Diphenhydramine hydrochloride injection and preparation method thereof

Abstract

The invention provides a diphenhydramine hydrochloride injection and a preparation method thereof. According to the preparation method, the diphenhydramine hydrochloride injection with stable pH value, stable chemical property and sterility assurance level SAL less than or equal to 10 <-6 > can be obtained by controlling the material of a liquid medicine pipeline and the water resistance of a medium borosilicate glass ampoule. The diphenhydramine hydrochloride injection does not contain preservatives and cannot generate safety risks.

Description

Technical Field

[0001] The invention belongs to the technical field of drug injections and relates to a diphenhydramine hydrochloride injection and a preparation method thereof. Background Art

[0002] Diphenhydramine hydrochloride, chemically known as N,N-dimethyl-2-(diphenylmethoxy)ethylamine hydrochloride, is a white crystalline powder that is easily soluble in water, easily hydrolyzed in acid, and stable in alkaline solution. Pure diphenhydramine hydrochloride is stable to light, and when it contains impurities such as benzhydrol, it gradually changes color in the presence of light. Diphenhydramine hydrochloride is an antihistamine drug that has a strong inhibitory effect on the central nervous system. It is mainly used clinically to eliminate various allergic symptoms, and can also be used to prevent motion sickness such as seasickness, motion sickness, and airsickness.

[0003] After oral absorption, diphenhydramine hydrochloride is metabolized by 50% before reaching the systemic circulation due to the first-pass effect of the liver. Injection can avoid the first-pass effect, reduce the dosage, and reduce side effects. In addition, injection also has the advantage of rapid onset. Therefore, stable diphenhydramine hydrochloride injection is of great significance for clinical use and ensuring drug safety and effectiveness.

[0004] In order to avoid high temperature damage to diphenhydramine hydrochloride injection, the existing production process of diphenhydramine hydrochloride injection is aseptic production without terminal sterilization, and sterile preparations are produced by sterilization filtration and production environment control, and the sterility assurance level is low. In order to better ensure the sterility level of the product, antibacterial agents such as benzalkonium chloride are usually added to the prescription. Although benzalkonium chloride can improve the sterility assurance level of diphenhydramine hydrochloride injection as a preservative, it usually has certain toxicity to the human body, which inevitably causes safety risks, especially greater risks to children.

[0005] For injections, the pH value should be stably controlled within a certain range during the validity period. Changes in the pH value mean that the drug is not stable. For diphenhydramine hydrochloride, the pH value not only affects the stability of the drug, but also reflects changes in the stability of the drug. Controlling its pH value within a certain range and maintaining stability is particularly important for ensuring quality and stability of the drug solution. In order to stabilize the pH value of the drug, adding a buffer is a commonly used technical means in the industry, but for injections, the addition of any non-essential ingredients means a decrease in product quality and an increase in the risk of medication. Avoiding the addition of buffers is obviously a better choice. Summary of the invention

[0006] The invention aims to provide a diphenhydramine hydrochloride injection and a preparation method thereof, so as to solve the problems of poor stability and low sterility assurance level of the existing diphenhydramine hydrochloride injection.

[0007] To achieve the above object, the present invention adopts the following technical solutions: The present application provides a method for preparing diphenhydramine hydrochloride injection, the method comprising: S01: Mix water for injection and diphenhydramine hydrochloride, stir to dissolve, and adjust the pH value to 4.5-6.0 to form a drug solution.

[0008] Add 70-80°C water for injection into the liquid preparation container, cool it to 0-40°C, add diphenhydramine hydrochloride, mix it, stir and dissolve it to form a mixed solution. In addition, the 70-80°C water for injection can be heated to 0-40°C by a heat exchanger, added to the liquid preparation container, and then diphenhydramine hydrochloride is added, mixed, stirred and dissolved to form a mixed solution. Preferably, the temperature of the water for injection is 0-30°C; more preferably, the temperature of the water for injection is 10-30°C.

[0009] The stability of diphenhydramine hydrochloride injection is significantly affected by the pH value. Controlling the pH value of the injection within an appropriate range is the key to ensuring its stability. Therefore, in this application, a sodium hydroxide solution with a concentration of 0.01-0.1 mol / L or a hydrochloric acid solution with a concentration of 0.01-0.1 mol / L is used to adjust the pH value of the mixed solution to 4.5-6.0 to ensure that the pH value before filling meets the requirements. Preferably, the pH value of diphenhydramine hydrochloride injection is adjusted to 4.5-5.5; more preferably, the pH value of diphenhydramine hydrochloride injection is adjusted to 5.0-5.5.

