Huang's Sound-Enhancing Spray, its Preparation Method and Application

Abstract

Huang's sound spray and its preparation method and application, specifically, the method comprises 1) subjecting Sterculia lychnophora, Platycodon grandiflorum, Periostracum cicadae, Licorice, Forsythia suspensa, Rhubarb, Chuanxiong, Terminalia chebula, Fritillaria thunbergii, Mentha oleracea, and Fang'er tea to water extraction treatment, filtering to obtain a de-impurity mother liquor, 2) subjecting the de-impurity mother liquor to de-impurity treatment under the condition that the de-impurity agent is ZTC1+1ⅡB and ZTC1+1ⅡA, 3) subjecting the product obtained after the de-impurity treatment in step 2) to alcohol precipitation treatment to obtain an alcohol precipitation clear paste, 4) mixing the alcohol precipitation clear paste with menthol to obtain Huang's sound spray. The method is simple, and the prepared Huang's sound spray is stable and has good efficacy.

Description

[0001] This application claims the priority of Chinese patent application No. 202111137951X filed on September 27, 2021. This application cites the entire text of the above Chinese patent application. Technical Field

[0002] The present invention belongs to the field of traditional Chinese medicine, and in particular, relates to Huang's sound spray and a preparation method and application thereof. Background Art

[0003] Oral and pharyngeal diseases are very common, such as oral ulcers, acute and chronic pharyngitis, tonsillitis, etc., especially among the elderly and the weak and some occupational groups. Although these diseases are not very serious, they are very painful for patients and are prone to recurrence. They can also cause other discomforts, which have a lot of impact on patients' lives and work. There are many drugs currently used to treat these diseases, but they are mainly antibiotics. Long-term use of antibiotics can make the human body resistant to them. Traditional Chinese medicine is mainly throat clearing and throat relieving, which can treat or alleviate oral and pharyngeal diseases to varying degrees, but the effect is not very significant.

[0004] Since some patients need timely treatment, in order to meet market needs, preparing Huang's Xiangsheng Pills into a spray is a good choice. However, as an oral drug, Huang's Xiangsheng Pills have lower requirements for extraction, while preparing them into a spray has higher requirements for extraction.

[0005] At present, the preparation method of Huang's sound spray still needs to be improved. Summary of the invention

[0006] There is little research on Huang's sound spray in the prior art. The applicant had proposed Huang's sound spray in the previous application document with application number CN201810763036.3, but the formula lacked Fang Cerca and Chuanxiong, and the method used was to fill it directly after water extraction. The inventor found in subsequent research that the spray after direct water extraction was very unstable and would precipitate, which did not meet the requirements of the spray. Based on this, the inventor obtained a clear and stable Huang's sound spray by discovering a new extraction and impurity removal method. At the same time, the inventor also discovered a new method for dissolving menthol, which further improved the stability of Huang's sound spray.

[0007] In the first aspect of the present invention, the present invention also proposes a Huang's sound spray. According to an embodiment of the present invention, the Huang's sound spray comprises: Sterculia lychnophora, Platycodon grandiflorum, Periostracum cicadae, Licorice, Forsythia suspensa, Rhubarb, Chuanxiong, Terminalia chebula, Fritillaria thunbergii, Menthol, Fangcacha, Menthol, Polysorbate 80 and Poloxamer-188. The inventor found that the formula has high efficacy, safety and high stability.

[0008] According to an embodiment of the present invention, the Huang's sound spray may further include at least one of the following additional technical features:

[0009] According to an embodiment of the present invention, the dosage of the Sterculia lychnophora is 1-50 parts, the dosage of the Platycodon grandiflorum is 10-200 parts, the dosage of the Periostracum Cicadae is 5-100 parts, the dosage of the Licorice is 10-200 parts, the dosage of the Forsythia suspensa is 10-200 parts, the dosage of the Rhubarb is 5-100 parts, the dosage of the Rhizoma Chuanxiong is 5-100 parts, the dosage of the Terminalia chebula is 5-100 parts, the dosage of the Fritillaria thunbergii is 15-250 parts, the dosage of the mint is 10-200 parts, the dosage of the Fructus catechu is 10-200 parts, the dosage of the menthol is 0.1-10 parts, the dosage of the Polysorbate 80 is 10-50 parts, and the dosage of the Poloxamer-188 is 10-50 parts.

[0010] According to an embodiment of the present invention, the amount of Sterculia lychnophora is 5 parts, the amount of Platycodon grandiflorum is 50 parts, the amount of Periostracum cicadae is 20 parts, the amount of licorice is 50 parts, the amount of Forsythia suspensa is 50 parts, the amount of Rhubarb is 20 parts, the amount of Ligusticum chuanxiong is 20 parts, the amount of Terminalia chebula is 20 parts, the amount of Fritillaria thunbergii is 60 parts, the amount of mint is 40 parts, the amount of Rhizoma Anemarrhenae is 40 parts, the amount of menthol is 1 part, the amount of Polysorbate 80 is 28 parts and the amount of Poloxamer-188 is 28 parts.

