Japanese cayratia herb formula granules and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine formula granules, and relates to cayratia japonica formula granules and a preparation method thereof. The preparation method comprises the following steps: adding Japanese cayratia herb decoction pieces into purified water, soaking, decocting and extracting twice, merging the first extraction filtrate and the second extraction filtrate, concentrating, drying and granulating to obtain the Japanese cayratia herb formula granules. The preparation method provided by the invention can effectively extract cayratia japonica, can ensure the extract yield and product quality, has simple steps and stable quality, and can be suitable for industrial production of pharmaceutical enterprises.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine formula granules, and relates to a formula granule of *Vaccaria segetalis* and its preparation method. Background Technology

[0002] Vaccaria segetalis is a plant belonging to the genus Vaccaria of the family Vitaceae. Cayratia japonica The whole herb of *Thunb.) Gagnep., also known as Five-Clawed Dragon Grass, Five-Leaf Vine, Five Dragon Grass, and Crow's Eye Vine, is bitter and sour in taste, and cold in nature. It enters the heart, liver, and stomach meridians, and has the effects of clearing heat and dampness, detoxifying, and reducing swelling. It has varying degrees of inhibitory effects on pathogenic bacteria such as *Escherichia coli*, *Shigella*, *Deptococcus pneumoniae*, *Haemophilus influenzae*, hemolytic Staphylococcus, and hemolytic Streptococcus. Clinically, it is often used for carbuncles, boils, snake and insect bites, rheumatic pain, jaundice, and diarrhea.

[0003] Traditional use of *Caulis Amaranthus chinensis* (a type of medicinal herb) presents numerous inconveniences, such as difficulty in accurately controlling dosage and cumbersome decoction processes. Formulated granules, however, are a novel type of traditional Chinese medicine preparation. They can be packaged in small doses for multiple administrations, improving patient compliance. Pediatric patients can adjust the taste of the granules (e.g., by adding flavoring agents) to overcome feeding difficulties, and the formulation of complex prescriptions can be flexibly adapted: personalized prescriptions with "one prescription, one dosage" can be achieved through the free combination of single-herb granules. According to the "Technical Requirements for Quality Control and Standard Formulation of Traditional Chinese Medicine Formulated Granules," these granules are made from traditional Chinese medicinal herbs that meet processing standards. They are produced through processes such as water extraction and separation, concentration and drying, formulation and molding, resulting in a new type of formulated medicine with uniform specifications, dosage, and quality standards. This process preserves the characteristics of the original Chinese medicinal herbs, meets the needs of clinicians for syndrome differentiation and treatment, and allows for adjustments based on symptoms. The granules are potent and highly effective, while also offering advantages such as no need for decoction, direct administration, small dosage, definite efficacy, and convenient carrying and storage, thus meeting the practical needs of patients. However, the amount of water used for decocting the granules, the decoction time, and the concentration and drying temperatures and times all significantly affect the yield and content of the extract, thus impacting the accuracy of the dosage. Therefore, developing a method for preparing *Cynanchum paniculatum* granules that is easy to carry, convenient to take, and provides accurate dosage has significant clinical implications and application prospects. Summary of the Invention

[0004] To address the aforementioned deficiencies, this invention provides a formula granule for *Vaccaria segetalis* and its preparation method. This formula granule has a high content of effective ingredients and good product quality.

[0005] The purpose of this invention is to provide a method for preparing *Vaccaria segetalis* formula granules. The preparation method includes: taking *Vaccaria segetalis* slices and adding them to purified water, soaking them, and then extracting them by decoction twice. The first and second extraction filtrates are combined, concentrated, dried, and granulated to obtain *Vaccaria segetalis* formula granules. During the two decoction processes, the amount of purified water used in the first decoction was 7 to 9 times the weight of the *Vaccaria segetalis* slices, and the amount of purified water used in the second decoction was 6 to 8 times the weight of the *Vaccaria segetalis* slices.

[0006] Preferably, in the above technical solution, the first decoction time is 45-120 minutes, and the second decoction time is 45-90 minutes.

