) preparing an oil phase: weighing aprepitant, an emulsifier and a cosolvent, stirring and mixing in a water bath at 25-80 ℃, then adding oil for injection, and stirring and mixing in a water bath at 25-80 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing pH regulator, osmotic pressure regulator and water for injection, and stirring and mixing at normal temperature to obtain water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, keeping the temperature at 25-40 ℃, and performing shearing emulsification at the rotating speed of 15000-20000 rpm for 2-8 min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing for 5-6 times at 12000-15000 psi, filtering the fine milk after homogenizing through a microporous filter membrane, filtering and sterilizing, wherein the pH value of the solution is 7.5-8.5, and thus obtaining the aprepitant emulsion injection;
wherein the weight percentage of each component is as follows: 0.2-1.2 wt% of aprepitant, 0.25-0.75 wt% of pH regulator, 3-8 wt% of osmotic pressure regulator, 56-75 wt% of water for injection, 12-15 wt% of emulsifier, 2-5 wt% of cosolvent and 5-15 wt% of oil for injection.
Further, the emulsifier is hydrogenated soybean phospholipid or hydrogenated soybean phosphatidylcholine.
Further, the pH regulator is any one of sodium hydroxide, sodium citrate, sodium dihydrogen phosphate or sodium oleate.
Further, the osmotic pressure regulator is any one of xylitol, sorbitol, mannitol and sucrose.
Furthermore, the cosolvent is any one or more of ethanol, glycerol, propylene glycol and polyethylene glycol.
Furthermore, the oil for injection is any one or more of soybean oil, peanut oil, hydrogenated corn oil, triglyceride, intermediate-linked triglyceride, sesame oil and sunflower seed oil.
Phospholipids are important components of biological membranes, are the basic substances of life, are the active components of all biological cells, and play an important role in cell penetration and metabolism. Hydrogenated lecithin is a stable emulsifier and humectant formed by hydrogenation of lecithin under the action of a catalyst, and the stability and emulsibility of hydrogenated lecithin are improved, so that the hydrogenated lecithin is widely applied to various industries such as food, pharmaceutical industry, cosmetics and the like. The hydrogenated lecithin has strong hydrophilicity and moisture retention, has strong affinity to skin and mucous membrane, and can play a role in moisturizing, emulsifying, dispersing, conditioning the skin and the like when being used in a cosmetic formula. Phosphatidylcholine (1, 2-diacyl-sn-glycerol-3-phosphatidylcholine) is an amphiphilic molecule consisting of a hydrophilic head and a hydrophobic tail, which is a phospholipid with a choline group inserted in the head. Phosphatidylcholine is an important component of biological membranes and can be easily extracted from a variety of sources, such as egg yolk and soy beans.
The invention adopts soybean phospholipid, preferably hydrogenated soybean phospholipid or hydrogenated soybean phosphatidylcholine as an emulsifier to replace the prior animal phospholipid egg yolk lecithin, thereby improving the medication safety.
Further, in the step (3), the fine milk is filtered through a microporous filter membrane, and the fine milk firstly passes through 0.45 μm and then passes through 0.22 μm.
Further, adding the coarse milk obtained in the step (3) into a high-pressure homogenizer, controlling the sample injection temperature to be 10-40 ℃ and controlling the sample outlet temperature to be 40-70 ℃.
According to the preparation method of the aprepitant emulsion injection, the aprepitant emulsion injection with good oxygen resistance and emulsification effect is prepared by controlling the content of the emulsifier, and parameters such as the shearing speed, the homogenizing pressure, the homogenizing temperature and the like in the emulsion preparation process, and meanwhile, the operability is ensured in the preparation process, the process is simplified, and the equipment loss is reduced.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to specific embodiments, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The materials or reagents required in the following examples of the invention were all commercially available from the open, unless otherwise specified, and the high pressure homogenizer equipment manufacturer used was GEA, model NS2006H, maximum pressure 27500 psi.
Example 1
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator sucrose 60g
720g of water for injection
Emulsifier hydrogenated Soybean Phospholipids 156g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 156g of hydrogenated soybean phospholipid and 30g of absolute ethyl alcohol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, sucrose and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 40 deg.C, emulsifying by shearing at 15000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sample injection temperature to be 20 ℃, the homogenizing pressure to be 15000psi, homogenizing for 6 times, controlling the sample outlet temperature to be within 60 ℃, filtering the fine milk after homogenizing through a microporous filter membrane, firstly passing through 0.45 mu m, then passing through 0.22 mu m, filtering and sterilizing, and obtaining the aprepitant emulsion injection with the pH value of the solution of 8.0, wherein the measured particle size is 70nm (the result of the particle size of a reference preparation is 65 nm).
