Sterile water containing sodium chloride and preparation method thereof

Abstract

The invention relates to the technical field of medical preparations for injection and medicine packaging, and discloses sterile water containing sodium chloride and a preparation method thereof.The sterile water is composed of a basic osmotic pressure adjusting system, a buffer anti-oxidation system and a bacteriostatic system, and the sterile water comprises, by volume, 0.85-0.95% of sodium chloride, 0.35-0.95% of sodium chloride, 0.35-0.95% of sodium chloride and the balance water. 0.01%-0.05% of sodium dihydrogen phosphate; 0.02% to 0.1% of disodium hydrogen phosphate; 0.001%-0.01% of reduced glutathione, 0.001%-0.01% of a surfactant; 0.795% to 0.805% of benzyl alcohol; by optimizing the prescription ratio and adopting a specific process for preparation, the obtained sterile water finished product has excellent physical and chemical stability in long-term storage, and also has good antibacterial performance after unsealing, so that the safety and convenience of clinical use are greatly improved; therefore, the problems that traditional sterile water is insufficient in stability, prone to secondary pollution and complex in repeated administration operation are effectively solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medical preparations for injection and pharmaceutical packaging technology, in particular to a sterile water containing sodium chloride and a preparation method thereof. BACKGROUND

[0002] Sterile water for injection is an indispensable basic carrier in the medical field, and is widely used for dissolving and diluting drugs. At present, the commercially available sterile water for injection products are mostly simple aqueous solutions, which have obvious technical limitations. First, the pH value lacks an effective buffer system for maintenance, and is prone to fluctuation during storage or use, which may affect the stability of the prepared drugs. Second, most products do not add bacteriostatic agents meeting the pharmacopoeia standards, and need to be used immediately after the package is opened, which cannot be used repeatedly as multi-dose packaging, otherwise there is a great risk of secondary microbial contamination. In addition, the traditional products lack antioxidant protection, and some oxygen-sensitive drugs are prone to degradation after preparation. Finally, the conventional single-dose packaging form increases the frequency and time cost of drug preparation operation for clinical medical staff, which is inefficient and prone to contamination. Therefore, it is of great clinical significance and application value to develop a sterile water for injection product with stable performance, ready-to-use and capable of supporting multi-dose administration. SUMMARY

[0003] (I) Technical problems solved

[0004] In view of the deficiencies of the prior art, the present application provides a sterile water containing sodium chloride and a preparation method thereof, which has the advantages of good physiological compatibility, high stability, reliable bacteriostatic effect and convenient clinical use, and solves the problems of unstable pH of traditional sterile water, easy contamination after opening, inability to support multi-dose use and complicated clinical operation.

[0005] (II) Technical solutions

[0006] To achieve the above-mentioned purpose, the present application provides the following technical solutions: a sterile water containing sodium chloride, which is composed of a basic osmotic pressure adjusting system, a buffer antioxidant system and a bacteriostatic system, and the specific components and their volume ratio ranges are as follows: sodium chloride 0.85% to 0.95%; sodium dihydrogen phosphate 0.01% to 0.05%; disodium hydrogen phosphate 0.02% to 0.1%; reduced glutathione 0.001% to 0.01%; benzyl alcohol 0.795% to 0.805%; and the balance is water for injection.

[0007] Preferably, the basic osmotic pressure adjusting system is composed of sodium chloride and water for injection; the buffer antioxidant system is composed of sodium dihydrogen phosphate, disodium hydrogen phosphate and reduced glutathione; and the bacteriostatic system is composed of benzyl alcohol alone.

[0008] Preferably, the sodium chloride purity ≥ 99.5%, drying loss ≤ 0.5%, heavy metal content ≤ 3ppm, pH value is 4.5-7.0, dry heat sterilization at 160-180℃ for 2-4 hours;

[0009] The sodium dihydrogen phosphate and the disodium hydrogen phosphate are both analytically pure, the heavy metal content is ≤ 5ppm, the clarity and color meet the requirements, and the dry heat sterilization treatment is carried out at 160-180℃ for 2-4 hours.

