A compound amino acid injection (15-HBC) composition and a method for preparing the same

Abstract

The application discloses a compound amino acid injection (15-HBC) composition and a preparation method thereof, and belongs to the technical field of medicines. The compound amino acid injection (15-HBC) composition provided by the application comprises the following components in an amount of 250mL of the composition: isoleucine 1.532-2.298g, leucine 2.756-4.134g, lysine acetate 1.160-1.740g, methionine 0.500-0.750g, phenylalanine 0.640-0.960g, threonine 0.400-0.600g, tryptophan 0.180-0.270g, valine 1.772-2.658g, alanine 0.800-1.200g, arginine 1.160-1.740g, histidine 0.320-0.480g, proline 1.260-1.890g, serine 0.660-0.990g, glycine 0.660-0.990g, cysteine hydrochloride 0.040-0.060g, and appropriate amount of glacial acetic acid for pH adjustment, and the rest is injection water. The application also provides a preparation method of the compound amino acid injection (15-HBC) without sulfite antioxidant. Meanwhile, the activated carbon adsorption process is removed in the preparation, the control of raw material packages, production processes and the like is strengthened to control bacterial endotoxins, the production process is simplified, and the product quality is ensured.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a compound amino acid injection (15-HBC) composition, and also to a method for preparing the compound amino acid injection (15-HBC) composition. Background Technology

[0002] Compound amino acid injection (15-HBC) is a parenteral nutrition drug used for nutritional support in patients with hyperactive muscle catabolism, digestive system dysfunction, nutritional deterioration, and decreased immune function under stress conditions such as extensive burns, trauma, and severe infection; and for improving nutrition in postoperative patients.

[0003] Compound amino acid injection (15-HBC) contains some unstable amino acids that are easily oxidized and degraded. Currently, all marketed compound amino acid injections (15-HBC) include sodium metabisulfite as an antioxidant. However, sulfites can easily induce hypersensitivity reactions and even toxic effects in susceptible individuals, increasing the risks of clinical application. Numerous adverse reactions have been reported clinically, the most common being sulfite allergy (especially in asthmatic patients), with symptoms including bronchospasm, wheezing, dyspnea, malignant laryngeal edema, hypotension, shock, and even death. Furthermore, some studies have reported that sulfites may cause damage to chromosomes and DNA, as well as irreversible reactions of disulfide bonds in proteins.

[0004] Currently, almost all manufacturers of compound amino acid injections (15-HBC) add sodium metabisulfite as an antioxidant to their products. Although the Chinese Pharmacopoeia clearly stipulates that the concentration of sodium metabisulfite used in injections is generally 0.1% to 0.2%, the risks of clinical application are still unavoidable.

[0005] Meanwhile, this product has a high concentration of raw materials. Currently, all marketed compound amino acid injections (15-HBC) use activated carbon adsorption in their preparation processes to effectively control bacterial endotoxins. According to the "Technical Requirements for Consistency Evaluation of Quality and Efficacy of Generic Chemical Injectable Drugs," "In order to effectively control pyrogens (bacterial endotoxins), it is necessary to strengthen the control of raw materials, excipients, packaging, and production processes. It is recommended not to use activated carbon in the production of injectable drugs."

[0006] Therefore, exploring the production of compound amino acid injections without sulfite antioxidants and optimizing the preparation process to reduce bacterial endotoxins is worthy of study.

[0007] This invention is applicable to patients who cannot receive oral or enteral nutrition, or whose nutritional needs cannot be met. This composition can be administered intravenously to meet the body's need for protein synthesis. It is used for nutritional support in patients with hyperactive muscle catabolism, digestive system dysfunction, nutritional deterioration, and decreased immune function under stress conditions such as extensive burns, trauma, and severe infection, as well as for improving the nutrition of postoperative patients.

[0008] The compound amino acid injection (15-HBC) of this invention, without the presence of sulfite antioxidants, effectively inhibits the degradation of unstable amino acids and eliminates the side effects of sulfite antioxidants by controlling the dissolved oxygen in the solution and the residual headspace oxygen in the infusion bottle after filling. Simultaneously, this invention eliminates the activated carbon adsorption process and effectively controls pyrogens (bacterial endotoxins) by strengthening the control of raw materials, excipients, packaging, and the production process. The preparation method of this invention is simple, the product quality is good, and it is more suitable for industrial production.

