Composition of 14 amino acids and glucose stored in double-chamber bag and preparation method thereof

Abstract

The invention provides a composition of 14 amino acids and glucose stored in a double-chamber bag and a preparation method of the composition. The composition of 14 amino acids and glucose stored in the double-chamber bag does not contain sulfite antioxidants and metal ion chelating agents. The preparation method comprises the following steps: pretreating production equipment by adopting a pretreatment solution containing inorganic acid, organic acid and ammonium salt, and then preparing liquid medicine, filtering, making bags, filling, sealing outer bags, sterilizing and the like. Double-chamber bag packaging is adopted, so that the Maillard reaction of amino acid and glucose in the production and storage process can be avoided, meanwhile, the aluminum migration risk in the packaging material is reduced, and the clinical medication safety and effectiveness of the product are improved. During clinical use, liquid medicine in the two cavities is mixed through extrusion, the bioavailability of all the components can be synergistically improved, meanwhile, osmotic pressure is reduced, and clinical infusion compliance is improved.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a composition of 14 kinds of amino acids and glucose stored in a double-chamber bag and a preparation method thereof. Background Art

[0002] Compound amino acid injection (14AA) is a sterile aqueous solution prepared with 14 kinds of amino acids and excipients. It is clinically used to improve the nutritional status of patients before and after surgery and protein digestion and absorption disorders, and to alleviate symptoms of mild malnutrition caused by insufficient protein intake or excessive consumption.

[0003] Amino acids and glucose will undergo a Maillard reaction under high temperature conditions, resulting in a darker color of the drug solution, an increase in impurities, and a decrease in content. Generally, amino acids and glucose are not mixed in the same container during drug production. Currently, it is more common in clinical practice to mix two drug solutions containing amino acids and glucose in a sterile bag or to co-infuse through a Y-tube before infusion, which increases the risk of microbial contamination and uneven mixing of drug solutions.

[0004] The harm of sulfites to the human body is mainly reflected in inducing hypersensitivity reactions, carcinogenicity, and damage to body tissues and organs, especially brain tissue. The Chinese Medical Association's clinical application guidelines and expert consensus clearly point out that amino acid preparations without antioxidants can reduce liver damage and are safer for people with a history of allergies.

[0005] Aluminum (Al) can accumulate in the human body and produce chronic toxicity. The U.S. Food and Drug Administration requires that the aluminum content in the solution of large-volume injections used for total parenteral nutrition, small-volume injections that require dilution or dissolution, lyophilized powder injections, etc., after clinical preparation according to the instructions, shall not exceed 25μg / L, and warnings should be issued in the instructions and labels.

[0006] Some amino acids are unstable, especially tryptophan. Under the catalysis of metal ions, they will degrade, causing the color of the drug solution to deepen, the transmittance and amino acid content to decrease, and the related substances to increase, thereby affecting the product quality and stability and increasing the risk of clinical medication. In order to improve product quality and stability, some drugs will add metal ion chelators such as disodium edetate and sodium calcium edetate to the prescription. Foreign countries have warned about the safety of edetic acid (EDTA) and its salts. The safety assessment report on EDTA and its salts published by the American Cosmetic Ingredient Review Expert Group clearly pointed out that EDTA and its salts (including disodium edetate) are cytotoxic and genotoxic. Disodium edetate can combine with divalent and tetravalent metal ions in the human body, resulting in element loss and inducing hypocalcemia. There have been many cases in the United States where children and adults have died due to accidental ingestion of disodium edetate for "chelation therapy."

[0007] Chinese patent CN110507604A describes a method for preparing a compound amino acid injection, which comprises the following steps: flushing the preparation container and pipeline with alkaline water, metal ion chelating agent solution and water for injection respectively.

[0008] Chinese patent CN115770217B describes a method for preparing a compound amino acid injection 18AA without an antioxidant, the steps comprising: firstly, circulate and flush the liquid preparation system and pipelines with a sodium carbonate solution, and after the sodium carbonate solution is completely drained, flush with injection water until the pH value of the rinse water is 5.0-7.0 and the conductivity is less than 1 μs / cm; then, circulate and flush the liquid preparation system and pipelines with a disodium edetate solution, and after the disodium edetate solution is completely drained, flush with injection water until the pH value of the rinse water is 5.0-7.0 and the conductivity is less than 1 μs / cm.

[0009] Chinese patent CN109381457B discloses a pharmaceutical composition containing 14 kinds of amino acids and its preparation method. The pharmaceutical composition containing 14 kinds of amino acids is a single amino acid drug, without glucose to provide energy, with high osmotic pressure during infusion and poor compliance during clinical use. The drug solution is packaged in a glass infusion bottle, which poses a risk of aluminum ion dissolution.

[0010] Chinese patent CN102600187A discloses an amino acid glucose injection packaged in a double-chamber bag and a preparation method thereof. The liquid medicine contains 18 components. In order to improve the stability of the product, a sulfite antioxidant sodium metabisulfite is added, which has a significant risk of adverse reactions in clinical practice.

[0011] Therefore, it is worthwhile to explore the combination of 14 amino acids and glucose in a formulation without sulfite antioxidants and metal ion chelators and packaged in a double-chamber bag. Summary of the invention

[0012] In view of this, the present invention proposes a composition as a parenteral nutrition preparation, comprising two chambers, namely an amino acid chamber and a glucose chamber. Among them, the amino acid chamber is composed of 14 kinds of amino acids, designed according to the characteristics of the human plasma amino acid spectrum, and contains 8 essential amino acids and 6 non-essential amino acids. The glucose chamber contains 5% to 10% glucose for providing energy. During clinical use, the cold weld sealing strip between the two chambers is opened by squeezing, and the liquid medicines in the two chambers are mixed and infused. Glucose can synergistically improve the bioavailability of each amino acid and improve the clinical effectiveness of the product. The composition of the present invention is suitable for improving the nutritional status of patients before and after surgery, and is also used to improve protein digestion and absorption disorders, and alleviate mild malnutrition caused by insufficient protein intake or excessive consumption.

