Preparation method of Sihuang dysentery stopping syrup

Abstract

The invention relates to the technical field of veterinary traditional Chinese medicine preparations, and particularly discloses a preparation method of rhizoma coptidis, radix scutellariae, cortex phellodendri, radix et rhizoma rhei, radix glycyrrhizae and radix isatidis dysentery stopping syrup, which comprises the following steps: crushing rhizoma coptidis, radix scutellariae, cortex phellodendri, radix et rhizoma rhei, radix glycyrrhizae and radix isatidis, performing ultrasonic treatment, performing reflux extraction, performing filtration, merging filtrate, performing vacuum concentration to obtain thick paste, mixing the thick paste and simple syrup according to a ratio of 1: 3, adding 0.3% sodium benzoate, and performing constant volume filling. According to the preparation method disclosed by the invention, the extraction rate of effective components is remarkably improved by optimizing an extraction process, the content of baicalin in the prepared Sihuang dysentery relieving syrup is 2.99-3.37 times that of commercially available granules, the content of berberine hydrochloride is 8.74-11.57 times that of the commercially available granules, and the preparation method of the novel Sihuang dysentery relieving preparation with high quality and high efficiency is provided.

Description

Technical Field

[0001] This invention relates to the field of veterinary traditional Chinese medicine preparations, specifically to a method for preparing a Sihuang Zhili Syrup. Background Technology

[0002] The Sihuang Zhili formula, a classic traditional Chinese veterinary medicine compound, is widely used in the treatment of bacterial enteritis and damp-heat diarrhea in livestock and poultry. Existing Sihuang Zhili granules are characterized by small dosage, convenient administration, and ease of storage and transportation; however, the granule formulation process is cumbersome, and the cost of the traditional Chinese medicine is high, significantly increasing farming costs. Although some research has attempted to improve the formulation through novel dosage forms such as nanoemulsions and sustained-release microgranules, the complexity of the process and the cost have not been significantly reduced. Therefore, it is necessary to develop a high-quality and efficient new method for preparing Sihuang Zhili formulations. Summary of the Invention

[0003] To develop a novel, high-quality, and efficient method for preparing a four-herb anti-dysentery formulation, this invention provides a method for preparing a four-herb anti-dysentery syrup. The method provided by this invention significantly simplifies the production process of the four-herb anti-dysentery formula and greatly improves the extraction rate of the core active ingredients baicalin and berberine hydrochloride. The content of baicalin and berberine hydrochloride in the four-herb anti-dysentery syrup reaches 3 to 11 times that of commercially available granules, thus providing a novel, high-quality, and efficient method for preparing a four-herb anti-dysentery formulation.

[0004] This invention provides a method for preparing Sihuang Zhishi Syrup, specifically including the following steps: Take Coptis chinensis, Scutellaria baicalensis, Phellodendron chinense, Rheum palmatum, Glycyrrhiza uralensis, and Isatis indigotica in a mass ratio of 3~5:3~5:3~5:1~3:1~3:3~5, combine and pulverize them, then sonicate them to obtain drug powder; Add solvent to the drug powder at a material-to-liquid ratio of 1:10~20 and reflux to extract the extract. Filter the extract to obtain the filtrate. The filtrate was concentrated under reduced pressure to a thick paste with a relative density of 1.15~1.2; Add monosaccharide syrup to the thick paste, then add sodium benzoate, stir well, add more monosaccharide syrup to make up the volume, fill and seal to obtain Sihuang Zhili Syrup.

[0005] The preparation method of Sihuang Zhili Syrup provided by this invention significantly simplifies the production process of Sihuang Zhili formula, and the content of baicalin and berberine hydrochloride in the prepared Sihuang Zhili Syrup is 3 to 11 times that of commercially available granules.

[0006] Furthermore, the mass ratio of Coptis chinensis, Scutellaria baicalensis, Phellodendron chinense, Rheum palmatum, Glycyrrhiza uralensis, and Isatis indigotica is 2:2:2:1:1:2.

[0007] Furthermore, the reflux extraction temperature is 85℃~95℃, and the extraction is performed 3 to 5 times.

