A 13 C methadone injection lyophilized powder and its preparation method and application

Abstract

The application discloses a kind of 13 The application discloses a mefedrone injection lyophilized powder injection and a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. 13 The mefedrone injection lyophilized powder injection is prepared by a freeze-drying method from raw materials, and the raw materials include 13 Mefedrone, excipients, cosolvents and pH regulators. 13 The raw drug mefedrone is prepared into 13 The mefedrone injection lyophilized powder injection is used, and the stability of the raw drug mefedrone is improved, and storage and transportation are facilitated. 13 The mefedrone injection lyophilized powder injection can be used for preparing drugs, reagents or kits for disease diagnosis, liver reserve function evaluation and preoperative and postoperative evaluation of liver surgery. 13 The mefedrone injection lyophilized powder injection can be used for preparing drugs, reagents or kits for disease diagnosis, liver reserve function evaluation and preoperative and postoperative evaluation of liver surgery.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical preparations, in particular to a 13 C methamphetamine injection lyophilized powder injection and its preparation method and application. BACKGROUND

[0002] Liver is an important metabolic organ of the human body, and although there are many indicators for clinical liver function tests, there are fewer tests that can quantitatively reflect liver reserve and compensatory capacity in the early stage of cirrhosis. 13 C methamphetamine breath test is a new method for detecting liver reserve function, and experiments have found that, 13 C methamphetamine breath test value can distinguish cirrhosis and non-cirrhosis, and has very high value in clinical practice. 13 C methamphetamine, the chemical name is p-acetylamino phenyl ether (methoxy-13C), and its structural formula is:

[0003] In 2018, the 13 C methamphetamine diagnostic reagent is listed in Germany, and its dosage form is injection, the administration route is intravenous injection, and the liver function is detected or monitored through non-invasive respiratory test. However, as a liquid preparation, the injection is not convenient for storage and transportation, and has poor stability.

[0004] Therefore, the present application is proposed. SUMMARY

[0005] One of the purposes of the present application is to provide a 13 C methamphetamine injection lyophilized powder injection to solve the above technical problems.

[0006] The second purpose of the present application is to provide a preparation method of the above 13 C methamphetamine injection lyophilized powder injection.

[0007] The third purpose of the present application is to provide an application of the above 13 C methamphetamine injection lyophilized powder injection.

[0008] The present application can be realized as follows:

[0009] In a first aspect, the present application provides a 13 C methamphetamine injection lyophilized powder injection, which is prepared from a preparation raw material by freeze-drying method, and the preparation raw material comprises 13 C methamphetamine, excipient, cosolvent and pH adjuster.

[0010] In an optional embodiment, the excipient comprises at least one of mannitol, sorbitol, glucose, glycine and cysteine.

[0011] In an alternative embodiment, the amount of the excipient is 10-85wt% of the 13 C methamphetamine injection lyophilized powder injection.

[0012] In an alternative embodiment, the co-solvent includes at least one of polyethylene glycol 4000, polyethylene glycol 6000, hydroxypropyl-β-cyclodextrin, glycerol and polysorbate 80.

[0013] In an alternative embodiment, the co-solvent includes at least one of polyethylene glycol 4000, polyethylene glycol 6000, hydroxypropyl-β-cyclodextrin, glycerol and polysorbate 80. 13 The mass ratio of C methamphetamine to the co-solvent is 1:0.5-1:5.

[0014] In an alternative embodiment, the pH regulator includes at least one of citric acid, sodium citrate, sodium dihydrogen phosphate, disodium hydrogen phosphate, hydrochloric acid and sodium hydroxide.

[0015] In an alternative embodiment, the pH regulator includes at least one of citric acid, sodium citrate, sodium dihydrogen phosphate, disodium hydrogen phosphate, hydrochloric acid and sodium hydroxide. 13 The pH value of the C methamphetamine injection lyophilized powder injection is 4-9.

[0016] In an alternative embodiment, the pH value of the C methamphetamine injection lyophilized powder injection is 6-8. 13 The pH value of the C methamphetamine injection lyophilized powder injection is 4-9.

[0017] In a second aspect, the present application provides a method for preparing the C methamphetamine injection lyophilized powder injection as described in any of the preceding embodiments. 13 The method for preparing the C methamphetamine injection lyophilized powder injection includes the following steps: mixing the raw materials according to the ratio, dispensing, and freeze-drying.

[0018] In an alternative embodiment, before dispensing, the co-solvent, the excipient and 13 The C methamphetamine is mixed with water, and then the pH regulator is added to adjust the pH value.

