Gentamicin procaine vitamin B12 particle and preparation method thereof

Abstract

The invention provides a preparation method of gentamicin procaine vitamin B12 granules, which comprises the following steps: A) mixing aspartame, sucrose powder and procaine hydrochloride, sieving, pouring the sieved material into an efficient mixing granulator for mixing, pouring the mixed solution, mixing, and discharging to obtain a soft material; the mixed solution comprises a vitamin B12 aqueous solution, a lemon yellow aqueous solution and a gentamicin sulfate solution; b) adding the soft material into a hopper of a swinging granulator, starting a pelleting pot, putting the swung wet granules into the pelleting pot, spraying purified water, and sieving to obtain wet granules; and C) drying the wet granules, finishing the granules, and totally mixing to obtain the traditional Chinese medicine composition. According to the preparation method of the gentamicin procaine vitamin B12 particles, the advantages that the prepared gentamicin procaine vitamin B12 particle product is less in fine powder, good in fluidity and stable in quality can be realized.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, in particular to a gentamicin, procain, and vitamin B6 12 Particles and methods for preparing the same. Background Art

[0002] Gentamicin, Procaine, and Vitamin B 12 Granules are commonly used drugs for the clinical treatment of chronic gastritis. Gentamycin has a strong killing effect on Helicobacter pylori and exerts a local bactericidal effect in the stomach; procaine has a blocking effect on the nerve endings on the damaged mucosal surface, which can block the stimulation of the lesions on the central nervous system, relieve stomach pain, improve blood microcirculation, and regulate gastric motility; Vitamin B 12 They are essential substances for the formation of normal epithelial cells in the digestive tract. The combination of these three can have antibacterial, analgesic, and gastric mucosal repair effects. They can both reduce inflammation and relieve pain in acute and chronic gastritis, increasing the cure rate, shortening hospital stays, reducing medical expenses, and improving patients' quality of life, achieving excellent therapeutic effects for gastritis.

[0003] Currently, most of the same drugs on the market have a validity period of only 24 months, a short shelf life, and low quality stability. Therefore, a gentamicin procaine vitamin B with uniform particle size, better fluidity and stability is provided. 12 Pellets are essential. Summary of the Invention

[0004] In view of this, the technical problem to be solved by the present invention is to provide a gentamicin procaine vitamin B 12 Preparation method of granules, gentamicin procain vitamin B prepared by the preparation method of the present invention 12 The particles have uniform size, good fluidity and stability.

[0005] The present invention provides a gentamicin, procain and vitamin B 12 The method for preparing the particles comprises the following steps:

[0006] A) Aspartame, sucrose powder and procaine hydrochloride are mixed and then sieved, the sieved material is poured into a high-efficiency mixing granulator for mixing, and then the mixed solution is poured into, mixed, and discharged to obtain a soft material; the mixed solution includes vitamin B 12 aqueous solution, tartrazine aqueous solution, and gentamicin sulfate solution;

[0007] B) Add the soft material into the hopper of the swing pelletizer, start the pelletizing pot, put the wet pellets after swinging into the pelletizing pot, spray purified water, and then sieve to obtain wet pellets;

[0008] C) Drying the wet granules, sizing the granules, and mixing the granules to obtain the product.

[0009] In some specific embodiments, in step A), the aspartame is passed through a 50-70 mesh sieve; the sucrose powder is crushed using a platform mill equipped with a 70-90 mesh sieve; and the procaine hydrochloride is crushed using a platform mill equipped with a 70-90 mesh sieve.

[0010] The vitamin B 12 The concentration of the aqueous solution is 6-7‰ (g / ml); the concentration of the lemon yellow aqueous solution is 6-7% (g / ml);

[0011] The gentamicin sulfate solution comprises: mixing gentamicin sulfate and water, then adding β-cyclodextrin, and continuing to stir for 0.5 to 1.5 hours to obtain the gentamicin sulfate solution; the ratio of the gentamicin sulfate, β-cyclodextrin and water is 410 million to 420 million units: (2 to 2.2 kg): (1 to 1.4 kg).

