Semaglutide injection and preparation method thereof

Abstract

The invention relates to the technical field of medicine preparation, and particularly provides a semaglutide injection and a preparation method thereof.The semaglutide injection comprises semaglutide, a polyorthoester polymer, a cosolvent and a diluent, based on the total mass of the semaglutide injection, the mass ratio of the polyorthoester polymer is 40-80%, and the mass ratio of the cosolvent to the diluent is 40-80%. The mass ratio of the poly orthoester polymer to the cosolvent is (40-80): (2-15). The polyorthoester polymer and the cosolvent are mutually compounded, so that the effect of the polyorthoester polymer serving as a sustained-release skeleton is fully volatilized, the drug release period is remarkably prolonged, meanwhile, the problem of burst release of the drug is avoided, the stable release performance of the drug is improved, the stability of the injection is high, and even if phenol is not added to serve as a preservative, the injection does not have toxic or side effect. And the injection also has a relatively long shelf life.

Description

Technical Field

[0001] The present invention relates to the technical field of drug preparation, and in particular to a semaglutide injection and a preparation method thereof. Background Art

[0002] Semaglutide (semaglutide) is a second-generation glucagon-like peptide-1 (GLP-1) analog developed by Novo Nordisk for the treatment of type 2 diabetes mellitus (T2DM). Semaglutide stimulates insulin secretion and inhibits glucagon secretion to achieve the effect of lowering blood sugar. In addition, it can also act on the digestive tract, delay gastrointestinal emptying, increase satiety, and thus achieve the effect of weight loss.

[0003] The semaglutide drugs currently on the market are semaglutide injection and semaglutide tablets. Although the semaglutide tablets have an absorption enhancer added to the prescription, which improves the bioavailability of semaglutide, daily medication increases the frequency of administration, which may reduce patient compliance, especially the risk of missed doses in elderly patients. Semaglutide injection is administered once a week, which reduces the frequency of administration, but there are still some problems: (1) Phenol is used as a preservative in semaglutide injection. On the one hand, phenol has certain physiological toxic side effects. On the other hand, phenol itself is sensitive to light and air, which poses certain challenges to the production and storage of the preparation. (2) The existing semaglutide injection is administered once a week. Although it can reduce the frequency of administration, for some patients with special needs who need to be administered for a longer time, the existing injection obviously cannot meet the requirements. Therefore, a preparation with a simple prescription composition, a mild production environment, and a low administration frequency is needed to overcome the shortcomings of the existing preparations. Summary of the invention

[0004] The present invention aims to solve one of the technical problems in the prior art at least to a certain extent. To this end, one object of the present invention is to provide a semaglutide injection and a preparation method thereof.

[0005] According to the first aspect of the present invention, a semaglutide injection is provided, which includes semaglutide, a polyorthoester polymer, a cosolvent and a diluent. Based on the total mass of the injection, the mass proportion of the polyorthoester polymer is 40% to 80%, and the mass ratio of the polyorthoester polymer to the cosolvent is (40 to 80): (2 to 15).

[0006] For example, based on the total mass of the injection, the mass ratio of the polyorthoester polymer is 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, etc., or a range between any two of the above values; for example, the mass ratio of the polyorthoester polymer to the co-solvent is 40:2, 40:4, 40:8, 40:10, 40:15, 60:2, 60:4, 60:6, 60:8, 60:10, 60:15, 80:2, 80:6, 80:8, 80:10, 80:15, etc.

[0007] According to the present invention, the above-mentioned semaglutide injection includes semaglutide, polyorthoester polymer, cosolvent and diluent. By adding polyorthoester polymer to the injection, the slow and sustained release of semaglutide can be achieved. Although the addition of polyorthoester polymer will increase the release cycle of semaglutide, there is still a problem of semaglutide burst release to varying degrees in the initial stage. By adding a suitable cosolvent, the above-mentioned burst release problem can be well solved, and a semaglutide injection with a long release cycle, good drug release stability and low administration frequency can be obtained. The semaglutide injection of the present invention does not add phenol as a preservative, thereby avoiding the biological toxicity and side effects caused by phenol. In particular, by controlling the addition amount of polyorthoester polymer and cosolvent within the above range, the mutual synergistic compounding effect of semaglutide, polyorthoester polymer and cosolvent can be fully exerted, the release cycle of the injection is extended, the stability of the injection is guaranteed, and the shelf life of the injection is improved. At the same time, the composition of the injection is simple, the raw materials are easily available, the cost is low, and it has important application value.

