A sodium creatine phosphate injection for myocardial protection

Abstract

The present invention belongs to the technical field of pharmaceutical preparations, and specifically relates to a sodium creatine phosphate injection for myocardial protection. The sodium creatine phosphate injection of the present invention comprises a sodium creatine phosphate inclusion compound, a buffer solution, an isotonicity regulator, and water for injection. The sodium creatine phosphate is encapsulated by the inclusion technology, which solves the problem that sodium creatine phosphate is difficult to dissolve in water, significantly improves the stability of the sodium creatine phosphate injection, and reduces the content of related substances.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a sodium creatine phosphate injection for myocardial protection. Background Art

[0002] Cardiovascular disease is a very common chronic disease among the middle-aged and elderly. Even if most patients can actively receive treatment after the disease, more than 50% of patients still cannot return to normal life. Therefore, it will pose a great threat to people's lives and life safety.

[0003] Creatine phosphate is a drug that protects the myocardium. It can effectively stabilize the cell membrane in the human body, inhibit platelet aggregation, improve the microcirculation of myocardial ischemia, and regulate blood circulation in the body, thereby effectively improving the nutrition of the human myocardium. It can be used clinically to treat myocardial damage caused by coronary heart disease and angina pectoris, to treat insufficient skeletal muscle activity, and to treat metabolic diseases in the human body.

[0004] Chinese patent 200910019997.4 discloses a sodium creatine phosphate liposome freeze-dried preparation, which is composed of 10-20 parts of sodium creatine phosphate, 10-40 parts of phospholipids, 0-10 parts of cholesterol, 1-10 parts of antioxidants, and 5-20 parts of freeze-drying support agents, thereby improving the stability of the product.

[0005] Chinese Patent 201210302310.X The present invention discloses a method for preparing sodium creatine phosphate for injection, which uses high-frequency ultrasonic technology to prepare sodium creatine phosphate nanospheres, uses a spray freeze dryer for pre-freezing, and uses a microwave freeze dryer for drying. The product formula is optimized, the product efficacy is improved, the product stability is increased, the production cycle is shortened, the cost is reduced, the product quality is guaranteed, and satisfactory results are achieved. Summary of the invention

[0006] To overcome the deficiencies of the prior art, the present invention provides a sodium creatine phosphate inclusion compound injection, which solves the problem that sodium creatine phosphate is poorly soluble in water and improves the stability of the sodium creatine phosphate injection.

[0007] Specifically, the technical solution of the present invention is as follows:

[0008] The present invention provides a sodium creatine phosphate injection for myocardial protection, wherein the sodium creatine phosphate injection comprises: a sodium creatine phosphate inclusion compound, a buffer solution, an isotonicity regulator, and water for injection;

[0009] The preparation method of the sodium creatine phosphate injection is as follows:

[0010] (1) preparing a saturated aqueous solution of hydroxypropyl-β-cyclodextrin, adding sodium creatine phosphate to dissolve it, adding a buffer solution A containing azone, stirring and mixing in a water bath at a temperature of 0 to 15° C. for 10 to 30 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0011] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with an isotonicity regulator and part of the water for injection, add buffer solution B to adjust the pH, add water for injection to a sufficient amount, filter, and sterilize.

[0012] In multiple embodiments, the components of the sodium creatine phosphate injection are: 1 to 4 parts by weight of hydroxypropyl-β-cyclodextrin, 0.1 to 0.5 parts by weight of azone, and 1 part by weight of sodium creatine phosphate.

[0013] In a most preferred embodiment, the components of the sodium creatine phosphate injection are: 2 parts by weight of hydroxypropyl-β-cyclodextrin, 0.2 parts by weight of azone, and 1 part by weight of sodium creatine phosphate.

[0014] In many embodiments, the buffer solution A is one of barbital-sodium chloride buffer, disodium hydrogen phosphate-citric acid buffer, and Tris-hydrochloric acid buffer.

