Ganjole capsule preparation method
By employing high-pressure homogenization and vacuum microwave drying technologies, the problems of uneven mixing of oleanolic acid and loss of heat-sensitive components in liver-enhancing capsules have been solved, achieving uniformity and efficient production of drug components.
Patent Information
- Application Number
- CN202511874864.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-12
- Publication Date
- 2026-02-03
AI Technical Summary
In the existing preparation method of liver-enhancing capsules, oleanolic acid is insoluble in water, which leads to uneven mixing with Schisandra chinensis extract and Acanthopanax senticosus extract, affecting the uniformity of drug content. In addition, the traditional drying method results in serious loss of heat-sensitive components.
Oleanolic acid particles were reduced to the nanoscale using high-pressure homogenization technology. Combined with vacuum microwave drying technology, the mixture was mixed using an equal-increment method, and air bubbles were eliminated during the vacuum microwave drying process to form a stable colloidal dispersion system. Finally, a lubricant was added and the mixture was encapsulated.
This method achieves uniform mixing of oleanolic acid with Schisandra chinensis extract and Acanthopanax senticosus extract, improving the uniformity of drug content. Furthermore, it preserves heat-sensitive components through low-temperature rapid drying, significantly improving production efficiency and component retention rate.
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Figure CN121445705A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application relates to the technical field of traditional Chinese medicine preparations, and particularly relates to a preparation method of Ganxile capsules. BACKGROUND
[0002] The Ganxile capsule is a kind of traditional Chinese medicine, and is mainly used for treating liver diseases, including acute hepatitis, chronic hepatitis and liver cirrhosis. The main components of the Ganxile capsule include: schisandra chinensis extract, acanthopanax senticosus extract and oleanolic acid.
[0003] In the preparation method of the existing Ganxile capsule, oleanolic acid is mixed with starch and calcium carbonate, and then high-viscosity schisandra chinensis extract and acanthopanax senticosus extract are added. Since the extract has high viscosity and oleanolic acid is insoluble in water, the mixture is not uniform, which affects the uniformity of the drug content. Therefore, a preparation method of the Ganxile capsule needs to be designed. SUMMARY
[0004] The application aims to solve the problems in the prior art, and provides a preparation method of Ganxile capsules.
[0005] In order to achieve the above-mentioned purpose, the application adopts the following technical scheme: a preparation method of Ganxile capsules, comprising the following steps:
[0006] S1: premixing and crushing: oleanolic acid and a stabilizer are mixed in a three-dimensional mixer according to an equal increment method, and then are crushed by an ultrasonic airflow crusher;
[0007] S2: preparation of oleanolic acid nanosuspension: schisandra chinensis extract and acanthopanax senticosus extract are added to the crushed material, and are transferred to a premixing tank to form a coarse suspension by stirring at 150-200 rpm for 10-15 min; the coarse suspension is treated by a high-pressure homogenizer to obtain a nanosuspension with a particle size of 260-290 nm;
[0008] S3: three-stage equal increment mixing: oleanolic acid nanosuspension, schisandra chinensis extract and acanthopanax senticosus extract are mixed according to an equal increment method to form a material;
[0009] S4: vacuum microwave drying: the material is laid on a microwave drying plate, and the parameters of a vacuum microwave drying box are set as follows: temperature 30-45 DEG C, vacuum degree -0.05 to -0.08 MPa, and time 20-35 min;
[0010] S5: post-treatment: the material is crushed into 80-mesh fine powder, lubricant is added and mixed, and the material is loaded into a capsule.
[0011] Further description is made to the above technical scheme:
[0012] The stabilizer is a compound of starch and calcium carbonate, and the mass ratio of the two is 2:5.
[0013] As a further description of the above technical solution:
[0014] The mixing speed in the step S1 is 15-30 rpm, and the mixing time is 25-35 min.
[0015] As a further description of the above technical solution:
[0016] The pressure of the high-pressure homogenizer is controlled at 800-1500 bar, and the cycle homogenization is 6-9 times.