[0010] S02: After filtering, the medicinal solution is filled into a medium-borosilicate glass ampoule, which is then filled with nitrogen and sealed. The infusion tube during filling is made of polytetrafluoroethylene or polypropylene, and the inner surface water resistance of the medium-borosilicate glass ampoule at 121°C is as follows: for a 1ml medium-borosilicate glass ampoule, no more than 0.5ml of 0.01mol / L hydrochloric acid titrant is consumed per 100ml of extract; for a 2ml medium-borosilicate glass ampoule, no more than 0.4ml of 0.01mol / L hydrochloric acid titrant is consumed per 100ml of extract.

[0011] The liquid medicine is filtered in two stages using filters with a filtration accuracy of 0.45 μm and / or 0.22 μm to remove water-insoluble impurities and microorganisms in the liquid medicine. Specifically, the liquid medicine is filtered through filters with a filtration accuracy of 0.45 μm and 0.22 μm in turn, or the liquid medicine is filtered through filters with a filtration accuracy of 0.22 μm and 0.22 μm in turn.

[0012] After the liquid medicine is filtered, it is filled into a medium borosilicate glass ampoule by a filling machine, and the medium borosilicate glass ampoule is sealed after nitrogen is filled until the residual oxygen content in the headspace is less than 5.0%. Preferably, the residual oxygen content in the headspace is less than 2.0%; more preferably, the residual oxygen content in the headspace is less than 1.0%.

[0013] The stability of diphenhydramine hydrochloride injection is significantly affected by pH value, and controlling the pH value of the solution within an appropriate range is the key to ensuring its stability. But in fact, the change of pH value of diphenhydramine hydrochloride injection during the production process is difficult to control, especially the pH value of the solution before and after filling will fluctuate significantly, and the fluctuation is irregular, which brings great challenges to its control, which is also an important reason why terminal sterilization process cannot be used.

[0014] Based on this, this application study found that the water resistance of the liquid medicine pipeline on the filling machine and the borosilicate glass ampoule are the main factors causing the fluctuation of the pH value of diphenhydramine hydrochloride injection.

[0015] When a certain amount of diphenhydramine hydrochloride injection is transported through a liquid medicine pipeline of a certain length and diameter, by monitoring the changes in the content and pH value before and after the liquid medicine is transported, it is found that there is a correlation between the change in content and the change in pH value. In addition, after a certain volume of liquid medicine is sealed in a liquid medicine pipeline of a certain length and diameter for 24 hours, by detecting the changes in the extract and the pH value when it is just sealed and 24 hours after sealing, it is found that there is a correlation between the amount of extract and the change in pH value. This is because the liquid medicine pipeline on the filling machine usually uses a silica gel pipeline, and silica gel has a certain adsorption capacity for diphenhydramine hydrochloride. At the same time, the components in the silica gel will migrate to the injection, causing the pH value of the injection to fluctuate.

[0016] Based on this, the preparation material of the liquid medicine pipeline on the filling machine in this application is polytetrafluoroethylene or polypropylene, and the connection of the pipeline and the accessories can adopt a silicone tube, but the silicone tube should be avoided from contacting with the diphenhydramine hydrochloride injection. This is because polytetrafluoroethylene has excellent chemical stability, corrosion resistance, high lubricity, non-adhesiveness and other characteristics, and has good compatibility with the diphenhydramine hydrochloride liquid medicine, avoids the adsorption of the medicine, and has a very low risk of component migration, so it is particularly suitable for the pipeline of the diphenhydramine hydrochloride liquid transportation or as the inner material of the delivery pipeline directly contacting the liquid medicine. Although the comprehensive performance of the polypropylene material is not as good as that of polytetrafluoroethylene, it can still meet the needs of the diphenhydramine hydrochloride injection, avoids the adsorption of the medicine, and the risk of pipeline component migration is low. Adopting the pipeline of polytetrafluoroethylene and / or polypropylene material or as the inner material of the delivery pipeline directly contacting the liquid medicine, it is possible to avoid the adverse effects of the pipeline on the pH value, content, and related substances of the liquid medicine.

