Preparation method of asiatic toddalia root formula granules

Abstract

The invention relates to the technical field of traditional Chinese medicinal materials, in particular to a preparation method of asiatic toddalia root formula granules. Based on the quality attribute of an asiatic toddalia root standard decoction, the asiatic toddalia root formula granule extraction process is investigated by utilizing a Box-Behnken response surface method. Meanwhile, the concentration and drying process of the liquid medicine and the dry granulation forming process of the formula granules are investigated through a single-factor experiment, and the preparation process parameters of the asiatic toddalia root formula granules are determined. Therefore, the optimal preparation process of the asiatic toddalia root formula granules is preferably selected, the quality standard of the asiatic toddalia root formula granules is established, scientific guarantee is provided for quality control and industrialization of the asiatic toddalia root formula granules, and certain theoretical support is provided for development and utilization of asiatic toddalia root resources.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a method for preparing a formula granule for treating dragon's palm blood. Background Technology

[0002] Standard decoctions of traditional Chinese medicine (TCM) are single-herb decoctions prepared using standardized processes, guided by TCM theory and based on clinical application, while referencing modern extraction methods. These decoctions are used for standardized clinical medication, ensuring accuracy and dosage consistency. In pharmaceutical research on formulation granules, establishing standard decoctions for representative raw materials, including content, characteristic spectra, and yield ranges, measures the consistency of quantitative transfer in preparation processes and quality control. Standard decoctions serve as the material benchmark throughout the research process, playing a crucial role in the transition from decoction pieces to granules. The "Technical Requirements for Quality Control and Standard Formulation of TCM Formulation Granules" stipulates that "the preparation of TCM formulation granules, except for the molding process, should be basically consistent with traditional decoctions." How to utilize modern processes to improve extraction efficiency without deviating from the fundamental properties of traditional decoctions is a key research direction.

[0003] Toddalia asiatica (L.) Lam., a plant in the Rutaceae family, is the root or root bark of the plant. It is distributed throughout my country south of the Qinling Mountains. First recorded in the Qing Dynasty's *Illustrated Compendium of Plants*, it is a medicinal herb used by the Yao and Zhuang ethnic minorities. In Yao medicine, it is described as bitter, pungent, astringent, and warm; slightly toxic; classified as a "penetrating medicine"; primarily used to dispel wind and dampness, promote blood circulation and remove blood stasis, stop bleeding, and relieve pain. It is used for metrorrhagia (rheumatism, rheumatoid arthritis), traumatic injuries, external bleeding, stomachache, abdominal pain, and hemiplegia. In Zhuang medicine, it is described as spicy, slightly bitter, and warm. It is primarily used to dispel wind and toxins, clear the meridians, remove blood stasis, and stop bleeding; used for arthralgia, lower back pain, stomachache, sprains, various blood disorders, amenorrhea, and dysmenorrhea. In Traditional Chinese Medicine, it is pungent, bitter, and warm in nature. It enters the liver and kidney meridians; it is used for rheumatic pain, stomachache, traumatic injuries, hematemesis, bleeding from cuts, dysmenorrhea, amenorrhea, dysentery, toothache, and malaria. Currently, there is no record of the preparation process for Flying Dragon Palm Blood Formula Granules. Based on this, the present invention aims to provide a method for preparing Flying Dragon Palm Blood Formula Granules. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing Flying Dragon Palm Blood Formula Granules to solve the problems existing in the prior art.

[0005] To achieve the above objectives, the present invention provides the following solution:

[0006] This invention provides a method for preparing Flying Dragon Palm Blood Formula Granules, comprising the following steps:

[0007] The slices of *Pterocarya stenoptera* blood were sequentially soaked, refluxed for extraction, concentrated, and spray-dried to obtain dried *Pterocarya stenoptera* blood extract powder.

[0008] The dried dragon palm blood ointment powder and excipients are mixed and granulated to obtain the dragon palm blood formula granules.

[0009] Optionally, the reflux extraction is performed 1-3 times for a duration of 30-120 minutes.

[0010] Optionally, the reflux extraction is performed once for 65 minutes.

[0011] Optionally, during the soaking process, the amount of water used is 8-12 times the mass of the *Pterocarya scabra* blood-nourishing slices, and the soaking time is 0.5 hours.

[0012] Optionally, during the soaking process, the amount of water used is 12 times the mass of the Flying Dragon Palm Blood Drink slices.

[0013] Optionally, the concentration pressure is 50-200 MPa, and the temperature is 50-90℃; the concentrated density of the resulting drug solution is 1.125-1.25 g / cm³. 3 .

[0014] Optionally, the injection rate of the spray drying is 8-14 mL / min, and the temperature is 160-180℃.

[0015] Optionally, the mass ratio of the dried dragon's paw blood ointment powder to the excipients is 1:(0.8-1).

[0016] Optionally, the granulation roller pressure is 100-120 bar, the feeding speed is 23-25 ​​rpm, and the roller speed is 2.8-4.0 rpm.

[0017] Optionally, the excipients include fillers; the fillers include soluble starch and / or dextrin.

[0018] The present invention discloses the following technical effects:

[0019] This invention, based on the quality properties of the standard decoction of *Pterocarya stenoptera* (a type of medicinal herb), utilizes the Box-Behnken response surface methodology to investigate the extraction process of *Pterocarya stenoptera* formula granules. Simultaneously, single-factor experiments were used to examine the concentration and drying processes of the decoction, as well as the dry granulation process for the formula granules, thus determining the preparation process parameters for *Pterocarya stenoptera* formula granules. Therefore, this invention optimizes the preparation process of *Pterocarya stenoptera* formula granules, establishes quality standards for *Pterocarya stenoptera* formula granules, provides a scientific guarantee for the quality control and industrialization of *Pterocarya stenoptera* formula granules, and also provides theoretical support for the development and utilization of *Pterocarya stenoptera* resources. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 The superimposed chromatograms of 15 batches of Flying Dragon Palm Blood Standard Decoction are shown; among them, peak 5 is hesperidin, peak 6 is cinnamomea oleiferin, and peak 7 is cinnamomea oleifera alkaloid chloride.

[0022] Figure 2 For reference spectrum R; in which peak 5 is hesperidin, peak 6 is tsaozoin, and peak 7 is tsaozoin chloride.

[0023] Figure 3 The chromatogram is for reference standards; peak 5 is hesperidin, peak 6 is zaoyangjianin, and peak 7 is zaoyangjian alkaloid chloride.

[0024] Figure 4 The results of the soaking time study;

[0025] Figure 5 The results of the number of extractions were examined.