[0009] Compared with the prior art, the present invention has the following advantages and effects:

[0010] 1. Nitrogen gas is used for protection throughout the preparation process, which can effectively inhibit or mitigate the degradation of unstable amino acids.

[0011] 2. The antioxidant properties of cysteine ​​hydrochloride itself can further ensure the stability of the product.

[0012] 3. The activated carbon adsorption process has been eliminated. By strengthening the control of raw materials, packaging, and production processes, pyrogens (bacterial endotoxins) can be effectively controlled.

[0013] 4. The preparation method of this invention is simple, the product quality is good, and it is more suitable for industrial production. Summary of the Invention

[0014] To address the shortcomings of existing technologies, the first objective of this invention is to provide a compound amino acid injection (15-HBC) composition that, without the presence of sulfite antioxidants, can effectively inhibit the degradation of unstable amino acids and eliminate the side effects of sulfite antioxidants by controlling the dissolved oxygen in the solution and the headspace residual oxygen in the infusion bottle after filling.

[0015] Another objective of this invention is to provide a method for preparing a compound amino acid injection (15-HBC) composition that eliminates the activated carbon adsorption process. By strengthening the control of raw materials, excipients, packaging, and the production process, pyrogens (bacterial endotoxins) can be effectively controlled. The preparation method of this invention is simple, produces high-quality products, and is more suitable for industrial production.

[0016] To achieve the above objectives, the present invention employs the following technical measures:

[0017] A compound amino acid injection (15-HBC) composition, each 250ml of the composition contains the following components in the following amounts: isoleucine: 1.532-2.298g; leucine: 2.756-4.134g; lysine acetate: 1.160-1.740g; methionine: 0.500-0.750g; phenylalanine: 0.640-0.960g; threonine: 0.400-0.600g; tryptophan 0.180-0.270g; Valine: 1.772-2.658g; Alanine: 0.800-1.200g; Arginine: 1.160-1.740g; Histidine: 0.320-0.480g; Proline: 1.260-1.890g; Serine: 0.660-0.990g; Glycine: 0.660-0.990g; Cysteine ​​hydrochloride: 0.040-0.060g;

[0018] Furthermore, a compound amino acid injection (15-HBC) composition is characterized in that the composition of each 250 mL injection solution is as follows:

[0019] Isoleucine: 1.724-2.298g; Leucine: 3.101-2.756g; Lysine acetate: 1.305-1.595g; Methionine: 0.563-0.688g; Phenylalanine: 0.720-0.880g; Threonine: 0.450-0.550g; Tryptophan: 0.203-0.248g; Valine: 1.994-2.437g; Alanine: 0.900-1.100g; Arginine: 1.305-1.595g; Histidine: 0.360-0.440g; Proline: 1.418-1.733g; Serine: 0.743-0.908g; Glycine: 0.743-0.908g; Cysteine ​​hydrochloride: 0.045-0.055g; pH adjusted with appropriate amount of glacial acetic acid, the remainder is water for injection;

[0020] Furthermore, a compound amino acid injection (15-HBC) composition is characterized in that the composition of each 250 mL injection solution is as follows:

[0021] Isoleucine: 1.819-2.011g; Leucine: 3.273-3.617g; Lysine acetate: 1.378-1.523g; Methionine: 0.594-0.656g; Phenylalanine: 0.760-0.840g; Threonine: 0.475-0.525g; Tryptophan: 0.214-0.236g; Valine: 2.1g. 0.4-2.326g; Alanine: 0.950-1.050g; Arginine: 1.378-1.523g; Histidine: 0.380-0.420g; Proline: 1.496-1.654g; Serine: 0.784-0.866g; Glycine: 0.784-0.866g; Cysteine ​​hydrochloride: 0.048-0.053g;

[0022] Furthermore, a compound amino acid injection (15-HBC) composition is characterized by the following composition per 250 mL of the injection composition:

[0023] Isoleucine: 1.877-1.953g; Leucine: 3.376-3.514g; Lysine acetate: 1.421-1.479g; Methionine: 0.613-0.638g; Phenylalanine: 0.784-0.816g; Threonine: 0.490-0.510g; Tryptophan: 0.221-0.230g; Valine: 2.1g 71-2.259g; Alanine: 0.980-1.020g; Arginine: 1.421-1.479g; Histidine: 0.392-0.408g; Proline: 1.544-1.607g; Serine: 0.809-0.842g; Glycine: 0.809-0.842g; Cysteine ​​hydrochloride: 0.049-0.051g;

[0024] Furthermore, a compound amino acid injection (15-HBC) composition is characterized in that the pH value of the injection composition is 5.5 to 7.0.

