A method for preparing a qingre sanjie capsule, and products and uses thereof

Abstract

The application provides a method for preparing Qingre Sanjie capsules, products and applications thereof, and relates to the technical field of medicines.The method comprises the following steps: (1) decocting Senecio scandens Buch.-Ham with water, filtering, and then filtering the decocting liquid through a ceramic membrane to obtain filtrate A; (2) first concentrating the filtrate A through an organic membrane, then concentrating under reduced pressure to obtain thick paste A; (3) adding an ethanol solution to the thick paste A, standing, filtering to obtain filtrate B; (4) recovering ethanol from the filtrate B, concentrating to obtain thick paste B; (5) vacuum drying the thick paste B, crushing, adding accessories, mixing, granulating, drying, and loading into capsules, and the Qingre Sanjie capsules are obtained. The preparation method increases the membrane separation technology in the filtering and concentrating process of the decocting liquid, improves the filtering effect, reduces the energy consumption cost of concentration, and further improves the product quality and optimizes the production process as a whole.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to topical acne-removing compositions, formulations, preparation methods, and applications. Background Technology

[0002] Qingre Sanjie Capsules are a pure traditional Chinese medicine preparation made from Senecio scandens extract. They possess anti-inflammatory, detoxifying, nodule-dispersing, analgesic, and anti-tumor effects, and are used for acute conjunctivitis, acute pharyngitis, acute tonsillitis, acute bacillary dysentery, upper respiratory tract infection, acute bronchitis, lymphadenitis, boils and carbuncles, otitis media, dermatitis, and eczema. The original production process uses traditional sieve filtration and vacuum concentration for filtration and concentration, which often encounters problems such as unsatisfactory filtration effects and high energy consumption during vacuum concentration. Therefore, there is an urgent need to provide a method for preparing Qingre Sanjie Capsules that can improve filtration effects, reduce energy consumption costs during concentration, and thus improve overall product quality and optimize the production process. Summary of the Invention

[0003] This invention addresses the problems existing in the prior art by providing a method for preparing heat-clearing and nodule-dispersing capsules, along with the product and its application. This preparation method applies membrane separation technology in the filtration and concentration processes of the decoction. Based on the original process, it adds ceramic membrane filtration and organic membrane concentration processes to improve the filtration effect, reduce the energy consumption cost of concentration, and thus improve the overall product quality and optimize the production process.

[0004] One objective of this invention is to provide a method for preparing heat-clearing and nodule-dispersing capsules, the method comprising the following steps: (1) Add water to Senecio scandens and decoct. After filtration, filter the decoction through a ceramic membrane to obtain filtrate A. (2) Filtrate A is first concentrated by an organic membrane and then concentrated under reduced pressure to obtain viscous paste A; (3) Add ethanol solution to thick paste A, let stand, filter, and obtain filtrate B; (4) Filtrate B is used to recover ethanol and concentrate it to obtain thick paste B; (5) Vacuum dry the thick paste B, pulverize it, add excipients, mix well, granulate, dry and encapsulate to obtain the final product.

[0005] Preferably, the pore size of the ceramic membrane in step (1) is 50-250 nm.

[0006] Preferably, the organic membrane in step (2) is a reverse osmosis membrane or a nanofiltration membrane.

[0007] Preferably, in step (2), the organic membrane is concentrated to 5%-30% of the volume of filtrate A.

[0008] Preferably, in step (2), the relative density of the paste A at 25°C is 1.15-1.20.

[0009] Preferably, in step (3), the volume of ethanol solution added is 0.5-1.5 times the weight of paste A, the volume fraction of ethanol solution is 70-95%, and the standing time is 10-15h.

[0010] Preferably, the relative density of the paste B in step (4) at 80°C is 1.25-1.35.

[0011] A second aspect of the present invention is a heat-clearing and nodule-dissolving capsule prepared according to the above method.

[0012] The second aspect of the present invention is the application of the above method in the preparation of heat-clearing and nodule-dissolving capsules.