[0010] Preferably, the reduced glutathione purity ≥ 98.0%, filtered in a sterile and inert gas environment by using a sterile filter membrane;

[0011] The benzyl alcohol purity ≥ 98.0%, colorless liquid, meets all test requirements of USP for benzyl alcohol, filtered in a sterile and inert gas environment by using a sterile filter membrane;

[0012] The water for injection meets USP, meets the resistivity ≥ 18.2MΩ·cm, TOC ≤ 5ppb, microorganisms <1 CFU / 100mL, multi-effect distillation in a sterile environment ≥ 121℃, terminal filtration after distillation, and meets the injection level standard.

[0013] A preparation method of sterile water containing sodium chloride, which is prepared according to the composition system of the sterile water containing sodium chloride described above, comprising the following preparation steps:

[0014] Step one, ingredient preparation: weigh the corresponding mass proportion of raw materials of sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, reduced glutathione, benzyl alcohol and water for injection according to the prescription volume range, and pretreat;

[0015] Step two, system solution preparation: prepare the basic osmotic pressure adjusting system, the buffer antioxidant system and the bacteriostatic system respectively;

[0016] Step three, system mixing and precision treatment: mix the three systems and remove the particles and metal ions;

[0017] Step four, sterile filling: use intelligent double-cavity bags for immediate-use filling;

[0018] Step five, disinfection treatment: multiple sterile protection is carried out on the finished product and the packaging;

[0019] Step six, quality detection and sealed storage: after the verification index is qualified, seal, and then carry out irradiation sterilization.

[0020] Preferably, the preparation process of the basic osmotic pressure adjusting system in step two is:

[0021] S1.1, take 59.5%-60.5% of the total amount of sterile water for injection, and place it in a sterile preparation tank A;

[0022] S1.2, control the temperature at 20-25°C, open the stirring speed at 150-200 r / min, add the calculated amount of sterile sodium chloride drop by drop, and stir for 30-40 min until complete dissolution;

[0023] S1.3, use the osmometer to detect the osmotic pressure until the osmotic pressure is between 280-320 mOsm / kg, and when it does not meet the standard, add sodium chloride or water for injection to adjust.

[0024] Preferably, the buffer antioxidant system preparation process in step two is as follows:

[0025] S2.1, take 19.05%-20.05% of the total amount of sterile water for injection, place it in sterile preparation tank B, add the calculated amount of sterile sodium phosphate monobasic and sodium phosphate dibasic, and stir for 20-25 min until dissolution;

[0026] S2.2, use a pH meter to detect the pH value, and when it deviates from the range of 7.0-7.4, add 0.10 mol / L sterile hydrochloric acid or sodium hydroxide solution drop by drop for fine adjustment;

[0027] S2.3, after adjustment, add the calculated amount of sterile reduced glutathione under the protection of nitrogen gas with a purity of more than 99.99%, continue to stir for 10-15 min until dissolution.

[0028] Preferably, the bacteriostatic system preparation process in step two is as follows:

[0029] S3.1, take 9.95%-10.05% of the total amount of sterile water for injection, place it in sterile preparation tank C, heat it to 30-35°C in a water bath, add the calculated amount of sterile benzyl alcohol, stir for 10-15 min, and until the solution is clear and transparent;

[0030] S3.2, after sufficient stirring, take a sample from preparation tank C, and use a calibrated ultraviolet spectrophotometer to measure the absorbance at a wavelength of 258 nm.

[0031] Preferably, the system mixing and precision treatment in step three is as follows:

[0032] S4.1, pump the buffer antioxidant system in preparation tank B into the preparation tank A basic osmotic pressure adjustment system at a flow rate of 5-10 L / min through a sterile peristaltic pump, keep the stirring speed of preparation tank A at 180-220 r / min during the pumping process, and mix for 15-20 min;

[0033] S4.2, the bacteriostatic system of the preparation tank C is pumped into the mixed solution in the preparation tank A by a sterile peristaltic pump at a flow rate of 5-10 L / min, stirring for 20-25 min, supplementing the remaining 9.95%-10.05% sterile water for injection to the total preparation volume, and continuing to stir for 8-10 min;

[0034] S4.3, the mixed solution is filtered through a coarse filter membrane and a polyether sulfone filter membrane in sequence, and when the metal ions exceed the standard, a chelating resin column adsorption treatment is started;

[0035] S4.4, 100-200 mL of the sample after filtration is taken for detection of sterility and particles, and after passing the test, the next step is entered.