[0012] In some specific embodiments, the step A) specifically includes: manually mixing aspartame, sucrose powder, and procaine hydrochloride for 10 minutes, then passing through a 60-mesh sieve, and then mixing the dry powder for 900 seconds; the mixing parameters include: adjusting the blade speed to 60 rpm, the knife speed to 1500 rpm, timing for 120 seconds, increasing the blade speed to 90 rpm, the knife speed to 1900 rpm, and cumulatively timing for 900 seconds; then adding the mixed solution and continuing mixing for 1320 seconds.

[0013] In some specific embodiments, the mass ratio of aspartame, sucrose powder, and procaine hydrochloride is 0.2-0.3:3:2-2.5.

[0014] In some specific embodiments, the step B) specifically includes: adding the soft material to the hopper of the swing granulator, starting the pelletizing pot, putting the wet granules after swinging into the pelletizing pot, spraying purified water, adding a small amount of wet granules, kneading the agglomerated wet granules while rotating, and then spraying a small amount of purified water, repeating this process, and then passing through a 12-mesh sieve. The large particles that cannot pass through the sieve are squeezed and sieved through the 12-mesh sieve and then transferred to the pelletizing machine for granulation, and repeating this process until all the wet granules are made into qualified granules.

[0015] In some specific embodiments, in step B), the soft material is granulated in a swing granulator using a 10-12 mesh sieve.

[0016] In some specific embodiments, the drying in step C) comprises: controlling the drying temperature in a hot air circulation oven to 50-60° C. for 3-4 hours.

[0017] In some specific embodiments, in step C), the gentamicin, procain, and vitamin B 12 The particle size of the particles is less than 10 mesh.

[0018] In some specific embodiments, the mixing in step C) comprises:

[0019] Add the granules after granulation into the three-dimensional motion mixer, set the frequency of the inverter to 30-40 Hz, and mix for 10-15 minutes.

[0020] The present invention provides a gentamicin, procain and vitamin B 12 The particles are prepared by the preparation method described in any one of the above technical solutions.

[0021] Compared with the prior art, the present invention provides a gentamicin procain vitamin B 12 The preparation method of the granules comprises the following steps: A) mixing aspartame, sucrose powder and procaine hydrochloride, and then sieving, pouring the sifted materials into a high-efficiency mixing granulator for mixing, and then pouring the mixed solution into the granulator, mixing, and discharging to obtain a soft material; the mixed solution includes vitamin B 12 Aqueous solution, lemon yellow aqueous solution and gentamicin sulfate solution; B) adding soft material into the hopper of the swing granulator, starting the pelleting pot, putting the wet granules after swinging into the pelleting pot, spraying purified water, and then sieving to obtain wet granules; C) drying the wet granules, granulating, and mixing them. 12 Preparation method of granules, capable of preparing gentamicin, procain and vitamin B 12 Granular products have the advantages of less fine powder, good fluidity and stable quality. DETAILED DESCRIPTION

[0022] The present invention provides a gentamicin, procain and vitamin B 12 The particles and their preparation methods can be achieved by those skilled in the art by referring to the contents of this document and appropriately modifying the process parameters. It should be noted that all similar substitutions and modifications are obvious to those skilled in the art and fall within the scope of protection of the present invention. The methods and applications of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications herein without departing from the content, spirit, and scope of the present invention to implement and apply the technology of the present invention.

[0023] The invention discloses a gentamicin, procain, and vitamin B 12 Granules, prepared materials include gentamicin sulfate, procaine hydrochloride, vitamin B 12 , β-cyclodextrin, aspartame, tartrazine, sucrose.

[0024] In one embodiment of the present invention, according to the 1000 bag method, gentamicin, procaine, and vitamin B 12The materials for preparing the granules include: a certain amount of gentamicin sulfate (calculated as 20 million gentamicin sulfate units), 100g of procaine hydrochloride, 0.02g of vitamin B 12 , 100g of β-cyclodextrin, 10g of aspartame, 0.12g of tartrazine, and appropriate amount of sucrose (added to 2g~5g / bag).