[0017] As a further description of the above technical solution:
[0018] In the step S1, nitrogen gas protection of-5 to-10℃ is introduced during mixing.
[0019] As a further description of the above technical solution:
[0020] The specific operation steps in the step S3 are:
[0021] First stage: 10% oleanolic acid nanosuspension is mixed with 10% schisandra extract and acanthopanax extract in a double-planetary mixer for 5 min;
[0022] Second stage: 20% oleanolic acid nanosuspension is added each time, and 20% schisandra extract and acanthopanax extract are mixed for 3 min each time until completely mixed;
[0023] Third stage: vacuum degassing for 5 min to eliminate air bubbles introduced during mixing.
[0024] As a further description of the above technical solution:
[0025] The lubricant is a composite of talc and magnesium stearate, and the mass ratio of the two is 1:3.
[0026] The present application has the following beneficial effects:
[0027] 1. Compared with the prior art, the present application reduces the particle size of oleanolic acid from microns to nanometers by using high-pressure homogenization technology, increases the specific surface area by more than 1000 times, forms a stable colloidal dispersion system with schisandra extract and acanthopanax extract, avoids stratification caused by gravity settling or viscosity difference, and simultaneously uses the equal increment method to make the mixing more uniform.
[0028] 2、Compared with the prior art, the application realizes low-temperature rapid drying by adopting vacuum microwave drying, using the microwave "internal heating" characteristics to make the internal moisture of the material directly vaporize, combining with the vacuum environment to reduce the boiling point, compared with the "heat conduction drying" of the traditional oven, not only shortens the drying time, but also improves the retention rate of heat-sensitive components by 30%-40%, thereby improving the production efficiency. BRIEF DESCRIPTION OF DRAWINGS
[0029] Figure 1 A flowchart of a preparation method of a liver joy capsule is proposed for the application. DETAILED DESCRIPTION
[0030] Example 1
[0031] Raw material composition: oleanolic acid 10 parts, starch 20 parts, calcium carbonate 50 parts, schisandra extract 100 parts, acanthopanax extract 50 parts, talc 10 parts, and magnesium stearate 10 parts.
[0032] Preparation steps
[0033] Premixing and crushing:
[0034] The oleanolic acid, starch and calcium carbonate are placed in a three-dimensional mixer according to the equal incremental method, the rotation speed is maintained at 20 rpm, the mixing time is 30 min, and -10 ℃ nitrogen gas protection is introduced; after mixing, an ultrasonic airflow crusher is used for crushing.
[0035] Preparation of oleanolic acid nanosuspension:
[0036] The schisandra extract and acanthopanax extract are added to the crushed material, transferred to a premixing tank, stirred at 200 rpm for 15 min to form a coarse suspension; the coarse suspension is treated by a high-pressure homogenizer, the pressure of the high-pressure homogenizer is 1200 bar, and the cycle homogenization is 8 times, to obtain a nanosuspension with a particle size of 280.
[0037] Three-stage equal incremental mixing:
[0038] First stage: 10% oleanolic acid nanosuspension is mixed with 10% schisandra extract and acanthopanax extract in a double-planetary mixer for 5 min;
[0039] Second stage: 20% oleanolic acid nanosuspension and 20% schisandra extract and acanthopanax extract are added each time, mixed for 3 min each time, until completely mixed;
[0040] Third stage: vacuum degassing for 5 min to eliminate air bubbles introduced during the mixing process to form the material.
[0041] Vacuum microwave drying:
[0042] The material is laid flat in a microwave drying tray, and the parameters of the vacuum microwave drying oven are set as follows: temperature 45℃, vacuum degree -0.08MPa, time 30min; the water content of the dried material is 2.1%.
[0043] Post-treatment:
[0044] Pulverized to 80 mesh, talcum powder and magnesium stearate are added, and mixed evenly in a mixer, and then loaded into the capsule to form the Ganxile capsule.