[0026] Figure 6 To extract the results of the time-based investigation;

[0027] Figure 7 The results of the water addition ratio investigation;

[0028] Figure 8 A three-dimensional response surface plot showing the interaction between the number of extractions and the extraction time;

[0029] Figure 9 A three-dimensional response surface plot showing the interaction between the number of extractions and the solid-liquid ratio;

[0030] Figure 10 A three-dimensional response surface plot showing the interaction between extraction time and the solid-liquid ratio;

[0031] Figure 11 A contour plot showing the interaction between the number of extractions and the extraction time;

[0032] Figure 12 A contour plot showing the interaction between the number of extractions and the solid-liquid ratio;

[0033] Figure 13 This is a contour plot showing the interaction between extraction time and the material-to-liquid ratio. Detailed Implementation

[0034] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0035] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0036] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0037] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0038] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0039] The "Technical Requirements for Quality Control and Standard Formulation of Traditional Chinese Medicine Formula Granules" requires that "the preparation of traditional Chinese medicine formula granules, except for the molding process, should be basically consistent with traditional decoctions." This indicates that all research on traditional Chinese medicine formula granules, including the determination of process parameters, must be compared with standard decoctions. This shows that standard decoctions play a very important role as a bridge between medicinal slices and formula granules. Stable process parameters are an important factor in restoring the properties of decoctions. Therefore, this invention uses standard decoctions as a benchmark and studies the extraction process of Feilong Palm Blood Formula Granules using the Box-Behnken Design method. At the same time, it uses the single-factor investigation method to determine the process parameters of concentration, drying, and molding processes, and establishes a scientific and stable preparation process for Feilong Palm Blood Formula Granules.

[0040] Example 1

[0041] 1. Materials

[0042] 1.1 Instruments

[0043] The instruments are shown in Table 1.

[0044] Table 1 Experimental Instruments

[0045] name model factory High Performance Liquid Chromatography Agilent Technologies 1260 Infinity II Agilent Technologies ultrasonic cleaner KQ5200B Kunshan Ultrasonic Instruments Co., Ltd. Ultrapure water preparation machine Direct-Q5UV Millipore (China) Co., Ltd. Electronic analytical balance ME204 Mettler Toledo Instruments Ltd. chromatographic column <![CDATA[ZORBA X SB-C 18 ]]> Agilent Technologies Circulating water type multi-purpose vacuum pump SHB-lll Zhengzhou Great Wall Science & Industry Trade Co., Ltd. Infrared oven CW2002-Z Aitemei Electric Appliances (Shenzhen) Co., Ltd. Rotary evaporator N-1300 Shanghai Airong Instrument Co., Ltd. Ceramic decoction pot - Jiangxi Huaguan Ceramics Co., Ltd. Electronic temperature-controlled heating mantle 98-1-B type Tianjin Tester Instruments Co., Ltd. Intelligent static microwave vacuum dryer WBZ-10 type Guizhou Guiyang Xinqi Company spray dryer Mobile minor experimental GEA Niro, Germany freeze dryer 7670570 Beijing Huayi Weiye Technology Co., Ltd. Vacuum drying DZF-6050 Shanghai Hengyi Scientific Instruments Co., Ltd. Dry granulation machine Alexanderwerk-BT 120 Alexanderwerk, Germany oscillating pellet mill YK100 type Fuzhou Famoyou Machinery Technology Co., Ltd.

[0046] 1.2 Materials

[0047] The test drugs are shown in Table 2.

[0048] Table 2 Experimental reagents

[0049] name model factory hesperidin TXD025-220318 The content is 97.20% (China Food and Drug Testing Institute). Hairy two-sided needle MUST-19022504 Content ≥98.00% (determined by area normalization method) Shanghai Ronghe Pharmaceutical Technology Development Co., Ltd. Chlorinated neem base MUST-190034625 The content is 91.00% (China Food and Drug Inspection Institute). Acetonitrile 20211206 Thermo Fisher Scientific (China) Co., Ltd. Phosphoric acid 20220103 Xilong Scientific Co., Ltd. methanol 20211206 Thermo Fisher Scientific (China) Co., Ltd. dextrin 190302 Hanzhong Qinfa Dextrin Co., Ltd. Soluble starch 20190102 Xilong Chemical Co., Ltd. sucrose 181902 Nanning Guizhilong Pharmaceutical Excipients Co., Ltd. Anhydrous lactose 20230201 Shaanxi Zhengyi Pharmaceutical Excipients Co., Ltd.

[0050] 1.3 Medicinal Materials

[0051] The experimental medicinal samples of *Toddalia asiatica* (L.) Lam. (numbered S1-S15) were identified by Zhu Yilin, a senior experimentalist at the Department of Medicinal Plants, Guangxi University of Traditional Chinese Medicine, as the roots of *Toddalia asiatica* (L.) Lam., a plant of the Rutaceae family. The sources of the 15 batches of *Toddalia asiatica* medicinal slices are shown in Table 3.

[0052] Table 3. Sources of blood samples from *Pterocarya stenoptera*.

[0053] Medicinal herb sample number Medicinal herb number source S1 20230902 Pingguo County, Baise, Guangxi S2 20210603 Nanning City, Guangxi S3 20220703 Nanxiao Town, Nanning, Guangxi S4 20211101 Guangxi Xianzhu Pharmaceutical S5 20220704 Guangxi Nanning Baiji S6 20230903 Nanning City, Guangxi S7 20230903 Pingguo County, Baise, Guangxi S8 20230303 Napo County, Baise, Guangxi S9 20230306 Long'an County, Nanning, Guangxi S10 20230302 Napo County, Baise, Guangxi S11 20230301 Napo County, Baise, Guangxi S12 20230906 Jingxi City, Baise, Guangxi S13 20230304 Long'an County, Nanning, Guangxi S14 20230904 Nanning City, Guangxi S15 20230905 Jingxi City, Baise, Guangxi

[0054] The slices of *Toddalia asiatica* were purchased from Guangxi Xianzhu Traditional Chinese Medicine Technology Co., Ltd. and Guangxi Huatai Pharmaceutical Co., Ltd. (batch numbers: 20211101, 20220105). They were identified by Zhu Yilin, Senior Experimentalist of the Department of Medicinal Plants at Guangxi University of Traditional Chinese Medicine, as the root of *Toddalia asiatica* (L.) Lam., a plant in the Rutaceae family.

[0055] 2. Methods and Results

[0056] 2.1 Study on Extraction Process of Flying Dragon Palm Blood Formula Granules Based on Benchmark Correlation

[0057] 2.1.1 Content Determination Study

[0058] 2.1.1.1 Chromatographic conditions

[0059] The chromatographic conditions are shown in Table 4.

[0060] Table 4 Chromatographic conditions

[0061]

[0062] 2.1.12 Preparation of Standard Decoction

[0063] A standard decoction was prepared from 15 representative batches of *Pterocarya stenoptera* (a type of medicinal herb) samples from the main producing areas of the authentic producing region, using the following method:

[0064] Take 100g of the experimental herbal sample of *Pterocarya stenoptera* (a type of herb), place it in a clay pot, add water and decoct twice. For the first decoction, add 9 times the amount of water, soak for 30 minutes, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter the decoction through a 100-mesh sieve while hot. For the second decoction, add 8 times the amount of water, bring to a boil over high heat, then simmer over low heat for 20 minutes. Filter and combine the two decoctions to obtain the final product.

[0065] Subsequently, the obtained standard decoction was concentrated to 100 mL under reduced pressure and then freeze-dried in an evaporating dish to obtain freeze-dried powder of the Flying Dragon Palm Blood Standard Decoction.

[0066] 2.1.1.3 Preparation of test solution

[0067] Take 0.1g of freeze-dried powder of Flying Dragon Palm Blood Standard Decoction, accurately weigh it, place it in an Erlenmeyer flask, add 10mL of methanol, weigh it, sonicate for 20min (40KHZ, 220W), cool and weigh it, filter it through a 0.22μm microporous membrane to obtain the final product.