[0008] Preferably, the release period of the semaglutide injection of the present invention is not less than 20 days.

[0009] According to the above-mentioned semaglutide injection of the present invention, based on the total mass of the injection, the mass proportion of semaglutide is 0.2%~2%. For example, the mass proportion of semaglutide is 0.2%, 0.3%, 0.4%, 0.8%, 1.2%, 1.6%, 2.0%, etc., or the range between any two of the above values. Controlling the mass proportion of semaglutide within the above range can meet the dosage of the organism within a longer release period.

[0010] Preferably, based on the total mass of the injection, the mass proportion of semaglutide is 0.2% to 2%, and the release period of semaglutide injection is 20 days to 30 days.

[0011] Preferably, based on the total mass of the injection, the mass proportion of semaglutide is 0.2% to 2%, and the mass proportion of the polyorthoester polymer is 40% to 80%.

[0012] According to the above-mentioned semaglutide injection of the present invention, the molecular weight of the polyorthoester polymer is 5000-40000, preferably 15000-25000. For example, the molecular weight of the polyorthoester polymer is 5000, 10000, 15000, 16000, 17000, 18000, 19000, 20000, 21000, 22000, 23000, 24000, 25000, 30000, 40000, etc., or the range between any two values ​​of the above. By controlling the molecular weight of the polyorthoester polymer within the above range, the drug release rate can be controlled so that the drug is completely released within a specified time.

[0013] Preferably, the polyorthoester polymer is formed by polymerizing 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5.5]undecane as a monomer, and contains latent acid and diol segments.

[0014] Preferably, the mass ratio of the polyorthoester polymer to the co-solvent is (40-78):(2-15).

[0015] According to the above-mentioned semaglutide injection of the present invention, based on the total mass of the injection, the mass proportion of the diluent is 4% to 58%. For example, the mass proportion of the diluent is 4%, 9%, 13%, 18%, 23%, 30%, 35%, 40%, 48%, 58%, etc. By controlling the mass proportion of the diluent within the above range, the preparation reaches the target viscosity, which is conducive to improving the long-term stable release effect of semaglutide.

[0016] Preferably, the diluent includes one of polyethylene glycol 400, glycerol, and liquid paraffin.

[0017] In some embodiments of the present invention, the semaglutide injection comprises 0.2wt% to 2wt% of the semaglutide, 40wt% to 80wt% of the polyorthoester polymer and 2wt% to 15wt% of the cosolvent. By controlling the addition amount of semaglutide, polyorthoester polymer and cosolvent within the above range, the synergistic effect of each component can be significantly exerted, the drug release stability of the injection can be effectively improved, the drug burst release problem can be avoided, and the drug release cycle can be extended.

[0018] Further preferably, the semaglutide injection comprises 0.2 wt% to 2 wt% of the semaglutide, 40 wt% to 80 wt% of the polyorthoester polymer, 2 wt% to 15 wt% of the cosolvent and the balance of the diluent.

[0019] In a second aspect of the present invention, the present invention provides a method for preparing the above-mentioned semaglutide injection, the method comprising: Mixing the polyorthoester polymer and the diluent to obtain an auxiliary material solution; Mixing and dissolving semaglutide and a co-solvent to obtain a drug solution; The sterilized auxiliary material solution and the drug solution are mixed.

[0020] According to the method for preparing semaglutide injection of the present invention, the polyorthoester polymer and the diluent are mixed to reduce the viscosity of the polyorthoester polymer so as to be mixed with the drug solution; semaglutide and the cosolvent are mixed and dissolved so that semaglutide is fully dissolved in the cosolvent; finally, the sterilized auxiliary material solution and the drug solution are mixed to obtain semaglutide injection. Thus, the method can be used to prepare semaglutide injection with a long drug release period and high drug release stability.

[0021] It should be noted that the sterilization of the excipient solution and the drug solution is a routine operation in the art. For example, the excipient solution can be sterilized at 121° C. for 30 min. For another example, the drug solution can be filtered through a 0.22 μm PTFE filter membrane for sterilization.

[0022] According to the method for preparing semaglutide injection of the present invention, the temperature during the mixing process of the polyorthoester polymer and the diluent is controlled to be 40°C to 80°C, for example, the temperature is 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, or a range between any two of the above values. By controlling the temperature of the mixing process within the above range, semaglutide can be evenly mixed with other excipients to form a stable preparation.