[0045] Example 2
[0046] Raw material composition: oleanolic acid 10 parts, starch 20 parts, calcium carbonate 50 parts, schisandra extract 100 parts, acanthopanax extract 50 parts, talcum powder 10 parts, and magnesium stearate 10 parts.
[0047] Preparation steps
[0048] Premixing and pulverization:
[0049] The oleanolic acid, starch, and calcium carbonate are placed in a three-dimensional mixer according to the equal incremental method, the rotation speed is maintained at 30rpm, the mixing time is 25min, and nitrogen gas protection at -10℃ is performed; after mixing, an ultrasonic airflow pulverizer is used for pulverization.
[0050] Preparation of oleanolic acid nanosuspension:
[0051] The schisandra extract and acanthopanax extract are added to the pulverized material, transferred to a premixing tank, and stirred at 180rpm for 15min to form a coarse suspension; the coarse suspension is treated by a high-pressure homogenizer, the pressure of the high-pressure homogenizer is 1500bar, and the cycle homogenization is 7 times, to obtain a nanosuspension with a particle size of 290nm.
[0052] Three-stage equal incremental mixing:
[0053] First stage: 10% oleanolic acid nanosuspension is mixed with 10% schisandra extract and acanthopanax extract in a double-planetary mixer for 5min;
[0054] Second stage: 20% oleanolic acid nanosuspension is added each time, and mixed with 20% schisandra extract and acanthopanax extract for 3min each time, until completely mixed;
[0055] Third stage: vacuum degassing for 5min to eliminate air bubbles introduced during the mixing process, and form the material.
[0056] Vacuum microwave drying:
[0057] The material is laid flat in a microwave drying tray, and the parameters of the vacuum microwave drying oven are set as follows: temperature 40℃, vacuum degree -0.05MPa, time 40min; the water content of the dried material is 3.1%.
[0058] Post-processing:
[0059] Pulverized to 80 mesh, add talc and magnesium stearate, mix evenly in a mixer, and load into the capsule to form Ganxile capsules.
[0060] Example 3
[0061] Raw material composition: oleanolic acid 10 parts, starch 20 parts, calcium carbonate 50 parts, schisandra extract 100 parts, acanthopanax extract 50 parts, talc 10 parts, magnesium stearate 10 parts.
[0062] Preparation steps
[0063] Premixing and pulverizing:
[0064] Oleanolic acid, starch, and calcium carbonate were placed in a three-dimensional mixer according to the equal incremental method, with a rotation speed of 25 rpm and a mixing time of 20 min, and nitrogen gas was introduced at -10°C for protection. After mixing, the material was pulverized using an ultrasonic airflow pulverizer.
[0065] Preparation of oleanolic acid nanosuspension:
[0066] Schisandra extract and acanthopanax extract were added to the pulverized material, and the mixture was transferred to a premixing tank and stirred at 160 rpm for 12 min to form a coarse suspension. The coarse suspension was then treated using a high-pressure homogenizer, with a pressure of 1000 bar and a cycle of 9 times, to obtain a nanosuspension with a particle size of 285 nm.
[0067] Three-stage equal incremental mixing:
[0068] First stage: 10% oleanolic acid nanosuspension was mixed with 10% schisandra extract and acanthopanax extract in a double-planetary mixer for 5 min.
[0069] Second stage: 20% oleanolic acid nanosuspension was added each time, and mixed with 20% schisandra extract and acanthopanax extract for 3 min each time, until complete mixing.
[0070] Third stage: vacuum degassing for 5 min to eliminate air bubbles introduced during the mixing process, and form the material.
[0071] Vacuum microwave drying:
[0072] The material was spread on a microwave drying tray, and the vacuum microwave drying box parameters were set as follows: temperature 40°C, vacuum degree -0.08 MPa, time 30 min. After drying, the moisture content of the material was 2.8%.
[0073] Post-processing:
[0074] Pulverized to 80 mesh, add talc and magnesium stearate, mix evenly in a mixer, and load into the capsule to form Ganxile capsules.