[0011] In another aspect of the present invention, the present invention proposes a method for preparing Huang's sound spray. According to an embodiment of the present invention, the method comprises: 1) subjecting Sterculia lychnophora, Platycodon grandiflorum, Periostracum cicadae, Licorice, Forsythia suspensa, Rhubarb, Chuanxiong, Terminalia chebula, Fritillaria thunbergii, Mentha oleracea, and Fang'ercha to water extraction treatment, and filtering to obtain a de-impurity mother liquor; 2) subjecting the de-impurity mother liquor to de-impurity treatment under the condition that the de-impurity agent is ZTC1+1ⅡB and ZTC1+1ⅡA; 3) subjecting the product obtained after the de-impurity treatment in step 2) to alcohol precipitation treatment to obtain an alcohol precipitation clear paste; 4) mixing the alcohol precipitation clear paste with menthol to obtain Huang's sound spray. The inventors have found that the spray obtained by only water extraction in the prior art is unstable and prone to precipitation. The inventors surprisingly found that water extraction followed by impurity removal and then alcohol precipitation can significantly improve stability, and the inventors also screened impurity removers and surprisingly found that using ZTC1+1ⅡB and ZTC1+1ⅡA can achieve better results. The method according to the embodiment of the present invention is simple to operate, and the obtained spray solution is clear and has high stability.

[0012] According to an embodiment of the present invention, the above method may further include at least one of the following additional technical features:

[0013] According to an embodiment of the present invention, before the water extraction treatment, the Sterculia lychnophora, Platycodon grandiflorum, Periostracum cicadae, Licorice, Forsythia suspensa, Rhubarb, Ligusticum chuanxiong, Terminalia chebula, Fritillaria thunbergii, Mentha, and Rhizoma catechu are soaked in 10 times the amount of water for 1 hour. Thus, the extraction efficiency of the medicinal materials can be further improved.

[0014] According to an embodiment of the present invention, the water extraction process is performed at a temperature of 100° C. for 1.5 hours. Thus, the extraction efficiency of the medicinal material can be further improved.

[0015] According to an embodiment of the present invention, the water extraction process is performed twice, thereby further improving the extraction efficiency of the medicinal material.

[0016] According to an embodiment of the present invention, the water extraction treatment further comprises concentrating the filtrate obtained after filtration in step 1) under reduced pressure at a temperature of 60° C. to 80° C. Thus, the extraction efficiency of the medicinal material can be further improved without destroying the effective ingredients.

[0017] According to an embodiment of the present invention, the material-liquid ratio of the impurity removal mother liquor is 1:5-1:10. The inventors found that under this material-liquid ratio, the impurity removal efficiency is high and the transfer rate of each effective component is high.

[0018] According to an embodiment of the present invention, the material-liquid ratio of the impurity removal mother liquor is 1: 8. The inventors found that under this material-liquid ratio, the impurity removal efficiency is higher and the transfer rate of each effective component is higher.

[0019] According to an embodiment of the present invention, the impurity removal treatment is performed at a temperature of 50° C. to 70° C. The inventors have found that at this temperature, it is more energy-efficient and more suitable for large-scale industrial production.

[0020] According to an embodiment of the present invention, the concentration of the ZTC1+1ⅡB component solution is 0.5%-5% (m / m, unit is g / g). The inventors found that at this concentration, the impurity removal efficiency is high.

[0021] According to an embodiment of the present invention, the concentration of the ZTC1+1ⅡB component solution is 1% (m / m, in g / g). The inventors found that at this concentration, the impurity removal efficiency is higher.

[0022] According to an embodiment of the present invention, the concentration of the ZTC1+1ⅡA component solution is 0.5%-5% (m / m, in g / g). The inventors found that at this concentration, the impurity removal efficiency is higher.

[0023] According to an embodiment of the present invention, the concentration of the ZTC1+1ⅡA component solution is 1% (m / m, in g / g). The inventors found that at this concentration, the impurity removal efficiency is higher.

[0024] According to an embodiment of the present invention, the dosage of the ZTC1+1ⅡB component solution is 10%-40% (m / v, in g / mL) of the dosage of the impurity removal mother solution. The inventors found that at this concentration, the impurity removal efficiency is high.

[0025] According to an embodiment of the present invention, the dosage of the ZTC1+1ⅡB component solution is 25% (m / v, in g / mL) of the impurity removal mother solution. The inventors found that at this concentration, the impurity removal efficiency is higher.