[0019] In an alternative embodiment, the co-solvent and the excipient are mixed with water first, and then 13 The C methamphetamine is mixed with water, and then the pH regulator is added to adjust the pH value.

[0020] In an alternative embodiment, the C methamphetamine is dispensed at 50-100mg per bottle. 13 C methamphetamine is dispensed at 50-100mg per bottle.

[0021] In an alternative embodiment, the C methamphetamine is dispensed at 75mg per bottle. 13 C methamphetamine is dispensed at 50-100mg per bottle.

[0022] In an alternative embodiment, the freeze-drying includes a pre-freezing stage, a sublimation stage and a desorption drying stage.

[0023] The pre-freezing stage has a plate temperature of -30 to -50℃, and a processing time of 4-6h; the sublimation stage has a plate temperature of -10 to 5℃, and a processing time of 15-40h; and the desorption and drying stage has a plate temperature of 20-40℃, and a processing time of 4-10h.

[0024] In a third aspect, the present application provides a method for preparing a medicament, reagent or kit for disease diagnosis, liver reserve function evaluation, and pre- and post-operation evaluation of liver, comprising the step of preparing the lyophilized powder injection of mesuximide according to any one of the preceding embodiments. 13 The lyophilized powder injection of mesuximide can be used for preparing a medicament, reagent or kit for disease diagnosis, liver reserve function evaluation, and pre- and post-operation evaluation of liver.

[0025] The beneficial effects of the present application include:

[0026] The present application provides a lyophilized powder injection of mesuximide, which has the following advantages. 13 The lyophilized powder injection of mesuximide is prepared from a preparation raw material by a freeze-drying method, which improves the stability of the raw drug material and facilitates storage and transportation. 13 The excipient in the preparation raw material is mainly used as a freeze-drying framework, and forms a loose and porous block solid structure after freeze-drying and water evaporation. The cosolvent can make the lyophilized powder injection quickly dissolve in water for injection or sodium chloride injection during use. The pH adjuster can make the lyophilized powder injection have a pH value close to that of blood during use, thereby reducing the irritation of injection. The lyophilized powder injection of mesuximide can be used for preparing a medicament, reagent or kit for disease diagnosis, liver reserve function evaluation, and pre- and post-operation evaluation of liver. 13 The lyophilized powder injection of mesuximide can be used for preparing a medicament, reagent or kit for disease diagnosis, liver reserve function evaluation, and pre- and post-operation evaluation of liver. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below. If the specific conditions are not indicated in the embodiments, the conventional conditions or the conditions suggested by the manufacturer are used. If the reagents or instruments are not indicated by the manufacturer, they are all conventional products that can be purchased in the market.

[0028] The present application provides a lyophilized powder injection of mesuximide, which has the following advantages. 13 The present application provides a lyophilized powder injection of mesuximide, a preparation method thereof and applications thereof.

[0029] The present application provides a lyophilized powder injection of mesuximide, which has the following advantages. 13 The lyophilized powder injection of mesuximide is prepared from a preparation raw material by a freeze-drying method, which improves the stability of the raw drug material and facilitates storage and transportation. 13 The lyophilized powder injection of mesuximide is prepared from a preparation raw material by a freeze-drying method, which improves the stability of the raw drug material and facilitates storage and transportation.

[0030] By way of reference, the excipient can exemplarily but non-limitatively include at least one of mannitol, sorbitol, glucose, glycine and cysteine.

[0031] The amount of the excipient can be 0.1-10% by weight.13 C methamphetamine injection lyophilized powder injection 10-85wt%, such as 10wt%, 20wt%, 30wt%, 40wt%, 50wt%, 60wt%, 70wt%, 80wt% or 85wt% and the like.

[0032] Excipients are mainly used as lyophilized framework, after freeze-drying, water is evaporated to form a loose porous block solid structure.

[0033] Based on 13 C methamphetamine has low solubility in water and slow dissolution rate, in order to ensure that the lyophilized powder injection can be quickly dissolved in water for injection or sodium chloride injection in use, the present application in 13 C methamphetamine injection lyophilized powder injection preparation raw materials added cosolvent.

[0034] For reference, the cosolvent exemplarily but not limitedly can include at least one of polyethylene glycol 4000, polyethylene glycol 6000, hydroxypropyl-β-cyclodextrin, glycerol and polysorbate 80.

[0035] 13 The mass ratio of C methamphetamine to cosolvent can be 1:0.5-1:5, such as 1:0.5, 1:0.8, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5 or 1:5 and the like.