[0008] Furthermore, the parameters for the reflux extraction are: temperature 90℃, extraction times 3 times, and material-to-liquid ratio 1:15.

[0009] Furthermore, the solvent is purified water.

[0010] Furthermore, the simple syrup is an 85% sucrose aqueous solution.

[0011] Furthermore, the mass ratio of the thick paste to the simple syrup is 1:3~5.

[0012] Furthermore, the ultrasonic processing power is 300 W, the frequency is 40 kHz, and the processing time is 25 min to 35 min.

[0013] Furthermore, the temperature for the vacuum concentration is 48°C to 52°C.

[0014] Furthermore, the amount of sodium benzoate added is 0.3% of the total mass of Sihuang Zhili Syrup.

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention utilizes a specific herbal ratio of Coptis chinensis: Scutellaria baicalensis: Phellodendron chinense: Rheum palmatum: Glycyrrhiza uralensis: Isatis indigotica (2:2:2:1:1:2), an optimized extraction process involving ultrasonic pretreatment, a 1:15 material-to-liquid ratio, three reflux extractions at 90°C, and vacuum concentration at 50°C to a specific density. It also employs a formulation with a thick paste: simple syrup ratio of 1:3 and the addition of 0.3% sodium benzoate. This significantly simplifies the production process of the Sihuang Zhili formula and greatly improves the extraction rate of the core active ingredients, baicalin and berberine hydrochloride. The content of baicalin and berberine hydrochloride in the Sihuang Zhili syrup reaches 3 to 11 times that of commercially available granules. Thus, while ensuring or improving product efficacy, it effectively reduces production costs and process complexity, providing a high-quality and efficient novel method for preparing Sihuang Zhili preparations. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art 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.

[0017] Figure 1 The HPLC chromatogram of the test sample; In the figure, A is the HPLC chromatogram of commercially available Sihuang Zhili Granules 1; B is the HPLC chromatogram of commercially available Sihuang Zhili Granules 2; C is the HPLC chromatogram of commercially available Sihuang Zhili Granules 3; D is the HPLC chromatogram of Sihuang Zhili Syrup.

[0018] Figure 2 The study analyzed the physical signs of chicks in each group during the administration period. T1 was the control group, T2 was the model group, T3 was the high-dose group of commercially available Sihuang Zhili granules, T4 was the low-dose group of commercially available Sihuang Zhili granules, T5 was the high-dose group of Sihuang Zhili syrup, T6 was the medium-dose group of Sihuang Zhili syrup, and T7 was the low-dose group of Sihuang Zhili syrup. In the figure, A represents the amount of food consumed by chicks in each group during the drug administration period; B represents the water consumption of each group of chicks during the drug administration period; C represents the survival rate of chicks in each group during the drug administration period; D represents the DAI score of each group of chicks during the drug administration period.

[0019] Figure 3 Anatomical diagrams of organs in each group of chicks. Detailed Implementation

[0020] The specific embodiments of the present invention are described in detail below, but it should be understood that the scope of protection of the present invention is not limited to the specific embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise specified, the experimental methods described in the embodiments of the present invention are conventional methods, and the materials and reagents used in the following embodiments are commercially available unless otherwise specified.

[0021] Example 1: A method for preparing a four-yellow dysentery syrup Take 200 g of the following medicinal materials: Coptis chinensis, Scutellaria baicalensis, Phellodendron chinense, Rheum palmatum, Glycyrrhiza uralensis, and Isatis indigotica. Combine and pulverize them, then treat them with an ultrasonic generator (DELIXI, Xinzhi Technology) at 300 W and 40 kHz for 30 min (to improve extraction efficiency and facilitate rapid dissolution of active ingredients) to obtain drug powder. Mix the drug powder with purified water at a material-to-liquid ratio of 1:15 and extract three times by reflux at 90℃ using a digital display electric heating mantle (SXKW, Beijing Zhongxing Weiye Instrument Co., Ltd.). Combine the three extracts, vacuum filter (filter diameter 20 μm), and then concentrate them under reduced pressure at 50℃ using a rotary evaporator (4500A, Yongkang Sufeng Industry and Trade Co., Ltd.) and a circulating water multi-purpose vacuum pump (SHZ-D, Huachen Instrument Co., Ltd.) until a thick paste with a relative density of 1.15 to 1.2 is obtained.