[0023] According to the method for preparing semaglutide injection of the present invention, the temperature during the mixing process of the sterilized auxiliary material solution and the sterilized drug solution is controlled to be 15°C to 40°C, for example, the temperature is 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, etc., or the range between any two of the above values. By controlling the temperature during the mixing process of the sterilized auxiliary material solution and the sterilized drug solution within the above range, the drug activity of semaglutide can be fully guaranteed, and the auxiliary material solution and the drug solution are fully mixed to ensure the sustained and stable release performance of the injection.

[0024] The present invention has at least the following technical effects: The present invention, by compounding semaglutide, polyorthoester polymer, cosolvent and diluent, not only fully exerts the role of polyorthoester polymer as a sustained-release skeleton, significantly prolongs the drug release period, avoids the problem of drug burst release, improves the stable release performance of the drug, and has high stability of the injection. Even if phenol is not added as a preservative, the injection has a long shelf life. At the same time, the injection has a simple composition, readily available raw materials, low cost, and important application value. DETAILED DESCRIPTION

[0025] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. The present invention is described below with reference to specific embodiments. It should be noted that these embodiments are merely illustrative and do not limit the present invention in any way.

[0026] Example 1 This embodiment provides a semaglutide injection, which has the following composition: 0.2 wt % of semaglutide, 80 wt % of polyorthoester polymer (molecular weight: 18694 g / mol), 4.8 wt % of polyethylene glycol 400, and 15 wt % of ethanol.

[0027] The polyorthoester polymer used in this embodiment is prepared by polymerization reaction using 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5.5]undecane as a monomer, and contains latent acid and diol segments.

[0028] The polyorthoester polymers of Examples 2-7 and Comparative Examples 1-2 are the same as those of Example 1.

[0029] The preparation process of the semaglutide injection of Example 1 is as follows: (1) Preparation of excipient solution: According to the above prescription, weigh polyorthoester polymer and polyethylene glycol 400 and place them in a preparation tank, and stir at 60°C until they are uniformly mixed; (2) Preparation of drug solution: weigh the prescribed amount of semaglutide and add it to the prescribed amount of ethanol at room temperature and stir until dissolved; (3) Sterilization: Sterilize the excipient solution at 121°C for 30 min, and then slowly cool it down to 20°C. Filter the drug solution through a 0.22 μm PTFE filter membrane for sterilization. (4) Mixing: After the excipient solution drops to 20°C, add the filtered drug solution to the excipient solution and stir until uniform.

[0030] The viscosity test process and results of the semaglutide injection of Example 1 are as follows: The viscosity of semaglutide injection was measured at 25°C using a DVNextCP cone viscometer from Brookfield and was found to be 38421 mPa·s.

[0031] The in vitro release test process and results of the semaglutide injection of Example 1 are as follows: 0.3g of semaglutide injection was placed in a vial containing 200ml of pH 7.4 phosphate buffer. The vial was placed in a 37°C water area for 30 days, and samples were taken at 0.5, 1, 2, 3, 5, 10, 15, 20, 25, and 30 days to detect the content of semaglutide in the buffer and calculate the release amount. The specific results are shown in Table 1.

[0032] Table 1

[0033] Example 2 This embodiment provides a semaglutide injection, which has the following composition: 0.2 wt % of semaglutide, 65 wt % of polyorthoester polymer (molecular weight: 18694 g / mol), 26.8 wt % of polyethylene glycol 400, and 8 wt % of ethanol.

[0034] The preparation process of the semaglutide injection of Example 2 is as follows: (1) Preparation of excipient solution: According to the above prescription, weigh polyorthoester polymer and polyethylene glycol 400 and place them in a preparation tank, and stir at 60°C until they are uniformly mixed; (2) Preparation of drug solution: weigh the prescribed amount of semaglutide and add it to the prescribed amount of ethanol at room temperature and stir until dissolved; (3) Sterilization: Sterilize the excipient solution at 121°C for 30 min, and then slowly cool it down to 20°C. Filter the drug solution through a 0.22 μm PTFE filter membrane for sterilization. (4) Mixing: After the excipient solution drops to 20°C, add the filtered drug solution to the excipient solution and stir until uniform.