[0025] Furthermore, the pH value of the injection composition is 6.0.

[0026] A method for preparing a compound amino acid injection (15-HBC) composition, comprising the following steps:

[0027] (1) Add 80% of the total volume of water for injection to the mixing tank, start stirring, maintain the temperature of the water for injection at 65℃~70℃, and introduce nitrogen gas until the dissolved oxygen <

[0028] 0.5 mg / L.

[0029] (2) Maintain nitrogen purging throughout the process, keep the temperature of water for injection at 65℃~70℃, and add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, alanine, arginine, histidine, proline, serine, and glycine in sequence and stir to dissolve.

[0030] (3) Cool the drug solution to 45℃~50℃, add tryptophan and cysteine ​​hydrochloride, and stir to dissolve.

[0031] (4) Test the pH value of the solution and adjust the pH to 5.9-6.1 using 36% (w / w) acetic acid solution. Make up to the full volume and circulate and stir for 15 minutes until the solution is homogeneous.

[0032] (5) Take samples for intermediate product testing, seal the dilute mixing tank and pressurize with nitrogen, cool the liquid and store it below 40°C.

[0033] (6) After the intermediate product passes the inspection, the drug solution is subjected to two passes: one at 0.45 μm and the other at 0.22 μm.

[0034] The solution is filtered through a 0.22μm polyethersulfone (PES) filter into a buffer tank, and then filtered from the buffer tank through a 0.22μm PES filter into the filling machine.

[0035] (7) Filling and capping: Vacuuming and nitrogen filling are performed on the infusion bottle before and after filling, and the process is repeated 3 times before capping. Crimping.

[0036] (8) Sterilize by water bath and cool to 60°C before removing from the box.

[0037] Furthermore, the preparation method of the compound amino acid injection is characterized in that, in step (7): the dissolved oxygen during the filling process should be ≤1mg / L and the headspace residual oxygen should be ≤1%.

[0038] Furthermore, the preparation method of the compound amino acid injection is characterized in that, in step (8): the sterilization temperature is 121℃ and the sterilization time is 12min. Detailed Implementation

[0039] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified, specific conditions were applied in the examples. Reagents or instruments used, unless otherwise specified, are all commercially available products.

[0040] Example 1

[0041] A compound amino acid injection (15-HBC) composition, each 250 mL of the composition contains:

[0042]

[0043]

[0044] The preparation method of the compound amino acid injection (15-HBC) composition is as follows:

[0045] (1) Add 80% of the total volume of water for injection to the mixing tank, turn on the stirrer, keep the temperature of the water for injection at 65℃~70℃, and introduce nitrogen gas until dissolved oxygen <0.5mg / L.

[0046] (2) Maintain nitrogen purging throughout the process, keep the temperature of water for injection at 65℃~70℃, and add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, alanine, arginine, histidine, proline, serine, and glycine in sequence and stir to dissolve.

[0047] (3) Cool the drug solution to 45℃~50℃, add tryptophan and cysteine ​​hydrochloride, and stir to dissolve.

[0048] (4) Test the pH value of the solution and adjust the pH to 5.9-6.1 using 36% (w / w) acetic acid solution. Make up to the full volume and circulate and stir for 15 minutes until the solution is homogeneous.

[0049] (5) Take samples for intermediate product testing, seal the dilute mixing tank and pressurize with nitrogen, cool the liquid and store it below 40°C.

[0050] (6) After the intermediate product passes the test, the liquid medicine is filtered through a 0.45μm and a 0.22μm polyethersulfone (PES) filter into a buffer tank, and then the liquid medicine is filtered from the buffer tank through a 0.22μm PES filter into the filling machine.

