Mecobalamin composition and preparation method thereof

Abstract

The invention discloses a mecobalamin composition. The mecobalamin composition comprises mecobalamin, a stabilizer, a suspending aid and an adsorbent. The applicant can improve the stability of mecobalamin to a certain extent by adopting edetate disodium or citric acid as a stabilizer, and can uniformly disperse mecobalamin in the solid dispersion through spray drying to construct a physical barrier, thereby improving the light instability of mecobalamin.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of pharmaceutical preparations, and particularly relates to a mecobalamin composition and a preparation method thereof. BACKGROUND

[0002] Mecobalamin is an endogenous vitamin B 12 , which plays an important role in the transmethylation reaction of homocysteine to methionine. Mecobalamin directly participates in nerve repair (axonal regeneration and myelination) and hematopoiesis, has the characteristics of not requiring liver metabolism and high bioavailability. In clinical applications, mecobalamin is often developed into oral solid preparations (such as tablets, capsules, dispersible tablets, etc.) and injections (such as intravenous injection solutions and intramuscular injection solutions) for promoting folate utilization, nucleic acid metabolism, maintaining normal functions of the nervous system, repairing damaged nerves (such as neuropathy caused by diabetes, trauma and cervical spondylosis), and treating vitamin B 12 deficiency anemia and improving erythropoiesis. Mecobalamin has the characteristic of poor stability and is easily decomposed into hydroxycobalamin under visible light, thereby losing the pharmacological effect. Meanwhile, mecobalamin also needs to be stored in the dark during storage. How to maintain the stability of mecobalamin is a technical difficulty in the field of pharmacy, and it is of great significance to develop a mecobalamin composition with good light stability. SUMMARY

[0003] The purpose of the present application is to provide a mecobalamin composition, which can solve the problem of instability of mecobalamin to light.

[0004] Another purpose of the present application is to provide a preparation method of the mecobalamin composition.

[0005] The mecobalamin composition provided by the present application comprises 1-5 parts by weight of mecobalamin, 0.5-5 parts by weight of a stabilizer, 1-10 parts by weight of a suspending agent, and 20-200 parts by weight of an adsorbent.

[0006] According to a preferred embodiment of the present application, the stabilizer is one or both of disodium edetate and citric acid.

[0007] According to a preferred embodiment of the present application, the stabilizer is disodium edetate.

[0008] According to a preferred embodiment of the present application, the suspending agent is one or more of hydroxypropyl cellulose, povidone and polyethylene glycol.

[0009] According to a preferred embodiment of the present application, the suspending agent is polyethylene glycol.

[0010] According to a preferred embodiment of the present application, the adsorbent is one or more of starch, dextrin, microcrystalline cellulose, sucrose, glucose, lactose, mannitol, sorbitol and xylitol.

[0011] According to a preferred embodiment of the present application, the adsorbent is microcrystalline cellulose.

[0012] According to a preferred embodiment of the present application, the methycobal is 2-4 parts by weight, the suspending agent is 2-6 parts by weight, the stabilizer is 2-4 parts by weight, and the adsorbent is 80-120 parts by weight.

[0013] The present application also provides a preparation method of the methycobal composition, comprising the following steps:

[0014] (1) dissolving the methycobal in an alcohol solvent, then adding the stabilizer, the suspending agent and the adsorbent, stirring uniformly to form a mixed solution;

[0015] (2) setting the inlet air temperature of the spray dryer to 40-60℃ and the outlet air temperature to 30-50℃, starting the atomizer after the temperature of the spray dryer rises to the set temperature, and spray drying the mixed solution to obtain the methycobal composition.

[0016] According to a preferred embodiment of the present application, the solvent in step (1) is one of ethanol and propylene glycol.

[0017] According to a preferred embodiment of the present application, the solvent in step (1) is ethanol.

[0018] The applicant has found through a large number of experiments that using edetate disodium or citric acid can improve the stability of methycobal to a certain extent, and using the spray drying technology can uniformly disperse the methycobal in the solid dispersion, which can improve the uniformity of the methycobal and build a physical barrier to improve the light instability of the methycobal. DETAILED DESCRIPTION

[0019] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0020] Example 1

[0021] Under red light or light shielding conditions, 5 parts by weight of methycobal was dissolved in 400 parts by weight of ethanol, and then 5 parts by weight of edetate disodium, 10 parts by weight of polyethylene glycol and 200 parts by weight of microcrystalline cellulose were added to the solution, which was stirred and mixed uniformly to obtain a mixed solution.

[0022] The mixed solution is spray dried to obtain the mecobalamin composition, with the inlet air temperature of the spray dryer being set at 50°C and the outlet air temperature being set at 40°C.

[0023] Example 2

[0024] Under red light or light-shielded conditions, 1 part by weight of mecobalamin is dissolved in 100 parts by weight of ethylene glycol, and then 0.5 parts by weight of edetate disodium, 1 part by weight of polyethylene glycol, and 20 parts by weight of microcrystalline cellulose are added to the solution, which is stirred and mixed to obtain a mixed solution.

[0025] The mixed solution is spray dried to obtain the mecobalamin composition, with the inlet air temperature of the spray dryer being set at 40°C and the outlet air temperature being set at 30°C.