[0017] Medium borosilicate glass is a commonly used packaging material for injections. Its main component is silicate substances, which are alkaline to a certain extent. When using medium borosilicate glass ampoules to fill diphenhydramine hydrochloride injection, even if the water resistance of the medium borosilicate glass ampoules meets the HC1 standard, the substances in the packaging material will inevitably migrate to the injection, affecting the pH value of the injection.

[0018] Water resistance is an indicator for evaluating the migration of alkaline substances in ampoules, and is also an indicator of the quality of reaction ampoules. The better the water resistance, the less substances migrate out, which is more conducive to ensuring the stability of the pH value of the drug and the stability of the drug solution. The effect of water resistance on the stability of the pH value of the drug solution is not inevitable, but is related to the properties of the drug, the formulation composition, and the production process. Our research found that the pH stability and chemical stability of diphenhydramine hydrochloride solution are significantly affected by the water resistance of the ampoule, and the water resistance index of the ampoule must be strictly controlled.

[0019] Based on this, according to the 121°C inner surface water resistance determination method and graded determination in the pharmaceutical packaging material standard YBB00242003-2015, the inner surface water resistance of the medium-borosilicate glass ampoule in this application is: for a 1ml medium-borosilicate glass ampoule, no more than 0.5ml of 0.01mol / L hydrochloric acid titration solution is consumed per 100ml of extract; for a 2ml medium-borosilicate glass ampoule, no more than 0.4ml of 0.01mol / L hydrochloric acid titration solution is consumed per 100ml of extract. When the above medium-borosilicate glass ampoule is used to fill diphenhydramine hydrochloride injection, the pH value of the injection does not change significantly.

[0020] S03: sterilize with wet heat at 120-124°C for 8-12 minutes to obtain diphenhydramine hydrochloride injection.

[0021] The sealed borosilicate glass ampoule is placed in a sterilization cabinet, and sterilized at 120-124°C for 8-12 minutes using steam or water as a medium by wet heat sterilization to achieve terminal sterilization to obtain diphenhydramine hydrochloride injection. The cumulative F0 value after sterilization is 10-20. Preferably, the sterilization temperature is 121-123°C, and the cumulative F0 value after sterilization is 12-18; more preferably, the sterilization temperature is 121-122°C, the sterilization time is 12 minutes, and the cumulative F0 value after sterilization is 13-15.

[0022] The related substances and pH value changes of the diphenhydramine hydrochloride injection prepared by the above method are within the acceptable range, and the sterility assurance level SAL≤10 can be achieved through terminal sterilization. -6 , without the need for filtration sterilization technology and the addition of preservatives.

[0023] The present application also provides a diphenhydramine hydrochloride injection, which is prepared by the above-mentioned preparation method.

[0024] The present invention has the following beneficial effects: (1) In this application, by controlling the material of the drug liquid pipeline and the water resistance of the borosilicate glass ampoule, it is possible to obtain a stable pH value, stable chemical properties, and a sterility assurance level SAL ≤ 10 -6 Diphenhydramine hydrochloride injection.

[0025] (2) The diphenhydramine hydrochloride injection prepared in this application does not contain preservatives and will not pose a safety risk. DETAILED DESCRIPTION

[0026] The technical solution of the present invention is further explained and illustrated by means of specific embodiments below.

[0027] Example 1 The present application embodiment provides a diphenhydramine hydrochloride injection with a specification of 1 ml: 20 mg, and the preparation method of the injection comprises: S101: Add 1000 ml of injection water at 70°C to a liquid preparation container, cool to 30°C, add 20 g of diphenhydramine hydrochloride, mix, stir and dissolve to form a mixed solution. Use a sodium hydroxide solution with a concentration of 0.01 mol / L to adjust the pH value of the mixed solution to 5.3.

[0028] S102: The liquid medicine is filtered through filters with a filtration accuracy of 0.45μm and 0.22μm in turn. After the liquid medicine is filtered, it is transported to the filling machine through a pipe made of polytetrafluoroethylene and filled into a 1ml medium-borosilicate glass ampoule. The water resistance of the inner surface of the medium-borosilicate glass ampoule is in accordance with the requirements of the pharmaceutical packaging material standard YBB00242003-2015: 0.3ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract. The medium-borosilicate glass ampoule is sealed after nitrogen is filled to the headspace residual oxygen content <1.0%.

[0029] S103: Place the sealed borosilicate glass ampoule in a sterilization cabinet and sterilize in a water bath at 121° C. for 12 minutes to obtain diphenhydramine hydrochloride injection.

