A sterile compound cinnabar freeze-dried stock solution and freeze-dried powder and a preparation process thereof

Abstract

The application provides a preparation process of a sterile compound cinnabar freeze-dried stock solution and relates to the technical field of traditional Chinese medicine deep processing. The preparation process comprises the following steps: S1: taking compound cinnabar liquid alcohol precipitation paste, adding purified water to a certain volume, and cold storage and standing to obtain a mixed solution; S2: taking supernatant of the mixed solution in step S1, performing sterile filtration at least i times through a filter membrane at a temperature of 28-45 DEG C to obtain a sterile compound cinnabar freeze-dried stock solution. In the application, i is a natural number and traverses from 1 to n, n is a natural number and is not less than 3. The pore size of the filter membrane for the (i+1)th filtration is not greater than the pore size of the filter membrane for the ith filtration; and the certain volume in step S1 is configured to be 580-1000 ml. The sterile compound cinnabar freeze-dried stock solution prepared by the application can reduce the volume of the sterile compound cinnabar freeze-dried stock solution while ensuring that the material basis does not change significantly through the improvement of the processing technology.

Description

[0001] This application claims priority to Chinese patent application 202310530146.6, filed on May 8, 2023. The entire contents of the aforementioned Chinese patent application are incorporated herein by reference. Technical Field

[0002] This invention relates to the field of deep processing technology of traditional Chinese medicine, specifically to a sterile compound Phellodendron amurense freeze-dried stock solution, a compound Phellodendron amurense freeze-dried powder, and a preparation process of a sterile compound Phellodendron amurense freeze-dried stock solution. Background Technology

[0003] Compound Phellodendron bark extract topical application has the effects of clearing heat and detoxifying, reducing swelling and removing necrotic tissue. It is used for post-ulceration sores and infected wounds, especially those with a Yang syndrome. In clinical use, it is applied to treat injuries ranging from superficial skin lesions to mucosal injuries of internal visceral cavities, demonstrating high clinical value.

[0004] Chinese invention patent CN104398642, published on March 11, 2015, provides a method for preparing and testing the quality of compound Phellodendron amurense extract. This quality testing method includes the identification of Forsythia suspensa, Phellodendron amurense, Lonicera japonica, and Taraxacum mongolicum; the examination of Lonicera japonica; and the determination of the content of forsythoside and berberine hydrochloride. This patent does not address the issue of changes in the dosage form of the compound Phellodendron amurense extract. Summary of the Invention

[0005] The inventors discovered that no preservatives or excipients were used in the production of Compound Phellodendron Amurense Liquid Topical Solution, and as a liquid preparation, the finished product was not safe enough for transportation. Therefore, to ensure the safety and stability of the product during transportation, a sterile lyophilized powder formulation was developed. According to the "Classification and Application Requirements for Registration of Traditional Chinese Medicine," Compound Phellodendron Amurense Lyophilized Powder falls under "2.2 Preparations that change the dosage form of an already marketed traditional Chinese medicine, i.e., preparations that change the dosage form while maintaining the same route of administration." It is necessary to ensure that the material basis does not change significantly (changes in indicative components must be within 5%). The safety, efficacy, and quality controllability of the original Compound Phellodendron Amurense Liquid Topical Solution have been verified in clinical use. By controlling the quality of the sterile Compound Phellodendron Amurense Lyophilized Liquid Topical Solution, the final lyophilized powder product can be controlled to ensure that the material basis is not significantly changed compared to the Compound Phellodendron Amurense Liquid Topical Solution, thus guaranteeing the safety, efficacy, and quality controllability of the final Compound Phellodendron Amurense Lyophilized Powder product.