[0007] Preferably, in the above technical solution, before preparing the *Ulva scutellariae* formula granules, the *Ulva scutellariae* medicinal material is first cleaned of impurities, slightly moistened, cut into shorter pieces, dried, and sieved to remove ash and debris, and then made into *Ulva scutellariae* slices; the *Ulva scutellariae* slices are soaked for 30±min before decoction. The length of the cut medicinal material has clear industry standards, mainly based on the *Chinese Pharmacopoeia* and the General Rules for Processing Traditional Chinese Medicine, combined with the properties of the medicinal material and clinical needs. *Ulva scutellariae* is a whole herb. Specifically, in this invention, the cut length is 2cm to 4cm.

[0008] Preferably, in the above technical solution, the steam pressure is controlled between 0.10 MPa and 0.25 MPa during the two boiling processes.

[0009] Specifically, in the above technical solution, the preparation method includes the following specific steps: S1. Take a certain amount of sliced ​​black mulberry and put it into the extraction tank. Add purified water and soak for 30 minutes. Then turn on the steam heating switch to carry out the first decoction. Filter to obtain the first filtrate and the first residue. S2. Put the first filter residue back into the extraction tank, add purified water, turn on the steam heating switch, and carry out a second decoction. Filter to obtain the second filtrate. S3. Combine the first and second filtrates, then concentrate, dry, pulverize and sieve, mix and granulate to obtain the purslane formula granules.

[0010] Preferably, in the above technical solution S3, the concentration temperature is 65℃~80℃, and the relative density of the concentrated paste is 1.05~1.12 (measured at 65℃).

[0011] Preferably, in the above technical solution S3, the spray drying parameters are as follows: liquid preheating temperature: 95℃~100℃, and holding time not less than 10 minutes; spray tower inlet air temperature: 165℃~185℃; spray tower outlet air temperature: 80℃~100℃; spray tower atomizer frequency: 40Hz~50Hz; screw pump frequency: 10Hz~25Hz.

[0012] Further, the extract is added to the mixing tank, a calculated amount of pharmaceutical dextrin is added, and the mixture is stirred evenly to obtain dried mulberry extract powder.

[0013] Preferably, in the above technical solution S3, the above-mentioned dried berry extract powder is crushed and sieved through an 80-mesh sieve. The fine powder after crushing and sieving is placed in a clean container, sealed, and weighed to obtain the sieved dried berry extract powder.

[0014] Preferably, in the above technical solution, the total mixing involves passing the dried extract powder of *Cymbidium goeringii*, pharmaceutical dextrin, silica, and magnesium stearate through an 80-mesh sieve, adding silica and magnesium stearate in a ratio of dried extract powder of *Cymbidium goeringii*: silica: magnesium stearate = 1:0.2%:0.3%, and finally adding the calculated amount of pharmaceutical dextrin (amount of pharmaceutical dextrin = total amount of granules produced - amount of silica used - amount of magnesium stearate used - amount of dried extract powder of *Cymbidium goeringii*). The total mixing time is set to 20 minutes, and the mixer is started for total mixing. After the total mixing time is completed, the material is discharged according to the equipment operation. The mixed material is placed in a clean container, sealed with a lid, weighed, and labeled.

[0015] Preferably, in the above technical solution S3, the granulation is carried out by dry granulation, and the excipients used are pharmaceutical dextrin, silica, and magnesium stearate. Specifically, each 1g of formulation granules is equivalent to 2.5g of medicinal slices. Therefore, the calculation method for excipients is: pharmaceutical dextrin = (amount of medicinal slices × 1000 / 2500 - amount of clear extract × solid content of clear extract) × 95%.