[0035] The viscosity test process and results of the semaglutide injection of Example 2 are as follows: The viscosity of the sample was measured at 25°C using a DVNextCP cone viscometer from Brookfield and was found to be 30145 mPa·s.

[0036] The in vitro release test process and results of the semaglutide injection of Example 2 are as follows: 0.3g of semaglutide injection was placed in a vial containing 200ml of pH 7.4 phosphate buffer. The vial was placed in a 37°C water area for 30 days, and samples were taken at 0.5, 1, 2, 3, 5, 10, 15, and 20 days to detect the content of semaglutide in the buffer and calculate the release amount. The specific results are shown in Table 2.

[0037] Table 2

[0038] Example 3 This embodiment provides a semaglutide injection, which has the following composition: 1 wt% semaglutide, 50 wt% polyorthoester polymer (molecular weight: 18694 g / mol), 47 wt% polyethylene glycol 400, and 2 wt% ethanol.

[0039] The preparation process of the semaglutide injection of Example 3 is as follows: (1) Preparation of excipient solution: According to the above prescription, weigh polyorthoester polymer and polyethylene glycol 400 and place them in a preparation tank, and stir at 60°C until they are uniformly mixed; (2) Preparation of drug solution: weigh the prescribed amount of semaglutide and add it to the prescribed amount of ethanol at room temperature and stir until dissolved; (3) Sterilization: Sterilize the excipient solution at 121°C for 30 min, and then slowly cool it down to 20°C. Filter the drug solution through a 0.22 μm PTFE filter membrane for sterilization. (4) Mixing: After the excipient solution drops to 20°C, add the filtered drug solution to the excipient solution and stir until uniform.

[0040] The viscosity test process and results of the semaglutide injection of Example 3 are as follows: The viscosity of the sample was measured at 25°C using a DVNextCP cone viscometer from Brookfield and was found to be 24398 mPa·s.

[0041] The in vitro release test process and results of the semaglutide injection of Example 3 are as follows: 0.3g of semaglutide injection was placed in a vial containing 200ml of pH 7.4 phosphate buffer. The vial was placed in a 37°C water area for 30 days, and samples were taken at 0.5, 1, 2, 3, 5, 10, 15, 20, 25, and 30 days to detect the content of semaglutide in the buffer and calculate the release amount. The specific results are shown in Table 3.

[0042] Table 3

[0043] Example 4 This embodiment provides a semaglutide injection, which has the following composition: 2 wt% semaglutide, 74 wt% polyorthoester polymer (molecular weight: 18694 g / mol), 20 wt% polyethylene glycol 400, and 4 wt% ethanol.

[0044] The preparation process of the semaglutide injection of Example 4 is as follows: (1) Preparation of excipient solution: According to the above prescription, weigh polyorthoester polymer and polyethylene glycol 400 and place them in a preparation tank, and stir at 60°C until they are uniformly mixed; (2) Preparation of drug solution: weigh the prescribed amount of semaglutide and add it to the prescribed amount of ethanol at room temperature and stir until dissolved; (3) Sterilization: Sterilize the excipient solution at 121°C for 30 min, and then slowly cool it down to 20°C. Filter the drug solution through a 0.22 μm PTFE filter membrane for sterilization. (4) Mixing: After the excipient solution drops to 20°C, add the filtered drug solution to the excipient solution and stir until uniform.

[0045] The viscosity test process and results of the semaglutide injection of Example 4 are as follows: The viscosity of the sample was measured at 25°C using a DVNextCP cone viscometer from Brookfield and was found to be 31248 mPa·s.

[0046] The in vitro release test process and results of the semaglutide injection of Example 4 are as follows: 0.3g of semaglutide injection was placed in a vial containing 200ml of pH 7.4 phosphate buffer. The vial was placed in a 37°C water area for 30 days, and samples were taken at 0.5, 1, 2, 3, 5, 10, 15, 20, 25, and 30 days to detect the content of semaglutide in the buffer and calculate the release amount. The specific results are shown in Table 4.

[0047] Table 4

[0048] Example 5 This embodiment provides a semaglutide injection, which has the following composition: 0.2 wt% of semaglutide, 40 wt% of polyorthoester polymer (molecular weight: 18694 g / mol), 55.8 wt% of polyethylene glycol 400, and 4 wt% of 1.2-propylene glycol.