[0026] According to an embodiment of the present invention, the dosage of the ZTC1+1ⅡA component solution is 5%-20% (m / v, in g / mL) of the dosage of the impurity removal mother solution. The inventors found that at this concentration, the impurity removal efficiency is high.

[0027] According to an embodiment of the present invention, the dosage of the ZTC1+1ⅡA component solution is 12.5% ​​(m / v, in g / mL) of the impurity removal mother solution. The inventors found that at this concentration, the impurity removal efficiency is higher.

[0028] According to an embodiment of the present invention, after the impurity removal treatment and before the alcohol precipitation treatment, the product after the impurity removal treatment is further filtered to obtain a filtrate, and the filtrate is concentrated to a relative density of 1.15 to 1.18 at a temperature of 60° C. to 80° C. The inventors found that at this concentration, the impurity removal efficiency is higher.

[0029] According to an embodiment of the present invention, the solvent used in the alcohol precipitation treatment is ethanol.

[0030] According to an embodiment of the present invention, the alcohol precipitation treatment is performed until the alcohol content of the supernatant is 75% (v / v, in mL / mL). The inventors found that at this alcohol content, the efficiency of alcohol precipitation is higher.

[0031] According to an embodiment of the present invention, the alcohol precipitation treatment time is 12 hours to 18 hours. The inventors found that under this treatment time, the alcohol precipitation efficiency is higher.

[0032] According to an embodiment of the present invention, the relative density of the alcohol precipitation clear paste is 1.15-1.20. The inventors found that at this density, the efficiency of alcohol precipitation is higher.

[0033] In the second aspect of the present invention, the present invention also proposes a method for preparing Huang's sound spray. According to an embodiment of the present invention, the above method includes: 1) crushing Fritillaria thunbergii and water extracting with Sterculia lychnophora, Platycodon grandiflorum, Periostracum cicadae, Licorice, Forsythia suspensa, Rhubarb, Ligusticum chuanxiong, Terminalia chebula, Mint, and Fangcaocha, wherein the water extraction is performed by adding 10 times the amount of water to soak for 1 hour, then extracting twice with 10 times the amount of water, filtering, and decompressing and concentrating at a temperature of 60°C to 80°C to a liquid-to-liquid ratio of 1:8 to obtain a de-impurity mother liquor; 2) adding ZTC1+1ⅡB component solution to the de-impurity mother liquor at a temperature of 50°C to 70°C, wherein the amount of ZTC1+1ⅡB component solution is 25% (m / v, in g / mL) of the amount of the de-impurity mother liquor, and the concentration of the ZTC1+1ⅡB component solution is 1% (m / m in g / g), stirring for 10 minutes, keeping warm and standing for 30 minutes, and then adding ZTC1+ 1ⅡA component solution, the dosage of the ZTC1+1ⅡA component solution is 12.5% ​​(m / v, in g / mL) of the dosage of the impurity removal mother solution, the concentration of the ZTC1+1ⅡA component solution is 1% (m / m in g / g), after stirring for 10 minutes, keep warm and stand for 30 minutes, then let it stand for 12 hours to 24 hours to obtain the impurity-removed liquid; 3) the impurity-removed liquid is centrifuged to obtain a filtrate, the filtrate is reduced pressure and concentrated to a relative density of 1.15 to 1.18, ethanol is added to precipitate until the supernatant contains 75% alcohol, the alcohol precipitation is allowed to stand for 12 hours to 18 hours, filtered, and the filtrate is reduced pressure and concentrated to a relative density of 1.15 to 1.20 at a temperature of 50°C to 70°C to obtain an alcohol precipitation clear paste; 4) the alcohol precipitation clear paste is mixed with menthol to obtain Huang's sound spray. The method according to the embodiment of the present invention is simple to operate, and the obtained spray solution is clear and has high stability.

[0034] According to an embodiment of the present invention, the above method may further include at least one of the following additional technical features:

[0035] According to an embodiment of the present invention, the amount of Sterculia lychnophora is 1-50 parts, the amount of Platycodon grandiflorum is 10-200 parts, the amount of Periostracum cicadae is 5-100 parts, the amount of licorice is 10-200 parts, the amount of Forsythia suspensa is 10-200 parts, the amount of rhubarb is 5-100 parts, the amount of Chuanxiong is 5-100 parts, the amount of Terminalia chebula is 5-100 parts, the amount of Fritillaria thunbergii is 15-250 parts, the amount of mint is 10-200 parts, the amount of Rhizoma Anemarrhenae is 10-200 parts, and the amount of menthol is 0.1-10 parts.

