Liquid pharmaceutical composition containing fosaprepitant, preparation method thereof and application

Abstract

A liquid pharmaceutical composition containing fosaprepitant, its preparation method and application. A liquid pharmaceutical composition containing fosaprepitant, which comprises: a pharmaceutically active ingredient, a chelating agent, a stabilizer and a pH regulator, wherein the pharmaceutically active ingredient is fosaprepitant, its pharmaceutically acceptable salt, hydrate or solvate; the liquid pharmaceutical composition containing fosaprepitant does not contain polysorbate 80 and lactose. The liquid pharmaceutical composition containing fosaprepitant has the advantages of simple preparation process, good physical and chemical stability, convenient clinical use without reconstitution, low risk of microbial contamination during the preparation process, and being suitable for industrial production, etc.

Description

[0001] This application claims the priority benefit of a prior application filed with the China National Intellectual Property Administration on November 2, 2021, with the patent application number 202111286261.0 and the invention title "Liquid Pharmaceutical Composition Containing Fosaprepitant, Its Preparation Method and Application". The full text of the prior application is incorporated into this application by reference. Technical Field

[0002] The present invention relates to a liquid pharmaceutical composition containing fosaprepitant, its preparation method and application. Background Art

[0003] Nausea and vomiting (CINV) are common adverse reactions during or after cancer chemotherapy. This syndrome can have a significant impact on the patient's functional status and quality of life, and patients may postpone chemotherapy plans or even refuse treatment due to CINV. The emetic response may be acute (within 24 hours after chemotherapy) or delayed (after 24 hours after chemotherapy). The underlying mechanisms of acute and delayed emesis are considered to be different. Current therapies include 5-hydroxytryptamine HT3 receptor antagonists such as ondansetron, tropisetron and granisetron, as well as the dopamine receptor antagonist metoclopramide. These compounds have sufficient effects on acute CINV, but have no effect on delayed CINV.

[0004] Fosaprepitant dimeglumine is an active pharmaceutical ingredient for injection marketed by Merck Sharp & Dohme Corp. Fosaprepitant is a water-soluble phosphorylated prodrug of aprepitant, which is rapidly converted to aprepitant in vivo after intravenous (IV) administration. Aprepitant is an antagonist of the human substance P neurokinin 1 (NK1) receptor. Therefore, the pharmacological activity and antiemetic effect of fosaprepitant reflect those of its parent compound aprepitant.

[0005] Due to the hydrolysis of fosaprepitant (or its salt) into water-insoluble aprepitant in an aqueous environment and at high temperatures, even in the solid state, such as in freeze-dried preparations, when the moisture is not well controlled, fosaprepitant can still hydrolyze and degrade to form aprepitant. Therefore, in order to prevent crystallization and precipitation caused by the hydrolysis degradation of potential fosaprepitant to form aprepitant during the product shelf life, the formulation of fosaprepitant meglumine for injection contains polysorbate 80 as a solubilizer for aprepitant; and the moisture control is very strict.

[0006] However, polysorbate 80 (a non-ionic surfactant often used as a solubilizer for poorly soluble products) can cause various adverse reactions, including severe infusion site reactions and potentially life-threatening allergic reactions; lactose, as a lyoprotectant, may have protein residues in the excipients, leading to a relatively high risk of allergies; the control of moisture in the lyophilized product is demanding, resulting in difficult lyophilization processes and high energy consumption.

[0007] The currently published patent documents are basically about the lyophilization process of fosaprepitant. However, the lyophilization process is time-consuming, energy-consuming, and costly, and the control of moisture for this product is extremely strict; moreover, when used clinically, it needs to be reconstituted first, which increases the operation and there is a risk of bacterial contamination.

