Compound amino acid injection for children and preparation method thereof

Abstract

The invention discloses a pediatric compound amino acid injection and a preparation method thereof, and relates to the technical field of medicines. The invention relates to a preparation method of a pediatric compound amino acid injection. The preparation method comprises the following steps: carrying out vacuumizing and nitrogen charging treatment on a pipeline and a preparation tank for preparation; the preparation method comprises the following steps: adding low-oxygen injection water into a preparation tank, heating, continuously charging nitrogen, adding isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, histidine, tyrosine, acetyl tyrosine, alanine, arginine, proline, serine, glycine, aspartic acid and taurine, and stirring for dissolving; cooling the preparation tank, adding glacial acetic acid, then adding tryptophan, glutamic acid and cysteine hydrochloride, stirring and dissolving, adding the residual water for injection, and then adding glacial acetic acid to adjust the pH value to obtain a liquid medicine; carrying out intermediate determination on the liquid medicine, filtering, filling, and sealing; and carrying out hot-pressing sterilization on the sealed liquid medicine, and loading the sterilized liquid medicine and an oxygen absorbent into a barrier bag for vacuum packaging. The safety of the compound amino acid can be improved.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a pediatric compound amino acid injection and a preparation method thereof. Background Art

[0002] The compound amino acid injection for children (19AA-Ⅰ) is suitable for nutritional support for infants (including low birth weight infants) and pediatric patients who need total parenteral nutrition through central or peripheral infusion. There are three types of compound amino acid injections for children on the market, namely, compound amino acid injection for children (18AA-Ⅰ), compound amino acid injection for children (18AA-Ⅱ) and compound amino acid injection for children (19AA-Ⅰ). The compound amino acid injection for children (19AA-Ⅰ) involved in the present invention is specially used for parenteral nutrition infusion for premature infants and children who cannot be taken orally or have various traumas. Its essential amino acids (EAA) are as high as 52%, and the dosage of phenylalanine, methionine and glycine is reduced in the formula, and the dosage of tyrosine and histidine is increased. It also contains taurine. Taurine is a metabolite of methionine and cysteine. It can protect cell membranes, promote brain development, maintain normal retinal function, prevent cholestasis and enhance myocardial cell function. It is an indispensable element in amino acids for children.

[0003] The prescription of this product contains amino acids with strong reducing properties, such as cysteine ​​hydrochloride, which are easily oxidized during the production process. Therefore, most of the products currently on the market contain sulfite antioxidants. However, the sulfite antioxidants contained in the injection may cause allergic reactions in clinical practice, posing a potential threat to human health; studies have found that the sulfite antioxidants contained in the injection will also lead to an increase in amino acid-related substances. At present, European and American countries have officially required pharmaceutical manufacturers to indicate the content of added antioxidants and their adverse reactions in the drug instructions. The "Announcement of the General Administration on the Revision of the Instructions for Compound Amino Acid Injection (18AA) and Similar Preparations" issued by the State Food and Drug Administration (CFDA) in September 2016 also made the same requirement. Therefore, how to reduce the amount of antioxidants in compound amino acid injections or even completely eliminate the use of antioxidants is the current research focus.

[0004] In view of this, it is very necessary to design an improved antioxidant-free compound amino acid injection for children to solve the above problems. Summary of the invention

[0005] The technical problem to be solved by the present invention is that antioxidants in compound amino acids pose a potential threat to health.

[0006] On the one hand, the purpose of the present invention is to provide a method for preparing a pediatric compound amino acid injection, so as to achieve the goal of not adding antioxidants to the compound amino acid and improve the safety of the compound amino acid.

[0007] On the other hand, the present invention aims to provide a compound amino acid injection solution that does not contain an antioxidant.

[0008] The present invention is achieved through the following technical solutions:

[0009] The present invention provides a method for preparing a pediatric compound amino acid injection, comprising the following steps:

[0010] The pipes and tanks used for preparation shall be vacuumed and filled with nitrogen;

[0011] Add hypoxic injection water into the preparation tank, heat it, continuously fill it with nitrogen, add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, histidine, tyrosine, acetyltyrosine, alanine, arginine, proline, serine, glycine, aspartic acid and taurine, and stir to dissolve;

[0012] Cool the preparation tank, add glacial acetic acid, then add glutamic acid, glutamic acid, and cysteine ​​hydrochloride, stir to dissolve, add the remaining water for injection, and then add glacial acetic acid to adjust the pH value to obtain a drug solution;

[0013] The drug solution is subjected to intermediate determination, and after filtration, it is filled and sealed;

[0014] The sealed liquid medicine is sterilized by hot pressing and packed together with the oxygen absorbent into a barrier bag for vacuum packaging.