[0049] The preparation process of the semaglutide injection of Example 5 is as follows: (1) Preparation of excipient solution: According to the above prescription, weigh polyorthoester polymer and polyethylene glycol 400 and place them in a preparation tank, and stir at 60°C until they are uniformly mixed; (2) Preparation of drug solution: Weigh the prescribed amount of semaglutide and add it to the prescribed amount of 1.2-propylene glycol at room temperature and stir until dissolved; (3) Sterilization: Sterilize the excipient solution at 121°C for 30 min, and then slowly cool it down to 20°C. Filter the drug solution through a 0.22 μm PTFE filter membrane for sterilization. (4) Mixing: After the excipient solution drops to 20°C, add the filtered drug solution to the excipient solution and stir until uniform.

[0050] The viscosity test process and results of the semaglutide injection of Example 5 are as follows: The viscosity of the sample was measured at 25°C using a DVNextCP cone viscometer from Brookfield and was found to be 21097 mPa·s.

[0051] The in vitro release test process and results of the semaglutide injection of Example 5 are as follows: 0.3g of semaglutide injection was placed in a vial containing 200ml of pH 7.4 phosphate buffer. The vial was placed in a 37°C water area for 30 days, and samples were taken at 0.5, 1, 2, 3, 5, 10, 15, 20, 25, and 30 days to detect the content of semaglutide in the buffer and calculate the release amount. The specific results are shown in Table 5.

[0052] Table 5

[0053] Example 6 This embodiment provides a semaglutide injection, which has the following composition: 0.2 wt % of semaglutide, 70 wt % of polyorthoester polymer (molecular weight: 18694 g / mol), 19.8 wt % of polyethylene glycol 400, and 10 wt % of dimethyl sulfoxide.

[0054] The preparation process of the semaglutide injection of Example 6 is as follows: (1) Preparation of excipient solution: According to the above prescription, weigh polyorthoester polymer and polyethylene glycol 400 and place them in a preparation tank, and stir at 60°C until they are uniformly mixed; (2) Preparation of drug solution: weigh the prescribed amount of semaglutide and add it to the prescribed amount of dimethyl sulfoxide at room temperature and stir until dissolved; (3) Sterilization: Sterilize the excipient solution at 121°C for 30 min, and then slowly cool it down to 20°C. Filter the drug solution through a 0.22 μm PTFE filter membrane for sterilization. (4) Mixing: After the excipient solution drops to 20°C, add the filtered drug solution to the excipient solution and stir until uniform.

[0055] The viscosity test process and results of the semaglutide injection of Example 6 are as follows: The viscosity of the sample was measured at 25°C using a DVNextCP cone viscometer from Brookfield and was found to be 37958 mPa·s.

[0056] The in vitro release test process and results of the semaglutide injection of Example 6 are as follows: 0.3g of semaglutide injection was placed in a vial containing 200ml of pH 7.4 phosphate buffer. The vial was placed in a 37°C water area for 30 days, and samples were taken at 0.5, 1, 2, 3, 5, 10, 15, 20, 25, and 30 days to detect the content of semaglutide in the buffer and calculate the release amount. The specific results are shown in Table 6.

[0057] Table 6

[0058] Example 7 This embodiment provides a semaglutide injection, which has the following composition: 0.2 wt % of semaglutide, 60 wt % of polyorthoester polymer (molecular weight: 18694 g / mol), 24.8 wt % of polyethylene glycol 400, and 15 wt % of ethanol.

[0059] The preparation process of the semaglutide injection of Example 7 is as follows: (1) Preparation of excipient solution: According to the above prescription, weigh polyorthoester polymer and polyethylene glycol 400 and place them in a preparation tank, and stir at 60°C until they are uniformly mixed; (2) Preparation of drug solution: weigh the prescribed amount of semaglutide and add it to the prescribed amount of ethanol at room temperature and stir until dissolved; (3) Sterilization: Sterilize the excipient solution at 121°C for 30 min, and then slowly cool it down to 20°C. Filter the drug solution through a 0.22 μm PTFE filter membrane for sterilization. (4) Mixing: After the excipient solution drops to 20°C, add the filtered drug solution to the excipient solution and stir until uniform.

[0060] The viscosity test process and results of the semaglutide injection of Example 7 are as follows: The viscosity of the sample was measured at 25°C using a DVNextCP cone viscometer from Brookfield and was found to be 27854 mPa·s.