[0016] Specifically, a dry granulator (perforated plate aperture 1.18mm~1.70mm) is used for granulation. The dry granulator parameters are set as follows: cylinder pressure 3MPa~22MPa, feeding motor frequency 40r / min~230r / min, roller motor frequency 10r / min~40r / min. The compressed air valve is opened, and the vacuum feeder is started. The mixed material is added to the hopper, and granulation begins. The granules produced by dry granulation are transferred to a circular vibrating screen for sizing via the vacuum feeder. The upper screen mesh is 14~16 mesh, and the lower screen mesh is 30~40 mesh. Coarse granules are returned to the dry granulator for sizing, while fine powder is returned to the granulator hopper for further granulation. The qualified granules (the sum of those that cannot pass through sieve No. 1 and those that can pass through sieve No. 5 should not exceed 8%) are collected in a clean container and sealed to obtain the *Ulanberry* formula granules.

[0017] Preferably, in the above technical solution, the yield of the processed scutellaria barbata is 23.6% to 31.8%, and the carotene content transfer rate is 66.1% to 79.4%.

[0018] The present invention also provides a granulated formula of *Vaccaria segetalis* prepared by the above preparation method, wherein the granulated formula of *Vaccaria segetalis* contains 1.19 mg / g to 1.43 mg / g of carotene.

[0019] Advantages compared to existing technologies: This invention optimizes the process by studying the ratio of raw materials (such as *Vaccaria segetalis* and purified water), the extraction time and pressure for the first and second extractions, and so on. This allows for the effective extraction of carotene from *Vaccaria segetalis*, while ensuring the yield of extract and effectively improving the extraction efficiency and transfer rate of carotene.

[0020] The preparation method of the present invention can efficiently extract the effective components from the berries of the plant, and can ensure the yield and product quality; that is, the effective components will not be insufficiently extracted due to short extraction time, nor will the heat-sensitive components be lost due to excessive extraction time. The preparation method is simple in steps, has stable quality, and is suitable for industrial production in pharmaceutical companies. Detailed Implementation

[0021] The above-described technical features of the present invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. However, the present invention is not limited to these embodiments, nor are these embodiments limited in any way.

[0022] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the formulations involved in the following examples are all commercially available products that can be purchased from the market.

[0023] The present invention will be further described in detail below with reference to embodiments: Example 1 A method for preparing *Vaccaria segetalis* formula granules, the specific preparation process includes the following steps: S1. First decoction: Put 10kg of dried black berry slices into the extraction tank, tighten the inlet cap of the extraction tank, and add 80kg of purified water through the water inlet; after soaking for 30 minutes, turn on the steam heating switch, start timing when it boils, control the steam pressure at 0.10MPa, boil for 60 minutes, and then filter the decoction through a 200-300 mesh filter to obtain the first filtrate.

[0024] S2. Second decoction: Put the first filter residue into the extraction tank, tighten the feed port cover, add 70kg of purified water, start timing when it boils, control the steam pressure at 0.10MPa, boil for 60 minutes, and then filter the decoction through 200-300 mesh to obtain the second filtrate.

[0025] S3. Concentration: Combine the first and second filtrates and concentrate them in a double-effect concentrator at a temperature of 65°C, a steam pressure of 0.03 MPa, a first-effect vacuum of -0.06 MPa, and a second-effect vacuum of -0.07 MPa. Concentrate until the relative density of the clear paste is 1.12. The yield of the clear paste is calculated to be 27.4% by measuring the solid content of the clear paste.

[0026] S4. The drying method adopted is spray drying: Add the above-mentioned clear extract to the mixing tank, add 1.197 kg of pharmaceutical dextrin, stir evenly, and carry out spray drying (spray drying parameters are: preheating temperature of the drug solution: 97℃, holding time: 10 minutes; inlet air temperature of the spray tower: 165℃; outlet air temperature of the spray tower: 80℃; atomizer frequency of the spray tower: 45 Hz; screw pump frequency: 15 Hz) to obtain dried extract powder of *Vaccaria segetalis*.

[0027] S5. Crushing and sieving: Crush the dried berry extract powder from S4 and sieve it through an 80-mesh sieve. Place the fine powder after crushing and sieving in a clean container, seal it, and weigh it to obtain 3.931 kg of dried berry extract powder after sieving.

