CN113350270A - Combination of aprepitant injection and container - Google Patents

Combination of aprepitant injection and container Download PDF

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Publication number
CN113350270A
CN113350270A CN202010140469.0A CN202010140469A CN113350270A CN 113350270 A CN113350270 A CN 113350270A CN 202010140469 A CN202010140469 A CN 202010140469A CN 113350270 A CN113350270 A CN 113350270A
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aprepitant
injection
container
glass
combination
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肖贵臣
林静文
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Beijing Landan Pharmaceutical Technology Co ltd
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Beijing Landan Pharmaceutical Technology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/1468—Containers characterised by specific material properties
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • 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

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  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides a stable aprepitant injection and container combination. Wherein, the aprepitant injection comprises aprepitant, an emulsifier, a coemulsifier, oil for injection and water for injection; the material of the container is glass. Wherein the glass comprises: SiO 22 70‑80%，B2O3 5‑20%，Al2O31-10% of alkali metal oxide; further, the glass comprises: SiO 22 70‑80%，B2O3 7.0‑11.5%，Al2O33-7% of alkali metal oxide and 3-10% of alkali metal oxide. The stable aprepitant injection and the container provided by the invention can avoid the precipitation of aprepitant crystals in the aprepitant injection and can reduce the generation of lysophosphatidylcholine which is a degradation product of phospholipid.

Description

Combination of aprepitant injection and container
Technical Field
The invention relates to the technical field of medicines, in particular to a stable combination of aprepitant injection and a container.
Background
Nausea and vomiting are among the more common adverse effects of current malignant patients after chemotherapy, and can be classified into acute, delayed and full-term according to the occurrence time. Untimely control of the symptoms will lead to a reduction in the quality of life of the patient and reduced treatment compliance. The NK-1 inhibitor is widely applied to the treatment of nausea and vomiting in chemotherapy at present, and has a remarkable curative effect. Aprepitant is a representative drug in NK-1 inhibitors, blocks the action point of substance P by combining with NK-1 receptors, can occupy the NK-1 receptors in the brain through a blood brain barrier, has high selectivity and high affinity, has low affinity to NK-2 and NK-3 receptors, and has better nausea and vomiting reducing effect than other drugs.
Aprepitant oral preparation is approved by FDA in the United states and marketed in 2003, but due to poor water solubility and membrane permeability of aprepitant, the aprepitant oral preparation has poor oral absorption and low bioavailability. To ameliorate the deficiencies of oral formulations, Heron treatment developed aprepitant as a fat emulsion injection and obtained FDA approval for marketing in 2017.
Generally, the container that is in direct contact with the drug must be pharmaceutically acceptable. Packaging materials and containers that directly contact the pharmaceutical product are an integral part of the pharmaceutical product, along with the entire process of production, distribution and use of the pharmaceutical product. For injection, the drug packaging material may be degraded, the degraded substance may react with the drug components, and the ingredients in the drug composition may be adsorbed too much in the packaging material, thereby affecting the stability of the drug. In addition, the long-term storage of the drug, the change of external environment such as light and temperature, may also cause the degradation of the components in the packaging material and the adsorption of the components in the drug in the packaging material. No matter what kind of changes, the stability of the preparation is possibly reduced, and potential safety hazards are brought to clinical use.
The aprepitant injection is a fat emulsion injection, the physical stability of the preparation of the aprepitant injection needs to be considered during the storage period of the aprepitant injection, and the fat emulsion injection belongs to a thermodynamically unstable system, so that emulsion droplets can be aggregated in the storage process, and finally, aprepitant crystals are precipitated. In addition, in the preparation process of the fat emulsion, phospholipid is needed to be used as an emulsifier, lysophosphatidylcholine is a main degradation product of the phospholipid, is a substance with strong surface activity, and can cause various biological effects, such as induction of cell shape change, promotion of cell fusion, hemolysis, change of cell permeability and the like. Therefore, formulations containing phospholipids require strict control of the lysophosphatidylcholine content. In the aprepitant injection emulsion system, the dosage of phospholipid is far higher than that of common fat emulsion injection, and the dosage of phospholipid is more than ten times of that of the common fat emulsion injection, so the content of lysophosphatidylcholine, a degradation product of phospholipid, is strictly controlled.