[0015] As a possible design, after the above-mentioned preparation tank is vacuumed and nitrogen-filled, the residual oxygen is ≤0.5%.

[0016] As a possible design, the amount of hypoxic water for injection added to the above configuration tank before heating is 70-80% of the weight of the hypoxic water for injection.

[0017] As a possible design, the dissolved oxygen content of the above-mentioned hypoxic water for injection is ≤0.5 mg / L.

[0018] As a possible design, the heating temperature is 80-100°C.

[0019] As a possible design, the preparation tank is cooled to below 60°C.

[0020] As a possible design, the pH value of the above-mentioned liquid medicine is 5.2-5.8.

[0021] As a possible design, each 1000 ml of the above-mentioned liquid medicine contains:

[0022] Isoleucine 8-8.4g, leucine 12-16g, lysine acetate 11-13g, methionine 3.3-3.5g, phenylalanine 4.5-5g, threonine 4-4.4g, tryptophan 1.8-2.2g, valine 7.5-8g, cysteine ​​hydrochloride 0.2-0.28g, histidine 4.5-5g, tyrosine 0.4-0.48g, acetyltyrosine 2.2-2.6g, alanine 5.2-5.6g, arginine 11.5-12.5g, proline 6.5-7g, serine 3.5-4g, glycine 3.4-3.8g, aspartic acid 3-3.4g, glutamic acid 4.8-5.2g, taurine 0.2-0.3g, glacial acetic acid 1.0ml-4.0ml, and the remainder is water for hypoxic injection.

[0023] As a possible design, the above-mentioned hot pressure sterilization conditions are: keeping warm at 121°C for 12 minutes.

[0024] The present invention also provides a compound amino acid injection prepared by any one of the above preparation methods.

[0025] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0026] The invention provides a weakly acidic environment for cysteine ​​hydrochloride by adding glacial acetic acid in advance, thereby ensuring the stability of cysteine ​​hydrochloride during preparation; and effectively avoids oxidation of amino acid raw materials during preparation by controlling the amount of dissolved oxygen and residual oxygen during the preparation process. Since oxidation of amino acids will produce degradation impurities, the API content will be reduced, which will affect the safety and effectiveness of the product. Therefore, avoiding oxidation of amino acids can improve the safety and effectiveness of the product; and further, by controlling the dissolved oxygen of sterilization water and residual oxygen in a sterilization cabinet during the sterilization process, effectively avoids oxidation of amino acid raw materials during the sterilization process.

[0027] The pediatric compound amino acid prepared by the method does not contain antioxidants, which can avoid the toxic effects caused by antioxidants. Especially for infants and young children with weak tolerance, it solves the clinical risks of products containing antioxidants from the root and improves the safety of clinical medication. In addition, after the antioxidant is eliminated, the content of each active amino acid in the production, storage, transportation and use of the product is guaranteed, ensuring the effectiveness of clinical medication. The above advantages make the quality of the product of the present invention better than the current commercially available products containing antioxidants. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with embodiments. The illustrative embodiments of the present invention and their description are only used to explain the present invention and are not intended to limit the present invention.

[0029] A method for preparing a pediatric compound amino acid injection comprises the following steps:

[0030] S1. Vacuum and nitrogen-fill the pipes and tanks used for preparation.

[0031] By evacuating and nitrogen-filling the preparation tanks and pipelines, the residual oxygen can be reduced to avoid affecting subsequent preparations and effectively prevent the amino acid raw materials from being oxidized during the sterilization process.

[0032] Preferably, after the preparation tank is vacuumed and nitrogen-filled, the residual oxygen is ≤ 0.5%, and more preferably, the residual oxygen is ≤ 0.3%.

[0033] When the residual oxygen is ≤0.5%, the influence of oxygen on the raw materials during the preparation process can be reduced.

[0034] S2. Add hypoxic water for injection into the preparation tank, heat it, continuously fill it with nitrogen, add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, histidine, tyrosine, acetyltyrosine, alanine, arginine, proline, serine, glycine, aspartic acid and taurine, and stir to dissolve.