[0022] Add monosaccharide syrup (paste:monosaccharide syrup = 1:3, the monosaccharide syrup is 85% sucrose aqueous solution) to the obtained thick paste, then add sodium benzoate at a mass fraction of 0.3%, stir thoroughly and then adjust the volume with monosaccharide syrup. Finally, use an oral liquid sealing machine (KFJ-1035, Wenzhou Hufeng Intelligent Technology Co., Ltd.) to fill and seal the contents to obtain Sihuang Zhili Syrup.

[0023] Example 2: A method for preparing a four-yellow dysentery syrup Take 150 g of the following medicinal materials: Coptis chinensis, Scutellaria baicalensis, Phellodendron chinense, Rheum palmatum, Glycyrrhiza uralensis, and Isatis indigotica. Combine and pulverize them, then process them with an ultrasonic generator (DELIXI, Xinzhi Technology) at 300 W and 40 kHz for 25 min to obtain the drug powder. Mix the drug powder with pure water at a ratio of 1:10 and extract four times by reflux at 85℃ using a digital display heating mantle (SXKW, Beijing Zhongxing Weiye Instrument Co., Ltd.). Combine the four extracts, filter them under vacuum (20 μm filter diameter), and then concentrate them under reduced pressure at 48℃ using a rotary evaporator (4500A, Yongkang Sufeng Industry and Trade Co., Ltd.) and a circulating water multi-purpose vacuum pump (SHZ-D, Huachen Instrument Co., Ltd.) until a thick paste with a relative density of 1.15 to 1.2 is obtained.

[0024] Add monosaccharide syrup (paste: syrup = 1:4) to the obtained thick paste, then add sodium benzoate at a mass fraction of 0.3%, stir thoroughly, and then adjust the volume with monosaccharide syrup. Finally, use an oral liquid sealing machine (KFJ-1035, Wenzhou Hufeng Intelligent Technology Co., Ltd.) to fill and seal the contents to obtain Sihuang Zhili Syrup.

[0025] Example 3: A method for preparing a four-yellow dysentery syrup Take 250 g of the following medicinal materials: Coptis chinensis, Scutellaria baicalensis, Phellodendron chinense, Rheum palmatum, Glycyrrhiza uralensis, and Isatis indigotica. Combine and pulverize them, then process them with an ultrasonic generator (DELIXI, Xinzhi Technology) at 300 W and 40 kHz for 35 min to obtain the drug powder. Mix the drug powder with pure water at a material-to-liquid ratio of 1:20 and extract five times at 95℃ using a digital display electric heating mantle (SXKW, Beijing Zhongxing Weiye Instrument Co., Ltd.). Combine the five extracts, filter them under vacuum (20 μm filter diameter), and then concentrate them under reduced pressure at 52℃ using a rotary evaporator (4500A, Yongkang Sufeng Industry and Trade Co., Ltd.) and a circulating water multi-purpose vacuum pump (SHZ-D, Huachen Instrument Co., Ltd.) until a thick paste with a relative density of 1.15 to 1.2 is obtained.

[0026] Add monosaccharide syrup (paste:monosaccharide syrup = 1:5) to the obtained thick paste, then add sodium benzoate at a mass fraction of 0.3%, stir thoroughly, and then adjust the volume with monosaccharide syrup. Finally, use an oral liquid sealing machine (KFJ-1035, Wenzhou Hufeng Intelligent Technology Co., Ltd.) to fill and seal the contents to obtain Sihuang Zhili Syrup.

[0027] The Sihuang Zhili Syrup prepared in Examples 1-3 of this invention has comparable performance. Taking the Sihuang Zhili Syrup prepared in Example 1 as an example, this invention conducts baicalin and berberine hydrochloride content detection and animal in vivo experiments.