[0061] The in vitro release test process and results of the semaglutide injection of Example 7 are as follows: 0.3 g of semaglutide injection was placed in a vial containing 200 ml of pH 7.4 phosphate buffer. The vial was placed in a 37°C water area for 30 days, and samples were taken at 0.5, 1, 2, 3, 5, 10, 15, and 20 days to detect the content of semaglutide in the buffer and calculate the release amount. The specific results are shown in Table 7.

[0062] Table 7

[0063] Comparative Example 1 This comparative example provides a semaglutide injection, which has the following composition: 0.4 wt % of semaglutide, 74 wt % of polyorthoester polymer, and 25.6 wt % of polyethylene glycol 400.

[0064] The preparation process of the semaglutide injection of Comparative Example 1 is as follows: (1) Preparation of excipient solution: According to the above prescription, weigh polyorthoester polymer and polyethylene glycol 400 and place them in a preparation tank, and stir at 60°C until they are uniformly mixed; (2) Sterilize the excipient solution at 121°C for 30 min. After sterilization, slowly cool the solution to 20°C and add semaglutide. Stir and mix until uniform.

[0065] The viscosity test process and results of the semaglutide injection of Comparative Example 1 are as follows: The viscosity of the sample was measured at 25°C using a DVNextCP cone viscometer from Brookfield and was found to be 29341 mPa·s.

[0066] The in vitro release test process and results of the semaglutide injection of Comparative Example 1 are as follows: 0.3 g of semaglutide injection was placed in a vial containing 200 ml of pH 7.4 phosphate buffer. The vial was placed in a 37°C water area for 30 days, and samples were taken at 0.5, 1, 2, 3, 5, and 10 days to detect the content of semaglutide in the buffer and calculate the release amount. The specific results are shown in Table 8.

[0067] Table 8

[0068] Example 8 In order to study the stability of the semaglutide injection of the present invention, Example 3, Example 4 and commercially available semaglutide injection (trade name Ozempic, generic name semaglutide) were placed at 2-8°C for 6 months, and samples were taken at 1, 2, 3 and 6 months to detect the content of the preparation (semaglutide).

[0069] The specific results of the stability tests of Example 3, Example 4 and commercially available semaglutide injection are shown in Table 9.

[0070] Table 9

[0071] It can be seen from Table 9 that the injection of the present application can ensure excellent stability without using phenol as a preservative, which is comparable to the stability of the commercially available semaglutide injection.

[0072] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A semaglutide injection, comprising semaglutide, characterized in that: It also includes a polyorthoester polymer, a co-solvent and a diluent. Based on the total mass of the injection, the mass of the polyorthoester polymer accounts for 40% to 80%, and the mass ratio of the polyorthoester polymer to the co-solvent is (40 to 80): (2 to 15).

2. The semaglutide injection according to claim 1, characterized in that: Based on the total mass of the injection, the mass proportion of semaglutide is 0.2% to 2%.

3. The semaglutide injection according to claim 1, characterized in that: The molecular weight of the polyorthoester polymer is 5000-40000, preferably 15000-25000.

4. The semaglutide injection according to any one of claims 1 to 3, characterized in that: The co-solvent is selected from one or more of ethanol, propylene glycol and dimethyl sulfoxide.

5. The semaglutide injection according to any one of claims 1 to 3, characterized in that: The mass ratio of the polyorthoester polymer to the co-solvent is (40-78):(2-15).

6. The semaglutide injection according to any one of claims 1 to 3, characterized in that: Based on the total mass of the injection, the mass proportion of the diluent is 4% to 58%; And / or, the diluent includes at least one of polyethylene glycol 400, glycerol, and liquid paraffin.

7. The semaglutide injection according to any one of claims 1 to 3, characterized in that: include: 0.2wt%~2wt% of the semaglutide, 40wt%~80wt% of the polyorthoester polymer, and 2wt%~15wt% of the cosolvent.

8. A method for preparing the semaglutide injection according to any one of claims 1 to 7, characterized in that: include: Mixing the polyorthoester polymer and the diluent to obtain an auxiliary material solution; Mixing and dissolving semaglutide and a co-solvent to obtain a drug solution; The sterilized auxiliary material solution and the drug solution are mixed.

9. The method according to claim 8, characterized in that The temperature is controlled at 40° C. to 80° C. during the mixing process of the polyorthoester polymer and the diluent.

10. The method according to claim 8 or 9, characterized in that: The temperature is controlled at 15° C. to 40° C. during the mixing process of the auxiliary material solution and the drug solution.

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