[0036] Preferably, the step four sterile filling process is as follows:

[0037] S5.1, the qualified liquid medicine obtained in step three is transferred to a buffer tank of a sterile filling system, under the protection of an A-level laminar flow, a sterile peristaltic pump is used to fill the main chamber of an intelligent double-cavity bag at a constant flow rate of 50-100 mL / min, and the filling amount is monitored in real time to ensure that the filling accuracy error is ≤±1%;

[0038] S5.2, during the filling process, pure nitrogen with a purity of ≥99.99% is continuously filled into the liquid surface space of the bag for protection;

[0039] S5.3, after the filling is completed, laser welding technology is used to seal the inlet and outlet of the double-cavity bag, and 100% online leak detection is performed on the sealing integrity;

[0040] The sterilization treatment condition in the step five is as follows:

[0041] S6.1, the sealed double-cavity bag product is placed in a double-door moist heat sterilization cabinet, and is subjected to final sterilization under the conditions of 121-125 DEG C, 0.10-0.12 MPa, and the heat penetration verification is performed.

[0042] S6.2, after sterilization, the outer surface of the double-cavity bag is uniformly wiped and disinfected with 75%-80% alcohol by using sterile non-woven fabric, and is transferred to an A-level environment for cooling and drying;

[0043] S6.3, the product inner packaging bag is subjected to Co60 irradiation pretreatment.

[0044] Compared with the prior art, the present application provides a sterile water containing sodium chloride and a preparation method thereof, which has the following beneficial effects:

[0045] 1、The present application achieves the beneficial effects of precisely maintaining the pH value of the solution in the physiological range during the storage period and effectively preventing the oxidative degradation of the active ingredients by constructing a composite stabilizing system containing a buffer and an antioxidant.

[0046] 2、The present application achieves the beneficial effects of ensuring that the product can effectively resist microbial contamination after being opened and meets the international pharmacopoeia standard by introducing and precisely controlling the concentration of the bacteriostatic agent benzyl alcohol.

[0047] 3、The present application achieves the beneficial effects of simplifying the clinical compounding operation process, reducing the operation time and the risk of secondary pollution, and improving the safety of medication by using intelligent double-cavity bag packaging and ready-to-use design. BRIEF DESCRIPTION OF DRAWINGS

[0048] Figure 1 The flow chart for the preparation of sterile water according to the present application. DETAILED DESCRIPTION

[0049] The technical solutions in the embodiments of the present application will be described in detail below with reference to the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0050] Please refer to Figure 1 A sterile water containing sodium chloride, the sterile water is composed of a basic osmotic pressure adjusting system, a buffer antioxidant system and a bacteriostatic system, and the specific components and their volume ratio ranges are as follows: sodium chloride 0.85%-0.95%; sodium dihydrogen phosphate 0.01%-0.05%; disodium hydrogen phosphate 0.02%-0.1%; reduced glutathione 0.001%-0.01%; benzyl alcohol 0.795%-0.805%; and the balance is water for injection (USP grade).

[0051] Specifically, the basic osmotic pressure adjusting system is composed of sodium chloride (USP grade) and water for injection (USP grade); the buffer antioxidant system is composed of sodium dihydrogen phosphate (NaH2PO4), disodium hydrogen phosphate (Na2HPO4) and reduced glutathione (GSH), which is used to stabilize the pH value (target range 7.0-7.4) and provide antioxidant protection; the bacteriostatic system is composed of benzyl alcohol (Benzyl Alcohol, USP grade) alone, which is used as an injection bacteriostatic agent meeting the standards of the United States Pharmacopoeia (USP), to ensure that the multi-dose package is free from secondary microbial contamination within a certain period after being opened.

[0052] Specifically, the components and their functions are as shown in Table 1:

[0053] Table 1

[0054]

[0055] Specifically, the purity of sodium chloride is ≥99.5%, the loss on drying is ≤0.5%, the heavy metal content is ≤3ppm, and the pH value is 4.5-7.0, which is subjected to dry heat sterilization at 160-180℃ for 2-4 hours;

[0056] Specifically, both the sodium dihydrogen phosphate and the disodium hydrogen phosphate are analytically pure, the heavy metal content is ≤5ppm, the clarity and color meet the requirements, and the sterilization is carried out by dry heat at 160-180℃ for 2-4 hours.