[0075] Comparative Example 1 is a traditional process for preparing Ganjiao Capsules.
[0076] Production cycle verification
[0077] Experimental purposes
[0078] The time consumption of the whole process of the process of the application and the traditional process is compared to verify the improvement of production efficiency.
[0079] Experimental methods
[0080] Timing range: the whole process time from the beginning of raw material preparation to the completion of capsule packaging, including the operation time of each process and the interval time of equipment start and stop.
[0081] Group design:
[0082] Example 1: The preparation steps are prepared, and the time consumption of each link of premixing, homogenizing, mixing, drying, granulating, total mixing, and filling and packaging is recorded.
[0083] Comparative Example 1: prepared according to the method in the traditional process technology, record the time consumption of each link of mixing, drying, crushing, total mixing, and filling and packaging.
[0084] Repeated experiments: each process is repeated 3 times, and the average value is taken to reduce errors.
[0085] Table 1 is the production cycle related data
[0086] Process step Example 1 (time spent / h) Comparative Example 1 (time spent / h) Difference rate Premixing + homogenization 2.5 - - Mixing + drying 1.0 50.0 98％ Crushing + granulation + total mixing 5.0 3.0 67％ Filling packaging 0.5 0.5 - Total cycle 8 53.5 85％
[0087] Analysis shows that the production time of the process of the application is less than that of the traditional process.
[0088] Verification of volatile component loss
[0089] Experimental purposes
[0090] By detecting the total amount of volatile components, the protection effect of vacuum microwave drying on heat-sensitive components is verified.
[0091] Experimental methods
[0092] Detection technology: gas chromatography-mass spectrometry (GC-MS), quantitative analysis by characteristic mass spectrum peak area of volatile components.
[0093] Sample preparation:
[0094] Take 3 parts of the samples in Example 1, Example 2, Example 3, and Comparative Example 1 after drying, add 5 mL of anhydrous ethanol, ultrasonic extraction for 30 minutes, filter and take the supernatant as the detection sample.
[0095] GC-MS conditions:
[0096] Chromatographic column: DB-5MS capillary column;
[0097] Temperature program: initial temperature 40℃ (hold for 2 min), increase to 280℃ at 5℃ / min (hold for 5 min);
[0098] Carrier gas: helium (flow rate 1.0 mL / min);
[0099] Mass spectrometry conditions: electron impact source (EI), ion source temperature 230℃, scan range m / z 30-500.
[0100] Data processing:
[0101] The total amount of volatile components was calculated as the sum of peak areas of all volatile components in the total ion chromatogram (TIC).
[0102] Loss rate was calculated:
[0103] Table 2 is the verification data of volatile component loss
[0104]
[0105] The traditional process resulted in a volatile component loss of about 48% due to high-temperature and long-time drying, while the loss rate of the present process was <5%, verifying the protective effect of vacuum microwave drying.
[0106] Oleanolic acid content verification
[0107] Experimental purpose
[0108] To detect the content and uniformity of oleanolic acid in the capsule contents and verify the improvement of ingredient uniformity by nanosuspension technology.
[0109] Experimental method
[0110] Content determination: high performance liquid chromatography (HPLC), quantified according to the characteristic absorption of oleanolic acid at ultraviolet wavelength.
[0111] Sample preparation:
[0112] Take about 0.1 g of capsule contents, place in a 50 mL volumetric flask, add 40 mL of methanol, ultrasonic extraction (power 250 W, frequency 40 kHz) for 30 minutes, cool to room temperature, dilute with methanol, shake well, filter through a 0.45 μm filter membrane, and take the filtrate as the test sample solution.
[0113] HPLC conditions:
[0114] Chromatographic column: C18 column;
[0115] Mobile phase: methanol-water (85:15, v / v), flow rate 1.0 mL / min;
[0116] Detection wavelength: 210 nm;
[0117] Injection volume: 10 μL.