[0030] Example 2 The present application embodiment provides a diphenhydramine hydrochloride injection with a specification of 1 ml: 50 mg, and the preparation method of the injection comprises: S201: Add 1000 ml of injection water at 70°C to a liquid preparation container, cool to 30°C, add 50 g of diphenhydramine hydrochloride, mix, stir and dissolve to form a mixed solution. Use a hydrochloric acid solution with a concentration of 0.01 mol / L to adjust the pH value of the mixed solution to 5.2.

[0031] S202: The liquid medicine is filtered through filters with a filtration accuracy of 0.45μm and 0.22μm in turn. After the liquid medicine is filtered, it is transported to the filling machine through a pipe made of polypropylene and filled into a 1ml medium-borosilicate glass ampoule. The inner surface water resistance of the medium-borosilicate glass ampoule is in accordance with the pharmaceutical packaging material standard YBB00242003-2015: 0.4ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract. The medium-borosilicate glass ampoule is filled with nitrogen until the residual oxygen content in the headspace is less than 1.0% and then sealed.

[0032] S203: Place the sealed borosilicate glass ampoule in a sterilization cabinet and sterilize in a water bath at 121° C. for 12 minutes to obtain diphenhydramine hydrochloride injection.

[0033] Example 3 The present application embodiment provides a diphenhydramine hydrochloride injection with a specification of 1 ml: 50 mg, and the preparation method of the injection comprises: S301: Add 1000 ml of injection water at 80°C to the liquid preparation container, cool to 10°C, add 50 g of diphenhydramine hydrochloride, mix, stir and dissolve to form a mixed solution. Use a sodium hydroxide solution with a concentration of 0.02 mol / L to adjust the pH value of the mixed solution to 4.7.

[0034] S302: The liquid medicine is filtered through filters with a filtration accuracy of 0.22μm and 0.22μm in turn. After the liquid medicine is filtered, it is transported to the filling machine through a pipe made of polytetrafluoroethylene and filled into a 1ml medium-borosilicate glass ampoule. The inner surface water resistance of the medium-borosilicate glass ampoule is in accordance with the requirements of the pharmaceutical packaging material standard YBB00242003-2015: 0.5ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract. The medium-borosilicate glass ampoule is sealed after nitrogen is filled to the headspace residual oxygen content <5.0%.

[0035] S303: Place the sealed borosilicate glass ampoule in a sterilization cabinet and sterilize in a water bath at 120° C. for 8 minutes to obtain diphenhydramine hydrochloride injection.

[0036] Example 4 The present application embodiment provides a diphenhydramine hydrochloride injection with a specification of 1 ml: 20 mg, and the preparation method of the injection comprises: S401: Add 1000 ml of injection water at 75°C to the liquid preparation container, cool to 25°C, add 20 g of diphenhydramine hydrochloride, mix, stir and dissolve to form a mixed solution. Use a hydrochloric acid solution with a concentration of 0.05 mol / L to adjust the pH value of the mixed solution to 5.8.

[0037] S402: The liquid medicine is filtered through filters with a filtration accuracy of 0.22μm and 0.22μm in turn. After the liquid medicine is filtered, it is transported to the filling machine through a pipe made of polypropylene and filled into a 1ml medium borosilicate glass ampoule. The inner surface water resistance of the medium borosilicate glass ampoule is in accordance with the requirements of the pharmaceutical packaging material standard YBB00242003-2015: 0.5ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract. The medium borosilicate glass ampoule is sealed after nitrogen is filled to the headspace residual oxygen content <2.0%.

[0038] S403: Place the sealed borosilicate glass ampoule in a sterilization cabinet and sterilize in a water bath at 124° C. for 12 minutes to obtain diphenhydramine hydrochloride injection.

[0039] Example 5 The present application embodiment provides a diphenhydramine hydrochloride injection with a specification of 1 ml: 20 mg, and the preparation method of the injection comprises: S501: Add 1000 ml of injection water at 75°C to the liquid preparation container, cool to 25°C, add 20 g of diphenhydramine hydrochloride, mix, stir and dissolve to form a mixed solution. Use a hydrochloric acid solution with a concentration of 0.05 mol / L to adjust the pH value of the mixed solution to 5.6.

[0040] S502: The liquid medicine is filtered through filters with a filtration accuracy of 0.22μm and 0.22μm in turn. After the liquid medicine is filtered, it is transported to the filling machine through a pipe made of polytetrafluoroethylene and filled into a 2ml medium-borosilicate glass ampoule. The inner surface water resistance of the medium-borosilicate glass ampoule is in accordance with the requirements of the pharmaceutical packaging material standard YBB00242003-2015: 0.4ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract. The medium-borosilicate glass ampoule is sealed after nitrogen is filled to the headspace residual oxygen content <2.0%.