[0057] Specifically, the purity of reduced glutathione is ≥98.0%, and the sterile filtration membrane is used for filtering in a sterile and inert gas environment.

[0058] Specifically, the purity of benzyl alcohol is ≥98.0%, it is a colorless liquid, and meets all test requirements of USP for benzyl alcohol, and the sterile filtration membrane is used for filtering in a sterile and inert gas environment.

[0059] Specifically, the water for injection meets USP, meets the requirements of resistivity ≥18.2MΩ·cm, TOC ≤5ppb, and microorganisms <1CFU / 100mL, is subjected to multiple effect distillation in a sterile environment ≥121℃, and after distillation, terminal filtration is used to remove pyrogens, microorganisms and impurities, and meets the injection grade standard.

[0060] A preparation method of sterile water containing sodium chloride, comprising the following steps:

[0061] Step one, ingredient preparation: according to the prescription volume range, the corresponding mass proportion of raw materials of sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, reduced glutathione, benzyl alcohol and water for injection is weighed and pretreated to ensure the initial purity and cleanliness of the ingredients;

[0062] Step two, system solution preparation: respectively prepare the basic osmotic pressure adjusting system, the buffer antioxidant system and the bacteriostatic system;

[0063] Step three, system mixing and precision treatment: mix the three systems and remove the particles and metal ions;

[0064] Step four, sterile filling: use intelligent double-cavity bag for immediate-use filling;

[0065] Step five, disinfection treatment: multiple sterile protection is carried out on the finished product and the packaging;

[0066] Step six, quality detection and sealed storage: after the verification index is qualified, it is sealed, then subjected to irradiation sterilization to ensure long-term stability.

[0067] Specifically, the preparation process of the basic osmotic pressure adjusting system in step two is as follows:

[0068] S1.1, 59.5% to 60.5% of the total amount of sterile water for injection is taken and placed in a sterile preparation tank A;

[0069] S1.2, the temperature is controlled at 20-25°C, the stirring speed is opened at 150-200 r / min, the calculated amount of sterile sodium chloride is added dropwise, and stirring is performed for 30-40 min until complete dissolution;

[0070] S1.3, the osmotic pressure is detected using an osmotic pressure instrument until the osmotic pressure is between 280-320 mOsm / kg, and when it does not meet the standard, sterile sodium chloride or water for injection is added for adjustment;

[0071] The advantages are that controlling the temperature and stirring speed can avoid uneven dissolution of sodium chloride; adding 59.5% to 60.5% of sterile water for injection first facilitates the adjustment of the volume during subsequent system mixing, real-time detection of osmotic pressure ensures compliance with human physiological needs, and guarantees biocompatibility.

[0072] Specifically, the preparation process of the buffer antioxidant system in step two is as follows:

[0073] S2.1, 19.05% to 20.05% of the total amount of sterile water for injection is taken and placed in a sterile preparation tank B, and the calculated amount of sterile sodium dihydrogen phosphate and disodium hydrogen phosphate is added, and stirring is performed for 20-25 min until dissolution;

[0074] S2.2, the pH value is detected using a pH meter, and when it deviates from the range of 7.0-7.4, 0.10 mol / L sterile hydrochloric acid or sodium hydroxide solution is added dropwise for fine adjustment;

[0075] S2.3, after adjustment, the calculated amount of sterile reduced glutathione is added under the protection of nitrogen gas with a purity greater than 99.99%, and stirring is continued for 10-15 min until dissolution;

[0076] The advantages are that stepwise dissolution of phosphates can ensure the accuracy of the buffer control, the pH is fine-tuned to the physiological range (7.0-7.4), solving the problem of existing sterile water pH deviation; adding glutathione under the protection of nitrogen gas can effectively prevent its oxidation failure, enhance the antioxidant capacity of the finished product, and prolong the storage stability.