[0026] Example 3

[0027] Under red light or light-shielded conditions, 4 parts by weight of mecobalamin is dissolved in 300 parts by weight of ethanol, and then 4 parts by weight of edetate disodium, 6 parts by weight of hydroxypropyl cellulose, and 120 parts by weight of microcrystalline cellulose are added to the solution, which is stirred and mixed to obtain a mixed solution.

[0028] The mixed solution is spray dried to obtain the mecobalamin composition, with the inlet air temperature of the spray dryer being set at 60°C and the outlet air temperature being set at 50°C.

[0029] Example 4

[0030] Under red light or light-shielded conditions, 3 parts by weight of mecobalamin is dissolved in 250 parts by weight of ethanol, and then 4 parts by weight of citric acid, 6 parts by weight of povidone, and 100 parts by weight of starch are added to the solution, which is stirred and mixed to obtain a mixed solution.

[0031] The mixed solution is spray dried to obtain the mecobalamin composition, with the inlet air temperature of the spray dryer being set at 50°C and the outlet air temperature being set at 40°C.

[0032] Example 5

[0033] Under red light or light-shielded conditions, 2 parts by weight of mecobalamin is dissolved in 200 parts by weight of ethanol, and then 2 parts by weight of citric acid, 2 parts by weight of povidone, and 100 parts by weight of starch are added to the solution, which is stirred and mixed to obtain a mixed solution.

[0034] The mixed solution is spray dried to obtain the mecobalamin composition, with the inlet air temperature of the spray dryer being set at 50°C and the outlet air temperature being set at 40°C.

[0035] Comparative Example 1

[0036] 5 parts by weight of methylcobalamin was dissolved in 500 parts by weight of ethanol under red light or light shielding condition, and then 5 parts by weight of polyethylene glycol and 50 parts by weight of microcrystalline cellulose were added to the solution and stirred to obtain a mixed solution.

[0037] The mixed solution was subjected to spray drying by setting the inlet air temperature of the spray dryer to 50℃ and the outlet air temperature to 40℃, to obtain the methylcobalamin composition.

[0038] Comparative Example 2

[0039] 5 parts by weight of methylcobalamin, 5 parts by weight of polyethylene glycol, 0.5 parts by weight of edetate disodium and 50 parts by weight of microcrystalline cellulose were mixed under red light or light shielding condition to obtain the methylcobalamin composition.

[0040] Comparative Example 3

[0041] 5 parts by weight of methylcobalamin was dissolved in 500 parts by weight of ethanol under red light or light shielding condition, and then 5 parts by weight of polyethylene glycol and 50 parts by weight of microcrystalline cellulose were added to the solution and stirred to obtain a mixed solution.

[0042] Test Example

[0043] According to the detection method of methylcobalamin related substances in the Chinese Pharmacopoeia 2025 edition, the related substances were detected under high temperature, high humidity and light conditions for 0 days, 10 days and 30 days, respectively.

[0044]

[0045] As can be analyzed from Table 1, the content of hydroxycobalamin of the methylcobalamin compositions prepared in Examples 1-5 can be kept stable within a certain range under light conditions, while the content of hydroxycobalamin of Comparative Examples 1-3 all increased significantly. This shows that the methylcobalamin composition provided by the present application has good stability under light conditions.

[0046] The above describes the embodiments of the present application in combination with the examples, but the present application is not limited to the above specific embodiments, which are only illustrative and not restrictive. Those skilled in the art can make many forms under the inspiration of the present application without departing from the scope of the present application and the protection scope of the claims.

Claims

1. A methylcobalamin composition, characterized in that, It contains 1-5 parts by weight of methylcobalamin, 0.5-5 parts by weight of stabilizer, 1-10 parts by weight of suspending agent, and 20-200 parts by weight of adsorbent; The stabilizer is one or both of disodium edetate and citric acid. The suspending agent is one or more of hydroxypropyl cellulose, povidone, and polyethylene glycol; The adsorbent is one or more of starch, dextrin, microcrystalline cellulose, sucrose, glucose, lactose, mannitol, sorbitol, and xylitol.

2. The methylcobalamin composition according to claim 1, characterized in that, The stabilizer is disodium edetate.

3. The methylcobalamin composition according to claim 1, characterized in that, The suspending agent is polyethylene glycol.

4. The methylcobalamin composition according to claim 1, characterized in that, The adsorbent is microcrystalline cellulose.

5. The methylcobalamin composition according to claim 1, characterized in that, The composition includes 2-4 parts by weight of methylcobalamin, 2-6 parts by weight of suspending agent, 2-4 parts by weight of stabilizer, and 80-120 parts by weight of adsorbent.

6. A method for preparing the methylcobalamin composition according to any one of claims 1 to 5, comprising the following steps: (1) Dissolve methylcobalamin in an alcohol solvent, then add stabilizer, suspending agent and adsorbent, stir evenly to form a mixed solution; (2) Set the air inlet temperature of the spray dryer to 40~60℃ and the air outlet temperature to 30~50℃. After the temperature of the spray dryer rises to the set temperature, start the atomizer to spray dry the mixed solution to obtain the methylcobalamin composition.

7. The method for preparing the methylcobalamin composition according to claim 6, characterized in that, The solvent in step 1 is either ethanol or ethylene glycol.

8. The method for preparing the methylcobalamin composition according to claim 7, characterized in that, The solvent in step 1 is ethanol.

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