[0036] According to an embodiment of the present invention, the amount of Sterculia lychnophora is 5 parts, the amount of Platycodon grandiflorum is 50 parts, the amount of Periostracum cicadae is 20 parts, the amount of licorice is 50 parts, the amount of Forsythia suspensa is 50 parts, the amount of rhubarb is 20 parts, the amount of Chuanxiong is 20 parts, the amount of Terminalia chebula is 20 parts, the amount of Fritillaria thunbergii is 60 parts, the amount of mint is 40 parts, the amount of Rhizoma Anemarrhenae is 40 parts, and the amount of menthol is 1 part.

[0037] According to an embodiment of the present invention, the menthol is preliminarily dissolved.

[0038] According to an embodiment of the present invention, the dissolution treatment is carried out under the condition that the solubilizing agent is polysorbate 80, poloxamer-188, and the solvent is water. The inventor finds that menthol is extremely slightly soluble in water and is soluble in ethanol. After the study finds that menthol is dissolved with ethanol, it is added in the alcohol immersion cream for easy emulsification and stratification. If a water-soluble auxiliary material such as HP-β-CD is used to enclose menthol, the inclusion compound consumption is large, leading to a large concentration of finished product liquid or a large single use amount. Thereby the method for dissolving menthol after enclosing commonly used in the prior art has defects, and the inventor introduces the solubilizing agent polysorbate 80, poloxamer-188 through creative experiments to solve the defects of the prior art.

[0039] According to an embodiment of the present invention, the dissolution treatment is performed at a temperature of 50°C to 60°C.

[0040] According to an embodiment of the present invention, the amount of polysorbate 80 is 10-50 parts.

[0041] According to an embodiment of the present invention, the amount of Poloxamer-188 is 10-50 parts.

[0042] According to an embodiment of the present invention, the amount of water used is 300-800 parts.

[0043] According to an embodiment of the present invention, the amount of polysorbate 80 used is 28 parts.

[0044] According to an embodiment of the present invention, the amount of Poloxamer-188 is 28 parts.

[0045] According to an embodiment of the present invention, the amount of water used is 500 parts.

[0046] According to the embodiments of the present invention, the present invention has at least one of the following advantages:

[0047] 1) In the extraction method of the present invention, after water extraction, impurity removal and alcohol precipitation operations are introduced to make the prepared spray clear and stable, thereby meeting the formulation requirements of the spray.

[0048] 2) The inventors screened the types and dosages of impurity removers to make the prepared spray clearer and more stable, thus meeting the formulation requirements of the spray.

[0049] 3) The inventors of the present invention solve the defects of the prior art method of dissolving menthol after inclusion by using solubilizer polysorbate 80 and poloxamer-188 as solvent menthol. DETAILED DESCRIPTION

[0050] The present application is described in detail below by way of examples, but it is not intended that there is any adverse limitation to the present application. The present application has been described in detail herein, and its specific embodiments are also disclosed therein. It will be apparent to those skilled in the art that various changes and modifications can be made to the specific embodiments of the present application without departing from the spirit and scope of the present application.

[0051] Unless otherwise specified, the raw materials used in the present invention are commercially available.

[0052] The auxiliary materials of the present invention are shown in Table 1 below.

[0053] Table 1

[0054]

[0055]

[0056] Note: * indicates the solvent used in the extraction and purification process.

[0057] Preparation process of ZTC1+1Ⅱ type clarifier:

[0058] 1) Preparation of 1% glacial acetic acid solution: Measure medicinal glacial acetic acid and purified water in a ratio of 1:99 (m / m, unit: g / g), add into a clean stainless steel bucket, stir evenly, and the solution is ready.

[0059] 2) Preparation of ZTC1+1ⅡA component solution: Weigh ZTC1+1ⅡA component and purified water in a ratio of 1:99 (m / m) and place in a clean stainless steel barrel, stir and dissolve with a mechanical stirring paddle to form a colloidal liquid, swell for more than 12 hours, filter through 180 mesh to obtain 1% (m / m, unit g / g) ZTC1+1ⅡA component viscose liquid.

[0060] 3) Preparation of ZTC1+1ⅡB component solution: Weigh ZTC1+1ⅡB component and purified water in a ratio of 1:99 (m / m) and place in a clean stainless steel barrel. Stir and dissolve with a mechanical stirring paddle to form a colloidal liquid. Swell for more than 12 hours and filter through a double layer of gauze (180 mesh) to obtain a 1% (m / m, unit: g / g) ZTC1+1ⅡB component viscose liquid.

[0061] The packaging materials and containers used in the present invention are shown in Table 2 below.