[0013] In view of the shortcomings of the prior art, the first object of the present invention is to provide a 14-amino acid and glucose composition packaged in a double-chamber bag, with a reasonable product formula, good stability after mixing the drug solution, appropriate osmotic pressure, and good compliance during clinical infusion. The use of soft bag packaging significantly reduces the risk of affecting product quality and clinical drug safety due to aluminum migration from the packaging material during long-term storage of the drug solution.

[0014] The second object of the present invention is to provide a method for preparing the composition, wherein the equipment is passivated before production to reduce the risk of metal element dissolution in the production equipment, the amino acid components are grouped according to their stability and solubility and then fed, and inert gas protection is used throughout the process to ensure the stability of the drug solution without the protection of sulfite antioxidants and metal ion chelators.

[0015] The technical solution of the present invention is implemented as follows: The present invention provides a method for preparing a composition of 14 amino acids and glucose stored in a double-chamber bag, the preparation method comprising:

[0016] Step S1: pretreating the liquid preparation tank and pipeline with a pretreatment liquid containing an inorganic acid, an organic acid and an ammonium salt;

[0017] Step S2: preparing amino acid solution and glucose solution in different liquid preparation tanks respectively, and then filling them into two chambers of the double-chamber bag respectively.

[0018] On the basis of the above technical solution, preferably, in step S1, based on the mass percentage of 100%, the inorganic acid in the pretreatment liquid is 5% to 10%, the organic acid is 0.05% to 1%, the ammonium salt is 0.5% to 2%, and the balance is water.

[0019] On the basis of the above technical solution, preferably, the inorganic acid is selected from at least one of nitric acid and phosphoric acid.

[0020] On the basis of the above technical solution, preferably, the organic acid is selected from at least one of citric acid, malic acid and acetic acid.

[0021] On the basis of the above technical solution, preferably, the ammonium salt is selected from at least one of ammonium nitrate, ammonium citrate, ammonium malate and ammonium acetate.

[0022] On the basis of the above technical solution, preferably, in the step S1, the pretreatment temperature is 40-70°C.

[0023] On the basis of the above technical scheme, preferably, in step S2, the amino acid solution contains isoleucine, leucine, valine, alanine, lysine acetate, histidine, arginine, serine, methionine, proline, phenylalanine, glycine, threonine, tryptophan and water.

[0024] Based on the above technical solution, preferably, the glucose solution contains glucose and water.

[0025] On the basis of the above technical solution, preferably, in the amino acid liquid, the mass volume ratio of the isoleucine to the water is 5.31g / L-6.49g / L; the mass volume ratio of the leucine to the water is 6.93g / L-8.47g / L; the mass volume ratio of the valine to the water is 5.04g / L-6.16g / L; the mass volume ratio of the alanine to the water is 5.40g / L-6.60g / L; the mass volume ratio of the lysine acetate to the water is 7.83g / L-9.57g / L; the mass volume ratio of the histidine to the water is 2.16g / L-2.64g / L; the mass volume ratio of the arginine to the water is 7.29 g / L~8.91g / L; the mass volume ratio of the serine to the water is 4.50g / L~5.50g / L; the mass volume ratio of the methionine to the water is 4.05g / L~4.95g / L; the mass volume ratio of the proline to the water is 8.55g / L~10.45g / L; the mass volume ratio of the phenylalanine to the water is 4.32g / L~5.28g / L; the mass volume ratio of the glycine to the water is 10.71g / L~13.09g / L; the mass volume ratio of the threonine to the water is 3.06g / L~3.74g / L; the mass volume ratio of the tryptophan to the water is 1.17g / L~1.43g / L;

[0026] In the glucose solution, the mass volume ratio of the glucose to the water is 40 g / L to 110 g / L.

[0027] On the basis of the above technical solution, preferably, in the amino acid liquid, the mass volume ratio of the isoleucine to the water is 5.61g / L-6.20g / L; the mass volume ratio of the leucine to the water is 7.32g / L-8.09g / L; the mass volume ratio of the valine to the water is 5.32g / L-5.88g / L; the mass volume ratio of the alanine to the water is 5.70g / L-6.30g / L; the mass volume ratio of the lysine acetate to the water is 8.27g / L-9.14g / L; the mass volume ratio of the histidine to the water is 2.28g / L-2.52g / L; the mass volume ratio of the arginine to the water is 7.70 g / L~8.51g / L; the mass volume ratio of the serine to the water is 4.75g / L~5.25g / L; the mass volume ratio of the methionine to the water is 4.28g / L~4.73g / L; the mass volume ratio of the proline to the water is 9.03g / L~9.98g / L; the mass volume ratio of the phenylalanine to the water is 4.56g / L~5.04g / L; the mass volume ratio of the glycine to the water is 11.31g / L~12.50g / L; the mass volume ratio of the ammonia to the water is 3.23g / L~3.57g / L; the mass volume ratio of the tryptophan to the water is 1.24g / L~1.37g / L;

[0028] In the glucose solution, the mass volume ratio of the glucose to the water is 50 g / L to 100 g / L.

[0029] On the basis of the above technical solution, preferably, in the amino acid liquid, the mass volume ratio of the isoleucine to the water is 5.90 g / L; the mass volume ratio of the leucine to the water is 7.70 g / L; the mass volume ratio of the valine to the water is 5.60 g / L; the mass volume ratio of the alanine to the water is 6.00 g / L; the mass volume ratio of the lysine acetate to the water is 8.70 g / L; the mass volume ratio of the histidine to the water is 2.40 g / L; the mass volume ratio of the arginine to the water is The mass volume ratio of the serine to the water is 8.10 g / L; the mass volume ratio of the serine to the water is 5.00 g / L; the mass volume ratio of the methionine to the water is 4.50 g / L; the mass volume ratio of the proline to the water is 9.50 g / L; the mass volume ratio of the phenylalanine to the water is 4.80 g / L; the mass volume ratio of the glycine to the water is 11.90 g / L; the mass volume ratio of the threonine to the water is 3.40 g / L; the mass volume ratio of the tryptophan to the water is 1.30 g / L;

[0030] In the glucose solution, the mass volume ratio of the glucose to the water is 50 g / L.

[0031] On the basis of the above technical solution, preferably, no sulfite antioxidant and metal ion chelating agent are added to the amino acid solution and the glucose solution.

[0032] On the basis of the above technical solution, preferably, the sulfite antioxidant is selected from at least one of sodium bisulfite, sodium pyrosulfite and sodium sulfite.