[0035] Preferably, the amount of hypoxic water for injection added to the preparation tank before heating is 70-80% of the weight of the hypoxic water for injection.

[0036] Preferably, the heating temperature is 80-100°C.

[0037] Preferably, the dissolved oxygen content of the hypoxic water for injection is ≤0.5 mg / L.

[0038] Preferably, the preparation tank is cooled to below 60°C.

[0039] Preferably, the materials are added into the configuration tank through a closed feeding tank.

[0040] S3. Cool the preparation tank, add glacial acetic acid, and then add tryptophan, glutamic acid, and cysteine ​​hydrochloride, stir to dissolve, add the remaining water for injection, and then add glacial acetic acid to adjust the pH value to obtain a drug solution.

[0041] Preferably, the pH value of the drug solution is 5.2 to 5.8, at which the product quality is more stable.

[0042] Preferably, the first addition amount of glacial acetic acid in step S3 is 1.8 mL / L.

[0043] S4. Perform intermediate determination on the drug solution, and fill and seal it after filtration.

[0044] Preferably, the dissolved oxygen content of the drug solution is controlled to be ≤0.5 mg / L during the entire preparation and canning process.

[0045] Preferably, the intermediates are measured with reference to the finished product standards, and the measurement can preliminarily confirm the product quality and prevent waste of resources caused by unqualified final products.

[0046] S5. Sterilize the sealed liquid medicine by hot pressing, and put it into a barrier bag together with the oxygen absorbent for vacuum packaging.

[0047] Preferably, the hot pressure sterilization condition is: keeping warm at 121° C. for 12 minutes.

[0048] Preferably, the spray water used for autoclaving should be low-oxygen water for injection, and its dissolved oxygen content should be ≤0.5 mg / L.

[0049] Preferably, the residual oxygen in the autoclave for hot pressure sterilization should be controlled to ≤0.1%.

[0050] Preferably, the filling is specifically filling into a three-layer co-extruded film bag for infusion.

[0051] Preferably, the medicinal solution contains per 1000 ml:

[0052] Isoleucine 8-8.4g, leucine 12-16g, lysine acetate 11-13g, methionine 3.3-3.5g, phenylalanine 4.5-5g, threonine 4-4.4g, tryptophan 1.8-2.2g, valine 7.5-8g, cysteine ​​hydrochloride 0.2-0.28g, histidine 4.5-5g, tyrosine 0.4-0.48g, acetyltyrosine 2.2-2.6g, alanine 5.2-5.6g, arginine 11.5-12.5g, proline 6.5-7g, serine 3.5-4g, glycine 3.4-3.8g, aspartic acid 3-3.4g, glutamic acid 4.8-5.2g, taurine 0.2-0.3g, glacial acetic acid 1.0ml-4.0ml, and the remainder is water for hypoxic injection.

[0053] Preferably, the above-mentioned liquid medicine does not contain antioxidants. The present invention can eliminate the threat of antioxidants to human health without adding antioxidants, reduce the risk of clinical use, and can reduce impurities in the liquid medicine compared to the liquid medicine with antioxidants added.

[0054] Example 1

[0055] This embodiment configures 300L of pediatric compound amino acid injection, and the preparation method includes the following steps:

[0056] Weigh the ingredients: 2.46kg of isoleucine, 4.2kg of leucine, 3.6kg of lysine acetate, 1.02kg of methionine, 1.44kg of phenylalanine, 1.26kg of threonine, 0.6kg of tryptophan, 2.34kg of valine, 0.072kg of cysteine ​​hydrochloride, 1.44kg of histidine, 0.132kg of tyrosine, 0.72kg of acetyltyrosine, 1.62kg of alanine, 3.6kg of arginine, 2.04kg of proline, 1.14kg of serine, 1.08kg of glycine, 0.96kg of aspartic acid, 1.5kg of glutamic acid, and 0.075kg of taurine.

[0057] Before preparation, the pipelines and containers should be evacuated and filled with nitrogen to control the residual oxygen in the preparation tank to ≤0.5%.