[0068] 2.1.1.4 Preparation of test solution

[0069] Take 0.1g of the experimental medicinal material sample (S4) of Flying Dragon Palm Blood, weigh it accurately, place it in an Erlenmeyer flask, add 20mL of methanol, weigh it, sonicate for 30min (40KHZ, 220W), cool and weigh it, filter it through a 0.22μm microporous membrane to obtain the final product.

[0070] 2.1.1.5 Determination of Ointment Yield

[0071] The standard decoction of *Pterocarya stenoptera* blood was obtained according to section "2.1.1.2". It was concentrated to a final volume of 1000 mL, and 25 mL was precisely pipetted into a constant-weight evaporating dish. The solution was evaporated to dryness in a water bath, dried at 105℃ for 3 hours, and then cooled in a desiccator for 30 minutes before being quickly weighed. The yield was calculated. The formula for the yield is: Yield = Dry extract weight × 1000 / Weight of medicinal slices × 25 × 100%.

[0072] 2.1.1.6 Preparation of reference solution

[0073] Accurately weigh appropriate amounts of hesperidin reference standard, sesquiterpenoid reference standard, and sesquiterpenoid chloride reference standard, place them in a 10 mL volumetric flask, add methanol to dilute to volume, and prepare a mixed reference standard solution with concentrations of 0.905 mg / mL for hesperidin, sesquiterpenoid, and sesquiterpenoid chloride, respectively.

[0074] 2.1.1.7 Plotting Standard Curves

[0075] The mixed reference solution from section "2.1.1.6" was taken and diluted to different concentrations according to the specified ratio. The solutions were then injected and determined under the chromatographic conditions described in "2.1.1.1". The reference solution content (μg) and peak area (A) were plotted as the x-axis (X) and y-axis (Y), respectively, for linear regression calculation. The results showed that hesperidin exhibited good linearity in the content range of 0.2173–9.0500 μg, with the regression equation being Y = 1792.2790X + 44.5531, r 2 =0.9999; Zanthoxylum bungeanum showed good linearity in the content range of 0.2154-8.9700 μg, with the linear regression equation being Y = 1370.1256X + 13.9286, r 2 =0.9999; the linear relationship of chlorinated thorn alkali is good in the content range of 0.0168-0.6980 μg, and the regression equation is Y = 6419.1979X - 18.9034, r 2 =0.9999.

[0076] 2.1.1.8 Precision Test

[0077] Take the mixed reference solution from section "2.1.1.6", inject it according to the chromatographic conditions in "2.1.1.1", inject it 6 times consecutively, record the peak area, and calculate the RSD. Results: The RSDs of the peak areas of hesperidin, taurenin, and chlorothalonil were 0.36%, 0.34%, and 0.26%, respectively, indicating that the instrument precision was good.

[0078] 2.1.1.9 Stability Test

[0079] The lyophilized powder (S4) of the *Pterocarya stenoptera* blood-nourishing decoction was prepared according to the method described in section "2.1.1.3". The chromatographic conditions described in section "2.1.1" were then followed, and the peak areas at 0, 2, 4, 8, 12, and 24 hours were recorded. The RSDs were calculated. Results: The RSDs of the peak areas for the three components were 0.53%, 0.52%, and 0.65%, respectively, indicating good stability of the sample within 24 hours.

[0080] 2.1.1.10 Repeatability Test

[0081] Six test solutions were prepared from the same batch of lyophilized *Pterocarya stenoptera* blood standard decoction powder (S4) according to the method described in section "2.1.1.3". The chromatographic conditions were followed as described in section "2.1.1.1", peak areas were recorded, and the contents of hesperidin, taurenin, and taurenin chloride were calculated. The RSDs were also calculated. Results: The RSDs for the three components were 0.51%, 0.38%, and 0.63%, respectively, indicating good reproducibility of the method.

[0082] 2.1.1.11 Spiking Recovery Test

[0083] Nine portions of 0.05g of lyophilized *Pterocarya stenoptera* blood standard decoction powder (S4) were taken and prepared into test solutions according to the method described in section "2.1.1.3" at a ratio of 1:0.5, 1:1, and 1:1.5 of sample content to reference content. The solutions were then analyzed under the conditions described in section "2.1.1.1". Peak areas were recorded, recoveries were calculated, and RSDs were calculated. Results: The average recoveries of hesperidin, taurenin, and taurenin chloride were 99.36%, 100.00%, and 96.5%, respectively, with RSDs of 0.86%, 1.23%, and 1.01%, respectively. The recoveries were within the acceptable range, indicating that the method is accurate.

[0084] 2.1.1.12 Determination of the main component content of the Flying Dragon Palm Blood Standard Decoction

[0085] Fifteen batches of *Pteris vittata* (a type of medicinal herb) from different origins were collected (Table 3). Standard decoctions were prepared according to the method in section "2.1.1.2", test solutions were prepared according to the method in section "2.1.1.3", and test solutions of *Pteris vittata* slices were prepared according to the method in section "2.1.1.4". The content was determined according to the chromatographic conditions in section "2.1.1.1", and the content and content transfer rate were calculated. The formula for calculating the content transfer rate is: Content transfer rate = Content of components in standard *Pteris vittata* decoction / Content of components in *Pteris vittata* slices × 100%. Based on the "Technical Requirements for Quality Control and Standard Formulation of Traditional Chinese Medicine Formula Granules", the range of standard decoction content, content transfer rate, and extract yield was established using the mean ± 3SD. The results showed that the concentrations of hesperidin, zeaxanthin, and zeaxanthin chloride ranged from 0.850 to 3.829 mg / g, 3.612 to 10.251 mg / g, and 0.087 to 0.335 mg / g, respectively; the content transfer rates ranged from 7.478 to 41.458%, 32.927 to 93.989%, and 3.235 to 17.392%, respectively; and the extract yield ranged from 7.241 to 14.466%.

[0086] 2.1.2 Characteristic Spectrum Study

[0087] 2.1.2.1 Preparation of Standard Decoction

[0088] The same standard decoction preparation as described in section "2.1.1.2" of this embodiment.

[0089] 2.1.2.2 Preparation of test solution

[0090] The test solution is prepared in accordance with the method described in section "2.1.1.3" of this embodiment.

[0091] 2.1.2.3 Preparation of reference solution

[0092] The preparation of the reference solution is the same as that described in section "2.1.1.6" of this embodiment.

[0093] 2.1.2.4 Chromatographic conditions

[0094] The chromatographic conditions are shown in Table 5.

[0095] Table 5 Chromatographic conditions

[0096]

[0097] 2.1.2.3 Precision Test

[0098] Prepare the test solution according to the method described in section "2.1.2.3". Accurately pipette the test solution and inject it six times consecutively under the chromatographic conditions described in section "2.1.2.4". Using peak 6 (Zanthoxylum nitidum) as the reference peak, calculate the relative retention time, relative peak area, and RSD of each common peak. The results show that the RSD of the relative retention time of the eight characteristic peaks is <0.79%, and the RSD of the relative peak area is <2.82%, indicating good instrument precision.