In the prior art, the selection of packing materials made of different materials is not considered to possibly influence the physical stability of aprepitant and the degradation of important auxiliary material phospholipid, so that the technical problem solved by the invention is to provide a stable combination of an aprepitant injection and a container, the separation of aprepitant crystals in the aprepitant injection can be avoided, and the generation of lysophosphatidylcholine as a degradation product of phospholipid can be reduced.
Disclosure of Invention
In order to achieve the above purpose, the invention provides a combination of an aprepitant drug injection and a container, wherein the aprepitant drug injection comprises aprepitant, an emulsifier, a co-emulsifier, oil for injection and water for injection; the container is made of glass.
The glass comprises: SiO 22 70-80％，B2O3 5-20％，Al2O31-10% of alkali metal oxide.
Preferably, the glass comprises: b is2O3 7.0-11.5％，Al2O33-7% of alkali metal oxide and 3-10% of alkali metal oxide.
The alkali metal oxide is Na2O、K2O and Li2O。
Such emulsifiers include, but are not limited to, phospholipids; the phospholipid is selected from phospholipids of natural origin, such as phospholipids extracted from egg yolk or soybean. Or selected from phospholipids obtained by synthetic or semi-synthetic means or combinations thereof.
The oil for injection includes, but is not limited to, soybean oil, corn oil, peanut oil, coconut oil, cottonseed oil, olive oil, castor oil, fish oil, medium-chain monoglyceride, medium-chain diglyceride, medium-chain triglyceride, ethyl oleate, acetylated monoglyceride, propylene glycol diester, glyceryl linoleate, macrogol lauric glyceride and the like. Hydrogenated and/or partially hydrogenated versions of the above-described oil for injection may also be used.
The coemulsifier includes, but is not limited to, short chain alcohols of 1 to 6 carbons, preferably ethanol.
The aprepitant drug injection can also contain a tonicity adjusting agent and a pH adjusting agent. The tonicity modifier includes, but is not limited to sucrose, mannitol, glycerol, glucose or a combination thereof, preferably the tonicity modifier is sucrose. The pH modifier includes, but is not limited to, sodium oleate, sodium hydroxide, potassium hydroxide, tromethamine, sodium carbonate, sodium linoleate, etc., and preferably, the pH modifier is sodium oleate.
The aprepitant injection can further comprise a buffer solution, and suitable buffer solutions include but are not limited to phosphate buffer solution, citrate buffer solution, carbonate buffer solution, succinate buffer solution, maleate buffer solution, Tris buffer solution and borate buffer solution.
The present application provides an exemplary method for preparing aprepitant, comprising the steps of:
(1) taking aprepitant, egg yolk lecithin Lipoid E80 and ethanol, and heating to dissolve the aprepitant and the egg yolk lecithin Lipoid E80;
(2) adding the mixture obtained in the step (1) into soybean oil, and heating and dissolving to obtain an oil phase;
(3) adding sucrose and sodium oleate into water for injection, and stirring uniformly to obtain a water phase;
(4) adding the oil phase in the step (2) into the water phase in the step (3), shearing at high speed to obtain primary emulsion, and adding sodium oleate to adjust the pH value to 7.0-9.0;
(5) homogenizing the primary emulsion in the step (4) under high pressure;
(6) and (5) sterilizing and encapsulating.
The sterilization according to the invention can be carried out by filtration sterilization or autoclaving sterilization.
The container of the present invention also has a closure means for storing the pharmaceutical composition.
According to one aspect of the object of the invention, the combination of the aprepitant injection and the container provided by the invention can avoid the generation of aprepitant crystals in the aprepitant injection during storage, and obtain the aprepitant injection with more stable physical properties.
According to another aspect of the object of the invention, the combination of the aprepitant injection and the container provided by the invention can reduce the generation of lysophosphatidylcholine which is a degradation product of phospholipid, and obtain the aprepitant injection which is safer in use.
The container has a volume of 10ml to 20ml, and alternative volumes may be any or any optional volume range within this volume range, for example 10ml to 20ml, 11ml to 19ml, 12ml to 18ml, 13ml to 17ml, 14ml to 16 ml. Wherein the concentration of aprepitant is 5-15 mg/ml, and preferably 7-8 mg/ml. Wherein, the preferable aprepitant injection comprises 13-15 wt/wt% of emulsifier phospholipid, 1-4 wt/wt% of coemulsifier, 0.3-0.7 wt/wt% of pH regulator, 9-10 wt/wt% of oil for injection and 100 wt/wt% of water for injection.