[0036] In order to control the pH value of the injection, make it close to the blood pH value, reduce the irritation of injection, the present application in 13 C methamphetamine injection lyophilized powder injection preparation raw materials also added pH regulator.

[0037] For reference, the pH regulator exemplarily but not limitedly can include at least one of citric acid, sodium citrate, sodium dihydrogen phosphate, disodium hydrogen phosphate, hydrochloric acid and sodium hydroxide.

[0038] In the present application, 13 The pH value of C methamphetamine injection lyophilized powder injection can be 4-9, such as 4, 5, 6, 7, 8 or 9 and the like. In some preferred embodiments, 13 The pH value of C methamphetamine injection lyophilized powder injection is 6-8.

[0039] It is worth mentioning that the 13 C methamphetamine injection lyophilized powder injection preparation raw materials can also be added other ingredients used in medicine as needed.

[0040] In use, the above 13 C methamphetamine injection lyophilized powder injection is dissolved with water to form 13 C methamphetamine injection.

[0041] Accordingly, the present application also provides a method for preparing the above-mentioned 13 The method for preparing the lyophilized powder injection of mesuximide C comprises the following steps: mixing the raw materials according to the proportion, sub-packaging, and freeze-drying.

[0042] For reference, before sub-packaging, the solubilizing agent, excipient and 13 The mesuximide C is mixed with water, and then the pH regulator is added to adjust the pH value. In some preferred embodiments, the solubilizing agent and excipient are mixed with water first, and then the pH regulator is added to adjust the pH value. 13 The mesuximide C is mixed, and then the pH regulator is added to adjust the pH value.

[0043] For reference, during sub-packaging, 50-100 mg (such as 50 mg, 60 mg, 70 mg, 80 mg, 90 mg or 100 mg, etc.) of 13 The mesuximide C is sub-packaged, preferably 75 mg of 13 The mesuximide C is sub-packaged.

[0044] In the present application, the freeze-drying includes a pre-freezing stage, a sublimation stage and a desorption drying stage.

[0045] In the pre-freezing stage, the plate temperature can be set to -30 to -50°C, and the processing time can be 4-6 h; in the sublimation stage, the plate temperature can be set to -10 to 5°C, and the processing time can be 15-40 h; in the desorption drying stage, the plate temperature can be set to 20-40°C, and the processing time can be 4-10 h.

[0046] In some specific embodiments, under a sterile production environment, water for injection is taken, the solubilizing agent, excipient and 13 The mesuximide C is added, stirred and dissolved, then the pH regulator is added to adjust the pH value to 4-9, water for injection is added to constant volume, the solution is filtered through a 0.22 μm microporous filter, filled into a Schlenk flask, and semi-tightened; the sample is placed in a freeze dryer for freeze-drying; after the freeze-drying program is completed, vacuum-tightening is performed, the box is taken out, and the cap is tightened.

[0047] In addition, the present application also provides the use of the above-mentioned 13 The lyophilized powder injection of mesuximide C, for example, can be used for preparing a drug, reagent or kit for disease diagnosis, liver reserve function evaluation, and preoperative and postoperative evaluation of liver surgery.

[0048] The disease can exemplarily but not limitedly include at least one of liver cirrhosis, primary biliary cirrhosis, simple steatosis, chronic liver disease staging, alcoholic liver disease, degree or stage of liver fibrosis, non-alcoholic fatty liver, neonatal cholestasis, biliary atresia, intrahepatic inflammation, acute liver failure, and hepatocellular carcinoma.

[0049] Liver reserve function assessment can exemplarily but not limitatively include at least one of related disease liver function evaluation, chemotherapy liver injury assessment, chronic liver failure death prediction and liver detoxification capacity assessment.

[0050] Pre- and post-surgery assessment can exemplarily but not limitatively include at least one of post-hepatectomy regeneration assessment, liver transplantation urgency assessment, post-surgery liver failure assessment and related pre- and post-surgery assessment.

[0051] The features and properties of the present application are further described in detail below in conjunction with the embodiments.

[0052] Embodiment 1

[0053] The present embodiment provides a 13 The formula of the lyophilized powder injection of C-methadone is shown in Table 1.