[0099] 2.1.2.6 Stability Test

[0100] The test solution was prepared according to the method described in section "2.1.2.3". The test solution was accurately pipetted and injected at 0, 2, 4, 8, 12, and 24 hours under the chromatographic conditions described in section "2.1.2.4". Peak 6 (Zanthoxylum nitidum) was used as the reference peak, and the relative retention time, relative peak area, and RSD of each characteristic peak were calculated. The results showed that the RSD of the relative retention time of the eight characteristic peaks was <1.31%, and the RSD of the relative peak area was <2.49%, indicating that the sample had good stability within 24 hours.

[0101] 2.1.2.7 Repeatability Test

[0102] Six test solutions were prepared in parallel according to the method described in section "2.1.2.3". The test solutions were accurately pipetted and injected for analysis under the chromatographic conditions described in section "2.1.2.4". Peak 6 (Zanthoxylum bungeanum) was used as the reference peak, and the relative retention time, relative peak area, and RSD of each characteristic peak were calculated. The results showed that the RSD of the relative retention time of the eight characteristic peaks was <0.76%, and the RSD of the relative peak area was <1.97%, indicating that the method has good repeatability.

[0103] 2.1.2.8 Establishment of the Blood Feature Atlas of the Flying Dragon Palm

[0104] Fifteen batches of lyophilized powder of *Pterocarya stenoptera* blood standard decoction from different origins were prepared according to the method in section "2.1.2.2". Test solutions were prepared according to the method in section "2.1.2.3" and analyzed under the chromatographic conditions in section "2.1.2.4". The obtained chromatograms were imported into the *Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System (Version 2012.1)* in AIA format. S4 was set as the reference chromatogram R. The median method was used, with a time window of 0.1 s. After multi-point correction and Mark peak matching, superimposed chromatograms of the 15 batches of *Pterocarya stenoptera* blood standard decoction from different origins were obtained. A total of eight characteristic peaks were identified, and three of them were identified: peak 5 (hesperidin), peak 6 (zanthoxylum bungeanum), and peak 7 (zanthoxylum bungeanum alkaloid chloride). A control chromatogram R was generated, and the results are as follows. Figures 1-3 As shown.

[0105] 2.1.2.9 Similarity Analysis of Characteristic Spectra of Flying Dragon Palm Blood Decoction

[0106] Similarity calculations were performed on the superimposed chromatograms of 15 batches of *Pterocarya stenoptera* blood samples. Compared with the control chromatogram R, the similarity was between 0.991 and 0.999.

[0107] 2.1.3 Single-factor analysis

[0108] 2.1.3.1 Investigation of soaking time

[0109] Weigh 100g of each of four slices of *Pterocarya stenoptera* (a type of herb) into a round-bottom flask, add 10 times the amount of water, and soak for 0.5h, 1h, 1.5h, and 2h respectively. Heat under reflux for 1h, extract once, filter through a 100-mesh screen, concentrate under reduced pressure, and freeze-dry to obtain a lyophilized powder. Determine the content of three components according to the conditions in section "2.1.1.1". The results are shown in Table 6. Figure 4 Different soaking times have virtually no effect on the extraction efficiency of the indicator components; therefore, 0.5 hours of soaking was chosen as the soaking time.

[0110] Table 6 Results of Soaking Time Examination

[0111] Soaking time (h) hesperidin mg / g Zanthoxylum bungeanum mg / g Calcium chloride mg / g 0.5h 2.202 5.924 0.237 1h 2.077 5.869 0.212 1.5h 2.156 5.693 0.216 2h 2.301 5.919 0.222

[0112] 2.1.3.2 Examination of the number of extractions

[0113] Weigh 100g of each of the three slices of *Pterocarya stenoptera* (a type of herb) into a round-bottom flask, add 10 times the amount of water, soak for 0.5h, heat under reflux for 1h, and extract 1, 2, and 3 times respectively. Filter through a 100-mesh sieve, concentrate under reduced pressure, and freeze-dry to obtain lyophilized powder. Determine the content of the three main components according to the conditions in section "2.1.1.1". The results are shown in Table 7. Figure 5 The content of the components increases positively with the number of extractions; therefore, 1-3 extractions were selected as the range for process evaluation.

[0114] Table 7 Results of the number of extractions

[0115] Number of extractions (times) hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g 1 2.077 5.869 0.212 2 3.094 9.435 0.307 3 3.229 10.243 0.300

[0116] 2.1.3.3 Examination of extraction time

[0117] Five portions of 100g each of *Pterocarya stenoptera* blood extract slices were weighed into round-bottom flasks, and 10 times the amount of water was added. The slices were soaked for 30 minutes each, then refluxed for 0.5h, 1h, 1.5h, 2h, and 2.5h, with one extraction. The extracts were passed through a 100-mesh filter, concentrated under reduced pressure, and freeze-dried. The contents of three components were determined according to the conditions in section “2.1.1.1”. The results are shown in Table 8. Figure 6 As the extraction time increases, the content of the index components increases. When the extraction time exceeds 2 hours, the extraction rate tends to stabilize and decreases slightly. Therefore, the extraction time is set at 0.5-2 hours.

[0118] Table 8 Results of the Extraction Time Examination

[0119] Extraction time (h) hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g 0.5 1.807 4.075 0.169 1 2.077 5.869 0.212 1.5 2.445 7.185 0.241 2 2.507 8.419 0.233 2.5 2.470 7.923 0.230

[0120] 2.1.3.4 Investigation of water addition ratio

[0121] Weigh 100g of each of the four portions of *Pterocarya stenoptera* blood extract into round-bottom flasks, and add 8, 10, 12, and 14 times the amount of water respectively. Soak for 30 minutes, heat under reflux for 1 hour, extract once, filter through a 100-mesh screen, concentrate under reduced pressure, and freeze-dry. Determine the content of three components according to the conditions in section "2.1.1.1". The results are shown in Table 9. Figure 7 As the water addition ratio increases, the content of the main component increases. When the water addition reaches 12 times, the extraction rate gradually stabilizes. Therefore, adding 8-12 times the water is defined as the water addition level.

[0122] Table 9 Results of the investigation on water addition ratio

[0123] Water adding times hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g 8 1.880 5.374 0.204 10 2.085 6.241 0.200 12 2.055 6.005 0.219 14 2.156 6.060 0.222

[0124] 2.1.4 Box-Behnken Test

[0125] This experiment used HPLC to determine the contents of hesperidin, zhennan, and zhennan chloride in the extract, as well as the similarity of characteristic peaks and the yield of the extract, as indicators in a Box-Behnken experimental design. The number of extractions, extraction time, and water addition ratio were used as factors to determine the extraction process of the Feilong Palm Blood Formula Granules. Based on the results of single-factor experiments and combined with industrial production requirements, the levels of relevant factors were determined. Using the experimental design software Design-Expert 10, a Box-Behnken experiment was conducted, resulting in 17 experimental schemes with 3 factors and 3 levels, including 12 factorial points and 5 central points. The experimental design is shown in Table 10. Extraction was performed according to the schemes, relevant evaluation indicators were measured, and data analysis was conducted. The results are shown in Table 11.