[0058] Open the preparation tank and stir, add hypoxic water for injection to a total of 240L in the preparation tank, heat to above 80°C, continuously fill with nitrogen, control the dissolved oxygen content of the water for injection to ≤0.5mg / L before adding, add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, histidine, tyrosine, acetyltyrosine, alanine, arginine, proline, serine, glycine, aspartic acid, taurine in turn, stir and dissolve;

[0059] Cool down to 50°C, add 540 mL of glacial acetic acid to lower the pH of the solution, stir for 5 min, then add glutathione, glutamic acid, and cysteine ​​hydrochloride, stir to dissolve, add water for injection to 300 L, and then add glacial acetic acid to adjust the pH to 5.5 to obtain a solution;

[0060] Take samples of the drug solution for intermediate determination, filter and fill them into three-layer co-extruded infusion film bags after passing the test, and seal them;

[0061] The sample was sterilized by hot pressing at 121℃ for 12min. Low oxygen water was used for sterilization, and the dissolved oxygen was ≤0.5mg / L, and the residual oxygen in the sterilization process control cabinet was ≤0.1%;

[0062] The sterilized sample and the oxygen absorbent are placed in a barrier bag and vacuum-sealed to obtain the compound amino acid injection.

[0063] According to the quality standard of the Draft for Comments on Pediatric Compound Amino Acid Injection (19AA-Ⅰ) issued by the State Pharmacopoeia Commission, three batches of trial-produced samples were tested, and the results are shown in Table 1.

[0064] Table 1

[0065]

[0066]

[0067] The molecular structures of impurity B, impurity C, impurity D, impurity E and impurity G in the present invention are shown in Table 2 below.

[0068] Table 2

[0069]

[0070] Example 2

[0071] The remaining operations of this embodiment are basically the same as those of Example 1, except that: acetyltyrosine, tyrosine, aspartic acid, isoleucine, leucine, threonine, valine, histidine, methionine, lysine acetate, phenylalanine, alanine, arginine, proline, serine, glycine, and taurine are added and stirred to dissolve. After the dissolution is complete, three batches of treatments at different cooling temperatures (40° C., 50° C., and 60° C.) are performed in sequence.

[0072] According to the quality standard of the Draft for Comments on Pediatric Compound Amino Acid Injection (19AA-I) of the State Pharmacopoeia Commission, three batches of samples prepared at three cooling temperatures in this embodiment were tested, and the results are shown in Table 3.

[0073] Table 3

[0074]

[0075]

[0076] Example 3

[0077] This embodiment configures 300L of pediatric compound amino acid injection, and the preparation method includes the following steps:

[0078] Weigh the ingredients: 2.4kg of isoleucine, 3.6kg of leucine, 3.3kg of lysine acetate, 0.99kg of methionine, 1.35kg of phenylalanine, 1.2kg of threonine, 0.54kg of tryptophan, 2.25kg of valine, 0.06kg of cysteine ​​hydrochloride, 1.35kg of histidine, 0.12kg of tyrosine, 0.66kg of acetyltyrosine, 1.56kg of alanine, 3.45kg of arginine, 1.95kg of proline, 1.05kg of serine, 1.02kg of glycine, 0.9kg of aspartic acid, 1.44kg of glutamic acid, and 0.06kg of taurine.

[0079] Before preparation, the pipelines and containers should be evacuated and filled with nitrogen to control the residual oxygen in the preparation tank to ≤0.5%.

[0080] Open the preparation tank and stir, add hypoxic water for injection to a total of 240L in the preparation tank, heat to above 80°C, continuously fill with nitrogen, control the dissolved oxygen content of the water for injection to ≤0.5mg / L before adding, add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, histidine, tyrosine, acetyltyrosine, alanine, arginine, proline, serine, glycine, aspartic acid, taurine in turn, stir and dissolve;

[0081] Cool down to 40°C, add 500 mL of glacial acetic acid to lower the pH of the solution, stir for 5 min, then add glutathione, glutamic acid, and cysteine ​​hydrochloride, stir to dissolve, add water for injection to 300 L, and then add glacial acetic acid to adjust the pH to 5.2 to obtain a solution;

[0082] Take samples of the drug solution for intermediate determination, filter and fill them into three-layer co-extruded infusion film bags after passing the test, and seal them;

[0083] The sample was sterilized by hot pressing at 121℃ for 12min. Low oxygen water was used for sterilization, and the dissolved oxygen was ≤0.5mg / L, and the residual oxygen in the sterilization process control cabinet was ≤0.1%;

[0084] The sterilized sample and the oxygen absorbent are placed in a barrier bag and vacuum-sealed to obtain the compound amino acid injection.