[0033] On the basis of the above technical solution, preferably, the metal chelator is selected from edetate disodium and / or edetate calcium sodium.

[0034] On the basis of the above technical scheme, preferably, the preparation method of the amino acid solution comprises: under a nitrogen atmosphere, controlling the temperature of water to temperature 1, adding leucine, isoleucine, valine, phenylalanine, threonine and methionine, stirring for 1, cooling to temperature 2, adding lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, stirring for 2, adjusting the pH value to 5.0-7.0, adding water to make up the volume, and obtaining an amino acid solution.

[0035] On the basis of the above technical solution, preferably, the temperature of temperature 1 is 70-90°C, and the temperature of temperature 2 is 40-60°C.

[0036] On the basis of the above technical solution, preferably, the rotation speed of the stirring 1 is 80-150 rpm, and the rotation speed of the stirring 2 is 30-100 rpm.

[0037] On the basis of the above technical solution, preferably, the pH value of the amino acid solution is 5.5-6.8, and the pH value of the glucose solution is 3.5-6.0.

[0038] On the basis of the above technical solution, preferably, the pH value of the amino acid solution is 5.5-6.5, and the pH value of the glucose solution is 3.8-5.8.

[0039] On the basis of the above technical scheme, preferably, the preparation method of the glucose solution includes: under a nitrogen atmosphere, controlling the temperature of water to temperature 3, adding glucose, stirring for 3, adjusting the pH value to 3.2-6.5, adding water to make up the volume, and obtaining the glucose solution.

[0040] On the basis of the above technical solution, preferably, the temperature of the temperature 3 is 40-70°C.

[0041] On the basis of the above technical solution, preferably, the rotation speed of the stirring 3 is 50-120 rpm.

[0042] According to another aspect of the present application, there is provided a composition of 14 kinds of amino acids and glucose stored in a double-chamber bag prepared by the preparation method described above, wherein the double-chamber bag comprises an amino acid solution chamber and a glucose solution chamber separated by a space.

[0043] On the basis of the above technical solution, preferably, the residual oxygen content in the headspace of the amino acid solution chamber and the glucose solution chamber is both below 2.0%.

[0044] On the basis of the above technical solution, preferably, the dissolved oxygen content of the amino acid solution chamber and the glucose solution chamber are both below 2 mg / L.

[0045] On the basis of the above technical solution, preferably, the packaging volume ratio of the amino acid solution chamber to the glucose solution chamber is 1:1 to 1:3.

[0046] On the basis of the above technical solution, preferably, the total aluminum content in the amino acid solution chamber and the glucose solution chamber is lower than 25 μg / L.

[0047] On the basis of the above technical solution, preferably, the double-chamber bag comprises an inner bag and an outer bag, the inner bag is divided into two chambers by a weak welding rod, the inner bag is placed in the outer bag, and a deoxidizer and an indicator are placed between the inner bag and the outer bag.

[0048] On the basis of the above technical solution, preferably, the specification of the inner bag is 300ml to 2000ml.

[0049] On the basis of the above technical solution, preferably, the specifications of the inner bag are independently selected from any value among 300ml, 500ml, 800ml, 1000ml, 1200ml, 1500ml, 1800ml, 2000ml or a range value between any two of the above.

[0050] As an optional implementation scheme, the present application is implemented through the following technical solutions:

[0051] A method for preparing the above-mentioned 14 amino acids and glucose composition stored in a dual-chamber bag comprises the following steps:

[0052] A. Pre-treat the equipment that comes in direct contact with the liquid medicine before production;

[0053] B. Add an appropriate amount of fresh water for injection to the clean liquid preparation tank 1, continue to introduce pure nitrogen, start stirring, control the water temperature at 70-90°C, add leucine, isoleucine, valine, phenylalanine, threonine and methionine, stir to dissolve, cool to 40-60°C, add lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, stir to dissolve, adjust the pH value of the liquid to 5.0-7.0, stir evenly, and add water to make up to volume;

[0054] C. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 2, continue to introduce pure nitrogen, start stirring, control the water temperature at 40-70°C, add glucose, stir to dissolve, adjust the pH value of the liquid to 3.2-6.5, stir evenly, and add water to make up to volume;

[0055] D. The liquid medicine is filtered through 0.45μm and 0.22μm microporous filter elements and then transported to the filling room;

[0056] E. The double-chamber inner bag is made by filming, printing, cold welding, bag making, mouth tube welding, and edge tearing and shaping the infusion film, and after filling the liquid medicine, it is sealed with a drug infusion plug and a drug adding plug, and then put into a high-barrier outer bag, a deoxidizer is added, and the bag is sealed;

[0057] F. Sterilize by moist heat at 121° C. to 123° C. for 8 to 15 minutes to obtain a composition of 14 amino acids and glucose stored in a double-chamber bag.

[0058] The basic principle of the present invention is to encapsulate two incompatible drugs in different chambers, and to open the cold-welded sealing strips between the chambers by squeezing them during clinical use to mix the drug solutions evenly, thereby improving the effectiveness of the drug in clinical use. Process control measures are adopted, such as reducing the levels of residual oxygen and metal ions in the drug solution, improving the quality and stability of the drug solution, and avoiding the introduction of too many functional excipients, such as malic acid, citric acid, phosphoric acid, etc., which may affect the internal environment of the human body.

[0059] Since amino acids and reducing sugars such as glucose will undergo Maillard reaction under high temperature conditions, the color of the drug solution will deepen, impurities will increase, and the content will decrease, thereby increasing the risk of clinical medication. The present invention can solve the unmet clinical needs by developing a composition of 14 amino acids and glucose packaged in a double-chamber bag. Since sulfite antioxidants and metal ion chelators will increase the incidence of adverse reactions of drugs to a certain extent, the present invention innovates from a process perspective and can achieve or even exceed the currently known effect of protecting the stability of the product by adding other functional excipients.