[0015] In a most preferred embodiment, the buffer A is a disodium hydrogen phosphate-citric acid buffer solution.

[0016] In many embodiments, the pH of the buffer solution A is 6.5-8.0.

[0017] In a most preferred embodiment, the pH of the buffer solution A is 7.6.

[0018] In multiple embodiments, the buffer B is one of acetic acid-sodium acetate buffer, citric acid-sodium citrate buffer, tartaric acid-sodium tartrate buffer, disodium hydrogen phosphate buffer, sodium dihydrogen phosphate buffer, sodium hydrogen phosphate buffer, and sodium carbonate buffer.

[0019] In a most preferred embodiment, the buffer B is citric acid-sodium citrate buffer.

[0020] In many embodiments, the isotonicity adjusting agent is one of sodium chloride, glucose, and glycerol.

[0021] In a most preferred embodiment, the isotonicity adjusting agent is sodium chloride.

[0022] In summary, the preparation method of the sodium creatine phosphate sodium creatine phosphate injection is:

[0023] (1) taking 1-4 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve it, adding 0.1-0.5 parts by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 6.5-8.0, stirring and mixing in a water bath at a temperature of 0-15° C. for 10-30 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0024] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH, add water for injection to a sufficient amount, filter, and sterilize.

[0025] Wherein, in step (2), the pH is adjusted to 6.0-8.0, which is within the commonly used pH selection range for injections. Preferably, the pH can be adjusted to 7.4.

[0026] Wherein, the optimal temperature for the reaction in step (1) is 8.

[0027] Wherein, the optimal time for stirring and mixing in step (1) is 20 minutes.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The present invention carries sodium creatine phosphate by inclusion technology, thereby solving the problem that sodium creatine phosphate is poorly soluble in water. The water solubility of the sodium creatine phosphate inclusion complex after inclusion with hydroxypropyl-β-cyclodextrin and azone is significantly increased.

[0030] The present invention significantly improves the quality of the sodium creatine phosphate inclusion compound and increases its drug loading and encapsulation rate by optimizing the inclusion material and the inclusion preparation method.

[0031] The sodium creatine phosphate injection prepared by the invention has lower content of related substances, more stable content and higher drug safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 : Content of related substances (creatine) in the sodium creatine phosphate injection of the examples and the comparative examples in the accelerated test

[0033] Figure 2 : Content of related substances (creatinine) in the sodium creatine phosphate injection of the examples and the comparative examples in the accelerated test

[0034] Figure 3 : Content of active ingredient in sodium creatine phosphate injection in the embodiment and the comparative example in the accelerated test DETAILED DESCRIPTION

[0035] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0036] Example 1 Creatine Phosphate Sodium Injection

[0037] (1) taking 2 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve, adding 0.2 parts by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 7.6, stirring and mixing in a water bath at a temperature of 8° C. for 20 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0038] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH to 7.4, add water for injection to a sufficient amount, filter, and sterilize.

[0039] Example 2 Creatine Phosphate Sodium Injection

[0040] (1) taking 1 part by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve, adding 0.1 part by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 6.5, stirring and mixing in a water bath at a temperature of 15° C. for 10 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0041] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH to 7.4, add water for injection to a sufficient amount, filter, and sterilize.

[0042] Example 3 Creatine Phosphate Sodium Injection

[0043] (1) taking 4 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve it, adding 0.5 parts by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 8.0, stirring and mixing in a water bath at a temperature of 0° C. for 30 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0044] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH to 7.4, add water for injection to a sufficient amount, filter, and sterilize.

[0045] Example 4 Creatine Phosphate Sodium Injection

[0046] (1) taking 2 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve it, adding a barbital-sodium chloride buffer solution containing 0.2 parts by weight of azone to adjust the pH to 7.6, stirring and mixing in a water bath at a temperature of 8° C. for 20 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0047] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with glucose and part of the water for injection, add sodium carbonate buffer solution to adjust the pH to 6.0, add water for injection to a sufficient amount, filter, and sterilize.