[0008] Therefore, finding a fosaprepitant dosage form with good physical and chemical stability, simple preparation process, and suitable for industrial production is a technical problem that urgently needs to be solved at present. Summary of the Invention

[0009] The present invention provides a liquid pharmaceutical composition containing fosaprepitant, which comprises: a pharmaceutically active ingredient, a chelating agent, a stabilizer, and a pH regulator. The pharmaceutically active ingredient is fosaprepitant, its pharmaceutically acceptable salt, hydrate, or solvate; the liquid pharmaceutical composition containing fosaprepitant does not contain polysorbate 80 and lactose.

[0010] According to an embodiment of the present invention, the pharmaceutically acceptable salt of fosaprepitant is preferably fosaprepitant meglumine.

[0011] According to an embodiment of the present invention, the drug loading amount of the pharmaceutically active ingredient is 1 mg / ml to 400 mg / ml, further preferably 3 mg / ml to 200 mg / ml. The drug loading amount refers to the ratio of the mass of fosaprepitant to the volume of the liquid pharmaceutical composition containing fosaprepitant.

[0012] According to an embodiment of the present invention, the chelating agent is selected from one or more of citric acid, tartaric acid, gluconic acid, and ethylenediaminetetraacetic acid or its pharmaceutically acceptable salts; in one embodiment, the chelating agent is disodium ethylenediaminetetraacetate. Preferably, the mass ratio of the chelating agent to the pharmaceutically active ingredient is 1:8 to 1:56 (w / w), such as 1:50, 1:45, 1:40, 1:30, and the mass of the pharmaceutically active ingredient is calculated based on the mass of fosaprepitant.

[0013] According to an embodiment of the present invention, the stabilizer is selected from one or more of oleic acid, sodium oleate, acetate, carbonate, phosphate, citrate, tartrate, and borate, preferably one or more of oleic acid, sodium oleate, and phosphate.

[0014] In some embodiments, the stabilizer is selected from oleic acid and / or sodium oleate.

[0015] In some embodiments, the stabilizer is selected from one or more of acetate, carbonate, phosphate, citrate, tartrate, and borate, preferably phosphate.

[0016] In some embodiments, the stabilizer is selected from a mixture of oleic acid and phosphate, or a mixture of sodium oleate and phosphate.

[0017] In some embodiments, the phosphate may be selected from one or both of disodium hydrogen phosphate and sodium dihydrogen phosphate, preferably disodium hydrogen phosphate.

[0018] According to an embodiment of the present invention, the pH regulator is selected from one or more of hydrochloric acid, sulfuric acid, phosphoric acid, glutamic acid, aspartic acid, sodium hydroxide, tromethamine, arginine, lysine, histidine, and meglumine.

[0019] According to an embodiment of the present invention, the pH value range of the fosaprepitant-containing liquid pharmaceutical composition is 7.0 to 10.0, more preferably 7.5 to 9.5, such as 8.0, 8.5, 8.8, 9.0.

[0020] In some embodiments, the amount of the stabilizer is 0.5 to 20% (W / V), for example 1 to 20% (W / V), such as 1 to 10% (W / V), and the amount refers to the percentage of the mass (g) of the stabilizer to the total volume (mL) of the fosaprepitant-containing liquid pharmaceutical composition;

[0021] In some embodiments, when the stabilizer is selected from oleic acid and / or sodium oleate, the amount of oleic acid and / or sodium oleate is preferably 0.5 to 10% (W / V); in some embodiments, the amount of oleic acid and / or sodium oleate is 1 to 5% (W / V), such as 1.44% (W / V), 2% (W / V), 2.11% (W / V), 2.88% (W / V), 4.23% (W / V);

[0022] In some embodiments, when the stabilizer is selected from one or more of acetate, carbonate, phosphate, citrate, tartrate, and borate, the amount of one or more of acetate, carbonate, phosphate, citrate, tartrate, and borate is preferably 0.5 to 10% (W / V); in some embodiments, the amount of one or more of acetate, carbonate, phosphate, citrate, tartrate, and borate is 1 to 5% (W / V), such as 1.6% (W / V), 2% (W / V), 3% (W / V), 4% (W / V).