[0028] S6. Final Mixing: Pass pharmaceutical dextrin, silica, and magnesium stearate through an 80-mesh sieve. Take the dried extract powder of *Cymbidium goeringii*, 8g of silica, 12g of magnesium stearate, and 49g of pharmaceutical dextrin from S5, add them all to the mixer, set the final mixing time to 20 minutes, start the mixer to perform final mixing, and after the final mixing time is completed, discharge the material according to the equipment operation. Place the final mixed material in a clean container and seal it with a lid.

[0029] S7. Dry granulation machine for granulation: Set the dry granulation machine parameters: perforated plate aperture 1.30mm, hydraulic cylinder pressure 12MPa, feeding motor frequency 100r / min, roller motor frequency 20r / min. Open the compressed air valve, start the vacuum feeder, add the mixed material into the hopper, and start granulation. Transfer the dry granules to a circular vibrating screen for granulation via the vacuum feeder. The upper screen of the circular vibrating screen is 15 mesh, and the lower screen is 30 mesh. Coarse particles are returned to the dry granulation machine for granulation, and fine powder is returned to the granulation machine hopper for granulation again. The qualified particles (the sum of those that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve should not exceed 8%) are placed in a clean container and sealed to obtain the *Ulanibrio pilosa* formula granules (marked code W1, each 1g of granules is equivalent to 2.5g of *Ulanibrio pilosa* slices), in which the content of carotene is 1.43mg / g.

[0030] The extraction yield of the extract from *Vaccaria segetalis* in this embodiment was 27.4%, and the transfer rate of carotene content was 79.4%.

[0031] Examples 2 to 5 Examples 2 to 5 are methods for preparing *Vaccaria segetalis* formula granules. Their steps are basically the same as those in Example 1, except that the amount of purified water used during decoction, the decoction time, the concentration temperature, and other process parameters are different. For details, please refer to Table 1.

[0032] Table 1. Process parameters and results in Examples 2-5

[0033] Comparative Example 1 A method for preparing *Vaccaria segetalis* formula granules differs from Example 1 in the number of decoctions. This comparative example involves only one decoction: 10 kg of *Vaccaria segetalis* slices are placed in an extraction tank, soaked in 150 kg of purified water for 30 minutes, and then heated to boiling. The steam pressure is controlled at 0.10 MPa. After boiling for 30 minutes, the decoction is filtered through a 200-300 mesh filter to obtain the filtrate. The remaining parameters S3-S7 are the same as those in Example 1.

[0034] Comparative Example 2 A method for preparing *Vaccaria segetalis* formula granules differs from Example 1 in the number of decoctions. This comparative example involves only one decoction: 10 kg of *Vaccaria segetalis* slices are placed in an extraction tank, soaked in 150 kg of purified water for 30 minutes, and then heated to boiling. The steam pressure is controlled at 0.10 MPa. After boiling for 60 minutes, the decoction is filtered through a 200-300 mesh filter to obtain the filtrate. The remaining parameters S3-S7 are the same as those in Example 1.

[0035] Comparative Example 3 A method for preparing *Vaccaria segetalis* formula granules differs from Example 1 in the number of decoctions. This comparative example involves only one decoction: 10 kg of *Vaccaria segetalis* slices are placed in an extraction tank, soaked in 150 kg of purified water for 30 minutes, and then heated to boiling. The steam pressure is controlled at 0.10 MPa. After boiling for 120 minutes, the decoction is filtered through a 200-300 mesh filter to obtain the filtrate. The remaining parameters S3-S7 are the same as those in Example 1.

[0036] Comparative Example 4 A method for preparing *Vaccaria segetalis* formula granules differs from Example 1 in that: the amount of purified water used in S1 is 100 kg, and the amount of purified water used in S2 is also 100 kg; all other process parameters are the same as in Example 1.

[0037] Comparative Example 5 A method for preparing *Vaccaria segetalis* formula granules differs from Example 1 in that the soaking time in S1 is changed from 30 min to 120 min.

[0038] Comparative Example 6 A method for preparing *Vaccaria segetalis* granules differs from Example 1 in that the 30-minute soaking time step is omitted in S1, i.e., heating is performed directly without soaking.

