Preparation method of pollen extract preparation

Abstract

The present invention provides a method for preparing a pollen extract preparation, relating to the field of preparation process technology. The preparation method comprises the following steps: (1) dissolving pollen extract EA10 in 95% ethanol to obtain solution I; (2) dissolving pollen extract P5 in water to obtain solution II; (3) spreading auxiliary material powders of colloidal silicon dioxide, microcrystalline cellulose, and cross-linked sodium carboxymethyl cellulose on a fluidized bed for preheating; (4) spraying solution I and solution II into the fluidized bed and mixing with the auxiliary material powders for granulation. The present invention uses a one-step granulation molding process with mild conditions, which will not cause degradation of related drug components during the molding process. In addition, when the auxiliary materials are in a certain composition ratio, the disintegration and tablet weight difference of the tablets compressed from the prepared granules meet the pharmacopoeial standards, and no long melting process is required during the granulation process, thereby shortening the operation time.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation technology, and particularly relates to a method for preparing a pollen extract preparation. Background Art

[0002] Prostatitis refers to a prostate disease caused by a variety of complex factors, with urethral irritation and chronic pelvic pain as primary clinical manifestations. It is a common urological disease, accounting for the highest incidence among male urology patients under 50 years old. Prostatitis is typically treated with Prostanol tablets. Currently, the preparation process for Prostanol tablet compositions is complex, making large-scale production difficult and resulting in high production costs. For example, Chinese invention patent application CN111419884A discloses a preparation process for a Sheniton tablet composition. The specific preparation steps are as follows: Step 1, Preparation of GBX Premix: EA10 (66 g) is placed in a white plastic container and maintained at 35°C in a heating cabinet for 20 hours to melt the EA10. The melted EA10 is then mixed with microcrystalline cellulose (462 g) in a mixing vessel for 8 minutes, followed by the addition of anhydrous silicon dioxide (70 g). However, the melting time in the aforementioned patent application is as long as 20 hours, which is a relatively long process.

[0003] Therefore, there is an urgent need to develop a method for preparing a pollen extract preparation that does not require a long melting process, shortens the operation time, and prevents drug degradation based on the characteristics of the pollen extract. Summary of the Invention

[0004] The present invention addresses the problems of the prior art and provides a method for preparing a pollen extract preparation. This method utilizes a one-step granulation and molding process, employing mild conditions that prevent drug degradation during the molding process. Furthermore, with a specific ratio of excipients, the resulting granules produce tablets with disintegration properties and tablet weight variability that meet pharmacopoeial standards. Furthermore, the granulation process eliminates the need for a lengthy melting step, shortening the operation time.

[0005] One of the purposes of the present invention is to provide a method for preparing a pollen extract preparation, which includes pollen extract EA10, pollen extract P5 and excipients. The preparation method comprises the following steps: (1) dissolving pollen extract EA10 in 95% ethanol to obtain solution I; (2) dissolving pollen extract P5 in water to obtain solution II; (3) spreading excipients such as colloidal silicon dioxide, microcrystalline cellulose and cross-linked sodium carboxymethyl cellulose on a fluidized bed for preheating; (4) mixing solution I and solution II, spraying them into a fluidized bed for mixing and granulating with the excipients, and the granulation time is 0.5-1 hour to obtain the product.

[0006] Preferably, in step (1), the mass ratio of the pollen extract EA10 to 95% ethanol is 1:4-6.

[0007] Preferably, in step (2), the mass ratio of the pollen extract P5 to water is 1:1-3.

[0008] Preferably, in step (3), the mass ratio of colloidal silicon dioxide, microcrystalline cellulose and cross-linked sodium carboxymethyl cellulose is 1:20-50:1-2.

[0009] Preferably, the mass ratio of the pollen extract EA10 to the pollen extract P5 is 1:15-25.

[0010] Preferably, the mass ratio of the pollen extract EA10 to the excipient is 1:30-40.

[0011] Preferably, during the granulation process in step (4), the inlet air temperature is controlled at 100-105° C., the material temperature is 50-70° C., and the atomization pressure is 0.45-0.6 MPa.