[0077] Specifically, the preparation process of the bacteriostatic system in step two is as follows:

[0078] S3.1, take 9.95%~10.05% of the total amount of sterile water for injection, placed in a sterile preparation tank C, heated to 30-35℃ in water bath (promote benzyl alcohol dissolution), add the calculated amount of sterile benzyl alcohol, stirring 10~15min, until the solution is clear and transparent, indicating that the benzyl alcohol has been completely dissolved, this mild heating step can significantly reduce the viscosity of benzyl alcohol, promote its diffusion and dissolution in water, while the temperature is strictly controlled below its boiling point (~205℃), which can effectively avoid the loss and potential degradation caused by high temperature, so as to ensure the accuracy of the material and the stability of the finished product;

[0079] S3.2, after stirring, take sample from the preparation tank C, use calibrated ultraviolet spectrophotometer to determine the absorbance at 258nm wavelength, by comparing with the pre-established benzyl alcohol standard curve, the concentration of benzyl alcohol in the solution is controlled in the target range of 0.79%~0.81% (w / v), which is judged as qualified and allowed to proceed to the next step, this intermediate process control (IPC) step ensures that the bacteriostatic effect of the final product meets the requirements of the United States Pharmacopoeia for multi-dose injection, solves the problem of secondary pollution after opening without preservative system, and provides key quality assurance for the product as multi-dose packaging;

[0080] Advantages: mild heating promotes benzyl alcohol dissolution and avoids its volatilization (benzyl alcohol boiling point 195-200℃, 30-35℃ safe); concentration detection can ensure the bacteriostatic effect, solve the problem of secondary pollution after opening of existing sterile water.

[0081] Specifically, in step three, the system is mixed and precisely treated:

[0082] S4.1, the buffer antioxidant system of preparation tank B is pumped into the preparation tank A basic osmotic pressure adjusting system through a sterile peristaltic pump at a flow rate of 5~10L / min, the preparation tank A keeps stirring at a speed of 180-220r / min during the pumping process, and the mixing time is 15~20min;

[0083] S4.2, then the bacteriostatic system of preparation tank C is pumped into the mixed solution in preparation tank A through a sterile peristaltic pump at a flow rate of 5~10L / min, stirring for 20~25min, adding the remaining 9.95%~10.05% sterile water for injection to the total preparation volume, and continuing to stir for 8~10min to ensure uniformity of the system;

[0084] S4.3, the mixed solution is filtered through 0.45μm coarse filter membrane (remove large particles) and 0.22μm polyether sulfone fine filter membrane (filter sterilization + remove particles) in sequence, and at the same time through online metal ion detector (detect metal ions, limit ≤0.0001%), when the metal ions exceed the limit, the chelating resin column adsorption treatment is started;

[0085] S4.4, after filtration, take 100-200 mL sample, detect sterility and particles, and then enter next step after passing;

[0086] Advantages: the step three receives step two, each system is mixed in order, and the safety, stability and effectiveness of the final product are ensured through precise filtration and strict quality detection.

[0087] Specifically, the sterile filling process in step four is as follows:

[0088] S5.1, the qualified liquid obtained in step three is transferred to the buffer tank of the sterile filling system, under the protection of A-level laminar flow (i.e. ISO 5 level cleanliness, vertical one-way flow), the sterile peristaltic pump is used to fill the main chamber of the intelligent double-cavity bag at a constant flow rate of 50-100 mL / min, and the filling amount is monitored in real time to ensure that the filling accuracy error is ≤±1%;

[0089] S5.2, during the filling process, pure nitrogen gas with a purity of ≥99.99% is continuously filled into the liquid surface space of the bag for protection to prevent drug oxidation;

[0090] S5.3, after filling is completed, laser welding technology is immediately used to seal the inlet and outlet of the double-cavity bag, and 100% online leak detection is performed on the sealing integrity;

[0091] Advantages: the intelligent double-cavity bag structure can realize immediate use after preparation, avoiding clinical preparation operation; A-level laminar flow protection and nitrogen protection maximize the reduction of oxygen contact and microbial contamination risk, and laser welding ensures the sealing reliability, providing convenience and safety guarantee for multiple dose administration;

[0092] Specifically, the sterilization treatment conditions in step five are as follows:

[0093] S6.1, the sealed double-cavity bag product is placed in a double-door moist heat sterilization cabinet, and is subjected to final sterilization under the conditions of 121-125℃ and 0.10-0.12 MPa, the holding time is 15-20 minutes, and complete temperature distribution and heat penetration verification are performed;

[0094] S6.2, after sterilization, the outer surface of the double-cavity bag is uniformly wiped with 75%-80% alcohol using sterile non-woven fabric, and is transferred to an A-level environment for cooling and drying;

[0095] S6.3, the product inner packaging bag (intelligent double-cavity bag) is subjected to Co60 irradiation pretreatment (minimum dose 25 kGy, maximum dose 40 kGy) to ensure the sterility of the primary packaging itself;

[0096] The advantages are that the multiple terminal sterilization mode (wet heat + irradiation + surface disinfection) constitutes a redundant sterile guarantee system, can completely kill microorganisms, eliminate the risk of microbial contamination inside and outside the finished product, and greatly improve the safety and sterile stability of the finished product.