[0039] Comparative Example 7 A method for preparing *Vaccaria segetalis* formulation granules differs from Example 1 in that the steam pressure is controlled at 0.25 MPa in S1 and S2.

[0040] Comparative Example 8 A method for preparing *Vaccaria segetalis* formulation granules differs from Example 1 in that, in S1 and S2, timing begins 60 minutes after heating to a slight boil (97°C), and the process is maintained at a slight boil throughout.

[0041] The process parameters and results for Comparative Examples 1 to 8 are shown in Table 2.

[0042] Table 2. Process parameters and results of Comparative Examples 1–8

[0043] The calculation formulas for each data point are as follows: 1. Extract yield (%) = (Total mass of extract × Solid content of extract) ÷ Total mass of medicinal slices × 100% 2. Carotene transfer rate (%) = (Total mass of granules × Carotene content in granules) ÷ Carotene content in medicinal materials × 100% 3. Method for determining the content of carotene: Determined by high performance liquid chromatography (2025 edition of Chinese Pharmacopoeia, Part IV, General Chapter 0512): Chromatographic conditions and system suitability test: A C18 reversed-phase column (250 mm × 4.6 mm, 5 μm) was used, with acetonitrile-water-phosphoric acid (85:15:0.1) as the mobile phase, the detection wavelength was 210 nm, and the theoretical plate number calculated based on the daunoside peak should not be less than 3000.

[0044] Preparation of reference solution: Take an appropriate amount of daucosterol reference standard, accurately weigh it, and add methanol to prepare a solution containing 20 μg per 1 mL.

[0045] Preparation of the test solution: Grind the granules of *Cymbidium goeringii* into a fine powder, weigh approximately 0.4 g, place it in a stoppered conical flask, add 25 mL of methanol, seal tightly, weigh, sonicate (150 W, 40 kHz) for 30 min, cool, weigh again, replenish the lost weight with methanol, shake well, filter, and collect the filtrate to obtain the test solution.

[0046] Determination method: Accurately measure 10 μL of the reference solution and the test solution respectively, inject them into the liquid chromatograph, and determine the result.

[0047] in conclusion: As shown in Tables 1 and 2, the number of decoctions, time, temperature, and water ratio of *Vaccaria segetalis* significantly affect the quality of the *Vaccaria segetalis* formulation granules. Data from Example 1 and Comparative Examples 1-3 show that two decoctions significantly increased the extract yield and carotene transfer rate compared to one decoction. The decoction times for Comparative Examples 1-3 were 30, 60, and 120 minutes, respectively. These results indicate that the extract yield and carotene transfer rate were low at a decoction time of 30 minutes. While the extract yield increased at a decoction time of 120 minutes, the carotene transfer rate was slightly lower than that at 60 minutes, suggesting that a 120-minute decoction resulted in the loss of some active ingredients. Data from Example 1 and Comparative Example 4 show that increasing the amount of purified water added in the first and second decoctions, while keeping other conditions unchanged, slightly increased the extract yield, but the carotene transfer rates remained essentially the same, indicating that the amount of purified water used in Example 1 was sufficient for extracting the active ingredients. Data from Example 1 and Comparative Example 5 show that increasing the soaking time from 30 min to 120 min did not significantly change the transfer rate of carotene. Data from Example 1 and Comparative Example 6 show that the transfer rate of carotene obtained without soaking was 3.1% lower than that obtained after 30 min of soaking and subsequent decoction, indicating that the extraction efficiency was reduced without soaking. Data from Example 1 and Comparative Example 7 show that increasing the steam pressure of the first and second decoctions from 0.10 MPa (approximately 1 atmosphere) to 0.25 MPa (approximately 2.5 atmospheres), i.e., increasing the boiling water temperature from 100℃ to 127℃, although the yield of extract increased, the transfer rate of carotene remained the same, indicating that increasing the boiling temperature to a certain extent does not lead to a reduction in the main components. Data from Example 1 and Comparative Example 8 show that if the extraction temperature was changed from boiling (100℃) to simmering (95℃~99℃) in both cases, the yield of extract and the transfer rate of carotene obtained in Comparative Example 8 both decreased, indicating that simmering did not achieve complete extraction of the effective components.