[0006] The freeze-dried powder preparation is a sterile preparation, therefore, it is used once after opening, according to the recommended dosage of 10-20 ml of compound cortex phellodendri liquid coating agent once, combined with the convenience of clinical application, the specification of 20 ml per bottle is selected for freeze-drying. The inventors have found that, according to the original process of compound cortex phellodendri liquid coating agent, the alcohol precipitation paste is configured to 1000 ml of refrigerated filtered freeze-dried stock solution, which can ensure that the material basis does not change, but in this case, the freeze-drying time is long, the energy consumption is high, and the production efficiency is very low in the later stage. In addition, the freeze-drying can only be carried out in the way of tray and then re-packaging under the configuration volume, not only the cleanliness of the production environment needs to be controlled, but also the humidity needs to be controlled, otherwise it will lead to difficulty in re-packaging and crushing, and the material will be adhered in the process of crushing and re-packaging. In order to solve the above problems, the inventors provide a sterile compound cortex phellodendri freeze-dried stock solution which reduces the volume while ensuring that the material basis does not change significantly. At the same time, the freeze-drying method can use bottle freeze-drying, the freeze-dried powder product form, reconstitution effect and re-packaging precision are good, which is more conducive to improving the production efficiency.

[0007] The first aspect of the present application provides a preparation process of sterile compound cortex phellodendri freeze-dried stock solution, which comprises the following steps:

[0008] S1: taking the alcohol precipitation paste of compound cortex phellodendri liquid, adding purified water to a certain volume, and refrigerating to obtain a mixed solution.

[0009] S2: taking the supernatant of the mixed solution, filtering it through a filter membrane at a temperature of 28-45 DEG C to obtain a sterile compound cortex phellodendri freeze-dried stock solution.

[0010] Wherein, i is a natural number and traverses from 1 to n, n is a natural number and is not less than 3; the pore size of the filter membrane for the i+1th filtration is not greater than that of the ith filtration. The certain volume in the S1 step is configured to 580-1000 ml.

[0011] The second aspect of the present application provides a sterile compound cortex phellodendri freeze-dried stock solution, which is prepared by the above preparation process.

[0012] The third aspect of the present application provides a compound cortex phellodendri freeze-dried powder, which is prepared by the above sterile compound cortex phellodendri freeze-dried stock solution. The preparation method comprises the following steps:

[0013] The sterile compound cortex phellodendri freeze-dried stock solution is pre-frozen at a pressure of 0-3 Pa and a temperature of-47 DEG C to-43 DEG C, then sublimated at a pressure of 8-12 Pa and a temperature of-12 DEG C to-8 DEG C, and finally desorbed and dried at a pressure of 28-32 Pa and a temperature of 38-42 DEG C to obtain the compound cortex phellodendri freeze-dried powder.

[0014] Compared with the prior art, the present application at least has one of the following beneficial effects:

[0015] (1) The sterile compound cypress bark freeze-dried stock solution prepared by the present application can be made into freeze-dried powder by bottle freeze-drying, with high precision in sub-packaging, improved production efficiency, and saved production cost.

[0016] (2) The sterile compound cypress bark freeze-dried stock solution prepared by the present application can be made into freeze-dried powder by bottle freeze-drying, with high precision in sub-packaging, improved production efficiency, and saved production cost.

[0017] (3) The sterile compound cypress bark freeze-dried stock solution prepared by the present application can be made into freeze-dried powder by bottle freeze-drying, with high precision in sub-packaging, improved production efficiency, and saved production cost.

[0018] (4) The sterile compound cypress bark freeze-dried stock solution prepared by the present application can be made into freeze-dried powder by bottle freeze-drying, with high precision in sub-packaging, improved production efficiency, and saved production cost. BRIEF DESCRIPTION OF DRAWINGS

[0019] The accompanying drawings, which are included to provide a further understanding of the present application, form a part of the present application and are included to further explain the present application and, together with the detailed description, serve to explain the present application. In the drawings:

[0020] Figure 1 The product state diagram of the compound cypress bark freeze-dried powder prepared by plate freeze-drying of the sterile compound cypress bark freeze-dried stock solution of the present application Comparative Example 3 is shown;

[0021] Figure 2 The product state diagram of the compound cypress bark freeze-dried powder prepared by bottle freeze-drying of the sterile compound cypress bark freeze-dried stock solution of the present application Example 1 is shown;

[0022] Figure 3 The product state diagram of the compound cypress bark freeze-dried powder prepared by bottle freeze-drying of the sterile compound cypress bark freeze-dried stock solution of the present application Comparative Example 3 is shown. DETAILED DESCRIPTION

[0023] In order to more clearly illustrate the overall concept of the present application, the following will be described in detail with reference to the accompanying drawings.