[0051] (7) Filling and capping: Vacuuming and nitrogen filling of the infusion bottle are performed before and after filling, and the bottle is capped after repeating this process 3 times. Dissolved oxygen should be ≤1mg / L and headspace residual oxygen should be ≤1% during filling. Crimping is then performed.

[0052] (8) Sterilize by water bath at 121℃ for 12 minutes, then cool down to 60℃ before removing from the box.

[0053] Example 2

[0054] A compound amino acid injection (15-HBC) composition, each 250 mL of the composition contains:

[0055] Element Dosage Isoleucine 1.915g Leucine 3.445g Lysine acetate 1.45g Methionine 0.625g Phenylalanine 0.8g threonine 0.5g Tryptophan 0.225g Valine 2.215g alanine 1g Arginine 1.45g Histidine 0.4g proline 1.575g Serine 0.825g glycine 0.825g Cysteine ​​hydrochloride 0.05g glacial acetic acid Appropriate amount Sodium metabisulfite 0.25g Water for Injection Up to 250ml

[0056] The preparation method of the compound amino acid injection (15-HBC) composition is as follows:

[0057] (1) Add 80% of the total volume of water for injection to the mixing tank, turn on the stirrer, keep the temperature of the water for injection at 65℃~70℃, and introduce nitrogen gas until dissolved oxygen <0.5mg / L.

[0058] (2) Maintain nitrogen purging throughout the process, keep the temperature of water for injection at 65℃~70℃, and add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, alanine, arginine, histidine, proline, serine, and glycine in sequence and stir to dissolve.

[0059] (3) Cool the drug solution to 45℃~50℃, add sodium metabisulfite, tryptophan and cysteine ​​hydrochloride, and stir to dissolve.

[0060] (4) Test the pH value of the solution and adjust the pH to 5.9-6.1 using 36% (w / w) acetic acid solution. Make up to the full volume and circulate and stir for 15 minutes until the solution is homogeneous.

[0061] (5) Take samples for intermediate product testing, seal the dilute mixing tank and pressurize with nitrogen, cool the liquid and store it below 40°C.

[0062] (6) After the intermediate product passes the test, the liquid medicine is filtered through a 0.45μm and a 0.22μm polyethersulfone (PES) filter into a buffer tank, and then the liquid medicine is filtered from the buffer tank through a 0.22μm PES filter into the filling machine.

[0063] (7) Filling and capping: Vacuuming and nitrogen filling of the infusion bottle are performed before and after filling, and the bottle is capped after repeating this process 3 times. Dissolved oxygen should be ≤1mg / L and headspace residual oxygen should be ≤1% during filling. Crimping is then performed.

[0064] (8) Sterilize by water bath at 121℃ for 12 minutes, then cool down to 60℃ before removing from the box.

[0065] Example 3

[0066] A compound amino acid injection (15-HBC) composition, each 250 mL of the composition contains:

[0067]

[0068]

[0069] The preparation method of the compound amino acid injection (15-HBC) composition is as follows:

[0070] (1) Add 80% of the total volume of water for injection to the mixing tank, turn on the stirrer, keep the temperature of the water for injection at 65℃~70℃, and introduce nitrogen gas until dissolved oxygen <0.5mg / L.

[0071] (2) Maintain nitrogen purging throughout the process, keep the temperature of water for injection at 65℃~70℃, and add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, alanine, arginine, histidine, proline, serine, and glycine in sequence and stir to dissolve.

[0072] (3) Cool the drug solution to 45℃~50℃, add sodium metabisulfite, tryptophan and cysteine ​​hydrochloride, and stir to dissolve.

[0073] (4) Test the pH value of the solution and adjust the pH to 5.9-6.1 using 36% (w / w) acetic acid solution. Make up to the full volume and circulate and stir for 15 minutes until the solution is homogeneous.

[0074] (5) Take samples for intermediate product testing, seal the dilute mixing tank and pressurize with nitrogen, cool the liquid and store it below 40°C.

[0075] (6) After the intermediate product passes the test, the liquid medicine is filtered through a 0.45μm and a 0.22μm polyethersulfone (PES) filter into a buffer tank, and then the liquid medicine is filtered from the buffer tank through a 0.22μm PES filter into the filling machine.