[0023] According to an embodiment of the present invention, the fosaprepitant liquid pharmaceutical composition may be selected from any one of the following formulations:

[0024] Formulation 1: 12.265% (W / V) fosaprepitant dimeglumine, 0.27% (W / V) EDTA-2Na, 1.44% (W / V) oleic acid, and the pH is adjusted with 0.1M / 1.0M NaOH, pH 8.5 - 9.5.

[0025] Formulation 2: 12.265% (W / V) fosaprepitant dimeglumine, 0.27% (W / V) EDTA-2Na, 2.88% (W / V) oleic acid, 3% (W / V) disodium hydrogen phosphate, and the pH is adjusted with 1.0M NaOH, pH 8.0 - 9.5.

[0026] The present invention also provides the use of the fosaprepitant-containing liquid pharmaceutical composition in the preparation of a pharmaceutical preparation.

[0027] The present invention also provides a pharmaceutical preparation containing the above-mentioned fosaprepitant-containing liquid pharmaceutical composition.

[0028] According to an embodiment of the present invention, the administration method of the pharmaceutical preparation is parenteral administration, such as injection administration.

[0029] According to an embodiment of the present invention, the pharmaceutical preparation may be an injection; intravenous infusion can be used clinically. If intravenous infusion is used, it can be diluted with physiological saline. The preferred dilution factor of the physiological saline is 25 to 500 times, and more preferably 50 to 125 times.

[0030] According to an embodiment of the present invention, the pharmaceutical preparation may include packaging materials, and the packaging materials may be plastic, borosilicate glass or coated borosilicate glass. The plastic is selected from one or more of PVC (polyvinyl chloride), PP (polypropylene), PE (polyethylene), COP (cycloolefin polymer), COC (cycloolefin copolymer) and Aclar (a copolymer and homopolymer of chlorotrifluoroethylene).

[0031] According to an embodiment of the present invention, the pharmaceutical preparation is used to treat diseases caused by the NK-1 receptor, and the diseases caused by the NK-1 receptor include but are not limited to vomiting.

[0032] The present invention also provides the use of the fosaprepitant-containing liquid pharmaceutical composition in the preparation of an NK-1 receptor antagonist.

[0033] The present invention also provides a method for treating diseases caused by NK-1 receptor, which is to administer an effective dose of the liquid pharmaceutical composition containing fosaprepitant or the pharmaceutical preparation to a patient in need. The diseases caused by NK-1 receptor include but are not limited to vomiting.

[0034] The beneficial effects of the present invention are as follows: The liquid pharmaceutical composition containing fosaprepitant of the present invention has the advantages of simple preparation process, good physical and chemical stability, convenient clinical use without reconstitution, low risk of microbial contamination during the preparation process, and suitability for industrial production.

[0035] It solves the defects in the prior art that the freeze-drying process of fosaprepitant is time-consuming, energy-consuming, costly, very strict in water control, and needs to be reconstituted before clinical use, which increases the operation and has a risk of bacterial contamination.

[0036] Term Definitions and Explanations

[0037] Unless otherwise specified, the term definitions recorded in the specification and claims of the present application, including their definitions as examples, exemplary definitions, preferred definitions, specific definitions in the embodiments, etc., can be combined and combined arbitrarily with each other. Such combinations and combinations should fall within the scope recorded in the specification of the present application.

[0038] The above “%(W / V)” refers to the percentage of the mass (g) of this component to the total volume (mL) of the liquid pharmaceutical composition containing fosaprepitant.

[0039] The term “therapeutically effective amount” refers to the amount of the active ingredient of the drug of the present invention sufficient to achieve the intended application (including but not limited to the treatment of diseases as defined below). The therapeutically effective amount can vary depending on the following factors: the intended application (in vitro or in vivo), or the subject and disease condition being treated, such as the weight and age of the subject, the severity of the disease condition, and the mode of administration, etc., which can be easily determined by those of ordinary skill in the art. The specific dose will vary depending on the following factors: the specific active ingredient selected, the dosing regimen followed, whether administered in combination with other compounds, the timing of administration, the tissue to which it is administered, and the physical delivery system carried. Detailed Embodiments

[0040] The technical solutions of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only for illustrative and explanatory purposes of the present invention, and should not be construed as limiting the protection scope of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0041] Unless otherwise specified, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods. For the experimental methods without specific conditions described in the following examples, they are carried out according to conventional methods and conditions, or selected according to the product instructions.