[0024] Many specific details are set forth in the following description in order to provide a thorough understanding of the present application. However, the present application can be practiced according to other embodiments that can not be described in detail herein. The present application is not limited to the embodiments described herein. Additionally, any step or block that is described herein can be combined with other steps or blocks, or divided into multiple steps or blocks, to facilitate implementation.

[0025] In an exemplary embodiment of the present application, the preparation process of the sterile compound cortex phellodendri freeze-dried stock solution comprises the following steps:

[0026] S1: Take the compound cortex phellodendri alcohol precipitation paste, add purified water to a certain volume, and store in a refrigerator to obtain a mixed solution. The certain volume is configured to 580-1000 ml. Preferably, the certain volume is configured to 600-800 ml. More preferably, the certain volume is configured to 600 ml.

[0027] Alternatively, the preparation method of the compound cortex phellodendri alcohol precipitation paste comprises the following steps: five kinds of traditional Chinese medicines in the compound cortex phellodendri liquid are weighed according to the weight component. Among them, forsythia 80±10 parts by weight, cortex phellodendri 40±5 parts by weight, honeysuckle 40±5 parts by weight, dandelion 40±5 parts by weight, and centipede 2.4±0.3 parts by weight. Water decoction extraction three times; combine the decoction, filter, and concentrate the filtrate to a clear paste with a relative density of 1.10-1.15 (50℃); then add ethanol to the clear paste to make the ethanol content reach 60-70%, stand, filter, and reduce pressure to concentrate the filtrate to obtain the compound cortex phellodendri alcohol precipitation paste.

[0028] Specifically, for example, in 1 weight component of the compound cortex phellodendri alcohol precipitation paste, forsythia 80±10g, cortex phellodendri 40±5g, honeysuckle 40±5g, dandelion 40±5g, and centipede 2.4±0.3g, 1 weight component of the compound cortex phellodendri alcohol precipitation paste is taken in step S1 and added to purified water to configure 580-1000ml.

[0029] When 20 weight components of the compound cortex phellodendri alcohol precipitation paste, forsythia 1600±200g, cortex phellodendri 800±100g, honeysuckle 800±100g, dandelion 800±100g, and centipede 48±6g, 20 weight components of the compound cortex phellodendri alcohol precipitation paste are taken in step S1 and added to purified water to configure 11600-20000ml. The ratio of the weight component of the compound cortex phellodendri alcohol precipitation paste to the certain volume is 1 weight component:580-1000ml.

[0030] Alternatively, the purified water is water for injection, which refers to water obtained by distillation of purified water. The water for injection has higher requirements for microbial limit than purified water, and has inspection requirements for bacterial endotoxin, and is more suitable for application in sterile products.

[0031] S2: taking the supernatant of the mixed solution of S1, sterilizing the supernatant by sterile filtration through a filter membrane at a temperature of 28-45℃ for at least i times to obtain a sterile compound cinnabar freeze-dried stock solution.

[0032] wherein i is a natural number and traverses from 1 to n, and n is a natural number and is not less than 3; the pore size of the filter membrane for the (i+1)th filtration is not greater than the pore size of the filter membrane for the ith filtration.

[0033] Optionally, the supernatant in the S2 step is incubated at a temperature of 28-45℃ for more than 3 hours. Preferably, the temperature in the S2 step is 30-40℃.