[0025] The present invention provides a gentamicin, procain and vitamin B 12 The method for preparing the particles comprises the following steps:

[0026] A) Aspartame, sucrose powder and procaine hydrochloride are mixed and then sieved, the sieved material is poured into a high-efficiency mixing granulator for mixing, and then the mixed solution is poured into, mixed, and discharged to obtain a soft material; the mixed solution includes vitamin B 12 aqueous solution, tartrazine aqueous solution, and gentamicin sulfate solution;

[0027] B) Add the soft material into the hopper of the swing pelletizer, start the pelletizing pot, put the wet pellets after swinging into the pelletizing pot, spray purified water, and then sieve to obtain wet pellets;

[0028] C) Drying the wet granules, sizing the granules, and mixing the granules to obtain the product.

[0029] The gentamicin, procain and vitamin B provided by the present invention 12 The preparation method of the particles firstly performs material pretreatment and solution preparation.

[0030] Aspartame is passed through a 50-70 mesh sieve; preferably, aspartame is passed through a 60 mesh sieve.

[0031] In some specific embodiments, the sucrose powder is crushed using a platform grinder equipped with a 70-90 mesh screen; specifically, it can be 70 mesh, 80 mesh, or 90 mesh;

[0032] Procaine hydrochloride is crushed using a platform grinder equipped with a 70-90 mesh screen; specifically, the screen may be 70 mesh, 80 mesh, or 90 mesh.

[0033] Vitamin B of the present invention 12 The concentration of the aqueous solution is 6 to 7‰ (g / ml); preferably 6.0‰ (g / ml), 6.1‰, 6.2‰, 6.3‰, 6.4‰, 6.5‰, 6.6‰, 6.7‰, 6.8‰, 6.9‰, 7‰; more preferably 6.41‰.

[0034] The concentration of the tartrazine aqueous solution is 6-7% (g / ml); preferably 6.0‰ (g / ml), 6.1‰, 6.2‰, 6.3‰, 6.4‰, 6.5‰, 6.6‰, 6.7‰, 6.8‰, 6.9‰, 7‰; more preferably 6.25‰.

[0035] The gentamicin sulfate solution of the present invention comprises: mixing gentamicin sulfate and water, adding β-cyclodextrin, and continuing to stir for 0.5 to 1.5 hours to obtain the gentamicin sulfate solution. The stirring time can preferably be 0.5 hours, 0.6 hours, 0.7 hours, 0.8 hours, 0.9 hours, 1.0 hours, 1.1 hours, 1.2 hours, 1.3 hours, 1.4 hours, or 1.5 hours.

[0036] According to the present invention, the ratio of gentamicin sulfate, β-cyclodextrin and water is 410-420 million units: (2-2.2 kg): (1-1.4 kg).

[0037] In some preferred embodiments, the ratio of gentamicin sulfate, β-cyclodextrin and water is 416.7 million units: 2.083 kg: 1.26 kg.

[0038] Aspartame, sucrose powder and procaine hydrochloride are mixed and then sieved to obtain a sieved material, which is then poured into a high-efficiency mixing granulator for mixing.

[0039] In some specific embodiments, the step A) specifically comprises: manually mixing aspartame, sucrose powder, and procaine hydrochloride for 10 minutes, then passing through a 60-mesh sieve, and then dry powder mixing for 900 seconds; the mixing parameters include: adjusting the blade speed to 60 rpm, the fly blade speed to 1500 rpm, timing for 120 seconds, increasing the blade speed to 90 rpm, the fly blade speed to 1900 rpm, and cumulatively timing for 900 seconds;

[0040] Then pour the mixed solution into the mixture, mix it, and discharge it to obtain a soft material; the mixed solution includes vitamin B 12 aqueous solution, tartrazine aqueous solution and gentamicin sulfate solution.

[0041] Keep the equipment running and pour the mixed solution into the high-efficiency granulator slowly and evenly in small amounts. Rinse the solution feed port with purified water and allow it to flow into the mixed powder. The equipment will continue to run until the accumulated time reaches 1320 seconds, after which it will automatically stop and discharge the material.

[0042] In some specific embodiments, the mass ratio of aspartame, sucrose powder, and procaine hydrochloride is 0.2-0.3:3:2-2.5.