[0042] Example 1

[0043] Table 1 Prescription of Example 1

[0044] Name Prescription 1 Prescription 2 Prescription 3 Fosaprepitant dimeglumine mg 245.3 245.3 245.3 EDTA-2Na mg 5.4 5.4 5.4 Oleic acid mg 28.8 28.8 28.8 0.1mol / L NaOH ml 1 1 1 pH regulator qs pH 8.79 qs pH 9.00 qs pH 9.29 Volume made up to ml 2 2 2

[0045] An exemplary preparation method for forming a stable fosaprepitant composition of Formulations 1 - 3 is described herein: After adding the prescribed amounts of EDTA-2Na, oleic acid, and 0.1M sodium hydroxide solution, according to the dissolution of the solution, 1M sodium hydroxide solution is added until it is stirred and dissolved, and then API (fosaprepitant dimeglumine) is added. The target pH value is adjusted with 1M NaOH / 20% HCl dilution solution. The prepared liquid medicine is pre-filtered with a 0.45μm filter element, filled and sealed to obtain the final product.

[0046] Stability of the simulated stability sample: It is placed at 60°C for 24 h and then temporarily stored in a refrigerator at 2 - 8°C. Observe the appearance of the stability sample before and after refrigeration, and detect the related substances after refrigeration. The test results are shown in Table 2.

[0047] Stability of the sample for simulated clinical dilution: The sample placed at 60°C for 24 h is diluted 100-fold with 0.9% sodium chloride dilution solution. The diluted sample is placed in a refrigerator at 2 - 8°C, sampled at 5 h and 24 h respectively, filtered through a 0.45μm PES filter head and then temporarily stored in a refrigerator at 2 - 8°C. Observe the appearance of the unfiltered sample and detect the content of the filtered liquid medicine. The test results are shown in Table 3.

[0048] Table 2 Test Results of the Prescription in Example 1

[0049]

[0050]

[0051] *The aprepitant results are calculated by area normalization.

[0052] The results show that under each condition of Formulations 1 - 3, they are all clear, transparent, and no foreign substances precipitate. Although the content of aprepitant (active ingredient) in the related substances increases, there is no precipitation risk under high temperature and low temperature conditions.

[0053] Table 3 Test Results of the Diluted Prescription in Example 1

[0054]

[0055] The results showed that for the samples of Prescriptions 1 - 3 placed at 60°C for 24 hours, after being diluted 100 times and placed at 2 - 8°C for 24 hours, the samples were all clear, transparent, and no foreign substances precipitated. Moreover, the API contents at 5 hours and 24 hours were basically the same, indicating that at low temperatures, insoluble aprepitant would not precipitate either.

[0056] Example 2

[0057] Investigate the influence of different dosages of oleic acid on the stability of the product.

[0058] Table 4 Prescriptions of Example 2

[0059]

[0060] The following describes an exemplary preparation method for forming the fosaprepitant composition of Prescriptions 4 - 9: In 60 - 70% of the prescription amount of injection water, add the prescription amounts of EDTA - 2Na, oleic acid, and API (fosaprepitant dimeglumine), stir evenly, add 1M sodium hydroxide, stir until a clear solution is obtained, and detect the pH value; adjust the pH value to 8.5 ± 0.1 using 1M NaOH / 20% HCl, and detect the pH value after volume fixation. The prepared liquid medicine is pre - filtered through a 0.45μm filter element, filled and sealed to obtain the final product.

[0061] The obtained samples were placed for stability investigation at 60°C, and the related substances were detected at 0, 4, 8, and 24 hours respectively. The results are shown in Table 5.