[0028] I. Detection of Baicalin and Berberine Hydrochloride Content Reference solutions containing 120 μg / ml of baicalin and berberine hydrochloride standards were prepared using methanol, and then serially diluted to other concentrations listed in Table 1 to obtain standard solutions. Using octadecylsilane-bonded silica gel as the stationary phase and methanol-water-phosphoric acid (v / v 43:57:0.2) as the mobile phase, with a detection wavelength of 278 nm and a column temperature of 40℃, 10 μL each of the baicalin and berberine hydrochloride standard solutions were accurately injected into the liquid chromatograph for high-performance liquid chromatography (HPLC) detection. Standard curves were then constructed based on the content of the standards and the HPLC peak areas.

[0029] Three commercially available Sihuang Zhili Granules (commercially available granule 1: Sichuan Wanxin Animal Pharmaceutical Co., Ltd., approval number: Veterinary Drug No. 220155045, production batch number: 20221101; commercially available granule 2: Henan Yinghua Biotechnology Co., Ltd., approval number: Veterinary Drug No. 163175045, production batch number: 20240122; commercially available granule 3: Hefei Zhonglong Shenli Animal Pharmaceutical Co., Ltd., approval number: Veterinary Drug No. 120155045, production batch number: 20231127) and the prepared Sihuang Zhili Syrup were selected as test samples. 0.5 g of each test sample was accurately weighed and placed in a 100 mL volumetric flask. After adding an appropriate amount of methanol, the mixture was sonicated (power 250 W, frequency 40 kHz) for 30 min. After cooling, methanol was added to make up to 100 mL. The filtrate was collected after filtration to obtain the test solution. Using octadecylsilane-bonded silica gel as the packing material and methanol-water-phosphoric acid (volume ratio 43:57:0.2) as the mobile phase, the detection wavelength was 278 nm, the column temperature was 40℃, and 10 μL of each test solution was accurately injected into the liquid chromatograph for HPLC detection. The contents of baicalin and berberine hydrochloride in the test sample were quantified using a standard curve.

[0030] The high performance liquid chromatography (HPLC) results of baicalin and berberine hydrochloride standards are shown in Table 1.

[0031] Table 1. Peak areas of baicalin and berberine hydrochloride standards The following standard curve is derived based on the relationship between the content of the standard and the peak area of ​​the HPLC: The standard curve for baicalin content is y = 9139.7x + 36033, where y is the HPLC peak area, x is the baicalin content (mg / mL), 9139.7 is the slope, and 36033 is the intercept. The standard curve for berberine hydrochloride content is y=14249x-19161, where y is the HPLC peak area, x is the berberine hydrochloride content (mg / mL), 14249 is the slope, and -19161 is the intercept.

[0032] Linear regression analysis showed that the coefficients of determination for the standard curves of baicalin and berberine hydrochloride were R²=0.9987 and R²=0.9992, respectively, indicating that the standard curves could accurately quantify the content of baicalin and berberine hydrochloride in the sample.

[0033] Based on the HPLC detection results of the test sample ( Figure 1 From A to D), the peak areas of commercially available granules 1, 2, and 3 and Sihuang Zhili Syrup are 148086, 123500, 129167, and 345869, respectively. The contents of baicalin and berberine hydrochloride in the test samples were calculated based on the standard curve. The baicalin contents of commercially available granules 1, 2, and 3 were 11.35 mg / mL, 10.04 mg / mL, and 11.13 mg / mL, respectively, while the baicalin content of Sihuang Zhili Syrup was 33.89 mg / mL. Compared with Sihuang Zhili Syrup, the baicalin content of Sihuang Zhili Syrup increased by 2.99 to 3.37 times, which is 7.06 times the limit specified in the pharmacopoeia. The contents of berberine hydrochloride in commercially available granules 1, 2, and 3 were 1.50 mg / mL, 1.97 mg / mL, and 1.95 mg / mL, respectively, while the berberine hydrochloride content of Sihuang Zhili Syrup was 17.49 mg / mL. Compared with Sihuang Zhili Syrup, the berberine hydrochloride content of Sihuang Zhili Syrup increased by 8.74 to 11.57 times.

[0034] The above results indicate that the content of baicalin and berberine hydrochloride in the Sihuang Zhili Syrup prepared by the method of the present invention is significantly higher than that in commercially available Sihuang Zhili Granules, effectively enhancing the medicinal active ingredients in the Sihuang Zhili formula.