The results are as follows: after the homogenization times reach 6 times, the homogenized grain size can basically reach the target value, and the pH value, the content and related substances meet the requirements.
Example 2
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator sucrose 60g
720g of water for injection
Emulsifier hydrogenated soybean phosphatidylcholine 156g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 156g of hydrogenated soybean phosphatidylcholine and 30g of absolute ethanol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, sucrose and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 40 deg.C, emulsifying by shearing at 15000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sample injection temperature to be 20 ℃, the homogenizing pressure to be 15000psi, homogenizing for 6 times, controlling the sample outlet temperature to be within 60 ℃, filtering the fine milk after homogenizing through a microporous filter membrane, firstly passing through 0.45 mu m, and then passing through 0.22 mu m, filtering and sterilizing, and obtaining the aprepitant emulsion injection with the pH value of 8.0, wherein the measured particle size is 69nm (the result of the particle size of a reference preparation is 65 nm).
The results are as follows: the final grain diameter can basically reach the target value, the homogenizing pressure and homogenizing times are superior to those of the prior art, the equipment loss is low, and the pH value, the content and related substances meet the requirements.
Example 3
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator sucrose 60g
720g of water for injection
Emulsifier hydrogenated soybean phosphatidylcholine 156g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 156g of hydrogenated soybean phosphatidylcholine and 30g of absolute ethanol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, sucrose and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 40 deg.C, emulsifying by shearing at 15000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sample injection temperature to be 30 ℃, the homogenizing pressure to be 15000psi, homogenizing for 6 times, controlling the sample outlet temperature to be within 60 ℃, filtering the fine milk after homogenizing through a microporous filter membrane, firstly passing through 0.45 mu m, then passing through 0.22 mu m, filtering and sterilizing, and obtaining the aprepitant emulsion injection with the pH value of the solution of 8.0, wherein the measured particle size is 65nm (the result of the particle size of a reference preparation is 65 nm).
The results are as follows: the final grain diameter can reach the target value, the homogenizing pressure and homogenizing times are superior to those of the prior art, the equipment loss is low, and the pH value, the content and related substances meet the requirements.
Example 4
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator sucrose 60g
720g of water for injection
Emulsifier hydrogenated soybean phosphatidylcholine 156g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 156g of hydrogenated soybean phosphatidylcholine and 30g of absolute ethanol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, sucrose and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 40 deg.C, emulsifying by shearing at 15000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sampling temperature to be 20-40 ℃ (designing the temperature in a step-type manner, shown in table 1 below), controlling the homogenizing pressure to be 15000psi, homogenizing for 5 times, controlling the sampling temperature to be within 60 ℃, filtering the fine milk after homogenizing through a microporous filter membrane, firstly passing through 0.45 mu m and then passing through 0.22 mu m, filtering and sterilizing, controlling the pH value of the solution to be 8.0, obtaining the aprepitant emulsion injection, and measuring the particle size to be 64nm (the result of the particle size of a reference preparation is 65 nm).
TABLE 1 stepped thermometer
| Number of homogenisations | 1 | 2 | 3 | 4 | 5 | 6 |
| Temperature control | 40℃ | 35℃ | 30℃ | 25℃ | 20℃ | 25℃ |
The results are as follows: the final grain diameter can reach the target value, the homogenization times and the pressure are reduced compared with the prior art, and the content, the pH value and related substances of the sample meet the requirements.
Comparative example 1
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator mannitol 60g
720g of water for injection
Emulsifier soybean lecithin 130g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 130g of soybean phospholipid and 30g of absolute ethyl alcohol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, mannitol and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 25 deg.C, shearing and emulsifying at 15000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sample injection temperature to be 20 ℃, the homogenizing pressure to be 15000psi, homogenizing for 8 times, controlling the sample outlet temperature to be within 60 ℃, filtering the fine milk after homogenizing through a microporous filter membrane, firstly passing through 0.45 mu m, then passing through 0.22 mu m, filtering and sterilizing, and obtaining the aprepitant emulsion injection with the pH value of 7.0, wherein the measured particle size is 101nm (the result of the particle size of a reference preparation is 65 nm).