[0034] Optionally, i can be 3, and the sterile compound cinnabar freeze-dried stock solution can be obtained by performing sterile filtration for 3 times. For example, the pore size of the filter membrane for the first filtration is not greater than 0.5μm, the pore size of the filter membrane for the second filtration is not greater than 0.3μm, and the pore size of the filter membrane for the third filtration is not greater than 0.3μm. For example, the pore size of the filter membrane for the first filtration is 0.45μm, the pore size of the filter membrane for the second filtration is 0.22μm, and the pore size of the filter membrane for the third filtration is 0.22μm.

[0035] In an exemplary embodiment of the present application, the compound cinnabar freeze-dried powder is prepared from the sterile compound cinnabar freeze-dried stock solution described above, and the preparation method comprises the following steps:

[0036] The sterile compound cinnabar freeze-dried stock solution is pre-frozen at a pressure of 0-3Pa and a temperature of -47℃ to -43℃, then sublimated at a pressure of 8-12Pa and a temperature of -12℃ to -8℃, and finally desorbed and dried at a pressure of 28-32Pa and a temperature of 38-42℃ to obtain the compound cinnabar freeze-dried powder. Compared with tray freeze-drying, the sterile compound cinnabar freeze-dried stock solution prepared by the present application can be directly used to obtain the compound cinnabar freeze-dried powder by bottle freeze-drying, without the need for crushing and sieving treatment. The problem of controlling the production environment for crushing and sub-packaging in the later stage is avoided.

[0037] Example 1

[0038] (1) Preparation of compound cinnabar liquid alcohol precipitation paste

[0039] Take the compound cinnabar liquid and five medicinal materials, wherein, 80g of forsythia, 40g of cinnabar, 40g of honeysuckle, 40g of dandelion, and 2.4g of centipede. Add water and decoct for three times, the first time for 1 hour, the second time for 45 minutes, and the third time for 30 minutes. Combine the decoction, filter, and concentrate the filtrate to a clear paste with a relative density of 1.10-1.15. Add ethanol to make the alcohol content reach 70%, stand for 24 hours, filter, and concentrate the filtrate under reduced pressure until there is no alcohol taste to obtain the compound cinnabar liquid alcohol precipitation paste.

[0040] (2) Take the above compound Phellodendron amurense extract, add purified water to make 600ml, stir for 15 minutes, refrigerate and stand for 24 hours, take the supernatant and sterile filter at 30℃ (first time 0.45μm filter membrane, second and third times 0.22μm filter membrane) to obtain sterile compound Phellodendron amurense freeze-dried stock solution.

[0041] Example 2

[0042] Based on Example 1, the above-mentioned compound Phellodendron amurense extract was taken, purified water was added to make 1000ml, stirred for 15 minutes, refrigerated and allowed to stand for 24 hours, and the supernatant was taken and kept at 40℃ for 3 hours for sterile filtration (first time through a 0.45μm filter membrane, second and third times through 0.22μm filter membranes) to obtain sterile compound Phellodendron amurense freeze-dried stock solution.

[0043] Example 3

[0044] Based on Example 1, the above-mentioned compound Phellodendron amurense extract was taken, purified water was added to prepare 800ml, stirred for 15 minutes, refrigerated and allowed to stand for 24 hours, and the supernatant was taken and sterilely filtered at 30℃ (first time through a 0.45μm filter membrane, second and third times through 0.22μm filter membranes) to obtain sterile compound Phellodendron amurense freeze-dried stock solution.

[0045] Example 4

[0046] (1) Preparation of compound Phellodendron amurense extract ethanol precipitation

[0047] Five medicinal materials were used in the compound Phellodendron amurense decoction: Forsythia suspensa 1600g, Phellodendron amurense 800g, Lonicera japonica 800g, Taraxacum mongolicum 800g, and Scolopendra subspinipes 48g. The herbs were decocted three times with water: 1 hour for the first decoction, 45 minutes for the second, and 30 minutes for the third. The decoctions were combined, filtered, and the filtrate was concentrated to a clear extract with a relative density of 1.10-1.15. Ethanol was added to bring the alcohol content to 70%, and the mixture was allowed to stand for 24 hours. The extract was then filtered, and the filtrate was concentrated under reduced pressure until no alcohol odor remained, yielding the compound Phellodendron amurense decoction alcohol precipitate.