[0048] Example 5 Creatine Phosphate Sodium Injection

[0049] (1) taking 2 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve, adding a Tris-hydrochloric acid buffer solution containing 0.2 parts by weight of azone to adjust the pH to 7.6, stirring and mixing in a water bath at a temperature of 8° C. for 20 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0050] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add tartaric acid-sodium tartrate buffer solution to adjust the pH to 8.0, add water for injection to a sufficient amount, filter, and sterilize.

[0051] Comparative Example 1 Creatine Phosphate Sodium Injection

[0052] (1) taking 2 parts by weight of β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve, adding 0.2 parts by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 7.6, stirring and mixing in a water bath at a temperature of 8° C. for 20 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0053] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH to 7.4, add water for injection to a sufficient amount, filter, and sterilize.

[0054] Comparative Example 2 Creatine Phosphate Sodium Injection

[0055] (1) taking 2 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve, adding disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 7.6, stirring and mixing in a water bath at a temperature of 8° C. for 20 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0056] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH to 7.4, add water for injection to a sufficient amount, filter, and sterilize.

[0057] Comparative Example 3 Creatine Phosphate Sodium Creatine Phosphate Injection

[0058] (1) taking 2 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve, adding 0.8 parts by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 7.6, stirring and mixing in a water bath at a temperature of 8° C. for 20 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0059] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH to 7.4, add water for injection to a sufficient amount, filter, and sterilize.

[0060] Comparative Example 4 Creatine Phosphate Sodium Injection

[0061] (1) taking 2 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve, adding 0.2 parts by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 5.0, stirring and mixing in a water bath at a temperature of 8° C. for 20 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0062] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH to 7.4, add water for injection to a sufficient amount, filter, and sterilize.

[0063] Comparative Example 5 Creatine Phosphate Sodium Injection

[0064] (1) taking 2 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, adding 1 part by weight of sodium creatine phosphate to dissolve it, adding 0.2 parts by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 7.6, stirring and mixing in a water bath at a temperature of 20° C. for 20 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex;

[0065] (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer solution to adjust the pH to 7.4, add water for injection to a sufficient amount, filter, and sterilize.

[0066] Comparative Example 6 Creatine Phosphate Sodium for Injection (National Medicine Standard H20073072)

[0067] Verification Example

[0068] 1. Drug loading and encapsulation efficiency of creatine phosphate sodium inclusion complex

[0069] Drug loading = amount of drug contained in the inclusion complex / total amount of drug-loaded inclusion complex × 100%

[0070] Encapsulation rate = (total amount of drug input - amount of free drug not encapsulated in the inclusion compound) / total amount of drug input × 100%

[0071] Table 1 Drug loading and encapsulation efficiency of creatine phosphate sodium inclusion complex

[0072]

[0073]

[0074] According to the determination of the drug loading amount and encapsulation efficiency of the sodium creatine phosphate inclusion complexes of Examples 1-5 and Comparative Examples 1-5 in Table 1, the sodium creatine phosphate inclusion complexes of the present invention have high drug loading amount, high encapsulation efficiency and high quality.

[0075] 2. Quality evaluation of creatine phosphate sodium injection

[0076] 1. Inspection of visible foreign matter and insoluble particles

[0077] Accelerated test: Place the product in commercial packaging at 40±2℃ and 75%±5% relative humidity for 6 months. Take samples at the end of the first and sixth months of the test and inspect them according to the visible foreign matter inspection method (General Rule 0904) and the insoluble particle inspection method (General Rule 0903).

[0078] Table 2 Visible foreign matter and insoluble particles inspection results

[0079]

[0080]

[0081] Table 2 shows the inspection of visible foreign matter and insoluble particles of the sodium creatine phosphate injection of Examples 1-5 and Comparative Examples 1-5. The inspections at the 1st and 6th months of the accelerated test show that the inspections of visible foreign matter and insoluble particles of the sodium creatine phosphate injection of Examples 1-5 of the present invention are all qualified.