[0097] The key use data of the sodium chloride-containing sterile water (intelligent double-cavity bag) of the present application and the existing six existing products are compared:

[0098] Table 2

[0099]

[0100] Summary: The sterile water prepared by the method and prescription amount of the present application can maintain excellent physical and chemical stability in long-term storage, provide reliable antibacterial protection after opening, and significantly improve the safety and convenience of clinical use, solving the problems of poor stability, easy secondary microbial contamination and complicated multiple drug administration operation of traditional sterile water for injection.

[0101] Although embodiments of the present application have been shown and described, it will be understood by those having ordinary skill in the art that various changes, modifications, substitutions and alterations can be made thereto without departing from the principles and spirit of the present application, the scope of which is defined by the appended claims and their equivalents.

Claims

1. Sterile water containing sodium chloride, characterized in that, The sterile water is composed of a basic osmotic pressure regulating system, a buffer antioxidant system and a bacteriostatic system, and specific components and volume ratio ranges thereof are as follows: sodium chloride 0.85%-0.95%; sodium dihydrogen phosphate 0.01%-0.05%; disodium hydrogen phosphate 0.02%-0.1%; reduced glutathione 0.001%-0.01%; benzyl alcohol 0.795%-0.805%; and the balance is water for injection.

2. Sterile water containing sodium chloride according to claim 1, characterized in that: The basic osmotic pressure regulating system is composed of sodium chloride and water for injection; the buffer antioxidant system is composed of sodium dihydrogen phosphate, disodium hydrogen phosphate and reduced glutathione; and the bacteriostatic system is composed of benzyl alcohol alone.

3. Sterile water containing sodium chloride according to claim 1, characterized in that: The sodium chloride has a purity of ≥99.5%, a loss on drying of ≤0.5%, a heavy metal content of ≤3 ppm, and a pH value of 4.5-7.0, and is subjected to dry heat sterilization at 160-180℃ for 2-4 hours; The sodium dihydrogen phosphate and the disodium hydrogen phosphate are both of analytical purity, have a heavy metal content of ≤5 ppm, and have a clarity and color meeting the requirements, and are subjected to dry heat sterilization at 160-180℃ for 2-4 hours.

4. Sterile water containing sodium chloride according to claim 1, characterized in that: The reduced glutathione has a purity of ≥98.0%, and is filtered in a sterile and inert gas environment by using a sterile filter membrane; The benzyl alcohol has a purity of ≥98.0%, is a colorless liquid, meets all test requirements of USP for benzyl alcohol, and is filtered in a sterile and inert gas environment by using a sterile filter membrane; The water for injection meets USP, satisfies a resistivity of ≥18.2 MΩ·cm, a TOC of ≤5 ppb, and a microorganism of <1 CFU / 100 mL, is subjected to multi-effect distillation in a sterile and ≥121℃ environment, is subjected to terminal filtration after distillation, and meets injection grade standards.

5. A method for the preparation of sterile water containing sodium chloride, characterized in that, A composition system of sterile water containing sodium chloride according to claim 1 is prepared, comprising the following preparation steps: Step one, ingredient preparation: ingredients of sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, reduced glutathione, benzyl alcohol and water for injection corresponding to the mass ratio of the prescription volume range are weighed and pretreated; Step two, system solution preparation: a basic osmotic pressure regulating system, a buffer antioxidant system and a bacteriostatic system are prepared respectively; Step three, system mixing and precision treatment: the three systems are mixed and the monitoring of microparticles and metal ions is removed; Step four, sterile filling: an intelligent double-cavity bag is used for immediate-use filling; Step five, disinfection treatment: multiple sterile guarantees are performed on the finished product and the packaging; Step six, quality detection and sealed storage: after the verification index is qualified, the product is sealed and then subjected to irradiation sterilization.