[0035] II. Animal live experiments 1. Grouping and Dosing Program for Chicks One-day-old white-feathered roosters were raised in the animal laboratory of Northwest A&F University. From day 1 to day 3, the room temperature was 34℃; from day 4 to day 7, the room temperature was 32℃. The temperature was then decreased by 2℃ weekly until 21 days of age. 210 chicks were randomly divided into 7 groups of 30 each: a control group, a model group, a high-dose group (1 g / d) of commercially available Sihuang Zhili granules, a low-dose group (0.5 g / d) of commercially available Sihuang Zhili granules, a high-dose group (0.5 g / d) of Sihuang Zhili syrup, a medium-dose group (0.25 g / d) of Sihuang Zhili syrup, and a low-dose group (0.1 g / d) of Sihuang Zhili syrup. Commercially available Sihuang Zhili granules were selected. The avian pathogenic Escherichia coli CMCC44102 (Nanjing Bianzhen Biotechnology Co., Ltd., product number BZW23116) was used in the experiment. Control group chicks were injected intraperitoneally with 1 mL of physiological saline, while chicks in the other groups were injected intraperitoneally with 1 mL of Escherichia coli suspension (7.5 × 10⁻⁶). 7 The CFU / mL solution was used for modeling. Treatment began 5 hours after the bacterial suspension was injected. For 6 consecutive days, 1 mL of the drug solution was administered orally twice a day (the corresponding mass of the drug was dissolved in water according to the required drug dosage for each group). The control group and the model group were given the same amount of physiological saline at the same time.

[0036] 2. Therapeutic indicators The feed intake, water intake, and survival rate of chicks after injection of the bacterial suspension were recorded, and a disease activity index (DAI) was established (Table 2). The overall condition of the chicks was assessed based on the proportion of weight loss, fecal moisture, and bleeding. After the oral administration of the drug, blood was collected from the heart, liver, intestines, and immune organs of each group of chicks. The collected blood samples were allowed to stand at room temperature for 30 min, centrifuged at 3000 rpm for 10 min, and the serum was collected and stored at -80℃.

[0037] Table 2 DAI Scores The results showed that the feed and water intake of chicks in the model group decreased, while the feed and water intake of chicks in the high-dose Sihuang Zhili Syrup group increased significantly compared to the model group, and were the closest to the control group among all treatment groups. Figure 2 A and Figure 2 (B); The survival rate of chicks in the model group decreased to 60% after 7 days. The survival rates of chicks in the high-dose, medium-dose, and low-dose groups of Sihuang Zhili Syrup after 7 days were 90%, 80%, and 70%, respectively. The survival rates of chicks in the high-dose and low-dose groups of commercially available Sihuang Zhili Granules after 7 days were 87% and 70%, respectively. Figure 2 The DAI score of the high-dose Sihuang Zhili Syrup group was closest to that of the control group (C); Figure 2(D). The above results indicate that Sihuang Zhili Syrup can effectively increase the amount of food and water consumed and the survival rate of chicks, and its therapeutic effect is better than that of commercially available Sihuang Zhili Granules.

[0038] The heart is visible on the outside ( Figure 3 In the model group, the heart had yellow fibrinous exudate covering the epicardial surface; the heart appearance of the medium-dose Sihuang Zhili Syrup group and the high-dose Sihuang Zhili Granules group was similar, indicating that the two had comparable protective effects on the heart; compared with the high-dose Sihuang Zhili Granules group, the heart appearance of the high-dose Sihuang Zhili Syrup group was closer to that of the control group, indicating that its protective effect on the heart was superior to that of the high-dose Sihuang Zhili Granules group.

[0039] The liver is visible on the outside ( Figure 3 In the model group, the liver parenchyma was scattered with yellowish-white necrotic foci ranging in size from pinhead to millet grain, and the liver was enlarged with yellowish-white fibrous exudate. The liver appearance of the medium-dose Sihuang Zhili Syrup group was similar to that of the high-dose Sihuang Zhili Granules group, with no obvious fibrinous exudate, indicating that the two had comparable protective effects on the liver. Compared with the high-dose Sihuang Zhili Granules group, the liver appearance of the high-dose Sihuang Zhili Syrup group was closer to that of the control group, indicating that its protective effect on the liver was superior to that of the high-dose Sihuang Zhili Granules group.