[0060] The 14 kinds of amino acids and glucose composition stored in the double-chamber bag of the present invention has the following beneficial effects compared with the prior art:

[0061] (1) The 14 amino acids and glucose compositions stored in the double-chamber bags were pretreated with a combination of inorganic acid, organic acid and ammonium salt before production, and the effect was significantly better than that of alkali solution (sodium hydroxide, sodium carbonate) and / or disodium edetate, which reduced the risk of metal elements in the production equipment migrating into the drug solution from the source, thereby improving product quality and stability;

[0062] (2) The combination of 14 amino acids and glucose stored in a dual-chamber bag uses glucose as a non-protein energy source, which can improve the utilization rate of amino acids during clinical use;

[0063] (3) Developing amino acids and glucose into double-chamber bags to avoid Maillard reactions between amino acids and glucose drugs;

[0064] (4) No sulfite antioxidants or metal ion chelators are added to the amino acid solution and the glucose solution in the combination of 14 amino acids and glucose stored in the double-chamber bag. The soft bags are used for packaging. Under the premise of ensuring product quality and stability, the aluminum element in the solution can be controlled at a low level, less than 25 μg / L, making clinical medication safer. DETAILED DESCRIPTION

[0065] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0066] The reagents and raw materials used in the present invention are commercially available.

[0067] In the following embodiments, chamber 1 is an "amino acid solution chamber" and chamber 2 is a "glucose solution chamber".

[0068] Embodiment 1:

[0069] The raw materials for the 14 kinds of amino acids and glucose composition packaged in a double chamber bag were prepared, and the components and amounts thereof were as follows:

[0070] In chamber 1: the mass volume ratio of isoleucine to water is 5.90 g / L; the mass volume ratio of leucine to water is 7.70 g / L; the mass volume ratio of valine to water is 5.60 g / L; the mass volume ratio of alanine to water is 6.00 g / L; the mass volume ratio of lysine acetate to water is 8.70 g / L; the mass volume ratio of histidine to water is 2.40 g / L; the mass volume ratio of arginine to water is 8.10 g / L; the mass volume ratio of serine to water is 1. The mass volume ratio of acid to water is 5.00 g / L; the mass volume ratio of methionine to water is 4.50 g / L; the mass volume ratio of proline to water is 9.50 g / L; the mass volume ratio of phenylalanine to water is 4.80 g / L; the mass volume ratio of glycine to water is 11.90 g / L; the mass volume ratio of threonine to water is 3.40 g / L; the mass volume ratio of tryptophan to water is 1.30 g / L; and the pH value of the solution is adjusted to 6.2.

[0071] In chamber 2: the mass volume ratio of the glucose to the water is 50 g / L; the pH value of the liquid medicine is adjusted to 4.3.

[0072] The preparation method of the above composition comprises the following steps:

[0073] A. Before production, pre-treat the equipment that comes in direct contact with the liquid medicine: use 8% nitric acid, 0.05% citric acid and 1% ammonium nitrate, stirring and circulating at 50°C.

[0074] B. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 1, continue to introduce pure nitrogen, start stirring, control the water temperature at 70°C, add leucine, isoleucine, valine, phenylalanine, threonine and methionine, and stir at 120rpm to dissolve; cool to 50°C, add lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, and stir at 80rpm to dissolve, adjust the pH value of the solution to 6.2, stir evenly, add water to the prescribed amount, and obtain an amino acid solution.

[0075] C. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 2, continue to introduce pure nitrogen, start stirring, control the water temperature at 55°C, add glucose, stir at 100rpm to dissolve, adjust the pH value of the solution to 4.3, stir evenly, add water to make up to the prescribed amount, and obtain glucose solution.

[0076] D. Filter the amino acid solution and glucose solution through 0.45μm and 0.22μm microporous filter elements respectively, and then transport them to the filling room.

[0077] E. In the filling room, the infusion film is subjected to film application, printing, cold welding, bag making, mouth tube welding, and edge tearing to obtain a 500ml double-chamber inner bag. After filling with the drug solution, it is sealed with a drug infusion plug and a drug adding plug; the headspace residual oxygen content of chamber 1 and chamber 2 is both below 2.0%, and the dissolved oxygen content is both below 2 mg / L. The packaging volume ratio of chamber 1 and chamber 2 is 1:1. It is put into a high-barrier outer bag, a deoxidizer and an indicator are added, and the bag is sealed to obtain a double-chamber pretreatment bag containing drug solution.

[0078] F. Sterilize the double-chamber pretreatment bag containing the drug solution by wet heat sterilization at 121° C. for 12 minutes to obtain the 14 amino acids and glucose composition stored in the double-chamber bag.

[0079] Embodiment 2:

[0080] The raw materials for the 14 kinds of amino acids and glucose composition packaged in a double chamber bag were prepared, and the components and amounts thereof were as follows:

[0081] In chamber 1: the mass volume ratio of isoleucine to water is 5.31 g / L; the mass volume ratio of leucine to water is 6.93 g / L; the mass volume ratio of valine to water is 5.04 g / L; the mass volume ratio of alanine to water is 5.40 g / L; the mass volume ratio of lysine acetate to water is 7.83 g / L; the mass volume ratio of histidine to water is 2.16 g / L; the mass volume ratio of arginine to water is 7.29 g / L; the silk The mass volume ratio of alanine to the water is 4.50 g / L; the mass volume ratio of methionine to the water is 4.05 g / L; the mass volume ratio of proline to the water is 8.55 g / L; the mass volume ratio of phenylalanine to the water is 4.32 g / L; the mass volume ratio of glycine to the water is 10.71 g / L; the mass volume ratio of threonine to the water is 3.06 g / L; the mass volume ratio of tryptophan to the water is 1.17 g / L; and the pH value of the solution is adjusted to 5.5.

[0082] In chamber 2: the mass volume ratio of the glucose to the water is 40 g / L; the pH value of the liquid medicine is adjusted to 3.8.

[0083] The preparation method of the above composition comprises the following steps:

[0084] A. Before production, pre-treat the equipment that comes in direct contact with the liquid medicine: use 5% phosphoric acid, 0.5% malic acid and 0.5% ammonium malate, stirring and circulating at 40°C.

[0085] B. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 1, continue to introduce pure nitrogen, start stirring, control the water temperature at 80°C, add leucine, isoleucine, valine, phenylalanine, threonine and methionine, and stir at 80rpm to dissolve; cool to 40°C, add lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, and stir at 100rpm to dissolve, adjust the pH value of the solution to 5.5, stir evenly, add water to make up to the prescribed amount, and obtain an amino acid solution.