[0085] Example 4

[0086] This embodiment configures 300L of pediatric compound amino acid injection, and the preparation method includes the following steps:

[0087] Weigh the ingredients: 2.52kg of isoleucine, 4.8kg of leucine, 3.9kg of lysine acetate, 1.05kg of methionine, 1.5kg of phenylalanine, 1.32kg of threonine, 0.66kg of tryptophan, 2.4kg of valine, 0.084kg of cysteine ​​hydrochloride, 1.5kg of histidine, 0.144kg of tyrosine, 0.78kg of acetyltyrosine, 1.68kg of alanine, 3.75kg of arginine, 2.1kg of proline, 1.2kg of serine, 1.14kg of glycine, 1.02kg of aspartic acid, 1.56kg of glutamic acid, and 0.09kg of taurine.

[0088] Before preparation, the pipelines and containers should be evacuated and filled with nitrogen to control the residual oxygen in the preparation tank to ≤0.5%.

[0089] Open the preparation tank and stir, add hypoxic water for injection to a total of 240L in the preparation tank, heat to above 90°C, continuously fill with nitrogen, control the dissolved oxygen content of the water for injection to ≤0.3mg / L before adding, add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, histidine, tyrosine, acetyltyrosine, alanine, arginine, proline, serine, glycine, aspartic acid, taurine in turn, stir and dissolve;

[0090] Cool down to 50°C, add 580 mL of glacial acetic acid to lower the pH of the solution, stir for 5 min, then add glutathione, glutamic acid, and cysteine ​​hydrochloride, stir to dissolve, add water for injection to 300 L, and then add glacial acetic acid to adjust the pH to 5.8 to obtain a solution;

[0091] Take samples of the drug solution for intermediate determination, filter and fill them into three-layer co-extruded infusion film bags after passing the test, and seal them;

[0092] The sample was sterilized by hot pressing at 121℃ for 12min. Low oxygen water was used for sterilization, and the dissolved oxygen was ≤0.5mg / L, and the residual oxygen in the sterilization process control cabinet was ≤0.1%;

[0093] The sterilized sample and the oxygen absorbent are placed in a barrier bag and vacuum-sealed to obtain the compound amino acid injection.

[0094] Comparative Example 1

[0095] The prescription and preparation method of the pediatric compound amino acid injection in Comparative Example 1 are the same as those in Example 1, except that all the glacial acetic acid in Comparative Example 1 is added after the feeding is completed.

[0096] The cystine hydrochloride content in the pediatric compound amino acid injection prepared in Comparative Example 1 was detected, and the cystine hydrochloride content was 86.4%.

[0097] The cystine hydrochloride content of the embodiment is 88.0% to 89.6%, while the content of comparative example 1 is 86.4%. By comparison, it can be seen that adding in batches can increase the cystine hydrochloride content. Due to the marginal effect, when the cystine hydrochloride content is already at a higher concentration, the concentration of cystine hydrochloride has stabilized and is difficult to increase. The improvement of 3.2% in embodiment 1 of the present invention relative to comparative example 1 is a prominent effect improvement.

[0098] Comparative Example 2

[0099] The prescription and preparation method of the pediatric compound amino acid injection in Comparative Example 2 are the same as those in Example 1, with the only difference being that the dissolved oxygen is not controlled during the preparation and filling process of Comparative Example 2.

[0100] The cystine hydrochloride content in the pediatric compound amino acid injection prepared in Comparative Example 2 was detected, and the cystine hydrochloride content was 81.2%.

[0101] Comparative Example 3

[0102] The prescription and preparation method of the pediatric compound amino acid injection in Comparative Example 3 are the same as those in Example 1, with the only difference being that residual oxygen is not controlled during the preparation and filling process of Comparative Example 3.

[0103] The cystine hydrochloride content in the pediatric compound amino acid injection prepared in Comparative Example 3 was detected, and the cystine hydrochloride content was 73.5%.

[0104] Comparative Example 4

[0105] The prescription and preparation method of the pediatric compound amino acid injection in Comparative Example 4 are the same as those in Example 1, with the only difference being that the residual oxygen in the cabinet was not controlled during the sterilization process in Comparative Example 4.

[0106] The cystine hydrochloride content in the pediatric compound amino acid injection prepared in Comparative Example 4 was detected, and the cystine hydrochloride content was 74.9%.

[0107] Comparative Example 5

[0108] The prescription and preparation method of the pediatric compound amino acid injection in Comparative Example 5 are the same as those in Example 1, with the only difference being that the dissolved oxygen in the spray water in the cabinet was not controlled during the sterilization process in Comparative Example 5.