[0054] Table 1 Formula

[0055]

[0056] The 13 The preparation process of the lyophilized powder injection of C-methadone is as follows:

[0057] (1) Take 1200 mL of water for injection and heat to 60°C;

[0058] (2) Weigh the prescribed amount of 13 C-methadone, mannitol and polyethylene glycol 4000 into the above water for injection and stir to dissolve;

[0059] (3) Weigh the prescribed amount of sodium dihydrogen phosphate into the above solution, measure the pH, add 1 mol / L sodium hydroxide to adjust the pH value to 6-8, and add water for injection to make up to 1500 mL;

[0060] (4) The solution is filtered through a 0.22 μm microporous filter to remove bacteria;

[0061] (5) The above solution is filled into a vial, the filling amount is 15 mL, and the half plug is pressed;

[0062] (6) Transfer to the freeze dryer for freeze-drying, and the freeze-drying parameters are shown in Table 2.

[0063] Table 2 Freeze-drying parameters

[0064] Freeze-drying stage Chamber temperature Time Vacuum level Pre-freezing -40℃ 4 hours / Vacuuming -40℃ / < 50 Pa Chamber warming Warming to 0°C 8 hours < 50 Pa Sublimation drying 0℃ 12 hours < 50 Pa Chamber warming Warming to 30°C 2 hours < 50 Pa Desorption drying 30℃ 6 hours <15 Pa End of freeze-drying / / /

[0065] (6) After the freeze-drying program is completed, vacuum plug, out of the box, and seal the cover to obtain the product.

[0066] Embodiment 2

[0067] The present embodiment provides a 13 C methadone injection lyophilized powder injection, the formula is shown in Table 3.

[0068] Table 3 formula

[0069]

[0070] The 13 The preparation process of C methadone injection lyophilized powder injection is as follows:

[0071] (1) Take 800 mL of water for injection and heat to 60°C;

[0072] (2) The prescribed amount of mannitol and polyethylene glycol 6000 is added to the above water for injection, and after stirring and dissolving, the prescribed amount of 13 C methadone is stirred and dissolved;

[0073] (3) The prescribed amount of citric acid and sodium citrate is added to the above solution, and the pH value is adjusted to 6.0-7.0, and the injection is made to 1000 mL;

[0074] (4) The solution is filtered through a 0.22 μm microporous filter to remove bacteria;

[0075] (5) The above solution is filled into a vial, the filling amount is 10 mL, and the half plug is pressed;

[0076] (6) Transfer to the freeze dryer for freeze drying, and the freeze drying parameters are shown in Table 4.

[0077] Table 4 Freeze drying parameters

[0078] Freeze-drying stage Chamber temperature Time Vacuum level Pre-freezing -45℃ 4 hours / Vacuuming -45℃ / <60 Pa Chamber warming Warming to 5°C 6 hours <60 Pa Sublimation drying 0℃ 10 hours <60 Pa Chamber warming Warming to 25°C 2 hours <60 Pa Desorption drying 25℃ 5 hours <20 Pa End of freeze-drying / / /

[0079] (6) After the freeze-drying program is completed, vacuum plug, out of the box, and seal the cover to obtain.

[0080] Example 3

[0081] The present embodiment provides a 13 C methadone injection lyophilized powder injection, the formula is shown in Table 1.

[0082] Table 5 formula

[0083]

[0084] The 13 The preparation process of C methadone injection lyophilized powder injection is as follows:

[0085] (1) Take 1000 mL of water for injection and heat to 50°C;

[0086] (2) Take the prescription amount of hydroxypropyl-β-cyclodextrin, glycine to the above injection water, stir and dissolve, then add the prescription amount of 13 C methamphetamine stir and dissolve;

[0087] (3) Take the prescription amount of citric acid to the above solution, measure the pH, add 1 mol / L of sodium hydroxide, adjust the pH to 6-8, add injection water to 1200 mL;

[0088] (4) The solution is filtered through a 0.22 μm microporous filter to remove bacteria;

[0089] (5) The above solution is filled into a vial, the filling amount is 12 mL, and the half plug is pressed;

[0090] (6) Transfer to the freeze dryer for freeze drying, and the freeze drying parameters are shown in Table 6.

[0091] Table 6 Freeze drying parameters

[0092] Freeze-drying stage Chamber temperature Time Vacuum level Pre-freezing -50℃ 5 hours / Vacuuming -50℃ / <45Pa Chamber warming Warming to -5°C 8 hours <45Pa Sublimation drying -5℃ 12 hours <45 Pa Chamber warming Warming to 30°C 3 hours <45 Pa Desorption drying 30℃ 5 hours <15 Pa End of freeze-drying / / /

[0093] (6) After the freeze-drying program is completed, vacuum plug, out of the box, and seal the cover to obtain it.