[0086] C. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 2, continue to introduce pure nitrogen, start stirring, control the water temperature at 50°C, add glucose, stir at 50rpm to dissolve, adjust the pH value of the solution to 3.8, stir evenly, add water to make up to the prescribed amount, and obtain glucose solution.

[0087] D. Filter the amino acid solution and glucose solution through 0.45μm and 0.22μm microporous filter elements respectively, and then transport them to the filling room.

[0088] E. In the filling room, the infusion film is subjected to filming, printing, cold welding, bag making, mouth tube welding, and edge tearing to obtain a 1000ml double-chamber inner bag, which is filled with the drug solution and sealed with a drug infusion plug and a drug adding plug. The headspace residual oxygen content of chamber 1 and chamber 2 is both below 2.0%, and the dissolved oxygen content is both below 2 mg / L. The packaging volume ratio of chamber 1 and chamber 2 is 1:1, and the bag is put into a high-barrier outer bag, a deoxidizer and an indicator are added, and the bag is sealed to obtain a double-chamber pretreatment bag containing drug solution.

[0089] F. Sterilize the double-chamber pretreatment bag containing the drug solution at 121° C. for 15 minutes to obtain the 14 amino acids and glucose composition stored in the double-chamber bag.

[0090] Embodiment 3:

[0091] The raw materials of 14 kinds of amino acids and glucose combination packaged in a double chamber bag were prepared, and the components and amounts thereof were as follows:

[0092] In chamber 1: the mass volume ratio of isoleucine to water is 6.49 g / L; the mass volume ratio of leucine to water is 8.47 g / L; the mass volume ratio of valine to water is 6.16 g / L; the mass volume ratio of alanine to water is 6.60 g / L; the mass volume ratio of lysine acetate to water is 9.57 g / L; the mass volume ratio of histidine to water is 2.64 g / L; the mass volume ratio of arginine to water is 8.91 g / L; the mass volume ratio of serine to water is 1. The mass volume ratio of acid to water is 5.50 g / L; the mass volume ratio of methionine to water is 4.95 g / L; the mass volume ratio of proline to water is 10.45 g / L; the mass volume ratio of phenylalanine to water is 5.28 g / L; the mass volume ratio of glycine to water is 13.09 g / L; the mass volume ratio of threonine to water is 3.74 g / L; the mass volume ratio of tryptophan to water is 1.43 g / L; and the pH value of the solution is adjusted to 5.0.

[0093] In chamber 2: the mass volume ratio of the glucose to the water is 100 g / L; the pH value of the liquid medicine is adjusted to 5.5.

[0094] The preparation method of the above composition comprises the following steps:

[0095] A. Before production, pre-treat the equipment that comes in direct contact with the chemical solution: use 10% nitric acid, 1% malic acid and 1% ammonium nitrate, stirring and circulating at 60°C.

[0096] B. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 1, continue to introduce pure nitrogen, start stirring, control the water temperature at 90°C, add leucine, isoleucine, valine, phenylalanine, threonine and methionine, and stir at 150rpm to dissolve; cool to 60°C, add lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, and stir at 30rpm to dissolve, adjust the pH value of the solution to 5.0, stir evenly, add water to the prescribed amount, and obtain an amino acid solution.

[0097] C. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 2, continue to introduce pure nitrogen, start stirring, control the water temperature at 70°C, add glucose, stir at 120rpm to dissolve, adjust the pH value of the liquid to 5.5, stir evenly, add water to make up to the prescribed amount, and obtain glucose liquid.

[0098] D. Filter the amino acid solution and glucose solution through 0.45μm and 0.22μm microporous filter elements respectively, and then transport them to the filling room.

[0099] E. In the filling room, the infusion film is subjected to film application, printing, cold welding, bag making, mouth tube welding, and edge tearing to obtain a 1500ml double-chamber inner bag. After filling with the drug solution, it is sealed with a drug infusion plug and a drug adding plug; the headspace residual oxygen content of chamber 1 and chamber 2 is both below 2.0%, and the dissolved oxygen content is both below 2 mg / L. The packaging volume ratio of chamber 1 and chamber 2 is 1:2. It is put into a high-barrier outer bag, a deoxidizer and an indicator are added, and the bag is sealed to obtain a double-chamber pretreatment bag containing drug solution.

[0100] F. Sterilize the double-chamber pretreatment bag containing the drug solution at 122° C. for 12 minutes to obtain the 14 amino acids and glucose composition stored in the double-chamber bag.

[0101] Embodiment 4:

[0102] The raw materials of 14 kinds of amino acids and glucose combination packaged in a double chamber bag were prepared, and the components and amounts thereof were as follows:

[0103] In chamber 1: the mass volume ratio of isoleucine to water is 5.61 g / L; the mass volume ratio of leucine to water is 7.32 g / L; the mass volume ratio of valine to water is 5.32 g / L; the mass volume ratio of alanine to water is 5.70 g / L; the mass volume ratio of lysine acetate to water is 8.27 g / L; the mass volume ratio of histidine to water is 2.28 g / L; the mass volume ratio of arginine to water is 7.70 g / L; the silk The mass volume ratio of alanine to the water is 4.75 g / L; the mass volume ratio of methionine to the water is 4.28 g / L; the mass volume ratio of proline to the water is 9.03 g / L; the mass volume ratio of phenylalanine to the water is 4.56 g / L; the mass volume ratio of glycine to the water is 11.31 g / L; the mass volume ratio of threonine to the water is 3.23 g / L; the mass volume ratio of tryptophan to the water is 1.24 g / L; and the pH value of the solution is adjusted to 7.0.

[0104] In chamber 2: the mass volume ratio of the glucose to the water is 80 g / L; the pH value of the liquid medicine is adjusted to 6.0.

[0105] The preparation method of the above composition comprises the following steps:

[0106] A. Before production, pre-treat the equipment that comes in direct contact with the liquid medicine: use 9% nitric acid, 1% acetic acid and 0.5% ammonium acetate, stir and circulate at 70°C.

[0107] B. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 1, continue to introduce pure nitrogen, start stirring, control the water temperature at 85°C, add leucine, isoleucine, valine, phenylalanine, threonine and methionine, and stir at 100rpm to dissolve; cool to 55°C, add lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, and stir at 50rpm to dissolve, adjust the pH value of the solution to 7.0, stir evenly, add water to make up to the prescribed amount, and obtain an amino acid solution.

