Tegoprazan injection and preparation method therefor

Abstract

The present invention provides a tegoprazan injection and a preparation method therefor. The injection comprises tegoprazan, pyroglutamic acid, a co-solvent, and water for injection. The preparation thereof comprises the following steps: formulating pyroglutamic acid into a pyroglutamic acid solution with a certain concentration by using water for injection; and adding tegoprazan to a co-solvent, then adding the pyroglutamic acid solution for dissolution, and performing filtration, pouring, filling with nitrogen, sealing, and sterilization. The product obtained in the present invention has good clarity and stability. The preparation method has a low production cost, a simple process flow, and strong operability, and is suitable for large-scale industrial production.

Description

Tigogarabine injection and preparation method thereof

[0001] The present application claims priority from Chinese patent application 2024113698918 with the filing date of 2024 / 9 / 29. The present application incorporates the entire text of the above-mentioned Chinese patent application. TECHNICAL FIELD

[0002] The present application relates to the field of pharmaceutical preparations, in particular to a kind of tigogarabine injection and preparation method thereof. BACKGROUND

[0003] Tigogarabine is a potassium ion competitive acid blocker (P-CAB), which inhibits the secretion of acid by competitively blocking potassium ions in H-K-ATPase.

[0004] The main component of the product is tigogarabine, and the chemical name is (S)-4-[(5,7-difluorobenzodihydro pyran-4-yl)oxy]-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide.

[0005] Chemical structural formula:

[0006] Molecular weight: 387.5.

[0007] Tigogarabine has the use of preventing and treating diseases mediated by acid pump antagonistic activity, including various diseases of duodenal ulcer, gastric ulcer and reflux esophagitis.

[0008] Tigogarabine itself is a poorly soluble drug, which is difficult to be prepared into an injection by dissolving in an aqueous solvent, therefore, it is urgent to study a new prescription and preparation method to solve the technical problems faced by the prior art. SUMMARY

[0009] To solve the problems existing in the prior art, the present application provides a kind of tigogarabine injection and preparation method thereof, which solves the problem of product solubility, and the preparation method adopted has fewer process steps, reduces production cost, is easy to operate, and is suitable for industrialized mass production.

[0010] One object of the present application is to provide a kind of tigogarabine injection, which comprises tigogarabine, pyroglutamic acid, cosolvent and water for injection.

[0011] Preferably, the weight content of tigogarabine in the tigogarabine injection is 2.5%.

[0012] Preferably, the weight content of pyroglutamic acid in the tigogarabine injection is 0.8%.

[0013] Preferably, the weight content of the cosolvent in the tegoprazan injection is 70-90%, more preferably 80-90%.

[0014] Preferably, the weight content of the water for injection in the injection is 6.7-26.7%, more preferably 6.7-16.7%.

[0015] Preferably, the weight ratio of the tegoprazan, pyroglutamic acid, cosolvent, and water for injection is 2.5%:0.8%:70-90%:6.7%-26.7%; further preferably, the weight ratio of the tegoprazan, pyroglutamic acid, cosolvent, and water for injection is 2.5%:0.8%:80-90%:6.7%-16.7%.

[0016] Preferably, the cosolvent is one or a combination of two of propylene glycol, polyethylene glycol, and anhydrous ethanol; further preferably, the cosolvent is propylene glycol.

[0017] Another object of the present application is to provide a preparation method of the above-mentioned tegoprazan injection, comprising the following steps:

[0018] 1) Pyroglutamic acid is prepared into a pyroglutamic acid solution with a mass percentage concentration of 3%-20% using water for injection;

[0019] 2) Tegoprazan is added to the cosolvent, and the pyroglutamic acid solution is added until the tegoprazan is completely dissolved, filtered, filled, filled with nitrogen, sealed, and sterilized.

[0020] Preferably, the sterilization conditions are: sterilization temperature 115-121℃, sterilization time 15-30 minutes.

[0021] The present application has the following beneficial effects:

[0022] 1) The tegoprazan injection provided by the present application solves the technical problem of product solubility, has good drug stability, and meets various quality requirements of injections;

[0023] 2) The present application salts tegoprazan, which is insoluble in water, with pyroglutamic acid in a solvent and simultaneously prepares an injection. This method has a simple process flow, strong operability, low production cost, and is suitable for industrial mass production. DETAILED DESCRIPTION

[0024] The present application will be described in detail below with reference to specific examples.

[0025] Example 1

[0026] A tegoprazan injection is prepared from the following weights of raw materials:

[0027] A method for preparing a tegoprazan injection, the steps of which are:

[0028] 1) pyroglutamic acid is prepared into a pyroglutamic acid solution with a mass percentage concentration of 5% using water for injection;

[0029] 2) tegoprazan is added to propylene glycol, and the pyroglutamic acid solution is continuously added until the tegoprazan is completely dissolved, filtered, filled, filled with nitrogen, sealed, and finally sterilized at 115°C for 30 minutes.

[0030] Example 2

[0031] A tegoprazan injection prepared from the following weights of raw materials:

[0032] A method for preparing a tegoprazan injection, the steps of which are:

[0033] 1) pyroglutamic acid is prepared into a pyroglutamic acid solution with a mass percentage concentration of 12% using water for injection;

[0034] 2) tegoprazan is added to propylene glycol, and the pyroglutamic acid solution is continuously added until the tegoprazan is completely dissolved, filtered, filled, filled with nitrogen, sealed, and finally sterilized at 121°C for 15 minutes.