[0048] (2) Take the above compound Phellodendron amurense extract and add water for injection to make 12000ml. Stir, let stand, and refrigerate for 24 hours. Take the supernatant and perform sterile filtration at 40℃ (first time through a 0.45μm filter membrane, second and third times through a 0.22μm filter membrane) to obtain sterile compound Phellodendron amurense freeze-dried stock solution.

[0049] Comparative Example 1

[0050] Based on Example 1, the compound Phellodendron amurense extract was taken, purified water was added to make 200ml, stirred for 15 minutes, refrigerated and allowed to stand for 24 hours, and the supernatant was taken and filtered at 50℃ using sterile filtration (first 0.45μm filter membrane, second and third 0.22μm filter membranes) to obtain sterile compound Phellodendron amurense freeze-dried stock solution.

[0051] Comparative Example 2

[0052] On the basis of Example 1, the compound cortex phellodendri liquid alcohol precipitated paste was added to 400 ml of purified water, stirred for 15 minutes, and refrigerated for 24 hours. The supernatant was filtered under refrigeration (2-10℃) using sterile filtration (0.45 μm filter membrane for the first time, 0.22 μm filter membrane for the second and third times) to obtain the sterile compound cortex phellodendri freeze-dried stock solution.

[0053] Comparative Example 3

[0054] On the basis of Example 1, the compound cortex phellodendri liquid alcohol precipitated paste was added to 1000 ml of purified water, stirred for 15 minutes, and refrigerated for 24 hours. The supernatant was filtered under refrigeration (2-10℃) using filter paper to obtain the compound cortex phellodendri freeze-dried stock solution.

[0055] According to the determination method of forsythoside, berberine hydrochloride, and total solids in the compound cortex phellodendri liquid coating agent in the Chinese Pharmacopoeia (2020 edition), the freeze-dried stock solutions prepared in Examples 1-4 and Comparative Examples 1-3 were subjected to two parallel tests. The processing conditions and material basis components of the freeze-dried stock solutions are shown in Table 1.

[0056] Table 1 Processing conditions and material basis components

[0057]

[0058]

[0059] To verify whether the material basis of the sterile compound cortex phellodendri freeze-dried stock solution prepared is changed compared with the compound cortex phellodendri liquid coating agent (Comparative Example 3 in Table 2), the configuration volume of the above examples and comparative examples was converted to 1000 ml, the average value of the content of each index component was calculated when the converted configuration volume was 1000 ml, and the deviation value of the content of each index component was calculated. The results are shown in Table 2.

[0060]

[0061] Table 2

[0062]

[0063] As shown in Table 2, from Examples 1-4, the deviation value of each index component (forsythoside, berberine hydrochloride, and total solids) was within 5%, which proved that the material basis of the sterile compound cortex phellodendri freeze-dried stock solution prepared by the preparation process of the present application did not change significantly.

[0064] The comparative example 3 is directly using the compound cortex phellodendri liquid alcohol precipitation paste to configure to 1000ml, and performing filter paper filtration at a refrigeration temperature of 2-10℃ to obtain a compound cortex phellodendri liquid coating process, which can guarantee that the material basis does not change, but can only adopt a tray method for freeze-drying in the later stage. Figure 1 as shown in the reference Figure 1 The product state diagram of the compound cortex phellodendri freeze-dried powder prepared by the comparative example 3 compound cortex phellodendri freeze-dried original liquid tray freeze-drying is shown in the reference

[0065] The main difference between the comparative example 1 and the example 1 is that the configuration volume is too low, and the deviation values of the index components (forsythia suspensa, berberine hydrochloride and total solids) all exceed 5% when the temperature is increased for sterile filtration, and the material basis components change.