[0062] Table 5 Stability Results of the Prescriptions of Example 2

[0063]

[0064] * The aprepitant results were calculated by area normalization.

[0065] In the above prescriptions, in the 2 - ml dosage form, when the dosage of oleic acid is 28.8 mg (1.44 W / V%), the maximum of aprepitant is 8.07% and the appearance is clear and transparent; in the 4 - ml dosage form, when the dosage of oleic acid is 28.8 mg (0.72 W / V%), the maximum of aprepitant is 9.24%, and precipitation appears after standing.

[0066] From the above results, it can be seen that the smaller the oleic acid concentration, the more the aprepitant content and the greater the precipitation risk.

[0067] Example 3

[0068] Investigate the influence of different buffer ions on the stability of the product. The specific prescriptions are shown in Table 6.

[0069] Table 6 Prescriptions of Example 3

[0070]

[0071] An exemplary preparation method for aprepitant composition for Formulations 10 - 16 is described herein: In 60 - 70% of the prescribed amount of water for injection, add the prescribed amount of EDTA-2Na and buffer salts, then add the API (aprepitant meglumine) and dissolve it, and then detect the pH value. Adjust the pH value to 10.0 with 1M NaOH / HCl, and detect the pH value after volume fixation. The prepared liquid medicine is pre-filtered with a 0.45μm filter element, filled and sealed to obtain the final product.

[0072] The obtained product was placed at 60°C to investigate its stability, and the related substances were detected at 0 and 24 hours respectively. The results are shown in Table 7.

[0073] Table 7 Detection Results of the Prescription Stability of Example 3

[0074]

[0075] *The aprepitant results were calculated by area normalization.

[0076] At the same pH level, the aprepitant content in Formulation 14 - citrate buffer, Formulation 15 - tartrate buffer, and Formulation 16 - borate buffer was relatively high at 60°C and 0h (the aprepitant content in most formulations was basically 0.2 - 0.3% at 0h), especially for Formulation 14, with an aprepitant content of 0.99% at 0h, much higher than other formulations.

[0077] At 60°C and 24h, the aprepitant content in Formulation 14 - citrate buffer and Formulation 15 - tartrate buffer was the highest, exceeding 4%. Among the buffer ion pairs, the aprepitant content in Formulation 11 - phosphate buffer system increased the slowest, and the final aprepitant content was the lowest, at 3.32%.

[0078] When the buffer pair is a phosphate system, the increase in aprepitant is the least and the system is the most stable.

[0079] Example 4

[0080] Table 8 Prescriptions of Example 4

[0081]

[0082] The above prescriptions were prepared according to the preparation method in Example 2, and the obtained products were placed at 60°C to investigate their stability, and the related substances were detected at 0, 4, 8, and 24 hours respectively. The results are shown in Table 9.

[0083] Table 9 Prescription Stability Results of Example 4

[0084]

[0085] *The results of aprepitant were calculated by area normalization.

[0086] From the above data, it can be seen that the prescription with only oleic acid (Prescription 4) has a clear and transparent appearance and good physical stability. After combining with phosphate, the stability is further improved, and the growth rate of aprepitant decreases significantly. This shows that the phosphate root system has a certain stabilizing effect on the stability of the product, and the higher the concentration, the more stable the system.

[0087] Example 5

[0088] Table 10 Prescription of Example 5

[0089] Name Prescription 21 Fosaprepitant dimeglumine mg 245.3 EDTA-2Na mg 5.4 Disodium hydrogen phosphate mg 60 Oleic acid mg 57.6 pH regulator Adjust pH to 8.5 Volume made up to ml 2

[0090] The products prepared from the above prescriptions according to the preparation method in Example 2 were placed upside down at 25 °C and 40 °C for high-temperature stability investigation. At the same time, a marketed preparation (trade name EMEND, license holder: MERCK SHARP&DOHME CORP., manufacturer: Patheon Manufacturing Services LLC, batch number: T037941) was used for comparison. The data are shown in Table 11.