[0082] 2. Content of related substances

[0083] Determine according to the high performance liquid chromatography method (General Rule 0512), prepare fresh before use, test solution: take an appropriate amount of this product, accurately weigh, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 1 mg per 1 ml. Control solution: accurately measure 1 ml of the test solution, place it in a 200 ml volumetric flask, dilute to the mark with mobile phase, and shake well. Impurity reference solution: take an appropriate amount of creatine reference and creatinine reference, accurately weigh them respectively, place them in the same volumetric flask, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 7.5 μg per 1 ml. System suitability solution: take an appropriate amount of sodium creatine phosphate reference, creatine reference and creatinine reference, place them in the same volumetric flask, add mobile phase to dissolve and quantitatively dilute to make solutions containing 1 mg, 7.5 μg and 7.5 μg per 1 ml respectively. Sensitivity solution: accurately measure 5 ml of the control solution, place it in a 100 ml volumetric flask, dilute to the mark with mobile phase, and shake well. Chromatographic conditions: Use octadecylsilane bonded silica gel as filler (Thermo, Hypersil GOLD, C18, 4.6mm×250mm, 5μm or chromatographic column with equivalent performance); use a solution containing 0.2% potassium dihydrogen phosphate and 0.1% tetrabutylammonium hydroxide (adjust the pH value to 6.6 with phosphoric acid or ammonia test solution) as the mobile phase; the detection wavelength is 210nm; the injection volume is 20μl. System suitability requirements: In the system suitability solution chromatogram, the peak order is creatine, creatinine and phosphocreatine peak, the theoretical plate number calculated based on the phosphocreatine peak is not less than 2000, and the separation between the creatine peak and the creatinine peak should be greater than 3.0. In the sensitivity solution chromatogram, the signal-to-noise ratio of the phosphocreatine peak height is greater than 10. Determination method: Accurately measure the test solution, control solution and impurity reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram to twice the retention time of the main peak of the test solution. Limits: If there are two chromatographic peaks with the same retention time as the reference solution in the chromatogram of the test solution, the peak areas calculated by the external standard method shall not exceed 0.75% for creatine and creatinine; the peak area of ​​other single unknown impurities shall not be greater than the main peak area of ​​the reference solution (0.5%); the total amount of impurities shall not exceed 2.0%; peaks smaller than the main peak area of ​​the sensitivity solution shall be ignored.

[0084] Accelerated test: Place the product in commercial packaging at 40±2℃ and 75%±5% relative humidity for 6 months. Take samples at the end of the 1st, 2nd, 3rd and 6th month to detect the content of related substances in creatine phosphate sodium injection.

[0085] Figure 1-2 The accelerated test changes of the contents of related substances (creatine, creatinine) in the sodium creatine phosphate injection of the embodiment and the comparative example show that the sodium creatine phosphate injection of the present invention is more stable and is not prone to oxidation and degradation reactions.

[0086] 3. Creatine Phosphate Sodium Content

[0087] Determine according to the high performance liquid chromatography method (General Rule 0512). Test solution: Take an appropriate amount of this product, accurately weigh it, add the mobile phase to dissolve it and quantitatively dilute it to make a solution containing about 0.1 mg per 1 ml. Reference solution: Take an appropriate amount of sodium creatine phosphate reference substance, accurately weigh it, add the mobile phase to dissolve it and quantitatively dilute it to make a solution containing about 0.1 mg per 1 ml. System suitability solution, chromatographic conditions and system suitability requirements: the same as those under the relevant substance detection method. Determination method: Accurately measure the test solution and the reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram. Calculate by peak area according to the external standard method.

[0088] Accelerated test: Place the product in commercial packaging at 40±2°C and 75%±5% relative humidity for 6 months. Take samples at the end of the first, second, third and sixth months of the test to detect the content of sodium creatine phosphate in the sodium creatine phosphate injection.