[0066] The main difference between the comparative example 2 and the comparative example 3 is that the configuration volume is too low, and the deviation value of the berberine hydrochloride exceeds 5% and the deviation value of the total solids exceeds 5% when the refrigeration temperature sterile filtration is performed, and the material basis components change.

[0067] The main difference between the example 2 and the comparative example 3 is that the forsythia suspensa pass rate slightly decreases and the berberine hydrochloride pass rate slightly increases when the supernatant is heated for sterile filtration. The present application controls the configuration volume and the holding temperature, so that the material basis components of the prepared sterile compound cortex phellodendri freeze-dried original liquid do not change obviously.

[0068] Under the condition of guaranteeing that the material basis does not change obviously, the sterile compound cortex phellodendri freeze-dried original liquid prepared in the example 1 is divided into 12ml, and the sample height is 15mm for bottle freeze-drying. The bottle freeze-drying is performed at a pressure of 2Pa and a temperature of-45℃ for pre-freezing, then at a pressure of 10Pa and a temperature of-10℃ for primary sublimation, and finally at a pressure of 30Pa and a temperature of 40℃ for analytical drying to obtain the compound cortex phellodendri freeze-dried powder. The compound cortex phellodendri freeze-dried powder obtained by the bottle freeze-drying is shown in the reference Figure 2 as shown in the reference Figure 2 It can be seen that the product form of the compound cortex phellodendri freeze-dried powder prepared by the present application is good, the reconstitution effect is good, and the division precision is high.

[0069] The compound cortex phellodendri freeze-dried original liquid prepared in the comparative example 3 is divided into 20ml by the freeze-drying method in the example 1, and the sample height is 23mm for bottle freeze-drying to obtain the compound cortex phellodendri freeze-dried powder. The compound cortex phellodendri freeze-dried powder obtained by the bottle freeze-drying is shown in the reference Figure 3 as shown in the reference Figure 3It can be seen that the compound cortex phellodendri liquid alcohol precipitation paste is configured to 1000ml, and is filtered by filter paper at a refrigeration temperature of 2-10℃, so as to realize a compound cortex phellodendri liquid coating process, which can guarantee that the material basis does not change, but when the bottle freeze-drying is carried out later, the compound cortex phellodendri freeze-dried powder cannot be prepared. Figure 3 It can be seen that when the bottle freeze-drying is carried out, the interlayer melting appears in the middle of the freeze-dried sample, or the whole appears to collapse and shrink.

[0070] The above merely illustrates the embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement and the like within the spirit and principle of the present application should be included in the scope of the claims of the present application.

Claims

1. A preparation process of a sterile compound cork tree bark freeze-dried stock solution, characterized in that, The preparation process comprises the following steps: S1: Take the compound cortex phellodendri alcohol precipitation paste, add purified water to a certain volume, and store in a refrigerator to obtain a mixed solution; S2: Take the supernatant of the mixed solution in step S1, and perform sterile filtration at least i times through a filter membrane at a temperature of 30-40℃ to obtain a sterile compound cortex phellodendri freeze-dried stock solution; Wherein, i is a natural number and traverses from 1 to n, n is a natural number and is not less than 3; the pore size of the filter membrane for the i+1th filtration is not greater than the pore size of the filter membrane for the ith filtration; The certain volume in the S1 step is configured to 600-800ml; The i is 3, the pore size of the filter membrane for the 1st filtration is not greater than 0.5μm, the pore size of the filter membrane for the 2nd filtration is not greater than 0.3μm, and the pore size of the filter membrane for the 3rd filtration is not greater than 0.3μm; The preparation method of the compound cortex phellodendri alcohol precipitation paste comprises the following steps: According to weight parts, 80±10 parts of forsythia, 40±5 parts of cortex phellodendri, 40±5 parts of honeysuckle, 40±5 parts of dandelion, and 2.4±0.3 parts of centipede are weighed; water is added for decoction and extraction three times; the decoction is combined, filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.10-1.15; then ethanol is added to the clear paste to make the ethanol content reach 60-70%, and the mixture is allowed to stand, filtered, and the filtrate is concentrated under reduced pressure to obtain the compound cortex phellodendri alcohol precipitation paste.