[0013] Compared with the prior art, the present invention has the following beneficial effects: on the basis of the original process, the addition of ceramic membrane filtration and organic membrane concentration steps improves the filtration effect and reduces the energy consumption cost of concentration. At the same time, the change in membrane filtration will not cause any change in the medicinal material basis of the Qingre Sanjie capsule. Attached Figure Description

[0014] Figure 1 : Stacked chromatogram of fingerprint spectrum for ceramic membrane filtration; Figure 2 Chromatogram of similarity between ceramic membrane filtration and other materials; Figure 3 Stacked chromatograms of concentrated fingerprints from organic membranes; Figure 4 : Chromatogram of similarity of organic membrane concentration. Detailed Implementation

[0015] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection of the present invention, and those skilled in the art can make various changes and modifications to the invention based on the disclosed content, which should also fall within the scope of protection of the present invention.

[0016] Experimental Example 1: Study on Changes in Filtration Process (Change to Ceramic Membrane Filtration) 1. Small-scale study (1) Ceramic membrane screening For the same batch of heat-clearing and nodule-dissolving capsule extract, under the same experimental conditions, by examining the average membrane flux, pH, turbidity, conductivity, and other data of the membrane filtrate passing through the membrane with different pore sizes, the most suitable ceramic membrane model was selected to adapt to this process.

[0017] The extracted heat-clearing and nodule-dispersing capsule extract was sequentially filtered through ceramic membranes with pore sizes of 200nm, 100nm, 15nm, and 5nm under specific experimental parameters. Membrane flux was monitored throughout the process, the average flux was calculated, and the turbidity, conductivity, and pH of both the extract and the filtrate were checked online. After filtration, the ceramic membranes were cleaned and maintained.

[0018] The extract of the heat-clearing and nodule-dissolving capsules was prepared in-house; sodium hydroxide, AR grade, was supplied by Inner Mongolia Junzheng Energy Chemical Co., Ltd.; citric acid, AR grade, was supplied by Guangzhou Keqi Biotechnology Co., Ltd.

[0019] The research instruments are shown in Table 1.

[0020] Table 1: List of Instruments for Small-Scale Research on Filter Changes

[0021] Parameters: Ceramic membrane area: 0.055m² 2 Frequency: 45Hz, pressure: 0.2MPa, stock solution temperature: 60℃, total drug volume: 20L, ceramic membrane pore size: 200nm / 100nm / 15nm / 5nm. The results of the small-scale test are shown in Table 2.

[0022] Table 2: Results of the small-scale study on filter modification

[0023] Summary: The comparison of the above data shows that the conductivity of the membrane filtrate decreased slightly, and some ions in the feed solution were also retained during the transfer to the supernatant. The performance of the different membrane specifications was not significantly different, with the 200nm and 100nm ceramic membranes being the best. The pH was almost unaffected.

[0024] (2) Investigation of residual substances in ceramic membrane By sending samples to a third-party testing institution, the elemental composition analysis and heavy metal residue of the ceramic membrane were tested according to the XRF testing method and GB 31604.49-2016 to examine the migration of heavy metals during the ceramic membrane filtration process. The test results showed that the risk of heavy metal contamination to the raw materials during the ceramic membrane filtration process was controllable and did not affect product quality.

[0025] 2. Pilot-scale study An appropriate amount of *Senecio scandens* was weighed and extracted according to the process to obtain an extract, which was then filtered through a ceramic membrane to obtain a ceramic membrane filtrate. The solid content, content of indicator components, fingerprint spectrum, pH, turbidity, conductivity, and membrane flux of the prepared concentrated and clear extracts were examined.

[0026] Research materials: Extract of Qingre Sanjie capsules, prepared in-house; Sodium hydroxide, AR grade, Inner Mongolia Junzheng Energy Chemical Co., Ltd.; Citric acid, AR grade, Guangzhou Keqi Biotechnology Co., Ltd.; Methanol and acetonitrile, HPLC grade, Merck Chemical Technology (Shanghai) Co., Ltd.; Phosphoric acid, hydrochloric acid, and acetic acid, AR grade, Jiangxi Hengxin Chemical Co., Ltd.; Reference solution, prepared in-house (reference standard, National Institutes for Food and Drug Control).