[0109] The cystine hydrochloride content in the pediatric compound amino acid injection prepared in Comparative Example 5 was detected, and the cystine hydrochloride content was 84.5%.

[0110] The contents of cysteine ​​hydrochloride in the compound amino acid injections of Example 1 and Comparative Examples 1 to 5 are shown in Table 4.

[0111] Table 4

[0112] sample Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Cysteine ​​hydrochloride content 89.6％ 86.4％ 81.2％ 73.5％ 74.9％ 84.5％

[0113] It can be seen from Table 2 that the cysteine ​​hydrochloride content in Example 1 is the highest, which indicates that the compound amino acid injection obtained by this method can avoid the oxidation of cysteine ​​hydrochloride to the greatest extent.

[0114] Comparative Example 6

[0115] The prescription and preparation method of the pediatric compound amino acid injection in Comparative Example 6 are the same as those in Example 1, except that 0.2 g / L of sodium bisulfite (antioxidant) is added during low temperature feeding in Comparative Example 6.

[0116] The tryptophan-related substances of Comparative Example 6 were detected, and the results are shown in Table 5.

[0117] Table 5

[0118]

[0119] According to the above data, the tryptophan-related substances in Comparative Example 6 are compared with those in Example 1 prepared simultaneously, and the impurities are increased to varying degrees, and the risk of clinical use is also higher.

[0120] The specific implementation methods described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific implementation method of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing a pediatric compound amino acid injection, characterized in that: The steps include: The pipes and tanks used for preparation shall be vacuumed and filled with nitrogen; Add hypoxic injection water into the preparation tank, heat it, continuously fill it with nitrogen, add isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, valine, histidine, tyrosine, acetyltyrosine, alanine, arginine, proline, serine, glycine, aspartic acid and taurine, and stir to dissolve; Cool the preparation tank, add glacial acetic acid, then add glutamic acid, glutamic acid, and cysteine ​​hydrochloride, stir to dissolve, add the remaining water for injection, and then add glacial acetic acid to adjust the pH value to obtain a drug solution; The drug solution is subjected to intermediate determination, and after filtration, it is filled and sealed; The sealed liquid medicine is sterilized by hot pressing and packed together with the oxygen absorbent into a barrier bag for vacuum packaging.

2. The method for preparing a pediatric compound amino acid injection according to claim 1, characterized in that: After the preparation tank is vacuumed and nitrogen-filled, the residual oxygen content is ≤0.5%.

3. The method for preparing a pediatric compound amino acid injection according to claim 1, characterized in that: The amount of the hypoxic water for injection added to the preparation tank before heating is 70-80% of the weight of the hypoxic water for injection.

4. The method for preparing a pediatric compound amino acid injection according to claim 1 or 3, characterized in that: The dissolved oxygen content of the hypoxic water for injection is ≤0.5 mg / L.

5. The method for preparing a pediatric compound amino acid injection according to claim 1, characterized in that: The heating temperature is 80-100°C.

6. The method for preparing a pediatric compound amino acid injection according to claim 1, characterized in that: The preparation tank is cooled to below 60°C.

7. The method for preparing a pediatric compound amino acid injection according to claim 1, characterized in that: The pH value of the medicinal solution is 5.2-5.

8.

8. The method for preparing a pediatric compound amino acid injection according to claim 1, characterized in that: The liquid medicine contains per 1000ml: Isoleucine 8-8.4g, leucine 12-16g, lysine acetate 11-13g, methionine 3.3-3.5g, phenylalanine 4.5-5g, threonine 4-4.4g, tryptophan 1.8-2.2g, valine 7.5-8g, cysteine ​​hydrochloride 0.2-0.28g, histidine 4.5-5g, tyrosine 0.4-0.48g, acetyltyrosine 2.2-2.6g, alanine 5.2-5.6g, arginine 11.5-12.5g, proline 6.5-7g, serine 3.5-4g, glycine 3.4-3.8g, aspartic acid 3-3.4g, glutamic acid 4.8-5.2g, taurine 0.2-0.3g, glacial acetic acid 1.0ml-4.0ml, and the remainder is water for hypoxic injection.

9. The method for preparing a pediatric compound amino acid injection according to claim 1, characterized in that: The hot pressure sterilization condition is: keeping warm at 121° C. for 12 minutes.

10. The compound amino acid injection prepared by the preparation method according to any one of claims 1 to 9.

Images