[0091] Table 11 Comparison of Stability Results between the Prescription of Example 5 and the Marketed Preparation

[0092]

[0093] *Aprepitant is the active ingredient, calculated by area normalization, and not included in the total impurity calculation.

[0094] The samples of Prescription 21 at each time point had a clear and transparent appearance. Although aprepitant had an increasing trend, it did not precipitate, and the system was stable. This shows that the stability of Prescription 21 is comparable to that of the marketed preparation.

[0095] Stability of samples simulating clinical dilution: Using the samples of Prescription 21 at 40 °C for 10 days above, they were diluted 75 times with 0.9% sodium chloride and placed at 25 °C. Samples were taken at 0, 4, 8, and 24 h respectively to observe the appearance of the diluted samples and detect the fosaprepitant content and related substances of the diluted liquid.

[0096] Table 12 Dilution Stability of the Samples of Prescription 21 with Stability at 40 °C for 10 Days

[0097]

[0098] *Aprepitant is the active ingredient, calculated by area normalization, and not included in the total impurity calculation.

[0099] The results of the dilution stability investigation showed that the API content was stable, aprepitant remained basically unchanged, the total impurities increased slightly, and the dilution stability was good.

[0100] Example 6

[0101] After Prescription 21 was placed at a high temperature of 80 °C for 4 h, the appearance was observed and related substances were detected. To simulate the stability of the clinically diluted sample, it was diluted 75-fold with 0.9% sodium chloride and placed at 25 °C. Samples were taken at 0, 14, and 24 h respectively to observe the appearance of the diluted sample and detect the related substances in the diluted liquid medicine. At the same time, a marketed preparation (trade name: EMEND, license holder: MERCK SHARP&DOHME CORP., manufacturer: Patheon Manufacturing Services LLC, batch number: T037941) was used for comparison.

[0102] Table 13 Comparison of the stability of Prescription 21 at 80 °C for 4 h and the diluted stability of the marketed preparation

[0103]

[0104] *Aprepitant is the active ingredient. Calculated by area normalization, it is not included in the total impurity calculation.

[0105] The results showed that after Prescription 21 was placed at 80 °C for 4 h, the content of aprepitant increased to 5.68%, the appearance remained clear and transparent, and the total impurities were comparable to those of the marketed preparation; after the stock solution was diluted and placed at 25 °C for 24 h, there was no change in appearance, and there were no significant changes in aprepitant and other impurities. The total impurity level was comparable to that of the marketed preparation, indicating good stability.

[0106] The liquid pharmaceutical composition containing fosaprepitant provided by the present invention has a simple preparation process. Although the content of the active ingredient aprepitant has increased, the physical and chemical stabilities are still good, and the physical and chemical stabilities of the administered samples after simulating clinical dilution are also good.

[0107] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A liquid pharmaceutical composition containing fosaprepitant, characterized in that, The liquid pharmaceutical composition consists of a pharmaceutically active ingredient, a chelating agent, a stabilizer and a pH regulator. The pharmaceutically active ingredient is fosaprepitant dimeglumine; The content of fosaprepitant dimeglumine is 12.265%, and the content refers to the percentage of the mass of fosaprepitant dimeglumine in grams to the total volume of the liquid pharmaceutical composition containing fosaprepitant in milliliters; The chelating agent is selected from one or more of ethylenediaminetetraacetic acid or its pharmaceutically acceptable salts; the weight ratio of the chelating agent to the pharmaceutically active ingredient is 1:30 to 1:56, and the mass of the pharmaceutically active ingredient is calculated based on the mass of fosaprepitant; The stabilizer is selected from one or two of oleic acid and sodium oleate, and the dosage of oleic acid and / or sodium oleate is 1-5% W / V; alternatively, the stabilizer further contains phosphate, and the dosage of the phosphate is 1-5%, and the dosage of the stabilizer refers to the percentage of the mass of the stabilizer in grams to the total volume of the liquid pharmaceutical composition containing fosaprepitant in milliliters; The pH regulator is selected from one or two of hydrochloric acid and sodium hydroxide; The pH value of the liquid pharmaceutical composition containing fosaprepitant is 8.0-9.5; The balance is water.