The results are as follows: after the homogenization times reach 8 times, the final particle size still cannot reach the target value, and the pH value, the content and related substances meet the requirements.
Comparative example 2
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator sucrose 60g
720g of water for injection
Emulsifier soybean lecithin 156g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 156g of soybean phospholipid and 30g of absolute ethyl alcohol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, sucrose and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 25 deg.C, and emulsifying by shearing at 15000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sample injection temperature to be 20 ℃, the homogenizing pressure to be 15000psi, homogenizing for 6 times, controlling the sample outlet temperature to be within 60 ℃, filtering the fine milk after homogenizing through a microporous filter membrane, firstly passing through 0.45 mu m, then passing through 0.22 mu m, filtering and sterilizing, and obtaining the aprepitant emulsion injection with the pH value of 8.0, wherein the measured particle size is 105nm (the result of the particle size of a reference preparation is 65 nm).
The results are as follows: after the homogenization times reach 6 times, the final particle size cannot reach the target value, and the pH value, the content and related substances meet the requirements.
Comparative example 3
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator sucrose 60g
720g of water for injection
Emulsifier soybean lecithin 156g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 156g of soybean phospholipid and 30g of absolute ethyl alcohol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, sucrose and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 25 deg.C, and emulsifying by shearing at 20000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sample injection temperature to be 20 ℃, the homogenizing pressure to be 15000psi, homogenizing for 6 times, controlling the sample outlet temperature to be within 60 ℃, filtering the fine milk after homogenizing through a microporous filter membrane, firstly passing through 0.45 mu m, then passing through 0.22 mu m, filtering and sterilizing, and obtaining the aprepitant emulsion injection with the pH value of the solution being 8.0, wherein the measured particle size is 106nm (the result of the particle size of a reference preparation is 65 nm).
The results are as follows: after the homogenization times reach 6 times, the homogenization grain size is not improved, the final grain size still does not reach the target value, and the pH value, the content and related substances meet the requirements.
Comparative example 4
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator sucrose 60g
720g of water for injection
Emulsifier hydrogenated soybean phosphatidylcholine 156g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 156g of hydrogenated soybean phosphatidylcholine and 30g of absolute ethanol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, sucrose and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 40 deg.C, emulsifying by shearing at 15000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sample injection temperature to be 20 ℃, the homogenizing pressure to be 10000psi, homogenizing for 6 times, controlling the sample outlet temperature to be within 60 ℃, filtering the fine milk after homogenizing through a microporous filter membrane, firstly passing through 0.45 mu m, and then passing through 0.22 mu m, filtering and sterilizing, and obtaining the aprepitant emulsion injection with the pH value of 8.0, wherein the measured particle size is 88nm (the result of the particle size of a reference preparation is 65 nm).
The results are as follows: the homogenizing pressure of the sample is reduced, the target value cannot be reached after the final particle size is homogenized for 6 times, and the pH value, the content and related substances meet the requirements.
Comparative example 5
An aprepitant emulsion injection comprises the following components in percentage by weight:
aprepitant 7.8g
pH adjustor sodium oleate 6g
Osmotic pressure regulator sucrose 60g
720g of water for injection
Emulsifier hydrogenated soybean phosphatidylcholine 156g
Cosolvent Anhydrous ethanol 30g
Soybean oil 102g for injection
The aprepitant emulsion injection of the embodiment is prepared by the following preparation method:
(1) preparing an oil phase: weighing 7.8g of aprepitant, 156g of hydrogenated soybean phosphatidylcholine and 30g of absolute ethanol, stirring and mixing in a water bath at 60 ℃, then adding soybean oil, and stirring and mixing in a water bath at 60 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing sodium oleate, sucrose and water for injection, and stirring and mixing at normal temperature to obtain a water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, maintaining the temperature at 40 deg.C, emulsifying by shearing at 15000rpm for 5min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing under high pressure, controlling the sample injection temperature at 40 deg.C, homogenizing pressure at 15000psi, homogenizing for 4 times, controlling the sample outlet temperature within 70 deg.C, filtering the fine milk with microporous membrane, passing through 0.45 μm and 0.22 μm, filtering, sterilizing, and adjusting pH to 8.0 to obtain aprepitant emulsion injection with particle size of 59nm (reference preparation particle size result of 65 nm).