[0089] Figure 3 The accelerated test changes of the active ingredient content of the sodium creatine phosphate injection of the embodiment and the comparative example show that the active ingredient content of the sodium creatine phosphate injection of the present invention is more stable.

Claims

1. A sodium creatine phosphate injection, characterized in that: The sodium creatine phosphate injection comprises: sodium creatine phosphate inclusion compound, buffer solution, isotonicity regulator and water for injection; The preparation method of the sodium creatine phosphate injection is as follows: (1) preparing a saturated aqueous solution containing 1 to 4 parts by weight of hydroxypropyl-β-cyclodextrin, adding 1 part by weight of sodium creatine phosphate to dissolve it, adding a pH=6.5-8.0 buffer solution A containing 0.1 to 0.5 parts by weight of azone, stirring and mixing in a water bath at a temperature of 0 to 15°C for 10 to 30 minutes, concentrating, filtering, washing, and drying to obtain a sodium creatine phosphate inclusion complex; (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with an isotonicity regulator and part of the water for injection, add buffer solution B to adjust the pH to 6.0-8.0, add water for injection to a sufficient amount, filter, and sterilize; The buffer solution A is one of barbital-sodium chloride buffer, disodium hydrogen phosphate-citric acid buffer, and Tris-hydrochloric acid buffer; the buffer solution B is one of acetic acid-sodium acetate buffer, citric acid-sodium citrate buffer, tartaric acid-sodium tartrate buffer, disodium hydrogen phosphate buffer, sodium dihydrogen phosphate buffer, sodium hydrogen phosphate buffer, and sodium carbonate buffer.

2. The creatine phosphate sodium injection according to claim 1, characterized in that: The components of the sodium creatine phosphate injection are: 2 parts by weight of hydroxypropyl-β-cyclodextrin, 0.2 parts by weight of azone, and 1 part by weight of sodium creatine phosphate.

3. The creatine phosphate sodium injection according to claim 1, characterized in that: The buffer solution A is a disodium hydrogen phosphate-citric acid buffer solution.

4. The creatine phosphate sodium injection according to claim 1, characterized in that: The pH of the buffer solution A is 7.

6.

5. The creatine phosphate sodium injection according to claim 1, characterized in that: The buffer solution B is a citric acid-sodium citrate buffer.

6. The creatine phosphate sodium injection according to claim 1, characterized in that: The isotonicity adjusting agent is one of sodium chloride, glucose and glycerol.

7. The creatine phosphate sodium injection according to claim 1, characterized in that: The isotonicity adjusting agent is sodium chloride.

8. The creatine phosphate sodium injection according to any one of claims 1 to 7, characterized in that: The preparation method of the sodium creatine phosphate injection comprises the following steps: (1) Take 1-4 parts by weight of hydroxypropyl-β-cyclodextrin to prepare a saturated aqueous solution thereof, add 1 part by weight of sodium creatine phosphate to dissolve it, add 0.1-0.5 parts by weight of azone dissolved in disodium hydrogen phosphate-citric acid buffer solution to adjust the pH to 6.5-8.0, stir and mix in a water bath at a temperature of 0-15°C for 10-30 minutes, concentrate, filter, wash, and dry to obtain a sodium creatine phosphate inclusion complex; (2) Mix the sodium creatine phosphate inclusion complex obtained in step (1) with sodium chloride and part of the water for injection, add citric acid-sodium citrate buffer to adjust the pH, add water for injection to a sufficient amount, filter, and sterilize.

9. The creatine phosphate sodium injection according to claim 8, characterized in that: In the step (2), the pH is adjusted to 7.

4.

10. The creatine phosphate sodium injection according to claim 8, characterized in that: The reaction temperature in step (1) is 8°C.

11. The creatine phosphate sodium injection according to claim 8, characterized in that: The stirring and mixing time in step (1) is 20 minutes.

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