[0094] Example 4

[0095] This example provides a kind of 13 C methamphetamine injection freeze-dried powder injection, the formula is shown in Table 7.

[0096] Table 7 Formula

[0097]

[0098]

[0099] The 13 The preparation process of C methamphetamine injection freeze-dried powder injection is as follows:

[0100] (1) Take 1200 mL of injection water, heat to 60℃;

[0101] (2) Take the prescription amount of Tween 80, polyethylene glycol 4000 and sorbitol to the above injection water, stir and dissolve, then add the prescription amount of 13 C methamphetamine stir and dissolve;

[0102] (3) Take the prescription amount of sodium citrate to the above solution, measure the pH, add 1 mol / L of hydrochloric acid, adjust the pH to 6-8, add injection water to 1500 mL;

[0103] (4) The solution is filtered through a 0.22 μm microporous filter to remove bacteria;

[0104] (5) The above solution is filled into a vial, with a filling amount of 15 mL, and semi-tamped;

[0105] (6) The solution is transferred into a freeze dryer for freeze drying, with freeze drying parameters shown in Table 8.

[0106] Table 8 Freeze drying parameters

[0107] Freeze-drying stage Chamber temperature Time Vacuum level Pre-freezing -45℃ 4 hours / Vacuuming -45℃ / <50 Pa Chamber warming Warming to -5°C 6 hours <50 Pa Sublimation drying -5℃ 10 hours <50 Pa Chamber warming Warming to 30°C 3 hours <50 Pa Desorption drying 30℃ 6 hours <15 Pa End of freeze-drying Freeze-drying stage Chamber temperature Time Vacuum level Pre-freezing 4 hours Vacuuming Chamber warming Warming to -5°C 6 hours Sublimation drying 10 hours Chamber warming Warming to 30°C 3 hours Desorption drying 6 hours End of freeze-drying Freeze-drying stage Chamber temperature Time Vacuum level Pre-freezing 4 hours Vacuuming Chamber warming Warming to -5°C 6 hours Sublimation drying 10 hours Chamber warming Warming to 30°C 3 hours Desorption drying 6 hours End of freeze-drying / / /

[0108] (6) After the freeze drying program is completed, the vial is vacuum-tamped, taken out of the box, capped, and obtained.

[0109] Comparative Example

[0110] The present comparative example provides a 13 C methadone injection, with a formula shown in Table 9.

[0111] Table 9 Formula

[0112]

[0113]

[0114] The 13 The preparation process of C methadone injection is as follows:

[0115] (1) 4500 mL of water for injection is taken and heated to 60°C;

[0116] (2) The prescribed amount of polyethylene glycol 400 and sodium dihydrogen phosphate is weighed into the above water for injection, stirred and dissolved, and then the prescribed amount of 13 C methadone is stirred and dissolved;

[0117] (3) The pH of the solution is measured, 1 mol / L sodium hydroxide is added, the pH is adjusted to 6-8, and water for injection is added to make up to 5000 mL;

[0118] (4) The solution is filtered through a 0.22 μm microporous filter to remove bacteria;

[0119] (5) The above solution is filled into an infusion bottle, with a filling amount of 50 mL, tamped, and capped;

[0120] (6) The filled injection is placed in a sterilization cabinet and autoclaved at 121°C for 15 minutes, and then cooled to obtain the product.

[0121] Test Example

[0122] The C methadone injection prepared in the above Examples 1-4 and the C methadone injection prepared in the comparative example are compared, with results shown in Table 10. 13 C methadone injection prepared in the above Examples 1-4 and the C methadone injection prepared in the comparative example are compared, with results shown in Table 10. 13 C methadone injection prepared in the above Examples 1-4 and the C methadone injection prepared in the comparative example are compared, with results shown in Table 10.

[0123] Table 10 Comparison Table

[0124]

[0125]

[0126] It should be noted that "Impurity A" in the table above refers to para-aminoanisole, a degradation impurity of methadone. Methadone raw material may undergo partial degradation of its amide structure in the presence of high-temperature water, forming para-aminoanisole. As can be seen from Table 10:

[0127] ①Stability: The embodiments provided in this application 13 The C-type methadone lyophilized powder for injection showed low levels of related substance impurity A, and after 3 months of exposure at 40°C, there was no significant increase or change in the content of related substance impurity A. In contrast, the comparative injection solution showed higher levels of related substance impurity A than the lyophilized powder for injection samples in each example, and after 3 months of exposure at 40°C, related substance impurity A increased significantly, while the content decreased slightly, and the solution color changed from colorless to pale yellow. The main reason for this is that the lyophilized powder for injection in each example was produced at low or room temperature, and the final sample was a solid, resulting in good stability. In contrast, the comparative sample underwent autoclaving at 121°C, leading to an increase in related substance levels, and the injection solution, being a liquid preparation, had poorer stability. Therefore, in this application, the related substance impurity A levels in the examples were higher than in the comparative examples. 13 C-methoxetine lyophilized powder for injection is of superior quality.