[0076] (7) Filling and capping: Vacuuming and nitrogen filling of the infusion bottle are performed before and after filling, and the bottle is capped after repeating this process 3 times. Dissolved oxygen should be ≤3mg / L and headspace residual oxygen should be ≤3% during filling. Crimping is then performed.

[0077] (8) Sterilize by water bath at 121℃ for 12 minutes, then cool down to 60℃ before removing from the box.

[0078] Example 4

[0079] A compound amino acid injection (15-HBC) composition, each 250 mL of the composition contains:

[0080]

[0081]

[0082] The preparation method of the compound amino acid injection (15-HBC) composition is as follows:

[0083] (1) Add 30% of the total volume of water for injection to the mixing tank, turn on the stirrer, keep the temperature of the water for injection at 65℃~70℃, and introduce nitrogen gas until dissolved oxygen <0.5mg / L.

[0084] (2) Maintain nitrogen purging throughout the process, keep the temperature of water for injection at 65℃~70℃, and add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, alanine, arginine, histidine, proline, serine, and glycine in sequence and stir to dissolve.

[0085] (3) Cool the drug solution to 45℃~50℃, add 0.05% (g / ml) pharmaceutical charcoal (for injection), stir and adsorb for 30 minutes, then filter through a titanium rod filter to remove the charcoal, and pump it into another mixing tank.

[0086] (4) Monitor dissolved oxygen to be below 1.0 mg / L, add tryptophan and cysteine ​​hydrochloride, stir to dissolve, add water for injection to 90% of the total volume of the composition, test the pH value of the drug solution, and adjust the pH to 5.9-6.1 using 36% (w / w) acetic acid solution, make up to the full volume, and circulate and stir for 15 minutes until the drug solution is homogeneous.

[0087] (5) Take samples for intermediate product testing, seal the dilute mixing tank and pressurize with nitrogen, cool the liquid and store it below 40°C.

[0088] (6) After the intermediate product passes the test, the liquid medicine is filtered through a 0.45μm and a 0.22μm polyethersulfone (PES) filter into a buffer tank, and then the liquid medicine is filtered from the buffer tank through a 0.22μm PES filter into the filling machine.

[0089] (7) Filling and capping: Vacuuming and nitrogen filling of the infusion bottle are performed before and after filling, and the bottle is capped after repeating this process 3 times. Dissolved oxygen should be ≤1mg / L and headspace residual oxygen should be ≤1% during filling. Crimping is then performed.

[0090] (8) Sterilize by water bath at 121℃ for 12 minutes, then cool down to 60℃ before removing from the box.

[0091] Example 5

[0092] Key quality attributes of the compound amino acid injection (15-HBC) composition were tested:

[0093] Table 1 Key Quality Attributes of Compound Amino Acid Injection (15-HBC) Composition

[0094]

[0095] Table 2. Key Quality Attributes of Compound Amino Acid Injection (15-HBC) Composition (Accelerated 3-Month Evaluation)

[0096]

[0097] As can be seen from Tables 1 and 2, the compound amino acid injection composition (15-HBC) provided by the present invention removes the antioxidant sodium metabisulfite. By strictly controlling the dissolved oxygen in the drug solution and the headspace residual oxygen in the infusion bottle after filling, the degradation of unstable amino acids can be effectively inhibited, and the product has good stability.

[0098] Table 3 Key Quality Attributes of Compound Amino Acid Injection (15-HBC) Composition

[0099]

[0100] Table 4. Key Quality Attributes of Compound Amino Acid Injection (15-HBC) Composition (Accelerated 3-Month Evaluation)

[0101]

[0102]

[0103] As can be seen from Tables 3 and 4, the compound amino acid injection composition (15-HBC) provided by the present invention eliminates the activated carbon adsorption process. By strengthening the control of raw materials, excipients, packaging, and production processes, the bacterial endotoxins of the finished product can be guaranteed to meet the standard requirements.