[0040] The bursa of Fabricius showed significant atrophy in the model group. Sihuang Zhili Syrup significantly alleviated the atrophy of the bursa of Fabricius. While the high-dose group of commercially available Sihuang Zhili granules showed improvement, the effect was not as good as the medium-high dose group of Sihuang Zhili Syrup. Figure 3 ).

[0041] The spleens in the model group were significantly enlarged, with grayish-white necrotic foci visible on the surface and cut surface, accompanied by fibrinous exudate. In the treatment group, the spleens of the high-dose Sihuang Zhili syrup group were closest in appearance to the control group, with mild enlargement, a smooth surface, and no exudate. Although the commercially available Sihuang Zhili granules showed varying degrees of improvement, a small amount of fibrinous exudate was still present. Figure 3 ).

[0042] In the model group, the ileocecal region showed shortening, swelling, congestion, and exudation, with petechiae visible in some areas. In the treatment group, the high-dose Sihuang Zhili Syrup group showed a significant reduction in intestinal lesions, effectively restoring intestinal length, and exhibiting smooth mucosa without significant swelling or bleeding, with only a small amount of exudation. The commercially available granule group still showed intestinal shortening and varying degrees of exudation. Figure 3 ).

[0043] Serum blood biochemical analysis of chicks in the control group, model group, high-dose group of commercially available Sihuang Zhili granules, and medium-dose group of Sihuang Zhili syrup showed (Table 3) that, compared with the control group, the model group significantly increased the expression levels of ALT, AST, LAC, and GGT (p<0.05) and decreased the expression levels of ALB and TP (p<0.05). Compared with the model group, the medium-dose group of Sihuang Zhili syrup significantly reversed the abnormal increases or decreases in ALT, AST, LAC, GGT, ALB, and TP (p<0.05), and the effect was comparable to that of the high-dose group of commercially available Sihuang Zhili granules.

[0044] Table 3 Results of blood biochemistry analysis Note: Lowercase letters in the table indicate the significance of differences in data within the same row.

[0045] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments.

[0046] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A process for the preparation of Siyad Syrup, characterized in that, Specifically comprising the following steps: Take Huanglian, Huangqin, Huangbo, Dahuang, Gancao and Banlangen in a mass ratio of 3-5:3-5:3-5:1-3:1-3:3-5, combine and crush, then ultrasonic treatment to obtain a drug powder; Add a solvent to the drug powder in a solid-liquid ratio of 1:10-20, reflux extraction to obtain an extract, and filter to obtain a filtrate; Concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.15-1.2; Add monosaccharide syrup to the thick paste, then add sodium benzoate, stir until uniform, add monosaccharide syrup to constant volume, fill and seal to obtain the Four-Huang Dysentery Stopping Syrup.

2. The process for the preparation of the Si-Yang Zhi Li syrup as claimed in claim 1, wherein, The temperature of the reflux extraction is 85-95°C, and the extraction is performed 3-5 times.

3. The process for the preparation of the Si-Yang Zhi Li syrup as claimed in claim 1, wherein, The solvent is water.

4. The process for the preparation of the Si-Yang Zhi Li syrup as claimed in claim 1, wherein, The monosaccharide syrup is 80-90% sucrose solution.

5. The process for the preparation of the Si-Yang Zhi Li syrup as claimed in claim 1, wherein, The mass ratio of the thick paste to the monosaccharide syrup is 1:3-5.

6. The process for the preparation of the Si-Yang Zhi Li syrup as claimed in claim 1, wherein, The ultrasonic treatment power is 250-350 W, the frequency is 35-45 kHz, and the treatment time is 25-35 min.

7. The process for the preparation of the Four Yellow Antidiarrheal Syrup as claimed in claim 1, wherein, The temperature of the reduced pressure concentration is 48-52°C.

8. The process for the preparation of the Four Yellow Antidiarrheal Syrup as claimed in claim 1, wherein, The amount of sodium benzoate added is 0.25-0.35% of the total mass of the Four-Huang Dysentery Stopping Syrup.

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