[0126] Table 10 Box-Behnken Experimental Design Scheme

[0127] Experiment No. Number of extractions (times) Extraction time (h) Add water multiples (times) 1 1 0.5 10 2 3 0.5 10 3 1 2 10 4 3 2 10 5 1 1.25 8 6 3 1.25 8 7 1 1.25 12 8 3 1.25 12 9 2 0.5 8 10 2 2 8 11 2 0.5 12 12 2 2 12 13 2 1.25 10 14 2 1.25 10 15 2 1.25 10 16 2 1.25 10 17 2 1.25 10

[0128] Table 11 Results of the Box-Behnken Test

[0129]

[0130]

[0131] 2.1.5 Establishment of Benchmark Correlation

[0132] The benchmark correlation (SRij) is a correlation index used to evaluate the consistency between a sample and a reference substance (standard decoction). RDij represents the relative deviation of the i-th sample under the j-th index, Zij represents the parameter of the i-th sample under the j-th index, and Sj represents the parameter of the reference substance under the j-th index. The smaller the RDij, the closer the sample is to the reference substance. The calculation formula is: RD... ij =|Z ij -S j | / S j ;

[0133] The closer SRij is to 1, the closer the correlation coefficient between the sample and the reference, and the greater the correlation and similarity between the sample and the reference. The calculation formula is: SR ij =1 - RD ij .

[0134] The results after correlation are shown in Table 12.

[0135] Table 12 Results of Correlation between Blood and Blood Standards in Flying Dragon Palm

[0136] Experiment No. hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g Ointment yield % Similarity 1 0.708 0.653 0.757 0.773 0.999 2 0.736 0.517 0.556 0.845 0.995 3 0.981 0.831 0.991 0.934 0.993 4 0.394 -0.158 0.207 0.679 0.992 5 0.815 0.863 0.879 0.859 0.996 6 0.474 0.035 0.546 0.716 0.982 7 0.979 0.925 0.946 0.994 0.997 8 0.327 -0.119 0.367 0.691 0.985 9 0.906 0.851 0.862 0.943 0.999 10 0.620 0.268 0.688 0.835 0.989 11 0.781 0.798 0.819 0.877 0.998 12 0.443 0.059 0.505 0.700 0.986 13 0.569 0.232 0.694 0.800 0.986 14 0.624 0.328 0.630 0.802 0.992 15 0.658 0.424 0.756 0.834 0.994 16 0.607 0.394 0.750 0.808 0.994 17 0.646 0.421 0.819 0.936 0.986

[0137] 2.1.6 Determination of Weighting Coefficients

[0138] 2.1.6.1 Subjective Weighting in AHP Method

[0139] This embodiment uses five indicators—multi-index components, extract yield, and characteristic spectrum similarity—as evaluation criteria to comprehensively evaluate the extraction process of Feilongzhangxue (Flying Dragon Palm Blood) formula granules. Characteristic spectra are crucial for comprehensively evaluating the chemical composition characteristics of traditional Chinese medicine and are also an important means of studying the quality transfer of formula granules, reflecting the quality of traditional Chinese medicine; therefore, their importance is paramount. Extract yield, as a physical property indicator of drug extraction, can reflect the dissolution rate of active ingredients to a certain extent and is also an evaluation indicator of the stability and homogeneity of intermediates, reflecting the stability of the extraction process; therefore, it is given slight importance. In this embodiment, Zanthoxylum bungeanum extract was found to be a differential marker for Feilongzhangxue and also an important material basis for its efficacy in vivo circulation. It is a unique secondary metabolite of Feilongzhangxue and a very important Q-Marker for it. Therefore, its position is placed on the same level as the yield rate; hesperidin and nephrolepis chloride are also the pharmacological material basis of Ficus pumila blood, and play a certain synergistic role in its efficacy. So they are placed in a slightly later position. The importance of different indicators is ranked from high to low: feature map similarity > yield rate = nephrolepis chloride > nephrolepis chloride = hesperidin. A 5×5 priority judgment matrix is ​​constructed, as shown in Table 13.

[0140] Table 13 Priority Matrix for Indicator Evaluation

[0141]

[0142] The weight coefficients (ω) of the priority judgment matrix were calculated using the square root method. Simultaneously, a consistency test was performed on the matrix, and the consistency ratio (CR) was calculated. The results showed that the weight coefficients for feature map similarity, extract yield, hair thorn extract, chlorhexidine chloride, and hesperidin were 0.368, 0.207, 0.207, 0.109, and 0.109, respectively, and CR = 0.0029, which is less than 0.1. The consistency test passed, indicating that the matrix is ​​consistent and the model is reasonable and reliable.

[0143] 2.1.6.2 Objective Assignment Using the CRITIC Method

[0144] The data after baseline correlation processing was imported into SPSSAU software for CRITIC analysis. The weight coefficients of feature map similarity, tung oil extract, extract yield, hesperidin, and tung oil chloride were 0.015, 0.332, 0.128, 0.188, and 0.338, respectively.

[0145] 2.1.6.3 AHP-CRITIC Comprehensive Weighted Assignment

[0146] The AHP-CRITIC comprehensive evaluation method includes both objective and subjective evaluations, making the entire process research more scientific and reasonable. The AHP weight coefficient and CRITIC weight coefficient are calculated according to the formula "ωAHP-CRITIC=ωAHPωCRITIC / ∑ωAHPωCRITIC" to obtain the comprehensive weight coefficient. The results show that the comprehensive weight coefficients of feature map similarity, hairy thorn, extract yield, hesperidin, and chlorinated thorn are 0.034, 0.434, 0.167, 0.130, and 0.234, respectively. After assigning weights, the comprehensive score is obtained. The calculation formula is: comprehensive score i = feature map similarity score i × 0.034 + hairy thorn score i × 0.434 + extract yield score i × 0.167 + hesperidin score i × 0.130 + chlorinated thorn score i × 0.234 (4). The comprehensive score is obtained by summing the scores of each index under each experimental scheme. The relevant results are shown in Tables 14 and 15.

[0147] Table 14 Overall Weighting Results

[0148]

[0149] Table 15 Overall Scoring Results of the Box-Behnken Test

[0150]

[0151]

[0152] 2.1.7 Analysis of Box-Behnken Test Results

[0153] Design-Expert 8.0.6 software was used, with extraction count (A), extraction time (B), and water addition ratio (C) as independent variables, and overall score as the dependent variable. A Quadratic model was selected to construct a binomial fitting equation: Overall Evaluation = 94.086 + 32.358A + 28.531B - 8.078C - 21.3672AB - 2.727AC - 1.984BC - 1.012A² + 6.481B² + 20.712C² (r 2 =0.9108, P=0.0062). Analysis of variance showed that the model was significant (P<0.05), and the lack-of-fit term was not significant (P=0.0542>0.0500), indicating that the model was reasonably constructed and could well reveal the relationship between the number of extractions, extraction time, and solid-liquid ratio. Results are shown in Table 16, and contour lines and response surface plots are shown below. Figures 8-13 According to the prediction, the optimal extraction process is to add 12 times the amount of water, extract once, for 1.077 hours, and the overall score is 87.82.