[0062] Table 2

[0063]

[0064] Example 1

[0065] Prescription: 5 parts of Sterculia lychnophora, 50 parts of Platycodon grandiflorum, 20 parts of Periostracum cicadais, 50 parts of Licorice, 50 parts of Forsythia suspensa, 20 parts of Rhubarb, 20 parts of Ligusticum chuanxiong, 20 parts of Terminalia chebula, 60 parts of Fritillaria thunbergii, 40 parts of Mint, 40 parts of Fang Catechu, and 1 part of menthol.

[0066] Method: Step 1: For the above twelve herbs, except menthol, crush Fritillaria thunbergii and combine with the rest of the herbs for water extraction, add 10 times the amount of water to soak for 1 hour, extract twice with 10 times the amount of water, each time for 1.5 hours, filter, and concentrate under reduced pressure at 60℃~80℃ to a drug liquid to liquid ratio of 1:8, and obtain the impurity-free mother liquor for standby use;

[0067] Step 2: Impurity removal: Add 1% ZTC1+1ⅡB component solution (impurity remover) of 25% (m / v) of impurity removal mother liquor to the impurity removal mother liquor (material-liquid ratio 1:8) under the condition of 50℃~70℃ insulation, stir while adding, stir for 10 minutes after all the addition, keep warm and let stand for 30 minutes, continue to add 1% ZTC1+1ⅡA component solution (impurity remover) of 12.5% ​​(m / v) of impurity removal mother liquor under the condition of 50℃~70℃ insulation, stir while adding, stir for 10 minutes after all the addition, keep warm and let stand for 30 minutes, let it cool and let stand for 12h~24h,

[0068] Alcohol precipitation: centrifugal filtration, the filtrate is concentrated under reduced pressure at 60℃~80℃ to a relative density of 1.15~1.18 (60℃), ethanol is added to precipitate until the alcohol content of the supernatant is 75%, the alcohol precipitation is allowed to stand for 12~18h, filtered, the filtrate is concentrated under reduced pressure at 50℃~70℃ to a relative density of 1.15~1.20 (60℃), and the alcohol precipitation clear paste is obtained for standby use;

[0069] Step 3: Weigh 28 parts of polysorbate 80 and 28 parts of poloxamer-188 and add them to a concentrated preparation tank, add an appropriate amount of purified water to completely dissolve them, stir them thoroughly under a heat preservation condition of 50°C to 60°C, then add the prescribed amount of menthol, stir them thoroughly to dissolve, add alcohol precipitation paste while stirring after the menthol is completely dissolved, then add 1.5 parts of potassium sorbate, 1.5 parts of acesulfame potassium, 1 part of aspartame, and 1 part of masking liquid flavor, stir them to dissolve, add water to 80% of the total amount of the preparation, stir them thoroughly to dissolve, and filter them with a 0.45μm membrane; then add water to the prescribed total amount of the preparation, stir them thoroughly, and finally sterilize them through a 0.22μm filter membrane, fill and cap them to obtain the finished preparation, and the total amount of one prescription preparation is 1000mL.

[0070] Example 2

[0071] Mother solution: according to the prescription amount of Example 1, except for menthol, the other eleven herbs were soaked in 10 times the amount of water for 1 hour, extracted twice, each time for 1.5 hours, to obtain 35306 parts of extract, and concentrated under reduced pressure to a solid-liquid ratio of 1:8 to obtain 16794 parts of concentrated solution;

[0072] ZTC impurity-removed mother liquor: Take 7 / 11 of the mother liquor, i.e. 9832 parts (about 500 parts are reserved for sample), add 20% of ZTC1+1II impurity-removing agent B component, add 10% of ZTC1+1II impurity-removing agent A component, remove impurities, and obtain 10941 parts of supernatant. Concentrate the supernatant to the ratio of crude drug: total liquid = 1:1, relative density 1.105 (60°C), and obtain 1230 parts of ZTC impurity-removed mother liquor.

[0073] Sample 1: Take 2 / 11 of the mother liquor, i.e. 3053 parts, and concentrate to 348 parts, with a relative density of 1.15 (60°C). Add 1 part of menthol, 12 parts of polysorbate 80, 0.5 parts of potassium sorbate, add water to make the volume to 500 parts, and add sodium bicarbonate to adjust the pH to 5, to obtain Sample 1.

[0074] Sample 2: Take 400 parts of ZTC impurity-removed mother liquor, concentrate to 270 parts, relative density ρ = 1.165 (60°C), add 1 part of menthol, 10 parts of polysorbate 80, 0.5 parts of potassium sorbate, add water to make the volume to 500 parts, add sodium bicarbonate to adjust the pH to 5, and obtain sample 2.

[0075] Sample 3: Dilute 100 parts of sample 2 to 200 parts.