[0041] S503: Place the sealed borosilicate glass ampoule in a sterilization cabinet and sterilize in a water bath at 123° C. for 12 minutes to obtain diphenhydramine hydrochloride injection.

[0042] Comparative Example 1 The comparative example of the present application provides a diphenhydramine hydrochloride injection with a specification of 1 ml: 50 mg, and the preparation method of the injection comprises: D101: Add 1000 ml of injection water at 70°C to the liquid preparation container, cool to 30°C, add 50 g of diphenhydramine hydrochloride and 100 mg of benzalkonium chloride, mix, stir and dissolve to form a mixed solution. Use 0.02 mol / L sodium hydroxide solution to adjust the pH value of the mixed solution to 5.2.

[0043] D102: The liquid medicine is filtered through filters with a filtration accuracy of 0.45μm and 0.22μm in turn. After filtration, the liquid medicine is transported to the filling machine through a pipe made of silicone rubber and filled into a 1ml medium borosilicate glass ampoule. The inner surface water resistance of the medium borosilicate glass ampoule is in accordance with the requirements of the pharmaceutical packaging material standard YBB00242003-2015: 1.8ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract. The medium borosilicate glass ampoule is sealed after nitrogen is filled to the headspace residual oxygen content <1.0%.

[0044] D103: Place the sealed borosilicate glass ampoule in a sterilization cabinet and sterilize in a water bath at 121°C for 12 minutes to obtain diphenhydramine hydrochloride injection.

[0045] Comparative Example 2 The comparative example of the present application provides a diphenhydramine hydrochloride injection with a specification of 1 ml: 50 mg, and the preparation method of the injection comprises: D101: Add 1000 ml of injection water at 70°C to the liquid preparation container, cool to 30°C, add 50 g of diphenhydramine hydrochloride and 100 mg of benzalkonium chloride, mix, stir and dissolve to form a mixed solution; the content of impurity A in diphenhydramine hydrochloride is 0.25%, which meets the requirements of the United States Pharmacopoeia. Use a sodium hydroxide solution with a concentration of 0.02 mol / L to adjust the pH value of the mixed solution to 5.2.

[0046] D102: The liquid medicine is filtered through filters with a filtration accuracy of 0.45μm and 0.22μm in turn. After filtration, the liquid medicine is transported to the filling machine through a pipe made of silicone rubber and filled into a 1ml medium borosilicate glass ampoule. The inner surface water resistance of the medium borosilicate glass ampoule is in accordance with the requirements of the pharmaceutical packaging material standard YBB00242003-2015: 1.5ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract. The medium borosilicate glass ampoule is sealed after nitrogen is filled to the headspace residual oxygen content <1.0%.

[0047] D103: Place the sealed borosilicate glass ampoule in a sterilization cabinet and sterilize in a water bath at 121°C for 12 minutes to obtain diphenhydramine hydrochloride injection.

[0048] The pH value, content and impurity content of the diphenhydramine hydrochloride injection prepared in Examples 1-5 and Comparative Examples 1 and 2 were respectively detected before and after filling, and Tables 1 and 2 were obtained to determine the effect of the water resistance of the medium borosilicate glass ampoule on the pH value and the stability of the diphenhydramine hydrochloride injection.

[0049] Table 1: Test results of the effect of water resistance of liquid medicine pipelines and ampoules on pH value As can be seen from Table 1, the pH value of the diphenhydramine hydrochloride injection prepared in Examples 1-5 of the present application changes from about 0 to 0.2 before and after filling, which is a small change, while the pH value of the diphenhydramine hydrochloride injection prepared in Comparative Examples 1 and 2 changes from about 0.7 to 0.8 before and after filling, which is a large change. This shows that the material of the drug delivery pipeline and the water resistance of the borosilicate glass ampoule have a very obvious effect on the pH value of the diphenhydramine hydrochloride injection. Therefore, by controlling the water resistance of the borosilicate glass ampoule, the pH value change of the diphenhydramine hydrochloride injection during filling and sterilization can be effectively controlled.