Detailed Description
Example 1
Prescription:
Figure BDA0002398905760000041
the preparation method comprises the following steps:
(1) taking aprepitant, egg yolk lecithin (Lipoid E80) and ethanol, and heating to dissolve the aprepitant, the egg yolk lecithin and the ethanol;
(2) adding the mixture obtained in the step (1) into soybean oil, and heating and dissolving to obtain an oil phase;
(3) adding sucrose and sodium oleate into water for injection, and stirring uniformly to obtain a water phase;
(4) adding the oil phase in the step (2) into the water phase in the step (3), shearing at high speed to obtain primary emulsion, and adding sodium oleate to adjust the pH value to 7.0-9.0;
(5) homogenizing the primary emulsion in the step (4) under high pressure;
(6) filtering for sterilization, and respectively filling the prepared aprepitant injection into containers of 20ml in specification, wherein the containers are made of glass type 1, glass type 2, glass type 3, glass type 4 and glass type 5.
Example 2
Prescription:
Figure BDA0002398905760000042
the preparation method comprises the following steps:
(1) taking aprepitant, egg yolk lecithin (Lipoid E80) and ethanol, and heating to dissolve the aprepitant, the egg yolk lecithin and the ethanol;
(2) adding the mixture obtained in the step (1) into soybean oil, and heating and dissolving to obtain an oil phase;
(3) adding sucrose and sodium oleate into water for injection, and stirring uniformly to obtain a water phase;
(4) adding the oil phase in the step (2) into the water phase in the step (3), shearing at high speed to obtain primary emulsion, and adding sodium oleate to adjust the pH value to 7.0-9.0;
(5) homogenizing the primary emulsion in the step (4) under high pressure;
(6) filtering for sterilization, and respectively filling the prepared aprepitant injection into containers of 20ml in specification, wherein the containers are made of glass type 1, glass type 2, glass type 3, glass type 4 and glass type 5.
Example 3
Prescription:
Figure BDA0002398905760000051
the preparation method comprises the following steps:
(1) taking aprepitant, egg yolk lecithin (Lipoid E80) and ethanol, and heating to dissolve the aprepitant, the egg yolk lecithin and the ethanol;
(2) adding the mixture obtained in the step (1) into soybean oil, and heating and dissolving to obtain an oil phase;
(3) adding sucrose and sodium oleate into water for injection, and stirring uniformly to obtain a water phase;
(4) adding the oil phase in the step (2) into the water phase in the step (3), shearing at high speed to obtain primary emulsion, and adding sodium oleate to adjust the pH value to 7.0-9.0;
(5) homogenizing the primary emulsion in the step (4) under high pressure;
(6) filtering for sterilization, and respectively filling the prepared aprepitant injection into containers of 20ml in specification, wherein the containers are made of glass type 1, glass type 2, glass type 3, glass type 4 and glass type 5.
The components of the glass materials of different types of glass bottles used by the invention are as follows:
glass type 1: SiO 22 75.3％，B2O3 3.5％，Al2O35.3 percent and 6.5 percent of alkali metal oxide.
Glass type 2: SiO 22 74.4％，B2O36.4％，Al2O35.7 percent and 6.6 percent of alkali metal oxide.
Glass type 3: SiO 22 76.2％，B2O3 7.0％，Al2O36.1 percent and 6.1 percent of alkali metal oxide.
Glass type 4: SiO 22 75.8％，B2O3 11.3％，Al2O36.2 percent and 6.3 percent of alkali metal oxide.
Glass type 5: SiO 22 75.1％，B2O37.1％，Al2O35.7 percent and 12.3 percent of alkali metal oxide.
Test example 1
The samples of examples 1 to 3 packed in different glass containers were placed at 2 to 8 ℃ and sampled at 0 month, 3 months, 6 months and 12 months, respectively. The emulsion was examined microscopically for the presence of aprepitant crystals. The results are shown in table 1 below:
TABLE 1 results of microscopic observation of samples stored at 2-8 deg.C for 12 months
Figure BDA0002398905760000061
The samples of examples 1 to 3 filled with glass type 2, glass type 3 and glass type 4 glass bottles in the above experiment were stored at 2 to 8 ℃ and found that a small amount of aprepitant crystals were found in the aprepitant injection packed in the glass type 2 glass bottle at 14 months. The aprepitant injections stored in glass bottles in glass model 3 and glass model 4 had no aprepitant crystals at 15 months.