[0027] The research instruments are shown in Table 3.

[0028] Table 3: List of Instruments for Pilot-Scale Research with Filter Changes

[0029] The results of the investigation of basic parameters of ceramic membrane filtration process are shown in Table 4.

[0030] Table 4: Results of Investigation on Basic Parameters of Ceramic Membrane Filtration Process

[0031] The results of the determination of the content of components in the ceramic membrane filtration process are shown in Table 5.

[0032] Table 5: Determination of Component Content in Ceramic Membrane Filtration Process Indicators

[0033] The results of the solid content analysis for the ceramic membrane filtration process are shown in Table 6.

[0034] Table 6: Solid Content Analysis of Ceramic Membrane Filtration Process

[0035] After filtration through the ceramic membrane, the sample was continuously injected and analyzed six times. The fingerprint spectra were recorded. The results of the fingerprint analysis are shown below. Figure 1 , Figure 2 .

[0036] In summary, the results of the analysis of the extract concentrate and supernatant, including component content and fingerprint spectroscopy, before and after the change in membrane filtration process (i.e., before and after using a 100nm ceramic membrane), indicate that the change in membrane filtration did not alter the medicinal material basis of this product, and component loss was very low. Meanwhile, data on solid content and turbidity show that while maintaining the material basis, membrane filtration effectively removed impurities, improved filtration efficiency, and met the requirements for stable quality control.

[0037] Experimental Example 2: Study on Changes to Concentration Process (Addition of Organic Membrane Concentration) 1. Small-scale study (1) Material selection for membrane concentration process The 20L filtrate from the heat-clearing and sludge-dispersing capsules, after passing through the ceramic membrane, was concentrated by passing it sequentially through an ultrafiltration organic membrane and a reverse osmosis organic membrane under specific experimental parameters. The total concentration was 5 times. The membrane flux was recorded throughout the process according to the concentration factor, and the turbidity, conductivity, pH, and other data of the concentrated stock solution and the membrane-passed solution were tested online.

[0038] Research materials: The ceramic membrane filtrate from the heat-clearing and nodule-dissolving capsules was prepared in-house; sodium hydroxide, AR grade, was supplied by Inner Mongolia Junzheng Energy Chemical Co., Ltd.; citric acid, AR grade, was supplied by Guangzhou Keqi Biotechnology Co., Ltd.

[0039] The research instruments are shown in Table 7.

[0040] Table 7: List of Instruments for Small-Scale Research on Concentration Process Modification

[0041] Research parameters: Organic membrane type 2540, frequency 45Hz, pressure 2MPa, feed solution temperature 30℃, total amount of reagent 20L, organic membrane type nanofiltration / reverse osmosis membrane.

[0042] The results are shown in Table 8.

[0043] Table 8: Results of Small-Scale Trial Study on Membrane Materials for Concentration Process Modification

[0044] In summary, the data shows that the average membrane flux of reverse osmosis membranes is higher than that of nanofiltration membranes, indicating a higher overall membrane concentration efficiency. Regarding turbidity and conductivity, as the concentration ratio increases, the permeate clarity of nanofiltration membranes slightly increases, while the change in reverse osmosis membranes is minimal, indicating a higher rejection rate for reverse osmosis membranes compared to nanofiltration membranes. In terms of pH, the difference between the two is not significant, with nanofiltration membranes showing slightly lower permeate clarity, indicating a higher proportion of acidic components, confirming a lower rejection rate for reverse osmosis membranes. Therefore, both can be used as materials for membrane concentration processes.