[0076] Sample 4: Take 300 parts of ZTC impurity-removed mother liquor, refrigerate and centrifuge at 10000rpm / min for 15min, concentrate to obtain 198 parts of concentrated solution, relative density 1.157 (60℃). Add 95% ethanol to the concentrated solution to make the alcohol content reach 75%, precipitate with alcohol, centrifuge, filter, concentrate, obtain 90 parts of alcohol precipitate concentrated solution, relative density 1.172 (60℃). Add 0.8 parts of menthol and 0.35 parts of potassium sorbate by grinding method, add water to make the volume 350 parts, adjust the pH value to 5 with sodium bicarbonate, and obtain sample 4.

[0077] Sample 5: Dilute 200 parts of sample 4 to 400 parts.

[0078] The purification process route screening sample preparation and test results are summarized in Table 3.

[0079] Table 3

[0080]

[0081] It can be seen from Table 1 above that if the mother liquor does not undergo two steps of ZTCⅡ impurity removal and alcohol precipitation, its stability is poor and it is difficult to meet the requirements of formulation molding (spraying).

[0082] Example 3

[0083] Young rats were used and randomly divided into 8 groups, including a blank control group, a model group, a Kaihoujian spray group, and 5 test drug groups, with 10 animals in each group.

[0084] Adopt 15% ammonia water, except normal control group, all other groups use open throat sword sprayer to spray 15% ammonia water on animal pharynx, 1 spray each time (about 0.1mL per spray), 1 time / d, continuous 3d, cause acute pharyngitis model, normal control group sprays distilled water under the same conditions, rats are administered by average body weight 140 μ L / (only·time) (2 sprays / time), and are respectively administered 8 times every day as required, continuous 5d, normal control group and model control group spray vehicle under the same conditions.Tissue from soft palate to pharynx is taken for gross tissue observation, specimen is put into formalin solution for fixing, and HE staining is carried out for pathological grading observation.Adopt the sample among embodiment 2 to test, see Table 4.

[0085] Table 4

[0086] Group Modeling Give medication blank Distilled water Oral spray pure water Model ammonia Oral spray pure water Sample 1 ammonia Oral spray 1.64g / kg sample 1

[0087] Sample 2 ammonia Oral spray 1.55g / kg sample 2 Sample 3 ammonia Oral spray 1.24g / kg sample 3 Sample 4 ammonia Oral spray 1.24g / kg sample 4 Sample 5 ammonia Oral spray 1.25g / kg sample 5 Throat-opening sword spray ammonia Oral spray 1.13g / kg Kaihoujian

[0088] Test results

[0089] Pharyngeal inflammation response of samples in pharyngitis model rats (pathological sections)

[0090] The grading criteria for HE staining observation of pharyngeal mucosa tissue are shown in Table 5. The grading statistics for HE staining observation of pharyngeal mucosa tissue (n=10 RIDIT test) are shown in Table 6.

[0091] Table 5

[0092]

[0093] Table 6

[0094]

[0095]

[0096] As shown in Table 6, compared with the blank group, the pharyngeal mucosa of the rats in the model group showed symptoms such as swelling, congestion, and ulcers, which were significantly different from the blank group (P<0.05); sample 1 alleviated the pharyngeal mucosal symptoms of the rats, which was significantly different from the model (P<0.05); sample 2 alleviated the pharyngeal mucosal symptoms of the rats, which was significantly different from the model (P<0.05); sample 3 did not alleviate the pharyngeal mucosal symptoms of the rats, and there was no significant difference compared with the model group; sample 4 alleviated the pharyngeal mucosal symptoms of the rats, which was significantly different from the model (P<0.05); sample 5 alleviated the pharyngeal mucosal symptoms of the rats, which was significantly different from the model (P<0.05).

[0097] Compared with the blank group, the outer layer of the tissue mucosal epithelium of the rats in the model group was keratinized and partially shed, the epithelial layer was significantly proliferated, the small blood vessels in the lamina propria were dilated, congested, and edematous; some mucous gland epithelial cells were dilated and proliferated; inflammatory cell infiltration was observed in the lamina propria and between it and the mucous glands, which was significantly different from the blank group (P<0.05); sample 1 improved the histological symptoms of the pharyngeal mucosa of rats, which was significantly different from the model (P<0.05); sample 2 improved the histological symptoms of the pharyngeal mucosa of rats, which was significantly different from the model (P<0.05); sample 3 did not improve the histological symptoms of the pharyngeal mucosa of rats, which was not significantly different from the model group; sample 4 improved the histological symptoms of the pharyngeal mucosa of rats, which was significantly different from the model (P<0.05); sample 5 improved the histological symptoms of the pharyngeal mucosa of rats, which was significantly different from the model (P<0.05).