[0108] C. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 2, continue to introduce pure nitrogen, start stirring, control the water temperature at 40°C, add glucose, stir at 60rpm to dissolve, adjust the pH value of the solution to 6.0, stir evenly, add water to make up to the prescribed amount, and obtain glucose solution.

[0109] D. Filter the amino acid solution and glucose solution through 0.45μm and 0.22μm microporous filter elements respectively, and then transport them to the filling room.

[0110] E. In the filling room, the infusion film is subjected to film application, printing, cold welding, bag making, mouth tube welding, and edge tearing to obtain a 2000ml double-chamber inner bag. After filling with the drug solution, it is sealed with a drug infusion plug and a drug adding plug; the headspace residual oxygen content of chamber 1 and chamber 2 is both below 2.0%, and the dissolved oxygen content is both below 2 mg / L. The packaging volume ratio of chamber 1 and chamber 2 is 1:3. It is put into a high-barrier outer bag, a deoxidizer and an indicator are added, and the bag is sealed to obtain a double-chamber pretreatment bag containing drug solution.

[0111] F. Sterilize the double-chamber pretreatment bag containing the drug solution at 123° C. for 8 minutes to obtain the 14 amino acids and glucose composition stored in the double-chamber bag.

[0112] Embodiment 5:

[0113] The raw materials of 14 kinds of amino acids and glucose combination packaged in a double chamber bag were prepared, and the components and amounts thereof were as follows:

[0114] In chamber 1: the mass volume ratio of isoleucine to water is 6.20 g / L; the mass volume ratio of leucine to water is 8.09 g / L; the mass volume ratio of valine to water is 5.88 g / L; the mass volume ratio of alanine to water is 6.30 g / L; the mass volume ratio of lysine acetate to water is 9.14 g / L; the mass volume ratio of histidine to water is 2.52 g / L; the mass volume ratio of arginine to water is 8.51 g / L; the silk The mass volume ratio of alanine to the water is 5.25 g / L; the mass volume ratio of methionine to the water is 4.73 g / L; the mass volume ratio of proline to the water is 9.98 g / L; the mass volume ratio of phenylalanine to the water is 5.04 g / L; the mass volume ratio of glycine to the water is 12.50 g / L; the mass volume ratio of threonine to the water is 3.57 g / L; the mass volume ratio of tryptophan to the water is 1.37 g / L; and the pH value of the solution is adjusted to 5.8.

[0115] In chamber 2: the mass volume ratio of the glucose to the water is 110 g / L; the pH value of the liquid medicine is adjusted to 6.5.

[0116] The preparation method of the above composition comprises the following steps:

[0117] A. Before production, pre-treat the equipment that comes in direct contact with the liquid medicine: use 7% phosphoric acid, 1% citric acid and 2% ammonium citrate, stirring and circulating at 55°C.

[0118] B. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 1, continue to introduce pure nitrogen, start stirring, control the water temperature at 72°C, add leucine, isoleucine, valine, phenylalanine, threonine and methionine, and stir at 90rpm to dissolve; cool to 53°C, add lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, and stir at 60rpm to dissolve, adjust the pH value of the solution to 5.8, stir evenly, add water to the prescribed amount, and obtain an amino acid solution.

[0119] C. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 2, continue to introduce pure nitrogen, start stirring, control the water temperature at 60°C, add glucose, stir at 80rpm to dissolve, adjust the pH value of the liquid to 6.5, stir evenly, add water to make up to the prescribed amount, and obtain glucose liquid.

[0120] D. Filter the amino acid solution and glucose solution through 0.45μm and 0.22μm microporous filter elements respectively, and then transport them to the filling room.

[0121] E. In the filling room, the infusion film is subjected to film application, printing, cold welding, bag making, mouth tube welding, and edge tearing to obtain a 300 ml double-chamber inner bag. After filling with the drug solution, it is sealed with a drug infusion plug and a drug adding plug; the headspace residual oxygen content of chamber 1 and chamber 2 is both below 2.0%, and the dissolved oxygen content is both below 2 mg / L. The packaging volume ratio of chamber 1 and chamber 2 is 1:2. It is put into a high-barrier outer bag, a deoxidizer and an indicator are added, and the bag is sealed to obtain a double-chamber pretreatment bag containing drug solution.

[0122] F. Sterilize the double-chamber pretreatment bag containing the drug solution at 121° C. for 10 minutes to obtain the 14 amino acids and glucose composition stored in the double-chamber bag.

[0123] Embodiment 6:

[0124] The raw materials for the 14 kinds of amino acids and glucose composition packaged in a double chamber bag were prepared, and the components and amounts thereof were as follows:

[0125] In chamber 1: the mass volume ratio of isoleucine to water is 6.00 g / L; the mass volume ratio of leucine to water is 7.50 g / L; the mass volume ratio of valine to water is 6.00 g / L; the mass volume ratio of alanine to water is 6.10 g / L; the mass volume ratio of lysine acetate to water is 8.50 g / L; the mass volume ratio of histidine to water is 2.20 g / L; the mass volume ratio of arginine to water is 7.50 g / L; the silk The mass volume ratio of alanine to the water is 5.15 g / L; the mass volume ratio of methionine to the water is 4.55 g / L; the mass volume ratio of proline to the water is 9.70 g / L; the mass volume ratio of phenylalanine to the water is 4.85 g / L; the mass volume ratio of glycine to the water is 11.50 g / L; the mass volume ratio of threonine to the water is 3.20 g / L; the mass volume ratio of tryptophan to the water is 1.00 g / L; and the pH value of the solution is adjusted to 6.7.

[0126] In chamber 2: the mass volume ratio of the glucose to the water is 60 g / L; the pH value of the liquid is adjusted to 3.2.

[0127] The preparation method of the above composition comprises the following steps:

[0128] A. Before production, pre-treat the equipment that comes in direct contact with the liquid medicine: use 6% phosphoric acid, 0.08% acetic acid and 2% ammonium acetate, stir and circulate at 45°C.