[0045] (2) Investigation of organic membrane residues: Samples were sent to a third-party testing institution for testing according to (EU) No. 10 / 2011 and its amendment directive (EU) 2020 / 1245. Sensory evaluation, primary aromatic amine residues, and heavy metal residues were examined to investigate the migration of aromatic amines and heavy metals during organic membrane concentration. The results of testing for total organic membrane migration, sensory evaluation (odor and taste), specific migration of primary aromatic amines, and specific migration of heavy metals all met EU standards, indicating that the risk of contamination of raw materials by heavy metals and aromatic amines during organic membrane concentration is controllable and does not affect product quality.

[0046] 2. Pilot-scale study Weigh an appropriate amount of Senecio scandens medicinal material, extract it according to the process, filter it through a ceramic membrane, concentrate the filtrate to 5%-30% of its original volume through an organic membrane, and then continue to concentrate it under reduced pressure to a thick paste with a relative density of 1.18-1.19 (80℃).

[0047] Take the concentrated liquid and clear liquid of the concentrate prepared in the modified process, and examine the solid content, content of index components, fingerprint spectrum, pH, turbidity, conductivity, membrane flux and other data.

[0048] Qingre Sanjie Capsule Extract, prepared in-house; Sodium Hydroxide, AR grade, Inner Mongolia Junzheng Energy Chemical Co., Ltd.; Citric Acid, AR grade, Guangzhou Keqi Biotechnology Co., Ltd.; Methanol and Acetonitrile, HPLC grade, Merck Chemical Technology (Shanghai) Co., Ltd.; Phosphoric Acid, Hydrochloric Acid, and Acetic Acid, AR grade, Jiangxi Hengxin Chemical Co., Ltd.; Reference Solution, prepared in-house (Reference Standard, National Institutes for Food and Drug Control).

[0049] The research instruments are shown in Table 9.

[0050] Table 9: List of Instruments for Pilot-Scale Research on Concentration Process Changes

[0051] The results of the investigation of basic parameters of organic membrane concentration process are shown in Table 10.

[0052] Table 10: Investigation of Basic Parameters of Organic Membrane Concentration Process

[0053] The results of the determination of the content of the components in the organic membrane concentration process are shown in Table 11.

[0054] Table 11: Determination of Component Content in Organic Membrane Concentration Process

[0055] The results of the solid content investigation of the organic membrane concentration process are shown in Table 12.

[0056] Table 12: Solid content analysis of organic membrane concentration process

[0057] After organic membrane concentration, the sample was continuously injected and analyzed 6 times, and the fingerprint spectrum was recorded. See details below. Figure 3 , Figure 4 .

[0058] In summary, the results of the concentration process changes—specifically, the addition of a reverse osmosis organic membrane before and after the original concentration step—including the determination of the content of key components in the concentrate and the supernatant, and fingerprint analysis, indicate that the membrane concentration change did not alter the pharmaceutical material basis of this product, and component loss was almost negligible. Furthermore, compared to traditional concentration methods, membrane concentration offers higher efficiency and lower cost, effectively alleviating the energy consumption problem in the concentration process.

[0059] Based on the test results above, the following implementation examples and comparative examples were designed.

[0060] Example 1: Take 3000g of Senecio scandens, extract it according to the process, filter it through a ceramic membrane with a pore size of 100nm, concentrate the filtrate to 10% of the original volume through a reverse osmosis membrane, and then continue to concentrate it under reduced pressure to a thick paste with a relative density of 1.15 (25℃). Add ethanol with a volume fraction of 95% equivalent to 1.5 times that of the thick paste, let it stand for 10h, filter the precipitate, recover the ethanol from the filtrate, concentrate it to a thick paste with a relative density of 1.35 (80℃), vacuum dry it, pulverize it into a fine powder, add an appropriate amount of excipients, mix well, granulate, dry, and encapsulate to obtain the final product.

[0061] Example 2: Take 3000g of Senecio scandens, extract it according to the process, filter it through a ceramic membrane with a pore size of 200nm, concentrate the filtrate to 20% of the original volume through a nanofiltration membrane, and then continue to concentrate it under reduced pressure to a thick paste with a relative density of 1.2 (25℃). Add 0.5 times the volume of the paste with a volume fraction of 70% ethanol, let it stand for 15h, precipitate and filter, recover the ethanol from the filtrate, concentrate it to a thick paste with a relative density of 1.25 (80℃), vacuum dry it, pulverize it into a fine powder, add an appropriate amount of excipients, mix well, granulate, dry, and encapsulate to obtain the final product.