[0035] Example 3

[0036] A tegoprazan injection prepared from the following weights of raw materials:

[0037] A method for preparing a tegoprazan injection, the steps of which are:

[0038] 1) pyroglutamic acid is prepared into a pyroglutamic acid solution with a mass percentage concentration of 3% using water for injection;

[0039] 2) tegoprazan is added to propylene glycol, and the pyroglutamic acid solution is continuously added until the tegoprazan is completely dissolved, filtered, filled, filled with nitrogen, sealed, and finally sterilized at 117°C for 18 minutes.

[0040] Example 4

[0041] A tegoprazan injection prepared from the following weights of raw materials:

[0042] A method for preparing a tegoprazan injection, the steps of which are:

[0043] 1) pyroglutamic acid is prepared into a pyroglutamic acid solution with a mass percentage concentration of 7% using water for injection;

[0044] 2) Add tegoprazan into anhydrous ethanol, continuously add pyroglutamic acid solution until tegoprazan is completely dissolved, filter, fill and seal, fill with nitrogen, seal, and finally sterilize at 121°C for 15 minutes.

[0045] Example 5

[0046] A tegoprazan injection is prepared from the following raw materials by weight:

[0047] A method for preparing a tegoprazan injection, the steps of which are:

[0048] 1) Pyroglutamic acid is prepared into a pyroglutamic acid solution with a mass percentage concentration of 7% using water for injection;

[0049] 2) Add tegoprazan into polyethylene glycol, continuously add pyroglutamic acid solution until tegoprazan is completely dissolved, filter, fill and seal, fill with nitrogen, seal, and finally sterilize at 121°C for 15 minutes.

[0050] Verification Example 1: Solution clarity investigation

[0051] The solution of the present application prepared according to the methods of Examples 1-5 is investigated for clarity before and after filtration, and for clarity after being mixed with 0.9% sodium chloride injection (1:5) and 5% glucose injection (1:5), and the experimental results are shown in Table 1.

[0052] Table 1: Solution clarity results before and after filtration, and after being mixed with glucose and sodium chloride

[0053] As can be seen from Table 1, the pyroglutamic acid tegoprazan solution prepared using anhydrous ethanol as a cosolvent has solid precipitated before filtration, and the pyroglutamic acid tegoprazan solution prepared using polyethylene glycol as a cosolvent has a significantly deepened clarity after being mixed, and therefore, the product prepared by the present application has a cosolvent propylene glycol, which is significantly superior to other cosolvents in terms of clarity.

[0054] Verification Example 2: Sterilization investigation

[0055] The injection prepared according to the methods of Examples 1-3 and Example 5 is investigated for clarity after sterilization, and for clarity after being mixed with 0.9% sodium chloride injection (1:5) and 5% glucose injection (1:5), and the experimental results are shown in Table 2.

[0056] Table 2: Investigation results of clarity after sterilization and after being mixed with glucose and sodium chloride

[0057] As shown in Table 2, the tigogliptin injection of the present application has no obvious influence on the clarity of the preparation after sterilization, and the use of polyethylene glycol for preparation of the preparation has deepened the color of the clarity.

[0058] Verification Example 3: Results of the related substance stability investigation

[0059] The injection of the present application was prepared according to the methods of Examples 1-3 and 5, and the results of the related substance stability investigation are shown in Table 3.

[0060] Table 3: Results of the stability investigation after sterilization

[0061] As shown in Table 3, the tigogliptin injection prepared in the present application has significantly reduced related substances with the increase of the proportion of the cosolvent propylene glycol, and the preferred proportion of propylene glycol is 80-90%.

Claims

1. A tegoprazan injection, characterized by, The tegoprazan injection contains tegoprazan, pyroglutamic acid, a cosolvent and water for injection.

2. Tigobarine injection as claimed in claim 1, wherein, The tegoprazan injection meets one or more of the following conditions: The tegoprazan injection contains 2.5% tegoprazan by weight; The tegoprazan injection contains 0.8% pyroglutamic acid by weight; The tegoprazan injection contains 70-90% cosolvent by weight, preferably 80-90% by weight; The injection contains 6.7-26.7% water for injection by weight, preferably 6.7-16.7% by weight.

3. Tigobarine injection as claimed in claim 1, wherein, The tegoprazan, pyroglutamic acid, cosolvent and water for injection are in a weight ratio of 2.5%:0.8%:70-90%:6.7%-26.7%.

4. Tigobarine injection as claimed in claim 3, wherein, The tegoprazan, pyroglutamic acid, cosolvent and water for injection are in a weight ratio of 2.5%:0.8%:80-90%:6.7%-16.7%.

5. Tigobarine injection as claimed in claim 1, wherein, The cosolvent is one or a combination of propylene glycol, polyethylene glycol or anhydrous ethanol.

6. Tigobarine injection as claimed in claim 5, wherein, The cosolvent is propylene glycol.

7. Tigobarine injection as claimed in claim 1, wherein, The preparation method of the tegoprazan injection includes the following steps: 1) Prepare a pyroglutamic acid solution by dissolving pyroglutamic acid in water for injection; 2) Add tegoprazan to the cosolvent, add the pyroglutamic acid solution until the tegoprazan is completely dissolved, filter, fill, fill with nitrogen, seal, sterilize.

8. Tigobarine injection as claimed in claim 7, wherein, The sterilization conditions are a sterilization temperature of 115-121°C and a sterilization time of 15-30 minutes.

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