[0129] B. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 1, continue to introduce pure nitrogen, start stirring, control the water temperature at 83°C, add leucine, isoleucine, valine, phenylalanine, threonine and methionine, and stir at 110rpm to dissolve; cool to 57°C, add lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, and stir at 40rpm to dissolve, adjust the pH value of the solution to 6.7, stir evenly, add water to the prescribed amount, and obtain an amino acid solution.

[0130] C. Add an appropriate amount of fresh water for injection into the clean liquid preparation tank 2, continue to introduce pure nitrogen, start stirring, control the water temperature at 65°C, add glucose, stir at 70rpm to dissolve, adjust the pH value of the solution to 3.2, stir evenly, add water to make up to the prescribed amount, and obtain glucose solution.

[0131] D. Filter the amino acid solution and glucose solution through 0.45μm and 0.22μm microporous filter elements respectively, and then transport them to the filling room.

[0132] E. In the filling room, the infusion film is subjected to film application, printing, cold welding, bag making, mouth tube welding, and edge tearing to obtain a 750ml double-chamber inner bag. After filling with the drug solution, it is sealed with a drug infusion plug and a drug adding plug; the headspace residual oxygen content of chamber 1 and chamber 2 is both below 2.0%, and the dissolved oxygen content is both below 2 mg / L. The packaging volume ratio of chamber 1 and chamber 2 is 1:3. It is put into a high-barrier outer bag, a deoxidizer and an indicator are added, and the bag is sealed to obtain a double-chamber pretreatment bag containing drug solution.

[0133] F. Sterilize the double-chamber pretreatment bag containing the drug solution at 123° C. for 15 minutes to obtain the 14 amino acids and glucose composition stored in the double-chamber bag.

[0134] The technical solution of the present invention is further described by the following relevant experiments:

[0135] Since there are many sources of aluminum in medicines, such as production equipment, containers, personnel, raw materials, packaging materials, etc., and since aluminum is cumulative and can be harmful to the human body, in order to minimize the aluminum residue in medicines, it is necessary to strengthen production management and control.

[0136] 1. Taking aluminum as a representative indicator, the test results are as follows:

[0137] The present invention adopts 13 different pretreatment methods, including method 1 to method 13, to pretreat the equipment before production. Except for the different pretreatment methods for the equipment before production, the remaining steps are consistent with the steps of preparing 14 kinds of amino acids and glucose compositions stored in a double-chamber bag in Example 1. After comparative study, the 14 kinds of amino acids and glucose compositions stored in a double-chamber bag were prepared according to the raw material formula for preparing amino acid liquid and glucose liquid in Example 1. It was found that the combination of inorganic acid, organic acid and ammonium salt was used to pretreat the production equipment, and unexpected effects were achieved: the metal elements in the equipment were dissolved out of the wind

[0138] The risk is lower and it is more friendly to production equipment, environment and operators. The specific results are shown in Table 1.

[0139] Table 1 Detection results of aluminum in the prepared liquid after treatment with different methods

[0140] Preprocessing methods Treatment Al(μg / L) Method 1 8% nitric acid + 0.2% citric acid + 1% ammonium nitrate 4.0 Method 2 5% nitric acid + 1% malic acid + 1% ammonium nitrate 4.1 Method 3 5% phosphoric acid + 0.2% citric acid + 1% ammonium citrate 4.8 Method 4 10% phosphoric acid + 0.5% malic acid + 0.5% ammonium malate 4.5 Method 5 5% nitric acid + 1% acetic acid + 1% ammonium acetate 5.0 Method 6 5% phosphoric acid + 1% acetic acid + 1% ammonium acetate 5.2 Method 7 0.5% citric acid 11.8 Method 8 5% nitric acid 8.6 Method 9 5% nitric acid + 0.5% citric acid 7.2 Method 10 0.05% Edetate Disodium 10.5 Method 11 First 3% sodium carbonate, then 0.1% edetate disodium 9.5 Method 12 3% Sodium carbonate 13.6 Method 13 1% Sodium Hydroxide 8.8

[0141] As can be seen from Table 1, inorganic acids are highly acidic and can quickly dissolve metal oxides deposited on the surface of equipment. Organic acids will form stable soluble substances with some metal elements, increase the degree of migration of metal elements from the surface of equipment, and delay the aging of equipment. Ammonium salts can form a buffer system with inorganic acids and organic acids to promote the migration speed of synergistic metal elements. The combination of the three can significantly reduce the risk of metal elements migrating from production equipment to the liquid medicine.

[0142] Then, the present invention studies the dosage and treatment conditions of inorganic acid, organic acid and ammonium salt, and determines the process of pre-treatment of equipment before production. The concentration of inorganic acid is 5% to 10%, the concentration of organic acid is 0.05% to 1%, and the concentration of ammonium salt is 0.5% to 2%. The inorganic acid is selected from at least one of nitric acid and phosphoric acid; the organic acid is selected from one or more of citric acid, malic acid and acetic acid; and the ammonium salt is selected from one or more of ammonium nitrate, ammonium citrate, ammonium malate and ammonium acetate.

[0143] 2. Determination results of aluminum element in Examples 1 to 6

[0144] Table 2 Sample test results in Examples 1 to 6

[0145] Test items Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Aluminum (μg / L) 4.5 5.1 5.3 4.7 5.2 5.3 result Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations

[0146] The results in Table 2 show that the aluminum content in the products obtained in Examples 1 to 6 is significantly lower than 25 μg / L, which is in compliance with the regulations.

[0147] 3. The quality of the product obtained in Example 1 was compared with the commercially available compound amino acid injection (14AA) containing sulfite (comparative group 1) and the pharmaceutical composition containing 14 amino acids disclosed in Chinese patent CN 109381457B (comparative group 2):

[0148] The prescription of the commercially available compound amino acid injection (14AA) containing sulfite is as follows:

[0149]

[0150]

[0151] The pharmaceutical composition containing 14 kinds of amino acids disclosed in Chinese patent CN 109381457B does not contain sulfite antioxidants, and the prescription is as follows:

[0152]

[0153]

[0154] In order to investigate the quality and stability of the samples in the test group and the control group, the products were placed under light (total illumination not less than 1.2×10 6 Lux·hr, near ultraviolet energy not less than 200w·hr / m 2 ), and placed under high temperature (60°C), and samples were taken at the end of the light exposure, the 10th day at high temperature, and the 30th day to measure its properties, pH value, light transmittance, visible foreign matter, aluminum, osmotic pressure molar concentration, amino acid labeled content and other indicators. The amino acid labeled content was determined by high performance liquid chromatography or amino acid analyzer. The results are shown in Tables 3-4.