[0098] Example 4

[0099] In this example, impurity removers and impurity removal methods were screened, as shown in Table 7 below.

[0100] Table 7

[0101]

[0102]

[0103]

[0104] The results of the investigation on different impurity removal agents and impurity removal methods are summarized in Table 8 below.

[0105] Table 8

[0106]

[0107]

[0108]

[0109]

[0110]

[0111]

[0112] It can be seen from Table 8 above that, with the impurity removal rate as the key indicator, the impurity removal effect of the clarifier is better than that of 50% alcohol precipitation and high-speed centrifugation. Combined with the clarity of the solution, the ZTC 1+1Ⅱ type clarifier has the best impurity removal effect. From the perspective of the content of the index components, different impurity removal methods have little effect on it. Although the content of medium-polar components catechins, gallic acid, and forsythiaside A in the impurity removal solution prepared by high-speed centrifugation and alcohol precipitation is slightly higher, the impurity removal rate of the two is much lower than that of the clarifier, which is not conducive to the subsequent preparation molding. The use of ZTC 1+1Ⅱ type clarifier for impurity removal can basically meet the impurity removal requirements, among which the amount of 1% concentration of component B, the amount added is 25% of the amount of impurity removal mother liquor, and the amount of 1% concentration of component A, the amount added is 12.5% ​​of the amount of impurity removal mother liquor, which has a better impurity removal effect.

[0113] Example 5

[0114] A single factor experimental design was used to investigate the effects of four factors, namely, the concentration of the impurity removal mother liquor (calculated by the solid-liquid ratio), the impurity removal temperature, the stirring time, and the water bath insulation time, on the purification effect during the purification process of the ZTC1+1Ⅱ type clarifier in the second step of the impurity removal process in Example 1.

[0115] 1) The influence of impurity removal liquid concentration on impurity removal effect

[0116] Take an appropriate amount of the impurity removal mother liquor in Example 1, dilute it with purified water, and prepare 500g of each impurity removal liquid with a material-liquid ratio of (feeding amount: liquid) 1:4, 1:6, 1:8, and 1:10. Add 25% of the ZTC1+1IIB component to the impurity removal liquid in a 70°C water bath, stir while adding, and stir for 10 minutes after adding. Stir once every 30 minutes in the middle. After 2 hours, add 12.5% ​​of the ZTC1+1II A component to the impurity removal liquid in a 70°C water bath, stir while adding, and stir for 10 minutes after adding. Let it stand and keep warm for 30 minutes, take it out and cool it, refrigerate (2-8°C) and let it stand for more than 12 hours, centrifuge it at 4000rpm for 15 minutes, take the supernatant and filter it to obtain a filtrate. Determine the solid content and index component content of the filtrate, calculate its paste yield, impurity removal rate, and index component transfer rate relative to the impurity removal liquid, and the results are shown in Table 9 below.

[0117] Table 9

[0118] serial number 1 2 3 4 Material-liquid ratio 1:4 1:6 1:8 1:10 Supernatant status Brown turbid Brown turbid Brown red clear Deep red clear Cream yield% 28.7 28.62 27.38 24.66 Impurity removal rate % 29.56 29.75 32.81 39.48 Gallic acid transfer rate % 85.15 79.07 76.37 56.06 Catechin transfer rate % 76.49 69.85 69.81 49.07 Transfer rate of forsythiaside A % 79.2 71.78 70.44 52.24 Polysaccharide transfer rate % 85.16 65.82 64.95 56.86 Transfer rate of platycodon saponin D % 86.38 91.17 94.69 87.65

[0119] It can be seen from Table 9 above that the smaller the solid-liquid ratio of the four liquids to be removed, the greater the relative removal rate. When the solid-liquid ratio is 1:8, the removed liquid begins to clarify, and the transfer rate of the platycodon saponin D content in the monarch drug is the highest; when the solid-liquid ratio is 1:10, the transfer rate of each component decreases significantly. Comprehensively considering the clarification condition, relative removal rate and component transfer rate, the solid-liquid ratio of the removed mother liquor concentration is 1:8, which has a better effect.

[0120] 2) The influence of temperature on impurity removal effect

[0121] Take the impurity removal mother liquor in Example 1, add purified water to make 500g of the impurity removal liquid with a material-liquid ratio of 1:8, a total of 5 parts, add 25% of the ZTC1+1IIB component to be removed at a water bath temperature of 50°C, 60°C, 70°C, 80°C, and 90°C, stir while adding, and stir for 10 minutes after adding. Stir once every 30 minutes in the middle. After 2 hours, add 12.5% ​​of the ZTC1+1II A component to be removed at the same water bath temperature, stir while adding, stir for 10 minutes after adding, keep warm for 30 minutes, take out and cool, refrigerate for more than 12 hours, take out, centrifuge at 4000rpm for 15 minutes, filter, separate the upper and precipitates. Determine the solid content of the filtrate and the content of the index components, calculate its paste yield, impurity removal rate, and index component transfer rate relative to the impurity removal mother liquor, and the results are shown in Table 10 below.