[0012] Preferably, the pollen extract preparation is a tablet, which is obtained by tableting and coating after a one-step granulation.

[0013] More preferably, the coating is specifically performed by spraying a 6% Opadry coating agent in 85% ethanol solution continuously with air flow until the coating layer weighs 1-6% of the tablet core weight, and then drying. Preferably, the coating layer weighs 2%-4% of the tablet core weight.

[0014] Compared with the prior art, the present invention has the following beneficial effects: through a one-step granulation molding process, the conditions are mild and the drug degradation during the molding process will not be caused; and under a certain composition ratio of the excipients, the disintegration and tablet weight difference of the tablets pressed from the prepared granules meet the pharmacopoeial standards, and the granulation process does not require a long melting process, thereby shortening the operation time. DETAILED DESCRIPTION

[0015] The following non-limiting examples are provided to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way. The following contents are merely illustrative of the scope of the present invention, and those skilled in the art may make various changes and modifications to the present invention based on the disclosed contents, which should also fall within the scope of the present invention.

[0016] In the examples of the present invention, the sources and batch numbers of the relevant substances are shown in Table 1.

[0017] Table 1: Sources and batch numbers of related substances

[0018]

[0019]

[0020] Example 1

[0021] The preparation method of the pollen extract preparation comprises the following steps:

[0022] (1) Dissolve 66 g of pollen extract EA10 in 5 times the volume of 95% ethanol aqueous solution to obtain solution I;

[0023] (2) Dissolve 1.2 kg of pollen extract P5 in 2 times the amount of water to obtain solution II;

[0024] (3) 70 g of colloidal silicon dioxide, 2130 g of microcrystalline cellulose, and 90 g of croscarmellose sodium were placed on a fluidized bed and preheated;

[0025] (4) Solution I and solution II are mixed and sprayed into a fluidized bed to mix with the auxiliary materials for granulation. The inlet air temperature is controlled at 100°C, the material temperature is 60°C, the atomization pressure is 0.5 MPa, and the granulation is carried out for 0.5 h.

[0026] Comparative Example 1:

[0027] The amounts of pollen extract EA10, pollen extract P5 and auxiliary materials such as colloidal silicon dioxide, microcrystalline cellulose and cross-linked carboxymethyl cellulose in Example 1 remain unchanged and are prepared by a conventional wet granulation method.

[0028] (1) Dissolve 66 g of EA10 in 5 times the volume fraction of 50% ethanol aqueous solution;

[0029] (2) Add 2130 g of microcrystalline cellulose and 90 g of cross-linked sodium carboxymethyl cellulose to a wet granulator and mix thoroughly. Add the solution to make granules, dry at 50°C, and pass through an 80-mesh sieve after drying.

[0030] (3) Add 1.2 kg of pollen extract P5 and 70 g of colloidal silicon dioxide to the above particles and mix well to obtain the product.

[0031] Comparative Example 2:

[0032] The preparation method of the pollen extract preparation comprises the following steps:

[0033] (1) Dissolve 66 g of EA10 in 5 times the volume fraction of 95% ethanol aqueous solution to obtain solution I;

[0034] (2) Dissolve 1.2 kg of P5 in twice the amount of water to obtain solution II;

[0035] (3) 70 g of colloidal silicon dioxide, 1970 g of microcrystalline cellulose, and 250 g of croscarmellose sodium were placed on a fluidized bed and preheated;

[0036] (4) Solution I and solution II are mixed and sprayed into a fluidized bed to mix with the auxiliary materials for granulation. The inlet air temperature is controlled at 100°C, the material temperature is 60°C, the atomization pressure is 0.5 MPa, and the granulation is carried out for 0.5 h.

[0037] The difference from Example 1 is that in step (3), the amount of microcrystalline cellulose is reduced to 1970 g, and the amount of cross-linked sodium carboxymethyl cellulose is increased to 250 g. The rest is the same as Example 1.

[0038] Comparative Example 3:

[0039] The preparation method of the pollen extract preparation comprises the following steps:

[0040] (1) Dissolve 66 g of EA10 in 5 times the volume fraction of 95% ethanol aqueous solution to obtain solution I;

[0041] (2) Dissolve 1.2 kg of P5 in twice the amount of water to obtain solution II;

[0042] (3) Preheat the excipients (30 g colloidal silicon dioxide, 2170 g microcrystalline cellulose, and 90 g croscarmellose sodium) on a fluidized bed.