[0043] In a specific embodiment, the mass ratio of the aspartame, sucrose powder, and procaine hydrochloride is 0.208:3:2.083.

[0044] The soft material is added to the hopper of the swing granulator, the pelletizing pot is started, the wet granules after swinging are put into the pelletizing pot, purified water is sprayed, and then sieved to obtain wet granules; in some specific embodiments, in step B), the soft material is granulated with a 10-12 mesh sieve in the swing granulator.

[0045] In some specific embodiments, the step B) specifically includes: adding the soft material to the hopper of the swing granulator, starting the pelletizing pot, putting the wet granules after swinging into the pelletizing pot, spraying purified water, adding a small amount of wet granules, kneading the agglomerated wet granules while rotating, and then spraying a small amount of purified water, repeating this process, and then passing through a 12-mesh sieve. The large particles that cannot pass through the sieve are squeezed and sieved through the 12-mesh sieve and then transferred to the pelletizing machine for granulation, and repeating this process until all the wet granules are made into qualified granules.

[0046] In one embodiment, the step B) specifically comprises: using a stainless steel spoon to add an appropriate amount of the prepared soft material (based on the principle of adding small amounts multiple times) to the hopper of the swing granulator, and granulating the soft material in the swing granulator with a 12-mesh sieve. Start the pelletizing pot, put the wet granules after shaking into the pelletizing pot, and spray purified water. Add a small amount of wet granules, and while rotating, use your hands (wearing sterilized latex gloves) to break up the agglomerated wet granules and then spray a small amount of purified water. Repeat this process to make them stronger granules, and then pass them through a 12-mesh sieve. After the large granules that cannot pass through the sieve are squeezed and sieved through the 12-mesh sieve, they are transferred to the pelletizing machine for granulation. Repeat this process until all the wet granules are made into qualified granules.

[0047] The present invention creatively rolls the prepared particles again to grow them, repeating the granulation process, ensuring that the prepared particles have a larger particle size, making the average particle size of the dried particles larger, greatly improving the fluidity of the dried particles, and promoting excellent control of the filling volume difference during particle packaging, and excellent particle size performance of the finished product.

[0048] The wet granules are dried, sized, and mixed to obtain the product.

[0049] In some specific embodiments, the drying comprises: controlling the drying temperature in a hot air circulation oven to 50-60° C. for 3-4 hours.

[0050] In some specific embodiments, the gentamicin, procain, and vitamin B 12 The particle size of the particles is less than 10 mesh.

[0051] In some specific embodiments, the total mixing includes:

[0052] Add the granules after granulation into the three-dimensional motion mixer, set the frequency of the inverter to 30-40 Hz, and mix for 10-15 minutes.

[0053] In a specific embodiment, qualified particles below 10 mesh are selected, and the qualified particles after granulation are added into a three-dimensional motion mixer, and the frequency of the frequency converter is set to 35 Hz. After mixing for 15 minutes, the mixer is stopped and the material is discharged.

[0054] The present invention provides a gentamicin, procain and vitamin B 12 The particles are prepared by the preparation method described in any one of the above technical solutions.

[0055] Compared with the existing technology, the present invention has the following beneficial effects:

[0056] (1) The present invention uses beta-cyclodextrin to exert inclusion complexation to encapsulate gentamicin sulfate, thereby improving product quality stability.

[0057] (2) In the present invention, the wet granules obtained by the swing granulator are pelletized in a pelletizing pot during the granulation stage, so that the product has less fine powder, more uniform particle size and better fluidity.

[0058] It should be understood that the expression "one or more of" includes individually each of the items recited after the expression and various combinations of two or more of the recited items, unless otherwise apparent from the context and usage. The expression "and / or" in conjunction with three or more recited items should be understood to have the same meaning, unless otherwise apparent from the context.

[0059] The terms "comprising", "having" or "containing", including their grammatical synonyms, should generally be understood as open and non-restrictive, e.g., not excluding other unrecited elements or steps, unless otherwise specifically stated or understood from the context.

[0060] In this application, the term "and / or" describes the association relationship between associated objects, indicating that three relationships may exist. For example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone. A and B can be singular or plural.