[0118] Standard curve:
[0119] Accurately weigh oleanolic acid reference substance, add methanol to prepare a series of reference substance solutions with concentrations of 0.1 mg / mL, 0.2 mg / mL, 0.5 mg / mL, 1.0 mg / mL and 2.0 mg / mL, inject for determination according to the above conditions, and plot a standard curve with peak area (Y) versus concentration (X, mg / mL).
[0120] Uniformity detection:
[0121] Randomly take 20 capsules from Example 1, Example 2, Example 3 and Comparative Example 1, respectively prepare test sample solutions according to the above method, determine the oleanolic acid content of each capsule, and calculate the labeled content range and relative standard deviation (RSD).
[0122] Table 3 is related data for oleanolic acid content verification
[0123]
[0124]
[0125] The uniformity of oleanolic acid content of the process of the present application is significantly better than that of the traditional process.
[0126] Through the above experimental methods, the significant advantages of the process of the present application in production efficiency, component retention rate and content uniformity can be systematically verified.
[0127] Finally, it should be noted that: the above only describes the preferred embodiments of the present application and is not intended to limit the present application, although the present application has been described in detail with reference to the foregoing embodiments, for those skilled in the art, the technical solutions recorded in the foregoing embodiments can still be modified, or some technical features can be replaced, any modification, equivalent replacement, improvement, etc. within the spirit and principles of the present application should be included in the protection scope of the present application.
Claims
1. A method for preparing liver-enhancing capsules, characterized in that: Includes the following steps: S1: Premixing and pulverizing: Oleanolic acid and stabilizer are mixed in an equal-incremental manner inside a three-dimensional mixer, and then pulverized using a supersonic airflow pulverizer. S2: Preparation of oleanolic acid nano-suspension: Add Schisandra chinensis extract and Acanthopanax senticosus extract to the pulverized material, transfer to a premix tank, and stir at 150-200 rpm for 10-15 min to form a coarse suspension; process the coarse suspension with a high-pressure homogenizer to obtain a nano-suspension with a particle size of 260-290 nm. S3: Three-stage equal-volume incremental mixing: Using the equal-volume incremental method, oleanolic acid nano suspension is mixed with Schisandra chinensis extract and Acanthopanax senticosus extract to form the material; S4: Vacuum microwave drying: Spread the material evenly in the microwave drying tray, and set the parameters of the vacuum microwave drying oven: temperature 30~45℃, vacuum degree -0.05~-0.08MPa, time 20~35min; S5: Post-processing: Grind into 80-mesh fine powder, add lubricant and mix well, then fill into capsules.
2. The method for preparing a liver-enhancing capsule according to claim 1, characterized in that: The stabilizer is a complex of starch and calcium carbonate in a mass ratio of 2:
5.
3. The method for preparing a liver-enhancing capsule according to claim 1, characterized in that: The mixing speed in step S1 is 15-30 rpm, and the mixing time is 25-35 min.
4. The method for preparing a liver-enhancing capsule according to claim 1, characterized in that: The pressure of the high-pressure homogenizer is controlled at 800-1500 bar, and the homogenization is repeated 6-9 times.
5. The method for preparing a liver-enhancing capsule according to claim 1, characterized in that: In step S1, nitrogen gas at -5 to -10°C is introduced for protection during the mixing process.
6. The method for preparing a liver-enhancing capsule according to claim 1, characterized in that: The specific operation steps in step S3 are as follows: First stage: Mix 10% oleanolic acid nano suspension with 10% Schisandra chinensis extract and Acanthopanax senticosus extract in a double planetary mixer for 5 minutes; Second stage: Add 20% oleanolic acid nano suspension, 20% Schisandra chinensis extract and Acanthopanax senticosus extract each time, mix for 3 minutes each time, until completely mixed; Third stage: Vacuum degassing for 5 minutes to eliminate air bubbles introduced during the mixing process.
7. The method for preparing a liver-enhancing capsule according to claim 1, characterized in that: The lubricant is a compound of talc and magnesium stearate in a mass ratio of 1:1.