[0155] Table 3 Comparison results under lighting conditions (light end point)

[0156]

[0157] Table 4 Comparison results under high temperature 60℃

[0158]

[0159] From the test results in Tables 3 and 4 above, it can be seen that the present invention and the comparison group 1 and the comparison group 2 respectively have different illumination levels (total illumination not less than 1.2×10 6 Lux·hr, near ultraviolet energy not less than 200w·hr / m 2), and high temperature (60°C) conditions. From the analysis of the changing trends of indicators such as properties, transmittance, aluminum, and tryptophan content, the quality and stability of the composition of the present invention are better than those of comparison group 1 and comparison group 2, especially the aluminum content is much lower than 25 μg / L, and there is no obvious change during the observation period; the osmotic pressure molar concentration of the mixed drug solution is closer to that of the isotonic solution, and the human body has higher tolerance. Therefore, the 14 amino acids and glucose composition stored in the double-chamber bag provided by the present invention has higher clinical drug safety.

[0160] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a composition of 14 amino acids and glucose stored in a double-chamber bag, characterized in that: The preparation method comprises: Step S1: pretreating the liquid preparation tank and pipeline with a pretreatment liquid containing an inorganic acid, an organic acid and an ammonium salt; Step S2: preparing amino acid solution and glucose solution in different liquid preparation tanks respectively, and then filling them into two chambers of the double-chamber bag respectively.

2. The preparation method according to claim 1, characterized in that: In the step S1, based on the mass percentage of 100%, the inorganic acid in the pretreatment solution is 5% to 10%, the organic acid is 0.05% to 1%, the ammonium salt is 0.5% to 2%, and the balance is water; The inorganic acid is selected from at least one of nitric acid and phosphoric acid; The organic acid is selected from at least one of citric acid, malic acid and acetic acid; The ammonium salt is selected from at least one of ammonium nitrate, ammonium citrate, ammonium malate and ammonium acetate; In the step S1, the pretreatment temperature is 40-70°C.

3. The preparation method according to claim 1, characterized in that: In step S2, the amino acid solution contains isoleucine, leucine, valine, alanine, lysine acetate, histidine, arginine, serine, methionine, proline, phenylalanine, glycine, threonine, tryptophan and water; The glucose solution contains glucose and water.

4. The preparation method according to claim 3, characterized in that: In the amino acid liquid, The mass volume ratio of the isoleucine to the water is 5.31 g / L to 6.49 g / L; The mass volume ratio of the leucine to the water is 6.93 g / L to 8.47 g / L; The mass volume ratio of the valine to the water is 5.04 g / L to 6.16 g / L; The mass volume ratio of the alanine to the water is 5.40 g / L to 6.60 g / L; The mass volume ratio of the lysine acetate to the water is 7.83 g / L to 9.57 g / L; The mass volume ratio of the histidine to the water is 2.16 g / L to 2.64 g / L; The mass volume ratio of the arginine to the water is 7.29 g / L to 8.91 g / L; The mass volume ratio of the serine to the water is 4.50 g / L to 5.50 g / L; The mass volume ratio of the methionine to the water is 4.05 g / L to 4.95 g / L; The mass volume ratio of the proline to the water is 8.55 g / L to 10.45 g / L; The mass volume ratio of the phenylalanine to the water is 4.32 g / L to 5.28 g / L; The mass volume ratio of the glycine to the water is 10.71 g / L to 13.09 g / L; The mass volume ratio of the threonine to the water is 3.06 g / L to 3.74 g / L; The mass volume ratio of the tryptophan to the water is 1.17 g / L to 1.43 g / L; In the glucose solution, The mass volume ratio of the glucose to the water is 40 g / L to 110 g / L.

5. The preparation method according to claim 3, characterized in that: The preparation method of the amino acid liquid comprises: in a nitrogen atmosphere, controlling the temperature of water to temperature 1, adding leucine, isoleucine, valine, phenylalanine, threonine and methionine, stirring for 1, cooling to temperature 2, adding lysine acetate, glycine, proline, alanine, serine, histidine, arginine and tryptophan, stirring for 2, adjusting the pH value to 5.0-7.0, adding water to make up the volume, and obtaining the amino acid liquid.

6. The preparation method according to claim 5, characterized in that: The temperature of temperature 1 is 70-90°C, and the temperature of temperature 2 is 40-60°C; The rotation speed of the stirring 1 is 80-150 rpm, and the rotation speed of the stirring 2 is 30-100 rpm.

7. The preparation method according to claim 1, characterized in that: The preparation method of the glucose solution comprises: in a nitrogen atmosphere, controlling the temperature of water to be 3, adding glucose, stirring for 3, adjusting the pH value to be 3.2-6.5, adding water to make up the volume, and obtaining the glucose solution.

8. The preparation method according to claim 7, characterized in that: The temperature of the temperature 3 is 40-70°C; The rotation speed of the stirring 3 is 50-120 rpm.

9. The composition of 14 kinds of amino acids and glucose stored in a double-chamber bag prepared by the preparation method according to any one of claims 1 to 8, characterized in that: The double chamber bag comprises an amino acid liquid chamber and a glucose liquid chamber separated by a space; The residual oxygen content in the headspace of the amino acid solution chamber and the glucose solution chamber is both below 2.0%; The dissolved oxygen content of the amino acid solution chamber and the glucose solution chamber is below 2 mg / L; The packaging volume ratio of the amino acid liquid chamber to the glucose liquid chamber is 1:1 to 1:3; The total aluminum content in the amino acid solution chamber and the glucose solution chamber is lower than 25 μg / L.

10. The composition of 14 amino acids and glucose stored in a double-chamber bag according to claim 9, characterized in that: The double-chamber bag comprises an inner bag and an outer bag, wherein the inner bag is divided into two chambers by a weak welding rod, the inner bag is placed inside the outer bag, and a deoxidizer and an indicator are placed between the inner bag and the outer bag.

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