[0061] In this application, "at least one" means one or more, and "more than one" means two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single or plural items.

[0062] It should be understood that the order of steps or the order in which certain actions are performed are not important as long as the present invention remains operable. Additionally, two or more steps or actions may be performed simultaneously.

[0063] The use of any and all examples or exemplary language, such as "such as" or "including," herein is intended merely to better illustrate the invention and does not limit the scope of the invention unless otherwise claimed. No language in this specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0064] In addition, the numerical ranges and parameters used to define the present invention are approximate values. The relevant numerical values ​​in the specific examples have been presented as accurately as possible. However, any numerical value inherently inevitably contains standard deviations due to individual testing methods. Therefore, unless otherwise expressly stated, all ranges, amounts, values, and percentages used in this disclosure should be understood to be modified by the word "about." As used herein, "about" generally means that the actual value is within plus or minus 10%, 5%, 1%, or 0.5% of a specified value or range.

[0065] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution. Some or all of the steps can be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0066] Some cases are described in the embodiments and comparative examples of the present invention, wherein the embodiments illustrate certain implementations of the present invention. However, this does not mean that the effects of the present invention can only be achieved in these cases.

[0067] In order to further illustrate the present invention, the following embodiments are combined with the present invention to provide a gentamicin procaine vitamin B 12 The particles and their preparation methods are described in detail.

[0068] Example 1

[0069] According to the preparation method of 1000 bags, gentamicin, procaine, vitamin B 12 The materials for preparing the granules include: a certain amount of gentamicin sulfate (calculated as 20 million gentamicin sulfate units), 100g of procaine hydrochloride, 0.02g of vitamin B 12 , 100g of beta-cyclodextrin, 10g of aspartame, 0.12g of tartrazine, and appropriate amount of sucrose (added to 2g / bag).

[0070] Gentamicin, procain, vitamin B 12 The method for preparing the particles comprises the following steps:

[0071] (1) Material pretreatment

[0072] Sieving: Aspartame was passed through a 60-mesh sieve.

[0073] Grinding: Procaine hydrochloride and sucrose were ground using a platform grinder equipped with an 80-mesh screen;

[0074] (2) Ingredients

[0075] Solution preparation: Prepare vitamin B with a concentration of 6.41‰ 12 Pour the aqueous solution (g / ml) into a brown glass bottle for use, at a rate of 31.2ml / 10,000 bags. Prepare a 6.25% lemon yellow aqueous solution (g / ml), pour it into a brown glass bottle for use, at a rate of 19.2ml / 10,000 bags.

[0076] Material mixing (single 20,830 bags preparation method):

[0077] Preparation of mixed solution: put the weighed 416.7 million units of gentamicin sulfate into a stainless steel barrel, add 1.26 kg of purified water, stir until the powder is completely dissolved, then add 2.083 kg of beta-cyclodextrin, and continue stirring for 1 hour. After stirring, add the prepared vitamin B 12 Aqueous solution, lemon yellow aqueous solution.

[0078] Weigh 0.208kg of aspartame, 3kg of sucrose powder, and 2.083kg of procaine hydrochloride, mix them manually in a stainless steel basin for 10 minutes (wearing sterilized latex gloves), then pass through a 60-mesh sieve once. The sieved material and the remaining sucrose powder are poured into a high-efficiency mixing granulator and mixed. After the dry powder is mixed for 900 seconds (adjust the blade speed to 60rpm and the flying knife speed to 1500rpm, and after 120 seconds, increase the blade speed to 90rpm and the flying knife speed to 1900rpm, for a cumulative time of 900 seconds), keep the equipment running, and pour the mixed solution into the high-efficiency mixing granulator in small amounts, slowly, and evenly. Rinse the solution feed port with 100ml of purified water and allow it to flow into the mixed powder. The equipment continues to run until the cumulative time is 1320 seconds and automatically stops, discharging.