[0104] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A compound amino acid injection (15-HBC) composition, characterized in that: The compound amino acid injection contains the following components in every 250ml of the composition: isoleucine: 1.532-2.298g; Leucine: 2.756-4.134g; Lysine acetate: 1.160-1.740g; Methionine: 0.500-0.750g; Phenylalanine: 0.640-0.960g; Threonine: 0.400-0.600g; Tryptophan: 0.180-0.270g; Valine: 1.772-2.658g; Alanine: 0.800-1.200g; Arginine ：1.160-1.740g； Group Amino acids: 0.320-0.480g; Proline: 1.260-1.890g; Serine: 0.660-0.990g; Glycine: 0.660-0.990g; Cysteine ​​hydrochloride: 0.040-0.060g.

2. The compound amino acid injection (15-HBC) composition according to claim 1, characterized in that: The composition of each 250mL injection solution is as follows: Isoleucine: 1.724-2.298g; Leucine: 3.101-2.756g; Lysine acetate: 1.305-1.595g; Methionine: 0.563-0.688g; Phenylalanine: 0.720-0.880g; Threonine: 0.450-0.550g; Tryptophan: 0.203-0.248g; Valine: 1.994-2.437g; Alanine: 0.900-1.100g; Arginine: 1.305-1.595g; Histidine: 0.360-0.440g; Proline: 1.418-1.733g; Serine: 0.743-0.908g; Glycine: 0.743-0.908g; Cysteine ​​hydrochloride: 0.045-0.0550g.

3. The compound amino acid injection (15-HBC) composition according to claim 1, characterized in that, The composition of each 250 mL injection solution is as follows: Isoleucine: 1.877-1.953g; Leucine: 3.376-3.514g; Lysine acetate: 1.421-1.479g; Methionine: 0.613-0.638g; Phenylalanine: 0.784-0.816g; Threonine: 0.490-0.510g; Tryptophan: 0.221-0.230g; Valine: 2.171-2.259g; Alanine: 0.980-1.020g; Arginine ：1.421-1.479g； Histidine: 0.392-0.408g; Proline: 1.544-1.607g; Serine: 0.809-0.842g; Glycine: 0.809-0.842g; hydrochloric acid Cysteine: 0.049-0.051g; pH adjusted with appropriate amount of glacial acetic acid, the remainder is water for injection.

4. The compound amino acid injection (15-HBC) composition according to claim 1, characterized in that, The pH value of the injection composition is 5.5 to 7.

0.

5. The compound amino acid injection (15-HBC) composition according to claim 4, characterized in that, The pH value of the injection composition is 6.

0.

6. The compound amino acid injection (15-HBC) composition according to any one of claims 1-5, characterized in that, The preparation method of the compound amino acid injection (15-HBC) composition comprises the following steps: (1) Add 80% of the total volume of water for injection to the mixing tank, turn on the stirrer, keep the temperature of the water for injection at 65℃~70℃, and introduce nitrogen gas until dissolved oxygen <0.5mg / L. (2) Maintain nitrogen purging throughout the process, keep the temperature of water for injection at 65℃~70℃, and add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, alanine, arginine, histidine, proline, serine, and glycine in sequence and stir to dissolve. (3) Cool the drug solution to 45℃~50℃, add tryptophan and cysteine ​​hydrochloride, and stir to dissolve. (4) Test the pH value of the solution and adjust the pH to 5.9-6.1 using 36% (w / w) acetic acid solution. Make up to the full volume and circulate and stir for 15 minutes until the solution is homogeneous. (5) Take samples for intermediate product testing, seal the dilute mixing tank and pressurize with nitrogen, cool the liquid and store it below 40°C. (6) After the intermediate product passes the test, the liquid medicine is filtered through a 0.45μm and a 0.22μm polyethersulfone (PES) filter into a buffer tank, and then the liquid medicine is filtered from the buffer tank through a 0.22μm PES filter into the filling machine. (7) Filling and capping: Vacuuming and nitrogen filling are performed on the infusion bottle before and after filling, and the process is repeated 3 times before capping. Crimping. (8) Sterilize by water bath and cool to 60°C before removing from the box.

7. The method for preparing the compound amino acid injection according to claim 6, characterized in that, In step (7): dissolved oxygen during filling should be ≤1mg / L and residual oxygen in the headspace should be ≤1%.

8. The method for preparing the compound amino acid injection according to claim 6, characterized in that, In step (8): the sterilization temperature is 121℃ and the sterilization time is 12min.

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