[0043] (4) Solution I and solution II are mixed and sprayed into a fluidized bed to mix with the auxiliary materials for granulation. The inlet air temperature is controlled at 100°C, the material temperature is 60°C, the atomization pressure is 0.5 MPa, and the granulation is carried out for 0.5 h.

[0044] The difference from Example 1 is that in step (3), the amount of colloidal silicon dioxide is reduced to 30 g, and the amount of microcrystalline cellulose is increased to 2170 g. The rest is the same as Example 1.

[0045] Test Example 1:

[0046] The contents of the main drug components EA10 and P5 in the granules after the preparation process were determined by HPLC, and the degradation rate was calculated using the following formula:

[0047]

[0048] Wherein, M1 is the input amount of EA10 or P5 before preparation, and M2 is the mass of EA10 or P5 in the granules after preparation.

[0049] The degradation rates of EA10 and P5 in three different batches of particles prepared in Example 1 and Comparative Example 1 are shown in Table 2.

[0050] Table 2: Degradation rates of EA10 and P5 in three different batches of granules prepared in Example 1 and Comparative Example 1

[0051]

[0052] According to the data in the table, the present invention adopts a one-step granulation method with mild conditions, which will not cause degradation of the pollen extract EA10 and pollen extract P5 components during the molding process. In contrast, traditional wet granulation will cause severe degradation of the components EA10 and P5 during the drying process, affecting the efficacy of the drug.

[0053] Test Example 2:

[0054] The granules obtained in Example 1, Comparative Example 2, and Comparative Example 3 were compressed and coated under the same experimental conditions to produce tablets weighing approximately 0.36 g per tablet. The coating was performed by continuously spraying a 6% Opadry coating agent solution in 85% ethanol with airflow until the coating layer weighed 3% of the tablet core weight, followed by drying. Tablet disintegration and tablet weight variability were determined according to the methods specified in the Chinese Pharmacopoeia. Relevant data are shown in Table 3.

[0055] Table 3: Performance test results of the tablets obtained by preparing the granules of Example 1, Comparative Example 2 and Comparative Example 3

[0056]

[0057] The one-step granulation material provided in Example 1 of the present invention has good fluidity, and the disintegration and tablet weight variation of the prepared tablets meet the pharmacopoeia standards. However, the disintegration of the tablets of Comparative Examples 2-3 deteriorates, and the tablet weight variation does not meet the pharmacopoeia standards.

[0058] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing a pollen extract preparation, comprising pollen extract EA10, pollen extract P5 and excipients, characterized in that: The preparation method comprises the following steps: (1) dissolving pollen extract EA10 in 95% ethanol to obtain solution I; (2) dissolving pollen extract P5 in water to obtain solution II; (3) spreading auxiliary materials such as colloidal silicon dioxide, microcrystalline cellulose, and cross-linked sodium carboxymethyl cellulose on a fluidized bed for preheating; (4) mixing solution I and solution II, spraying them into the fluidized bed for mixing with the auxiliary materials for granulation, the granulation time being 0.5-1 hour, tableting, and coating to obtain the product; wherein The mass ratio of the pollen extract EA10 to the pollen extract P5 is 1:15-25; The mass ratio of the pollen extract EA10 to the excipients is 1:30-40; In the step (3), the mass ratio of colloidal silicon dioxide, microcrystalline cellulose and cross-linked sodium carboxymethyl cellulose is 1:20-50:1-2.

2. The preparation method according to claim 1, characterized in that In the step (1), the mass ratio of the pollen extract EA10 to 95% ethanol is 1:4-6.

3. The preparation method according to claim 1, characterized in that In the step (2), the mass ratio of the pollen extract P5 to water is 1:1-3.

4. The preparation method according to claim 1, characterized in that During the granulation process in step (4), the inlet air temperature is controlled at 100-105° C., the material temperature is 50-70° C., and the atomization pressure is 0.45-0.6 MPa.

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