2. The liquid pharmaceutical composition containing fosaprepitant according to claim 1, wherein: The chelating agent is disodium ethylenediaminetetraacetate.

3. The liquid pharmaceutical composition containing fosaprepitant according to claim 1, characterized in that: The phosphate is selected from one or two of disodium hydrogen phosphate and sodium dihydrogen phosphate.

4. The liquid pharmaceutical composition containing fosaprepitant according to claim 1, characterized in that: The pH value of the liquid composition containing fosaprepitant is 8.0, 8.5, 8.8 or 9.

0.

5. The liquid pharmaceutical composition containing fosaprepitant according to claim 1, characterized in that: The dosage of oleic acid and / or sodium oleate is 1.44%, 2%, 2.11%, 2.88% or 4.23% W / V.

6. The liquid pharmaceutical composition containing fosaprepitant as claimed in claim 1, wherein: The content of the phosphate is 1.6%, 2%, 3% or 4% W / V.

7. The liquid pharmaceutical composition containing fosaprepitant as claimed in claim 1, wherein: The water is water for injection.

8. The liquid pharmaceutical composition containing fosaprepitant according to claim 1, characterized in that: The liquid pharmaceutical composition containing fosaprepitant is selected from any of the following formulations: Formulation 1: 12.265% W / V fosaprepitant dimeglumine, 0.27% W / V EDTA-2Na, 1.44% W / V oleic acid, and the pH is adjusted with 0.1M or 1.0M NaOH, pH 8.5-9.5; Formulation 2: 12.265% W / V fosaprepitant dimeglumine, 0.27% W / V EDTA-2Na, 2.88% W / V oleic acid, 3% W / V disodium hydrogen phosphate, and the pH is adjusted with 1.0M NaOH, pH 8.0-9.

5.

9. The liquid pharmaceutical composition containing fosaprepitant according to any one of claims 1-8, characterized in that: The liquid composition containing fosaprepitant is a parenterally administered liquid composition.

10. Use of the liquid pharmaceutical composition containing fosaprepitant according to any one of claims 1-9 in the preparation of a pharmaceutical preparation for treating vomiting caused by the NK-1 receptor.

11. The use according to claim 10, characterized in that: The pharmaceutical preparation is an injection.

12. The use according to claim 10 or 11, characterized in that: The pharmaceutical preparation includes a packaging material, and the packaging material is plastic or borosilicate glass.

13. The use according to claim 10 or 11, characterized in that: The pharmaceutical preparation includes a packaging material, and the packaging material is coated borosilicate glass.

14. The use according to claim 12, characterized in that: The plastic is selected from one or more of polyvinyl chloride, polypropylene, polyethylene, cycloolefin polymer and acryl; 15. The use according to claim 12, wherein: The plastic is cycloolefin copolymer.

16. A pharmaceutical preparation, characterized in that, It includes the liquid pharmaceutical composition containing fosaprepitant according to any one of claims 1-9.

17. The pharmaceutical preparation according to claim 16, characterized in that, The pharmaceutical preparation is an injection.

18. The pharmaceutical preparation according to claim 16 or 17, characterized in that, The pharmaceutical preparation described above contains a packaging material, and the packaging material is plastic or borosilicate glass.

19. The pharmaceutical preparation according to claim 16 or 17, characterized in that, The pharmaceutical preparation described above contains a packaging material, and the packaging material is coated borosilicate glass.

20. The pharmaceutical preparation according to claim 18, characterized in that, The plastic is selected from one or more of polyvinyl chloride, polypropylene, polyethylene, cycloolefin polymer, and acryl.

21. The pharmaceutical preparation according to claim 18, characterized in that, The plastic is a cycloolefin copolymer.

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