[0062] Comparative Example 1: Take 3000g of Senecio scandens and extract it according to the process. Concentrate the extract under reduced pressure to a thick paste with a relative density of 1.18 (25℃). Add ethanol with a volume fraction of 95% equal to one volume of the paste. Let it stand for 12 hours, precipitate and filter. Recover the ethanol from the filtrate and concentrate it to a thick paste with a relative density of 1.30 (80℃). Vacuum dry, pulverize into a fine powder, add an appropriate amount of excipients, mix well, granulate, dry, and encapsulate to obtain the final product.

[0063] Comparative Example 2: Take 3000g of Senecio scandens, extract it according to the process, filter it through a ceramic membrane with a pore size of 100nm, concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.18 (25℃), add ethanol with a volume fraction of 95% equivalent to one volume of the paste, let it stand for 12h, precipitate and filter, recover the ethanol from the filtrate, concentrate it to a thick paste with a relative density of 1.30 (80℃), vacuum dry it, pulverize it into a fine powder, add an appropriate amount of excipients, mix well, granulate, dry, and encapsulate to obtain the final product.

[0064] The capsule formulations obtained in Examples 1-2 and Comparative Examples 1-2 were subjected to relevant index determinations according to the experimental methods in the test examples. The results are shown in Tables 13, 14 and 15.

[0065] Table 13: Results of Basic Parameter Measurements for Examples 1-2 and Comparative Examples 1-2

[0066] Table 14: Energy consumption cost results of capsule formulations (10kg) in Examples 1-2 and Comparative Examples 1-2

[0067] Table 15: Results of Indicator Component Content in Capsule Formulations of Examples 1-2 and Comparative Examples 1-2

[0068] Based on the above results, combined with the energy consumption cost and the results of multi-component content determination, the heat-clearing and nodule-dispersing capsules prepared by the preparation process provided in the various embodiments of the present invention can slightly increase the content of several main components, chlorogenic acid and hyperoside, while improving the filtration effect, and significantly reduce the overall process cost.

[0069] The above detailed description is a specific description of one of the feasible embodiments of the present invention. This embodiment is not intended to limit the patent scope of the present invention. All equivalent implementations or modifications that do not depart from the present invention should be included within the scope of the technical solution of the present invention.

Claims

1. A method for preparing heat-clearing and nodule-dispersing capsules, the method comprising the following steps: (1) Add water to Senecio scandens and decoct. After filtration, filter the decoction through a ceramic membrane to obtain filtrate A. (2) Filtrate A is first concentrated by an organic membrane and then concentrated under reduced pressure to obtain viscous paste A; (3) Add ethanol solution to the thick paste A, let it stand, filter, and obtain filtrate B; (4) Filtrate B is used to recover ethanol and concentrate it to obtain thick paste B; (5) Vacuum dry the thick paste B, pulverize it, add excipients, mix well, granulate, dry, and encapsulate to obtain the final product; The pore size of the ceramic membrane in step (1) is 100-200 nm; In step (2), the organic membrane is a reverse osmosis membrane or a nanofiltration membrane; In step (2), the organic membrane is concentrated to 5%-30% of the volume of filtrate A. In step (2), the relative density of paste A at 25°C is 1.15-1.20; In step (3), the volume of ethanol solution added is 0.5-1.5 times the weight of paste A, the volume fraction of ethanol solution is 70-95%, and the standing time is 10-15h. In step (4), the relative density of paste B at 80°C is 1.25-1.

35.

2. A heat-clearing and nodule-dispersing capsule prepared according to the method of claim 1.

3. The application of the method according to claim 1 in the preparation of heat-clearing and nodule-dispersing capsules.

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