[0154] Table 16 Results of ANOVA for the extraction process of blood from *Pterocarya stenoptera*

[0155] Source of variance Sum of Squared Deviations (SS) Degrees of freedom F Mean Square MS F value p-value Significance Model 8085.45 9 898.38 7.94 0.0062 Extremely significant AA 5273.3 1 5273.3 46.61 0.0002 Extremely significant BB 1432.24 1 1432.24 12.66 0.0092 Extremely significant CC 101.54 1 101.54 0.8974 0.375 AB 1027.22 1 1027.22 9.08 0.0196 Significant AC 119.02 1 119.02 1.05 0.3392 BC 35.42 1 35.42 0.3131 0.5932 <![CDATA[A 2 ]]> 4.31 1 4.31 0.0381 0.8507 <![CDATA[B 2 ]]> 55.95 1 55.95 0.4945 0.5046 <![CDATA[C 2 ]]> 34.11 1 34.11 0.3015 0.6 residual 791.99 7 113.14 Missing item 653.07 3 217.69 6.27 0.0542 Not significant Pure error 138.92 4 34.73 Total Correction 8877.44 16

[0156] 2.1.8 Validation of Extraction Process

[0157] The optimal extraction process was obtained based on software simulation. After actual adjustment, 12 times the amount of water was added, and extraction was performed once for 65 minutes. After three verification experiments, the comprehensive score was 96.814, which was higher than the predicted score. The RSD of each index was less than 3%, indicating that the extraction process is reasonable, stable and reliable. The relevant results are shown in Table 17.

[0158] Table 17 Validation Experiment Results

[0159]

[0160]

[0161] 2.2 Research on Concentration Process

[0162] There are various methods for concentrating traditional Chinese medicine. Currently, production mainly uses atmospheric pressure concentration and vacuum concentration. However, atmospheric pressure concentration has drawbacks such as high energy consumption and high temperature, which can damage heat-sensitive components. Large-scale industrial production mostly uses vacuum concentration, which is more efficient, has a lower temperature, and retains the components completely. Therefore, vacuum concentration was chosen as the method for investigation.

[0163] 2.2.1 Investigation of the concentration density of the drug solution

[0164] An appropriate amount of *Pterocarya stenoptera* blood extract slices were extracted using the aforementioned optimal extraction process. The resulting liquid was divided into four equal portions. The liquids were then concentrated under reduced pressure at a constant temperature of 60℃ and a pressure of 120 MPa to different states. The relative density was determined using the hydrostatic flask method (Chinese Pharmacopoeia 2022 Edition, Part IV, 0601) at 20℃. The results showed that the relative density of the liquids was approximately 1.125 g / cm³. 3 The liquid was initially quite viscous and left no residue after pouring. When the liquid was concentrated to a relative density of 1.25 g / cm³... 3 The concentrated medicinal liquid is viscous and sticks to the walls, leaving residue after pouring. Therefore, the relative density of the concentrated medicinal liquid can be defined as 1.125-1.25 g / cm³. 3 This can greatly improve the subsequent drying efficiency, and the relevant results are shown in Table 18.

[0165] Table 18 Investigation of drug solution concentration density

[0166] <![CDATA[Relative density g / cm 3 > state 1.030 Thin, doesn't stick to the sides of the container, can be poured out completely. 1.060 It's quite thin, doesn't stick to the sides of the container, and can be poured out completely. 1.125 It's quite thick, doesn't stick to the sides of the bowl, and can be poured out completely. 1.250 Thick, clings to the sides of the bowl, leaves residue after pouring.

[0167] 2.2.2 Pressure test for drug concentration

[0168] Take an appropriate amount of *Pterocarya stenoptera* blood extract slices and extract them according to the optimal extraction process. The resulting liquid was divided into four equal portions. The liquid was concentrated under reduced pressure at a fixed temperature of 60℃ and with vacuum levels of 50 MPa, 100 MPa, 150 MPa, and 200 MPa. The liquid was concentrated to a fixed density (specific gravity bottle method) and the content was determined according to the content determination method under section “2.1.1.1”. The results showed that different vacuum levels had no effect on the content of the liquid. Therefore, the vacuum level for reduced pressure concentration can be set between 50-200 MPa. The results are shown in Table 19.

[0169] Table 19 Results of Vacuum Degree Test for Drug Concentration

[0170] vacuum MPa hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g <![CDATA[Relative density g / cm 3 > 50 2.441 7.112 0.243 1.180 100 2.446 7.091 0.243 1.170 150 2.443 7.112 0.245 1.180 200 2.468 7.170 0.247 1.170

[0171] 2.2.3 Investigation of drug concentration temperature

[0172] Take an appropriate amount of *Pterocarya stenoptera* blood extract slices and extract them according to the optimal extraction process. The resulting liquid was divided into four equal portions. The liquid was concentrated under reduced pressure at temperatures of 50℃, 60℃, 70℃, 80℃, and 90℃, with a vacuum degree of 150 MPa. The liquid was concentrated to a fixed density (specific gravity bottle method) and the content was determined according to the content determination method under section “2.1.1.1”. The results showed that different temperatures had almost no effect on the content of the components. Therefore, the concentration temperature range can be set to 50℃-90℃. The results are shown in Table 20.

[0173] Table 20 Results of the study on drug concentration temperature

[0174] Temperature ℃ hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g <![CDATA[Relative density g / cm 3 > 50 2.431 7.107 0.254 1.180 60 2.445 7.090 0.254 1.180 70 2.443 7.132 0.239 1.170 80 2.397 7.290 0.234 1.180 90 2.264 7.223 0.227 1.170

[0175] 2.3 Research on Drying Process

[0176] There are various methods for drying traditional Chinese medicine. In industrial production, drying methods include forced-air drying, vacuum drying, freeze drying, microwave vacuum drying, and spray drying, each with its own advantages and disadvantages. This embodiment investigates vacuum drying, freeze drying, microwave vacuum drying, and spray drying, and also examines the drying temperature and vacuum level to determine the optimal drying process.

[0177] 2.3.1 Investigation of different drying methods

[0178] Take an appropriate amount of *Pterocarya stenoptera* blood-staining slices and extract them according to the aforementioned optimal extraction process. Concentrate the liquid to a relative density of 1.15-1.25 g / cm³. 3The sample was then divided into four equal portions and dried using vacuum drying, microwave vacuum drying, freeze-drying, and spray drying, respectively, to obtain *Pterocarya stenoptera* blood extract powder. The relevant instrument parameters are shown in Table 21. After drying, the content was determined according to the conditions in section "2.1.1.1". The results showed that freeze-drying resulted in higher component retention, while the other three drying methods showed slight losses in component content, but the differences were negligible, possibly due to excessively high temperatures and long drying times. In terms of drying time, freeze-drying and vacuum drying are time-consuming and energy-intensive, making them unsuitable for industrial production. Microwave vacuum drying and spray drying are short and efficient, but microwave vacuum drying, due to internal microwave heating and intense molecular thermal motion, can easily cause internal charring and loss of the drug. Spray drying can rapidly atomize and dry the liquid drug into powder, with a short time and high efficiency, making it very suitable for large-scale industrial production. Therefore, spray drying was chosen as the drying method. The results are shown in Table 22.