The samples of examples 1 to 3 packed in different glass containers were allowed to stand at 25 ℃ for 2 months, and were sampled at each time point of 0 month, 1 month, and 2 months, respectively. The emulsion was examined microscopically for the presence of aprepitant crystals. The results are shown in table 2 below:
TABLE 2 results of microscopic observation of samples stored at 25 ℃ for 2 months
Figure BDA0002398905760000071
According to the test results, the aprepitant injection can be stored in a preferable glass container of the invention, the aprepitant crystal is not generated for at least 15 months at the temperature of 2-8 ℃, and the aprepitant injection with better physical stability is obtained. At 25 ℃, aprepitant crystals can be prevented from being generated for at least 2 months, and an aprepitant injection with good physical stability is obtained.
It is presumed that the reason why the change in physical stability is caused is that the different glass materials adsorb the emulsion to different extents to cause aggregation and breakage of the emulsion to different extents.
Test example 2 detection of lysophosphatidylcholine content in aprepitant injection.
The samples of examples 1 to 3 packed in different glass containers were allowed to stand at 25 ℃ for 60 days, and the contents of lysophosphatidylcholine in the samples were measured by sampling at 0 day, 30 days and 60 days, respectively.
The detection method of lysophosphatidylcholine is as follows:
precisely measuring 1ml of the product, placing the product in a 50ml measuring flask, adding isopropanol-n-heptane-methanol (5:2:3) to dilute to scale, and shaking up to obtain a test solution. Taking a proper amount of lysophosphatidylcholine reference substance, precisely weighing, adding isopropanol-n-heptane-methanol (5:2:3) to dissolve, and quantitatively diluting to obtain a solution containing 0.025, 0.05, 0.1, 0.15 and 0.2mg of lysophosphatidylcholine per 1ml as a reference substance solution. Performing high performance liquid chromatography (China pharmacopoeia 2015 edition general rule 0512) test, using silica gel as filler (250mm × 4.6mm, 5 μm); taking n-hexane-isopropanol-water (600:800:75, v/v) as a mobile phase A, and taking n-hexane-isopropanol-methanol-water (45:100:300:25, v/v) as a mobile phase B; flow rate was 1.5ml per minute; gradient elution was performed as follows. The column temperature was 40 ℃ and the detector was an evaporative light scattering detector. Precisely measuring each 50 μ l of the above reference solution, injecting into liquid chromatograph, and recording chromatogram. Selecting 3 reference substance solutions with adjacent concentrations according to the content of lysophosphatidylcholine in the test sample, and calculating a regression equation by using the logarithm value of the concentration of the reference substance solution and the corresponding logarithm value of the peak area. And precisely measuring 50 mu l of test solution, injecting the test solution into a liquid chromatograph, recording a chromatogram, and calculating the content of lysophosphatidylcholine in the test solution by using a regression equation.
Figure BDA0002398905760000081
The results are shown in table 3 below:
TABLE 3 detection results of lysophosphatidylcholine content
Figure BDA0002398905760000091
According to the above test results, it can be found that the samples of examples 1 to 3 filled with glass type 1 and glass type 5 bottles have a significantly increased content of lysophosphatidylcholine at 25 ℃. The content of lysophosphatidylcholine in the samples packaged by the glass type 2/3/4 glass bottles is lower, wherein the content of lysophosphatidylcholine in the samples packaged by the glass type 3 and 4 glass bottles is obviously lower. Therefore, the aprepitant injection with lower content of lysophosphatidylcholine and higher safety can be obtained by combining the aprepitant injection and the glass packaging material.
Example 4
Prescription:
Figure BDA0002398905760000092
Figure BDA0002398905760000101
the preparation method comprises the following steps:
(1) taking aprepitant, egg yolk lecithin (Lipoid E80) and ethanol, and heating to dissolve the aprepitant, the egg yolk lecithin and the ethanol;
(2) adding the mixture obtained in the step (1) into soybean oil, and heating and dissolving to obtain an oil phase;
(3) adding sucrose and sodium oleate into water for injection, and stirring uniformly to obtain a water phase;
(4) adding the oil phase in the step (2) into the water phase in the step (3), shearing at high speed to obtain primary emulsion, and adding sodium oleate to adjust the pH value to 7.0-9.0;
(5) homogenizing the primary emulsion in the step (4) under high pressure;
(6) sterilizing, filtering, and filling the obtained aprepitant injection into containers of 10ml, wherein the containers are respectively made of glass type 1, glass type 2, glass type 3, glass type 4 and glass type 5.