[0079] (3) Granulation

[0080] Use a stainless steel spoon to add the prepared soft material in an appropriate amount (based on the principle of adding small amounts multiple times) into the hopper of the swing granulator, and granulate the soft material in the swing granulator with a 12-mesh sieve. Start the pill-making pot, put the wet granules after shaking into the pill-making pot, and spray purified water. Add a small amount of wet granules, and while rotating, use your hands (wearing sterilized latex gloves) to break up the agglomerated wet granules and then spray a small amount of purified water. Repeat this process to make them stronger granules, and then pass them through a 12-mesh sieve. The large granules that cannot pass through the sieve are squeezed and sieved through a 12-mesh sieve and then transferred to the pill-making machine for granulation. Repeat this process until all the wet granules are made into qualified granules.

[0081] (4) Drying

[0082] Load the wet granules evenly into each drying tray by weight, spread them evenly, and place the drying tray on a drying cart. Push the drying cart into a hot air circulation oven. Control the drying temperature at 50-60°C and the drying time for 3.5 hours (excluding the turning time).

[0083] (5) Whole granules and total mixing.

[0084] Take the qualified particles below 10 mesh, add the qualified particles after granulation into the three-dimensional motion mixer, set the frequency of the inverter to 35Hz, mix for 15 minutes, and then stop the machine to discharge the material.

[0085] The gentamicin, procain and vitamin B prepared in Example 1 12 The particles were divided into granules and the results are shown in Table 1.

[0086] Table 1 Gentamicin, Procaine, and Vitamin B 12 Determination of particle size differences

[0087]

[0088]

[0089] From the test in Table 1, it can be seen that the gentamicin procaine vitamin B prepared by the present invention 12 The particles are fine, with little powder and excellent particle size uniformity. The particles are used for particle packaging, and the ability to control the difference in filling amount is excellent, and the filling amount difference is far lower than the standard requirement, which proves that the particles prepared by the present invention have good fluidity.

[0090] The gentamicin, procain and vitamin B prepared in Example 1 12 After the granules were divided into granules and packaged, they were inspected under long-term conditions (25±2°C, 65±5%) in accordance with the provisions of the 2020 edition of the "Chinese Pharmacopoeia". The inspection results are shown in Table 2.

[0091] Table 2 Gentamycin, Procain, and Vitamin B 12 Particle stability test results (25±2℃, 65±5%)

[0092]

[0093]

[0094] As can be seen from Table 2, the gentamicin, procain, and vitamin B prepared by the present invention 12 The particles were inspected under long-term conditions (25±2℃, 65±5%) for 48 months. All indicators met the standard requirements, and the fluctuation was far lower than the standard requirements, with excellent quality stability.

[0095] Comparative Example 1

[0096] According to the preparation method of 1000 bags, gentamicin, procaine, vitamin B 12 The materials for preparing the granules include: a certain amount of gentamicin sulfate (calculated as 20 million gentamicin sulfate units), 100g of procaine hydrochloride, 0.02g of vitamin B 12 , 0.3g of lemon yellow, appropriate amount of sucrose (up to 5g / bag), appropriate amount of sodium carboxymethyl cellulose syrup.

[0097] The preparation method is as follows:

[0098] Gentamycin sulfate (20 million gentamicin sulfate units), 100g of procaine hydrochloride, 0.02g of vitamin B 12 , 0.3g of lemon yellow, and an appropriate amount of sucrose (added to 5g / bag) are fully mixed manually, and sodium carboxymethyl cellulose slurry is weighed according to 1.5% of the weight of the mixed powder to make a soft material, granulated through a 14-mesh sieve, and dried below 60°C. After drying, the total mixing is carried out manually.

[0099] The gentamicin, procain and vitamin B prepared in Comparative Example 1 were 12 After the granules were divided into granules and packaged externally, they were tested under long-term conditions (25±2°C, 65±10%). The test results are shown in Table 3.

[0100] Table 3 Gentamycin, Procaine, and Vitamin B 12 Particle stability test results (25±2℃, 65±10%)

[0101]

[0102]

[0103] Comparative Example 2

[0104] The prescription and preparation method are basically the same as those in the embodiment, except for (3) granulation. The granulation process of this comparative example is as follows:

[0105] (3) Granulation

[0106] Use a stainless steel spoon to add an appropriate amount of the prepared soft material (adding in small amounts and multiple times is the principle) into the hopper of the swing granulator, and granulate the soft material through a 12-mesh sieve in the swing granulator.