The results are as follows: the grain size of the sample is obviously reduced, but the sample is homogenized until the later sample has obvious floatage, the demulsification phenomenon occurs, related substances do not meet the requirements, the content is lower, and the pH value meets the requirements.
The main process parameters and performance test results of examples 1-4 and comparative examples 1-5 are shown in Table 2.
Table 2 results of performance testing
As can be seen from the results of examples 1-4 and comparative examples 1-5, the particle size results are substantially unaffected by shear with greater shear rotation. Through the homogeneity, pressure is big more, and the particle size decline effect is more obvious after the homogeneity, and 15000psi contrast 10000psi, pressure is obvious to the particle size influence, through changing the emulsifier kind, trades hydrogenated soybean phosphatidylcholine, and the homogeneous same number of times particle size result obviously improves. The temperature of the sample solution before homogenization has obvious influence on the particle size result, the particle size is obviously reduced when the temperature is higher, but the sample is sensitive to the temperature and emulsion breaking easily occurs when the temperature is too high, so the homogenization temperature needs to be controlled in the preparation process. According to the invention, the use amount of the emulsifier, the type of the emulsifier and the homogenization temperature are improved, so that the operability of the sample solution in the preparation process is ensured, the process is simplified, and the equipment consumption is reduced.
The present invention has been further described with reference to specific embodiments, but it should be understood that the detailed description should not be construed as limiting the spirit and scope of the present invention, and various modifications made to the above-described embodiments by those of ordinary skill in the art after reading this specification are within the scope of the present invention.
Claims (8)
1. A preparation method of aprepitant emulsion injection is characterized by comprising the following steps:
(1) preparing an oil phase: weighing aprepitant, an emulsifier and a cosolvent, stirring and mixing in a water bath at 25-80 ℃, then adding oil for injection, and stirring and mixing in a water bath at 25-80 ℃ to obtain an oil phase;
(2) preparation of an aqueous phase: weighing pH regulator, osmotic pressure regulator and water for injection, and stirring and mixing at normal temperature to obtain water phase;
(3) preparing an emulsion: adding the water phase into the oil phase, keeping the temperature at 25-40 ℃, and performing shearing emulsification at the rotating speed of 15000-20000 rpm for 2-8 min to obtain coarse emulsion; adding the coarse milk into a high-pressure homogenizer, homogenizing for 5-6 times at 12000-15000 psi, filtering and sterilizing the fine milk through a microporous filter membrane after homogenizing, wherein the pH value of the solution is 7.5-8.5, and obtaining the aprepitant emulsion injection;
wherein the weight percentage of each component is as follows: 0.2-1.2 wt% of aprepitant, 0.25-0.75 wt% of pH regulator, 3-8 wt% of osmotic pressure regulator, 56-75 wt% of water for injection, 12-15 wt% of emulsifier, 2-5 wt% of cosolvent and 5-15 wt% of oil for injection.
2. The method of preparing an aprepitant emulsion injection as claimed in claim 1, wherein the emulsifier is hydrogenated soybean phospholipid or hydrogenated soybean phosphatidylcholine.
3. The method for preparing aprepitant emulsion injection according to claim 1, wherein the pH regulator is any one of sodium hydroxide, sodium citrate, sodium dihydrogen phosphate or sodium oleate.
4. The method for preparing aprepitant emulsion injection according to claim 1, wherein the osmotic pressure regulator is any one of xylitol, sorbitol, mannitol and sucrose.
5. The method for preparing aprepitant emulsion injection according to claim 1, wherein the cosolvent is any one or more of ethanol, glycerol, propylene glycol and polyethylene glycol.
6. The method for preparing aprepitant emulsion injection according to claim 1, wherein the oil for injection is any one or more of soybean oil, peanut oil, hydrogenated corn oil, triglyceride, middle-linked triglyceride, sesame oil and sunflower seed oil.
7. The process for preparing an aprepitant emulsion injection according to claim 1, wherein the fine emulsion in step (3) is filtered through a microporous membrane, first through 0.45 μm and then through 0.22 μm.