[0128] ② Other aspects: The embodiments provided in this application 13 C-methoxetine lyophilized powder for injection is small in size, easy to store and transport. Clinically, it can be used simply by reconstitution with water for injection or sodium chloride injection, and can perfectly replace the injection solution.

[0129] In summary, the application provides 13 C-methoxetine lyophilized powder for injection is prepared by freeze-drying, which improves the efficiency of the raw material. 13 C-methoxetine's stability facilitates storage and transportation. 13 C-methoxetine lyophilized powder for injection can be used after reconstitution and can be used to prepare drugs, reagents or kits for disease diagnosis, liver reserve function assessment, and pre- and post-operative assessment of liver surgery.

[0130] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A 13 C methadone for injection in the form of a lyophilized powder, characterized in that, The 13 C methamphetamine injection lyophilized powder injection is prepared by a freeze-drying method from a preparation raw material including 13 C methamphetamine, excipient, co-solvent, and pH adjuster The amount of the excipient is 10-85wt% of the 13 C methamphetamine injection lyophilized powder injection 10-85wt%; the 13 The mass ratio of C methamphetamine to the cosolvent is 1:0.5-1:5; the 13 The pH value of C methamphetamine injection lyophilized powder injection is 4-9; The 13 The preparation of the injection of methamphetamine hydrochloride lyophilized powder includes: mixing the cosolvent and the excipient with water according to the proportion, then adding the 13 C methamphetamine mixed, then adding the pH adjuster to adjust the pH value; dispensing, freeze-drying; The freeze-drying comprises a pre-freezing stage, a sublimation stage and a desorption drying stage; the plate layer temperature of the pre-freezing stage is -30 to -50 DEG C, and the processing time is 4-6 h; the plate layer temperature of the sublimation stage is -10 to 5 DEG C, and the processing time is 15-40 h; the plate layer temperature of the desorption drying stage is 20-40 DEG C, and the processing time is 4-10 h. The excipient comprises at least one of mannitol, sorbitol and glycine. The co-solvent comprises at least one of polyethylene glycol 4000, polyethylene glycol 6000, hydroxypropyl-beta-cyclodextrin, glycerol and polysorbate 80.

2. The method of claim 1, 13 C Methadone hydrochloride for injection in lyophilized powder form, characterized in that, The pH regulator comprises at least one of citric acid, sodium citrate, sodium dihydrogen phosphate, disodium hydrogen phosphate, hydrochloric acid and sodium hydroxide.

3. The method of claim 1 or 2, wherein the method is performed in a single step. 13 C Methamphetamine injection lyophilized powder injection, characterized in that, The 13 C The pH of the lyophilized powder for injection of methamphetamine is 6-8.

4. The method of any one of claims 1-3 13 A process for the preparation of methamphetamine hydrochloride injection lyophilized powder, characterized in that, comprising the steps of mixing the co-solvent and the excipient with water in a ratio, followed by adding the 13 C mixing with methamphetamine, and adding the pH adjusting agent to adjust the pH value; aliquoting, freeze-drying; The freeze-drying comprises a pre-freezing stage, a sublimation stage and a desorption drying stage; the plate layer temperature of the pre-freezing stage is -30 to -50 DEG C, and the processing time is 4-6 h; the plate layer temperature of the sublimation stage is -10 to 5 DEG C, and the processing time is 15-40 h; the plate layer temperature of the desorption drying stage is 20-40 DEG C, and the processing time is 4-10 h.

5. The preparation method according to claim 4, characterized in that, containing 50-100 mg of the active ingredient per bottle 13 C methamphetamine is divided into portions.

6. The production method according to claim 5, characterized by, containing 75 mg of the active ingredient per bottle 13 C methamphetamine is divided into portions.

7. The method of any one of claims 1-3 13 Use of a lyophilized powder injection of methamphetamine for injection, characterized in that, The 13 C methamphetamine injection lyophilized powder injection for preparing liver reserve function evaluation, liver preoperative and postoperative evaluation of drugs, reagents or kits.

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