[0048] In summary, by optimizing the preparation process, including the amount of water used for decoction, decoction time, pressure, and whether or not to soak, this invention can effectively improve the extraction efficiency and transfer rate of active ingredients, ensuring the yield of extract and product quality. The preparation method is simple, has stable quality, and is suitable for industrial production in pharmaceutical companies.

[0049] Finally, it should be emphasized that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing *Vaccaria segetalis* formula granules, characterized in that, The preparation method includes: taking slices of *Vaccaria segetalis* and adding them to purified water, soaking them, and then extracting them by decoction twice. The first and second extract filtrates are combined, concentrated, dried, and granulated to obtain *Vaccaria segetalis* formula granules. During the two decoction processes, the amount of purified water used in the first decoction was 7 to 9 times the weight of the *Vaccaria segetalis* slices, and the amount of purified water used in the second decoction was 6 to 8 times the weight of the *Vaccaria segetalis* slices.

2. The method for preparing *Vaccaria segetalis* formula granules according to claim 1, characterized in that, The first decoction time is 45 min to 120 min, and the second decoction time is 45 min to 90 min.

3. The method for preparing *Vaccaria segetalis* formula granules according to claim 1, characterized in that, Before preparing the formula granules of *Vaccaria segetalis*, the *Vaccaria segetalis* medicinal material is first removed of impurities, slightly moistened, cut into short pieces, dried, and sieved to remove dust before being made into *Vaccaria segetalis* slices; the *Vaccaria segetalis* slices are soaked for 30±5 minutes before decoction.

4. The method for preparing *Vaccaria segetalis* formula granules according to claim 1, characterized in that, During both boiling processes, the steam pressure should be controlled between 0.10 MPa and 0.25 MPa.

5. A method for preparing *Vaccaria segetalis* formula granules according to any one of claims 1-4, characterized in that, The preparation method includes the following specific steps: S1. Take a certain amount of black berry slices and put them into the extraction tank. Add purified water, soak for 30 minutes, turn on the steam heating switch, and carry out the first decoction. Filter to obtain the first filtrate and the first residue. S2. Put the first filter residue back into the extraction tank, add purified water, turn on the steam heating switch, and carry out a second decoction. Filter to obtain the second filtrate. S3. Combine the first and second filtrates, then concentrate, dry, pulverize and sieve, mix and granulate to obtain the purslane berry formula granules.

6. The method for preparing *Vaccaria segetalis* formula granules according to claim 5, characterized in that, In S3, the concentration temperature is 65℃~80℃, and the relative density of the concentrated extract is 1.05~1.

12.

7. The method for preparing *Vaccaria segetalis* formula granules according to claim 5, characterized in that, In S3, the spray drying parameters are as follows: liquid preheating temperature: 95℃~100℃, holding time not less than 10 minutes; spray tower inlet air temperature: 165℃~185℃; spray tower outlet air temperature: 80℃~100℃; spray tower atomizer frequency: 40Hz~50Hz; screw pump frequency: 10Hz~25Hz.

8. The method for preparing *Vaccaria segetalis* formula granules according to claim 5, characterized in that, In S3, granulation is performed using a dry granulation method, and the excipients used are pharmaceutical dextrin, silicon dioxide, and magnesium stearate.

9. A method for preparing *Vaccaria segetalis* formula granules according to any one of claims 1-8, characterized in that, The yield of the processed herbal extract from *Vaccaria segetalis* was 23.6%–31.8%, and the transfer rate of carotene content was 66.1%–79.4%.

10. A type of *Vaccaria segetalis* granule prepared by the preparation method according to any one of claims 1-9, characterized in that, The content of carotene in the *Vaccaria segetalis* formula granules is 1.19 mg / g to 1.43 mg / g.

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