8. The method for preparing aprepitant emulsion injection according to claim 1, wherein the coarse emulsion in the step (3) is added into a high-pressure homogenizer, the injection temperature is controlled to be 10-40 ℃, and the sampling temperature is controlled to be 40-70 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110018100.7A CN113712915A (en) | 2021-01-07 | 2021-01-07 | Preparation method of aprepitant emulsion injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110018100.7A CN113712915A (en) | 2021-01-07 | 2021-01-07 | Preparation method of aprepitant emulsion injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113712915A true CN113712915A (en) | 2021-11-30 |
Family
ID=78672484
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110018100.7A Pending CN113712915A (en) | 2021-01-07 | 2021-01-07 | Preparation method of aprepitant emulsion injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113712915A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130317016A1 (en) * | 2012-05-24 | 2013-11-28 | Innopharma, Inc. | Aprepitant Injectable Formulations |
| US20160206622A1 (en) * | 2014-09-19 | 2016-07-21 | Heron Therapeutics Inc. | Emulsion formulations of aprepitant |
| CN109010272A (en) * | 2018-09-27 | 2018-12-18 | 北京睿悦生物医药科技有限公司 | Aprepitant emulsion formulation and preparation method thereof |
| CN111388419A (en) * | 2019-01-03 | 2020-07-10 | 齐鲁制药有限公司 | Aprepitant emulsion |
-
2021
- 2021-01-07 CN CN202110018100.7A patent/CN113712915A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130317016A1 (en) * | 2012-05-24 | 2013-11-28 | Innopharma, Inc. | Aprepitant Injectable Formulations |
| US20160206622A1 (en) * | 2014-09-19 | 2016-07-21 | Heron Therapeutics Inc. | Emulsion formulations of aprepitant |
| CN109010272A (en) * | 2018-09-27 | 2018-12-18 | 北京睿悦生物医药科技有限公司 | Aprepitant emulsion formulation and preparation method thereof |
| CN111388419A (en) * | 2019-01-03 | 2020-07-10 | 齐鲁制药有限公司 | Aprepitant emulsion |
Non-Patent Citations (2)
| Title |
|---|
| 中国饮料工业协会编: "《饮料制作工》", 31 January 2010, 中国轻工业出版社 * |
| 姚静编: "《药用辅料应用指南》", 31 August 2011, 中国医药科技出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113521004B (en) | Preparation method of high-load cannabidiol oil-in-water macromolecular particle emulsion | |
| CN101396343B (en) | Paclitaxel submicron emulsion using lipid composite as middle carrier | |
| BR112015008721B1 (en) | emulsifying composition containing phospholipid, water-in-oil emulsion, countercurrent extraction process and use of said emulsifier | |
| CN113845677B (en) | Emulsion film and preparation method thereof | |
| Chevalier et al. | Role of aqueous phase composition and hydrophilic emulsifier type on the stability of W/O/W emulsions | |
| CN113876658B (en) | Oil-in-water emulsion composition and method for producing same | |
| CN113712915A (en) | Preparation method of aprepitant emulsion injection | |
| CN113952253B (en) | Composition for improving stability of cosmetics, cosmetics containing composition and preparation method of composition | |
| JP4397906B2 (en) | Fresh cream manufacturing method | |
| CN104490780B (en) | Preparation method of propofol fat emulsion injection | |
| Hu et al. | Recovered Camellia oleifera lecithin by acid and enzymatic oil‐degumming: chemical composition and emulsifying properties | |
| CN116392411A (en) | Bionic fetal fat, preparation method thereof and skin care product application | |
| CN113730351B (en) | High-stability emulsion with high load of cannabidiol and preparation method thereof | |
| CN114259467B (en) | Multiple emulsion based on modified egg white protein stabilization | |
| CN110368362B (en) | Preparation method of phosphatidylserine emulsion | |
| CN113083173B (en) | Water-in-oil Pickering emulsion gel and preparation method thereof | |
| Koubaa et al. | Multiple emulsions | |
| CN117821157B (en) | Preparation method of soybean oil liposome using flavone and obtained product | |
| KR102583074B1 (en) | Water-soluble emulsion composition comprising natural polyphenolic compound | |
| CN110623856A (en) | Lecithin emulsion without emulsifier and preparation method thereof | |
| CN116426038B (en) | Synergistically stable starch-based pickering emulsion and application thereof in medicine and food fields | |
| CN117427021B (en) | Plant composition with external oil balancing function, preparation method and application | |
| CN116077421B (en) | Tacrolimus ointment and preparation method thereof | |
| US20240049759A1 (en) | Pea protein emulsifier | |
| KR20220085855A (en) | Water-soluble emulsion composition comprising ecdysteroid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211130 |