2. The manufacturing process according to claim 1, characterized in that, The certain volume in the S1 step is configured to 600ml.

3. The manufacturing process of claim 1, wherein, The purified water in the S1 step is water for injection.

4. The manufacturing process of claim 1, wherein, The pore size of the filter membrane for the 1st filtration is 0.45μm, the pore size of the filter membrane for the 2nd filtration is 0.22μm, and the pore size of the filter membrane for the 3rd filtration is 0.22μm.

5. A sterile compound cortex phellodendri freeze-dried stock solution, characterized in that, The sterile compound cortex phellodendri freeze-dried stock solution is prepared by the preparation process according to any one of claims 1-4.

6. A compound cortex phellodendri freeze-dried powder, characterized in that, The compound cortex phellodendri freeze-dried powder is prepared from the sterile compound cortex phellodendri freeze-dried stock solution, comprising the following steps: The sterile compound cortex phellodendri freeze-dried stock solution is pre-frozen at a pressure of 0-3Pa and a temperature of-47℃ to-43℃, then sublimated once at a pressure of 8-12Pa and a temperature of-12℃ to-8℃, and finally desorbed and dried at a pressure of 28-32Pa and a temperature of 38-42℃ to obtain the compound cortex phellodendri freeze-dried powder; The preparation process of the sterile compound cortex phellodendri freeze-dried stock solution comprises the following steps: S1: Take the compound cortex phellodendri alcohol precipitation paste, add purified water to a certain volume, and store in a refrigerator to obtain a mixed solution; S2: Take the supernatant of the mixed solution in step S1, and perform sterile filtration at least i times through a filter membrane at a temperature of 30-40℃ to obtain a sterile compound cortex phellodendri freeze-dried stock solution; Wherein, i is a natural number and traverses from 1 to n, n is a natural number and is not less than 3; the pore size of the filter membrane for the i+1th filtration is not greater than the pore size of the filter membrane for the ith filtration; The certain volume in the S1 step is configured to 600-800ml; The i is 3, the pore size of the filter membrane for the 1st filtration is not greater than 0.5μm, the pore size of the filter membrane for the 2nd filtration is not greater than 0.3μm, and the pore size of the filter membrane for the 3rd filtration is not greater than 0.3μm; The preparation method of the compound cortex phellodendri alcohol precipitation paste comprises the following steps: Take forsythia 80±10 parts, cortex phellodendri 40±5 parts, honeysuckle 40±5 parts, dandelion 40±5 parts, and centipede 2.4±0.3 parts by weight; add water to decoct and extract three times; combine the decoction, filter, and concentrate the filtrate to a clear extract with a relative density of 1.10-1.15; then add ethanol to the clear extract to make the ethanol content reach 60-70%, stand, filter, and reduce pressure to concentrate the filtrate to obtain the compound cortex phellodendri liquid-ethanol precipitated paste.

7. The compound cortex phellodendri freeze-dried powder of claim 6, characterized in that, The volume in the S1 step is configured to be 600 ml.

8. The compound cortex phellodendri freeze-dried powder of claim 6, characterized in that, The purified water in the S1 step is injection water.

9. The compound cortex phellodendri freeze-dried powder of claim 6, characterized in that, The pore size of the filter membrane for the first filtration is 0.45 μm, the pore size of the filter membrane for the second filtration is 0.22 μm, and the pore size of the filter membrane for the third filtration is 0.22 μm.

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