Example 5
Prescription:
Figure BDA0002398905760000102
the preparation method comprises the following steps:
(1) taking aprepitant, egg yolk lecithin and ethanol, and heating to dissolve the aprepitant, the egg yolk lecithin and the ethanol;
(2) adding the mixture obtained in the step (1) into soybean oil, and heating and dissolving to obtain an oil phase;
(3) adding sucrose and sodium oleate into water for injection, and stirring uniformly to obtain a water phase;
(4) adding the oil phase in the step (2) into the water phase in the step (3), shearing at high speed to obtain primary emulsion, and adding sodium oleate to adjust the pH value to 7.0-9.0;
(5) homogenizing the primary emulsion in the step (4) under high pressure;
(6) sterilizing, filtering, and filling the obtained aprepitant injection into containers of 10ml, wherein the containers are respectively made of glass type 1, glass type 2, glass type 3, glass type 4 and glass type 5.
Test example 3
The samples of examples 4 to 5 packed in different glass containers were placed at 25 ℃ and sampled at 0 day, 10 days, 30 days, and 45 days, respectively. The emulsion was examined microscopically for the presence of aprepitant crystals. The results are shown in table 4 below:
TABLE 4 results of observation under microscope of samples after leaving at 25 deg.C
Figure BDA0002398905760000111
The samples of examples 4 to 5 filled with glass type 2, glass type 3 and glass type 4 glass bottles in the above experiment were stored at 25 ℃ and it was found that at 60 days, aprepitant crystals were observed under a microscope in aprepitant injection packed in a glass type 2 glass bottle. The aprepitant injections stored in glass bottles in glass model 3 and glass model 4 had no aprepitant crystals at 60 days.
The content of lysophosphatidylcholine in the samples of examples 4 to 5, which were stored at 25 ℃ using different glass packs, was measured, and it was found that the content of lysophosphatidylcholine was significantly lower in the samples packed with glass type 3 and glass type 4 under the same conditions.
The foregoing has described in detail preferred embodiments of the present invention. However, the present invention is not limited to the specific details in the above-described embodiments, and various simple modifications can be made to the technical solution of the present invention within the technical spirit of the present invention. These simple variants are within the scope of protection of the present invention.
It should be noted that the respective technical features described in the above embodiments may be combined in any manner without contradiction. The invention is not described in detail in order to avoid unnecessary repetition.
In addition, any combination of the various embodiments of the present invention is also possible, and the same should be considered as the disclosure of the present invention as long as the idea of the present invention is not violated.

Claims (10)

1. The combination of an aprepitant injection and a container is characterized in that the aprepitant injection comprises aprepitant, an emulsifier, a co-emulsifier, oil for injection and water for injection; the container is made of glass.
2. The aprepitant injection in combination with a container of claim 1 wherein the glass comprises: SiO 22 70-80%，B2O3 5-20%，Al2O31-10% of alkali metal oxide.
3. The aprepitant injection in combination with a container of claim 2 wherein the glass comprises: SiO 22 70-80%，B2O3 7.0-11.5%，Al2O33-7% of alkali metal oxide and 3-10% of alkali metal oxide.
4. An aprepitant injection liquid and container combination as claimed in any one of claims 2 to 3 wherein the alkali metal oxide is Na2O、K2O and Li2O。
5. The aprepitant injection in combination with a container of claim 1 wherein the emulsifier is a phospholipid.
6. The aprepitant injection in combination with a container of claim 1 wherein the co-emulsifier is a short chain alcohol, preferably ethanol.
7. The aprepitant injection in combination with a container of claim 1, wherein the aprepitant injection further comprises a pH adjusting agent and a tonicity adjusting agent.
8. The aprepitant injection in combination with a container of claim 1, wherein the aprepitant injection further comprises a buffer.
9. The aprepitant injection in combination with a container according to claim 1 wherein the container has a closure means for storing a pharmaceutical composition.
10. The aprepitant injection in combination with a container according to claim 1 wherein the container has a volume of 10ml to 20 ml; the concentration of aprepitant is 5-15 mg/ml, and preferably 7-8 mg/ml.
CN202010140469.0A 2020-03-03 2020-03-03 Combination of aprepitant injection and container Pending CN113350270A (en)

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