[0179] Table 21 Parameters of Drying Instrument

[0180] Drying method Temperature ℃ Vacuum degree Kpa Vacuum drying 60 -0.06 Microwave vacuum drying 55 -0.07 freeze-drying -80 -0.03 Spray drying 165 0

[0181] Table 22 Results of investigation on different drying methods

[0182] Drying method hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g Drying time (h) freeze-drying 1.841 4.878 0.177 96 Microwave drying 1.844 4.821 0.164 1.5 Spray drying 1.868 4.768 0.166 2 Vacuum drying 1.791 4.955 0.148 168

[0183] 2.3.2 Investigation of different feed rates

[0184] Take an appropriate amount of *Pterocarya stenoptera* blood-sucking slices and extract them according to the aforementioned optimal extraction process. After obtaining the medicinal liquid, concentrate it to a relative density of 1.15-1.25 g / cm³. 3 The samples were then divided into four equal portions. The spray drying inlet air temperature was set to 170℃, the exhaust air temperature to 110℃, and the atomization pressure to 0.2-0.4 MPa. When the temperature reached the preset conditions, the samples were injected at the following rates: 8 mL / min, 10 mL / min, 12 mL / min, and 14 mL / min, and the spray-dried powder was collected. The content was determined according to the conditions in section “2.1.1.1”, and the moisture content of the powder was also determined (according to the “drying method” under section 0832 of the Moisture Determination Method in Part IV of the 2022 edition of the Chinese Pharmacopoeia). The results showed that different injection rates had little effect on the content of the main component. The moisture content increased with the increase of the injection rate, but the moisture content did not exceed 8% (Moisture content of granules in the 2022 edition of the Chinese Pharmacopoeia). Therefore, the injection rate range for spray drying can be set to 8-14 mL / min. The results are shown in Table 23.

[0185] Table 23 Results of Spray Drying Injection Rate Investigation

[0186] Injection rate mL / min hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g Moisture content % 8 3.228 8.277 0.183 3.49 10 3.196 8.188 0.182 3.37 12 3.110 8.280 0.177 3.69 14 3.098 8.380 0.177 4.40

[0187] 2.3.3 Investigation at different temperatures

[0188] Take an appropriate amount of *Pterocarya stenoptera* blood-sucking slices, extract them using the optimal extraction process, and then concentrate the resulting liquid to a relative density of 1.15-1.25 g / cm³. 3 The powder was then divided into five equal portions. The inlet air temperature for spray drying was set to 160℃, 170℃, 180℃, 190℃, and 200℃, respectively, with an exhaust air temperature of 110℃, a feed rate of 12 mL / min, and an atomization pressure of 0.2-0.4 MPa. Feeding was initiated when the preset conditions were met, and the spray-dried powder was collected. The content was determined according to the conditions in section “2.1.1.1”, and the powder moisture content was also measured (according to the Chinese Pharmacopoeia 2022, Moisture Determination Method, “Drying Method”). The results showed that the content of cinnamon oleracea decreased with increasing temperature, and the moisture content also decreased with increasing temperature. Considering all factors, the spray drying temperature was set between 160-180℃. Excessively high temperatures would result in component loss and cause the powder to soften and stick to the drying walls. The results are shown in Table 24.

[0189] Table 24 Results of spray drying temperature investigation

[0190] Inlet air temperature ℃ hesperidin mg / g Zanthoxylum bungeanum (mg / g) Calcium chloride mg / g Moisture content % 160 3.210 8.821 0.187 5.08 170 3.145 8.382 0.178 4.11 180 3.135 8.233 0.177 4.07 190 3.162 8.019 0.177 3.85 200 3.229 8.068 0.175 3.61

[0191] 2.4 Molding Process Research

[0192] There are various methods for forming traditional Chinese medicine granules, such as wet granulation, dry granulation, and fluidized bed granulation, each with its own advantages and disadvantages. Currently, wet granulation is the most commonly used method. However, wet granulation requires more excipients and involves more complex steps. In contrast, dry granulation requires fewer excipients and has simpler steps, does not require drying, and better preserves the medicinal components, making it highly suitable for the large-scale industrial production of formulated granules. Therefore, this study selects dry granulation as the forming process for Feilong Palm Blood Formula Granules to determine its process parameters and provide experimental basis for subsequent pilot-scale production.

[0193] 2.4.1 Investigation of Filler Types

[0194] Weigh out 4 parts of the dried dragon's paw blood ointment powder, and add soluble starch, dextrin, anhydrous lactose, and sucrose in a ratio of 1:1 between the dry ointment powder and excipients. The dry granulation equipment was set with a roller pressure of 100 bar, a roller speed of 2.8 rpm, a feeding speed of 21 rpm, and a roller distance of 1.5 mm. The sticking to the rollers was observed. After obtaining the granules, the following were measured: First-pass forming rate (first-pass forming rate = granules passing through sieve No. 1 but not sieve No. 5 / total granules × 100%); moisture absorption rate (a certain mass of granules was accurately weighed and placed in a weighing bottle, then placed open in a 75% constant temperature and humidity chamber for 24 hours, and the weight was accurately measured to calculate the moisture absorption rate. The formula for calculating the moisture absorption rate is: dilution rate = (mass after moisture absorption - mass before moisture absorption) / mass before moisture absorption × 100%); angle of repose (a certain amount of granules was weighed and allowed to fall freely into a funnel; the angle α formed by the conical inclined plane of the granules and the horizontal plane is the angle of repose, with α < 40° considered acceptable); solubility (according to the method under 0104 Granules in the 2020 edition of the Chinese Pharmacopoeia). The results are shown in Table 25. The results show that anhydrous lactose has poor compressibility and is prone to clogging the feeding channel. Sucrose has a low forming rate, serious sticking to the wheel, and high hygroscopicity. Soluble starch and dextrin have higher one-time forming rates, less sticking to the wheel, and lower hygroscopicity. From an economic point of view, dextrin, which is cheaper, is more suitable as a filler for dry granulation.

[0195] Table 25 Screening Results of Dry Granulation Fillers

[0196] Types of auxiliary materials One-time molding rate % Angle of repose ° Moisture absorption rate % Adhesive wheel Solubility starch 71.37 26.92 8.43 ** Dissolved completely within 5 minutes dextrin 72.31 25.28 6.07 ** Dissolved completely within 5 minutes sucrose 61.35 25.31 11.28 **** Dissolved completely within 5 minutes Anhydrous lactose Difficult to granulate - - - -

[0197] Note: "*" indicates the degree of stickiness, same as in Table 26.

[0198] 2.4.2 Investigation on filler dosage

[0199] Four parts of dry granulation powder were weighed and dextrin was added according to the following ratios: dry granulation powder to excipients: 1:0.2, 1:0.5, 1:0.8, and 1:1. The dry granulation equipment was set with a roller pressure of 100 bar, a roller speed of 2.8 rpm, a feeding speed of 21 rpm, and a roller distance of 1.5 mm. The sticking to the rollers was observed. After obtaining the granules, the one-time molding rate, hygroscopicity, angle of repose, and solubility were measured. The results showed that a lower excipient ratio slightly increased the one-time molding rate, but also increased roller sticking and hygroscopicity, which was detrimental to granule preservation. Therefore, a filler ratio between 1:0.8 and 1:1 is more suitable. The results are shown in Table 26.