[0107] The gentamicin, procain and vitamin B prepared in Comparative Example 2 were 12 The particles were packaged into granules, and the results are shown in Table 4.

[0108] Table 4 Gentamycin Procaine Vitamin B 12 Determination of particle size differences

[0109]

[0110] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A gentamicin, procaine, and vitamin B 12 The method for preparing particles is characterized in that: The steps include: A) Aspartame, sucrose powder and procaine hydrochloride are mixed and then sieved, the sieved material is poured into a high-efficiency mixing granulator for mixing, and then the mixed solution is poured into, mixed, and discharged to obtain a soft material; the mixed solution includes vitamin B 12 aqueous solution, tartrazine aqueous solution, and gentamicin sulfate solution; B) Add the soft material into the hopper of the swing pelletizer, start the pelletizing pot, put the wet pellets after swinging into the pelletizing pot, spray purified water, and then sieve to obtain wet pellets; C) Drying the wet granules, sizing the granules, and mixing the granules to obtain the product.

2. The preparation method according to claim 1, characterized in that Step A) the aspartame is passed through a 50-70 mesh sieve; the sucrose powder is crushed using a platform grinder equipped with a 70-90 mesh sieve; and procaine hydrochloride is crushed using a platform grinder equipped with a 70-90 mesh sieve; The vitamin B 12 The concentration of the aqueous solution is 6-7‰ (g / ml); the concentration of the lemon yellow aqueous solution is 6-7% (g / ml); The gentamicin sulfate solution comprises: mixing gentamicin sulfate and water, then adding β-cyclodextrin, and continuing to stir for 0.5 to 1.5 hours to obtain the gentamicin sulfate solution; the ratio of the gentamicin sulfate, β-cyclodextrin and water is 410 million to 420 million units: (2 to 2.2 kg): (1 to 1.4 kg).

3. The preparation method according to claim 1, characterized in that The step A) specifically includes: manually mixing aspartame, sucrose powder, and procaine hydrochloride for 10 minutes, then passing through a 60-mesh sieve, and then dry powder mixing for 900 seconds; the mixing parameters include: adjusting the blade speed to 60 rpm and the knife speed to 1500 rpm, timing for 120 seconds, increasing the blade speed to 90 rpm and the knife speed to 1900 rpm, and cumulatively timing for 900 seconds; then adding the mixed solution and continuing mixing for 1320 seconds.

4. The preparation method according to claim 3, characterized in that The mass ratio of the aspartame, sucrose powder and procaine hydrochloride is (0.2-0.3):3:(2-2.5).

5. The preparation method according to claim 1, characterized in that The step B) specifically comprises: adding the soft material into the hopper of the swing granulator, starting the pelletizing pot, putting the wet granules after swinging into the pelletizing pot, spraying purified water, adding a small amount of wet granules, kneading the agglomerated wet granules while rotating, and then spraying a small amount of purified water, repeating the process, and then passing the wet granules through a 12-mesh sieve. After the large granules that cannot pass through the sieve are squeezed and sieved through the 12-mesh sieve, they are then transferred to the pelletizing machine for granulation, and the process is repeated until all the wet granules are made into qualified granules.

6. The preparation method according to claim 5, characterized in that Step B) the soft material is granulated in a swing granulator with a 10-12 mesh sieve.

7. The preparation method according to claim 1, characterized in that Step C) the drying comprises: controlling the drying temperature in a hot air circulation oven at 50-60° C. for 3-4 hours.

8. The preparation method according to claim 1, characterized in that Step C) Gentamycin, procaine, vitamin B 12 The particle size of the particles is less than 10 mesh.

9. The preparation method according to claim 1, characterized in that Step C) the total mixing comprises: Add the granules after granulation into the three-dimensional motion mixer, set the frequency of the inverter to 30-40 Hz, and mix for 10-15 minutes.

10. A gentamicin, procaine, and vitamin B 12 Particles, characterized in that The compound is prepared by the preparation method according to any one of claims 1 to 9.

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