6. A process for the preparation of sterile water containing sodium chloride according to claim 5, characterized in that: The preparation process of the basic osmotic pressure regulating system in step two is as follows: S1.1, 59.5%-60.5% of the total amount of sterile water for injection is taken and placed in a sterile preparation tank A; S1.2, the temperature is controlled at 20-25℃, the stirring speed is opened at 150-200 r / min, the calculated amount of sterile sodium chloride is added dropwise, and stirring is performed for 30-40 min until complete dissolution; S1.3, an osmotic pressure instrument is used to detect the osmotic pressure until the osmotic pressure is between 280-320 mOsm / kg, and when it does not meet the standard, sodium chloride or water for injection is added for adjustment.

7. A process for the preparation of sterile water containing sodium chloride according to claim 5, characterized by: The preparation process of the buffer antioxidant system in step two is as follows: S2.1, take 19.05% to 20.05% of the total amount of sterile water for injection, place in sterile preparation tank B, add the calculated amount of sterile sodium phosphate dibasic and sodium phosphate dibasic, stir for 20-25 min until dissolved; S2.2, use a pH meter to detect the pH value, when deviating from the range of 7.0-7.4, add 0.10 mol / L sterile hydrochloric acid or sodium hydroxide solution drop by drop for fine adjustment; S2.3, after adjustment, under the protection of nitrogen gas with a purity of more than 99.99%, add the calculated amount of sterile reduced glutathione, continue to stir for 10-15 min until dissolved.

8. A sterile water containing sodium chloride according to claim 5, characterized by: The preparation process of the bacteriostatic system in step two is as follows: S3.1, take 9.95% to 10.05% of the total amount of sterile water for injection, place in sterile preparation tank C, heat to 30-35℃ in water bath, add the calculated amount of sterile benzyl alcohol, stir for 10-15 min until the solution is clear and transparent; S3.2, after sufficient stirring, take a sample from the preparation tank C, use a calibrated ultraviolet spectrophotometer to measure the absorbance at a wavelength of 258 nm.

9. A process for the preparation of sterile water containing sodium chloride according to claim 5, characterized by: The system mixing and precision treatment in step three: S4.1, the buffer antioxidant system in preparation tank B is pumped into the preparation tank A basic osmotic pressure adjusting system through a sterile peristaltic pump at a flow rate of 5-10 L / min, the preparation tank A is kept stirring at a speed of 180-220 r / min during the pumping process, and the mixing time is 15-20 min; S4.2, then the bacteriostatic system in preparation tank C is pumped into the mixed solution in preparation tank A through a sterile peristaltic pump at a flow rate of 5-10 L / min, stir for 20-25 min, add the remaining 9.95% to 10.05% sterile water for injection to the total preparation volume, and continue to stir for 8-10 min; S4.3, the mixed solution is filtered through a coarse filter membrane and a polyether sulfone filter membrane in sequence, and when the metal ions exceed the standard, a chelating resin column adsorption treatment is started; S4.4, after filtration, take 100-200 mL of sample for detection of sterility and particles, and then proceed to the next step after passing the test.

10. A process for the preparation of sterile water containing sodium chloride according to claim 5, characterized by: The sterile filling process in step four: S5.1, transfer the qualified liquid obtained in step three to the buffer tank of the sterile filling system, under A-level laminar flow protection, use a sterile peristaltic pump to fill the main chamber of the intelligent double-cavity bag at a constant flow rate of 50-100 mL / min, and monitor the filling amount in real time to ensure that the filling accuracy error is ≤±1%; S5.2, during the filling process, continuously fill the liquid surface space of the bag with sterile nitrogen gas with a purity of ≥99.99% for protection; S5.3, after filling is completed, immediately seal the inlet and outlet of the double-cavity bag using laser welding technology, and perform 100% online leak detection on the sealing integrity; The sterilization treatment conditions in step five: S6.1, place the sealed double-cavity bag product in a double-door moist heat sterilization cabinet, and perform final sterilization at 121-125℃, 0.10-0.12 MPa, with a holding time of 15-20 minutes, and perform complete temperature distribution and heat penetration verification. S6.2, after sterilization, the outer surface of the double cavity bag is uniformly wiped with sterile non-woven fabric dipped with 75%-80% alcohol for disinfection, and is transferred to the A-level environment for cooling and drying; S6.3, the finished product inner packaging bag is subjected to Co60 irradiation pretreatment.

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