[0050] Table 2: Stability test results of diphenhydramine hydrochloride injection As can be seen from Table 2, the properties of the diphenhydramine hydrochloride injection prepared in Examples 1-5 before and after sterilization are all colorless clear liquids, with a maximum content change of 0.7% and a maximum impurity content change of 0.23%; while the properties of the diphenhydramine hydrochloride injection prepared in Comparative Examples 1 and 2 are all colorless clear liquids before and after sterilization, with a maximum content change of 1.6% and a maximum impurity content change of 0.97%. This shows that the preparation method provided in the present application can greatly improve the stability of the diphenhydramine hydrochloride injection, and the impurity level of the obtained product is much lower than that specified in the Chinese Pharmacopoeia.

[0051] In addition, in the examples of the present application, three batches of diphenhydramine hydrochloride injection were produced under industrial conditions by the method shown in Example 1, and one batch of diphenhydramine hydrochloride injection was produced under industrial conditions by the method shown in Comparative Example 1, and four batches of diphenhydramine hydrochloride injection were subjected to accelerated tests to obtain the results shown in Table 3. The test conditions were 40°C ± 2°C and 75% RH ± 5% RH.

[0052] Table 3: Accelerated test results As can be seen from Table 3, after 6 months of accelerated test, the maximum change in pH value of the diphenhydramine hydrochloride injection prepared by the embodiment of the present application is 0.2, the maximum change in content is 1.0%, and the maximum change in total impurities is 0.4%, which are not much changed, and all maintain good stability; while the maximum change in pH value of the diphenhydramine hydrochloride injection of the control batch is 0.9, the maximum change in content is 2.1%, and the maximum change in total impurities is 1.01%, which is relatively large. This shows that the preparation method provided by the embodiment of the present application can greatly improve the drug safety of diphenhydramine hydrochloride injection, and all indicators meet the requirements.

[0053] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing diphenhydramine hydrochloride injection, characterized in that: include: Mix the water for injection and diphenhydramine hydrochloride, stir to dissolve, and adjust the pH value to 4.5-6.0 to form a drug solution; After filtering, the drug solution is filled into a medium-borosilicate glass ampoule, filled with nitrogen and sealed; wherein, the material of the infusion pipeline during filling or the inner layer of the pipeline directly contacting the drug solution is polytetrafluoroethylene or polypropylene, and the inner surface water resistance of the medium-borosilicate glass ampoule at 121°C is: for a medium-borosilicate glass ampoule of 1ml specification, no more than 0.5ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract; for a medium-borosilicate glass ampoule of 2ml specification, no more than 0.4ml of 0.01mol / L hydrochloric acid titration solution is consumed for every 100ml of extract; Sterilize with moist heat at 120-124°C for 8-12 minutes to obtain diphenhydramine hydrochloride injection.

2. The method for preparing diphenhydramine hydrochloride injection according to claim 1, characterized in that: The mixing of the water for injection and diphenhydramine hydrochloride comprises: adding the water for injection at 70-80° C. into a liquid preparation container, cooling the water for injection to 0-40° C., and then adding the diphenhydramine hydrochloride for mixing.

3. The method for preparing diphenhydramine hydrochloride injection according to claim 1, characterized in that: The mixing of the injection water and diphenhydramine hydrochloride comprises: cooling the injection water at 70-80° C. to 0-40° C. through a heat exchanger, and then adding the diphenhydramine hydrochloride and mixing.

4. The method for preparing the diphenhydramine hydrochloride injection according to any one of claims 1 to 3, characterized in that: The temperature of the water for injection is 10-30°C.

5. The method for preparing diphenhydramine hydrochloride injection according to claim 1, characterized in that: The pH value is adjusted to 4.5-6.0 using sodium hydroxide solution or hydrochloric acid solution.

6. The method for preparing diphenhydramine hydrochloride injection according to claim 1, characterized in that: The pH was adjusted to 5.0-5.

5.

7. The method for preparing diphenhydramine hydrochloride injection according to claim 1, characterized in that: The drug solution is filtered in two stages using filters with a filtering accuracy of 0.45 μm and / or 0.22 μm.

8. The method for preparing diphenhydramine hydrochloride injection according to claim 1, characterized in that: The residual oxygen content at the top of the borosilicate glass ampoule is less than 5.0%.

9. The method for preparing diphenhydramine hydrochloride injection according to claim 1, characterized in that: The cumulative F0 value after sterilization is 10-20.

10. A diphenhydramine hydrochloride injection, characterized in that: The method is prepared by any one of claims 1 to 9.

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