[0200] Table 26 Results of the investigation on filler dosage

[0201] Excipients: Dry ointment powder One-time molding rate % Angle of repose ° hygroscopicity % Adhesive wheel Solubility 0.2:1 74.59 27.92 13.19 ***** Dissolved completely within 5 minutes 0.5:1 71.17 26.39 11.56 **** Dissolved completely within 5 minutes 0.8:1 70.98 26.74 10.25 ** Dissolved completely within 5 minutes 1:1 67.89 24.28 7.85 ** Dissolved completely within 5 minutes

[0202] 2.4.3 Roll Pressure Examination

[0203] Five parts of dry granulation powder were weighed and dextrin was added at a ratio of dry granulation powder to excipients of 1:0.8. The dry granulation equipment was set with roller pressures of 80 bar, 90 bar, 100 bar, 110 bar, and 120 bar, roller speed of 2.8 rpm, feeding speed of 21 rpm, and roller distance of 1.5 mm. After obtaining granules, the roller pressure range was optimized using the one-time forming rate as an indicator. The results showed that the one-time forming rate of granules increased with increasing pressure. When the pressure reached 100 bar, the one-time forming rate tended to stabilize. Therefore, the roller pressure could be set at 100-120 bar. The results are shown in Table 27.

[0204] Table 27 Results of Roll Pressure Investigation

[0205] Pressure / bar One-time molding rate % 80 60.16 90 64.90 100 78.29 110 77.14 120 78.34

[0206] 2.4.4 Inspection of feeding speed

[0207] Weigh out 4 parts of dry powder and add dextrin at a ratio of dry powder to excipients of 1:0.8. Set the dry granulation equipment with a roller pressure of 100 bar, a roller speed of 2.8 rpm, and feeding speeds of 19 rpm, 21 rpm, 23 rpm, and 25 rpm, and a roller distance of 1.5 mm. After obtaining the granules, the roller speed range was optimized using the one-time forming rate as an indicator. The results showed that the one-time forming rate increased with the increase of the feeding speed. When the feeding speed reached 23 rpm, the one-time forming rate tended to stabilize. Therefore, the feeding speed range was set between 23-25 ​​rpm. The results are shown in Table 28.

[0208] Table 28 Results of Feeding Speed ​​Evaluation

[0209] Feeding speed rpm One-time molding rate % 19 58.14 21 61.48 23 77.16 25 77.39

[0210] 2.4.5 Roll Speed ​​Examination

[0211] Weigh out 4 parts of dry powder and add dextrin at a ratio of dry powder to excipients of 1:0.8. Set the dry granulation equipment to roller pressure of 100 bar, roller speed of 2.8 rpm, 3.2 rpm, 3.6 rpm, and 4.0 rpm, feed speed of 23 rpm, and roller distance of 1.5 mm. After obtaining the granules, the roller speed range was optimized based on the one-time forming rate. The results showed that the roller speed had little effect on the one-time forming rate. Therefore, the roller speed range can be selected between 2.8-4 rpm. The results are shown in Table 29.

[0212] Table 29 Results of Roll Speed ​​Investigation

[0213] Roll speed rpm One-time molding rate % 2.8 80.64 3.2 80.66 3.6 80.34 4.0 79.68

[0214] 3. Summary

[0215] Decoctions, as a traditional dosage form, require immediate preparation and are inconvenient to carry and preserve. Converting traditional decoctions into granules offers advantages such as no-decoction preparation, easy administration, portability, and convenient dispensing. The "Technical Requirements for Quality Control and Standard Formulation of Traditional Chinese Medicine Formula Granules" stipulates that "the preparation of traditional Chinese medicine formula granules, except for the molding process, should be basically consistent with traditional decoctions." How to improve extraction efficiency using modern technology without deviating from the basic attributes of traditional decoctions is a key research direction. However, traditional earthenware pot decoction cannot meet the mass production needs of large-scale industry; therefore, transforming traditional open decoction into closed reflux extraction is essential. Using the quality attributes of standard decoctions as a reference in the extraction process research is the core of the entire extraction process optimization. Therefore, this embodiment uses the standard decoction yield, main component content, and characteristic spectrum similarity as criteria, introduces the concept of benchmark correlation (SRij), and compares the closed reflux extraction method with the traditional decoction method. The larger the correlation coefficient, the more similar the quality. At the same time, the AHP method and CRITIC method are used to determine scientific and reasonable weight coefficients from both objective and subjective perspectives. The Box-Behnken design-response surface methodology is used to study the transformation from traditional decoction process to modern extraction process. The optimal extraction process was determined to be 12 times water, one extraction, and 65 minutes, with a comprehensive score of 96.814, providing a basis for subsequent concentration, drying, and shaping processes.

[0216] Vacuum concentration, as an important concentration method in large-scale industrial production, has the advantages of low temperature, high efficiency, and relatively complete component retention. This embodiment focuses on vacuum concentration, examining the range of relative density, temperature, and vacuum degree during the concentration process of the pharmaceutical solution, aiming to improve production efficiency and identify process parameters that ensure stable quality of the pharmaceutical solution. Ultimately, the relative density of the concentrated pharmaceutical solution was determined to be 1.125-1.25 g / cm³. 3 The temperature was 50-90℃, and the vacuum degree was 50-200Mpa. This embodiment also determined the feed rate for spray drying to be 8-14mL / min and the drying temperature to be 160-180℃. However, during spray drying, powder adherence to the wall was observed, which could lead to drug loss. This adhesion can be categorized into adhesion of semi-wet materials, adhesion of hot-melt materials, and adhesion to the surface of dry powder. Therefore, parameters can be adjusted appropriately during the drying process, and excipients can be added to improve the adhesion phenomenon. This embodiment uses dry granulation to study the forming process of Feilong Palm Blood Formula Granules. Dextrin was determined as the filler, the dry powder:excipient ratio was between 1:0.8 and 1:1, the roller pressure was 100-120 bar, the feed rate was 23-25 ​​rpm, and the roller speed was 2.8-4.0 rpm, providing assurance for the production and quality research of Feilong Palm Blood Formula Granules.

[0217] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing a formula granule for treating dragon's blood stasis, characterized in that, Includes the following steps: The slices of *Pterocarya stenoptera* blood were sequentially soaked, refluxed for extraction, concentrated, and spray-dried to obtain dried *Pterocarya stenoptera* blood extract powder. The dried dragon palm blood ointment powder and excipients are mixed and granulated to obtain the dragon palm blood formula granules.

2. The preparation method according to claim 1, characterized in that, The reflux extraction is performed 1-3 times, with a time of 30-120 minutes.

3. The preparation method according to claim 2, characterized in that, The reflux extraction was performed once, and the extraction time was 65 minutes.

4. The preparation method according to claim 1, characterized in that, During the soaking process, the amount of water used is 8-12 times the mass of the Flying Dragon Palm Blood Drink slices, and the soaking time is 0.5 hours.

5. The preparation method according to claim 4, characterized in that, During the soaking process, the amount of water used is 12 times the mass of the Flying Dragon Palm Blood Drink slices.

6. The preparation method according to claim 1, characterized in that, The concentration process is carried out at a pressure of 50-200 MPa and a temperature of 50-90°C; the concentrated solution obtained after concentration has a density of 1.125-1.25 g / cm³. 3 .

7. The preparation method according to claim 1, characterized in that, The injection rate for spray drying is 8-14 mL / min, and the temperature is 160-180℃.

8. The preparation method according to claim 1, characterized in that, The mass ratio of the dried blood ointment powder and excipients in the Flying Dragon Palm is 1:(0.8-1).

9. The preparation method according to claim 1, characterized in that, The granulation roller pressure is 100-120 bar, the feeding speed is 23-25 ​​rpm, and the roller speed is 2.8-4.0 rpm.

10. The preparation method according to claim 1, characterized in that, The excipients include fillers; the fillers include soluble starch and / or dextrin.

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