[0122] Table 10

[0123] batch number 1 2 3 4 5 Material-liquid ratio 1:8 1:8 1:8 1:8 1:8 Water bath temperature / ℃ 50 60 70 80 90 Cream yield% 27.25 27.75 27.65 27.03 26.61 Impurity removal rate % 27.50 26.19 26.45 28.10 29.21 Polysaccharide transfer rate % 59.64 55.06 61.12 59.25 58.42 Transfer rate of platycodon saponin D % 80.64 81.69 81.71 83.20 80.33 Gallic acid transfer rate % 83.28 85.42 86.95 87.00 93.90 Catechin transfer rate % 80.69 81.10 79.90 75.72 73.18 Transfer rate of forsythiaside A % 82.93 82.61 81.99 77.77 75.02

[0124] It can be seen from Table 10 above that the impurity removal rate and the relative retention rate of each component at each temperature are not much different. Considering energy saving and consumption reduction as well as the situation of large-scale production equipment, the water bath temperature is preferably 50℃~70℃.

[0125] 3) Effect of stirring time on impurity removal effect

[0126] Take the impurity removal mother liquor in Example 1, add purified water to make 500g of the mother liquor to be removed with a material-liquid ratio of 1:8, a total of 5 parts, add 25% of the ZTC1+1IIB component to be removed in a 50°C water bath, stir while adding, stir for 10 minutes after adding, stir once every 30 minutes in the middle, stand and heat for 2 hours, add 12.5% ​​of the ZTC1+1IIA component to be removed in a 50°C water bath, stir for 10 minutes and 20 minutes at the same stirring speed, keep warm and stand for 30 minutes, take out and cool, refrigerate (2-8°C) and stand for more than 12 hours, centrifuge at 4000rpm for 15 minutes, take the supernatant and filter, separate the supernatant and the precipitate. Determine the solid content of the filtrate and the content of the index component, calculate its paste yield, impurity removal rate, and the transfer rate of the index component relative to the impurity removal mother liquor, and the results are shown in Table 11 below.

[0127] Table 11

[0128]

[0129]

[0130] It can be seen from Table 11 above that the stirring time of 10 to 20 minutes has little effect on the index component transfer rate, paste yield and impurity removal rate.

[0131] 4) Effect of water bath holding time on impurity removal effect

[0132] Take the impurity removal mother liquor in Example 1, add purified water to make 500g of the impurity removal liquid with a material-liquid ratio of 1:8, a total of 5 parts, add 25% of the ZTC1+1IIB component to be removed in a 50°C water bath, stir while adding, stir for 10 minutes after adding, stand and keep warm for 0.5, 1.0, 1.5, and 2 hours respectively, and stir once every 30 minutes during the insulation process; then add 12.5% ​​of the ZTC1+1II A component to be removed in a 50°C water bath, stir while adding, stir for 10 minutes after adding, keep warm and stand for 0.5h respectively, take out and cool, refrigerate (2-8°C) and stand for more than 12h, centrifuge at 4000rpm for 15min, take the supernatant and filter, separate the supernatant and the precipitate. Determine the solid content of the filtrate and the content of the index component, calculate its paste yield, impurity removal rate, and the transfer rate of the index component relative to the impurity removal mother liquor, and the results are shown in Table 12 below.

[0133] Table 12

[0134]

[0135]

[0136] It can be seen from Table 12 above that the water bath holding time has little effect on the index component transfer rate, impurity removal rate and paste yield rate, and a good impurity removal effect can be achieved with a holding time of 0.5h.

[0137] Example 6

[0138] The alcohol precipitation process in the second step of the method of Example 1 was studied, and the relative density of the alcohol-precipitated clear paste (A), alcohol precipitation concentration (B), and standing time (C) were used as the investigation factors. L9 (3 4 ) Orthogonal test, under parallel operation conditions, with precipitation amount (impurity removal rate) and index component transfer rate as the main investigation indicators, variance analysis was used to optimize the best process of alcohol precipitation. The experimental results are shown in Table 14 below.

[0139] Table 13

[0140]

[0141] Table 14

[0142]

[0143]

[0144] It can be seen from Table 14 above that different alcohol precipitation process parameters have little effect on the transfer rate of gallic acid, catechins, forsythiaside A, and platycodon saponin D, and the transfer rate is basically above 90%; the main influences are the polysaccharide transfer rate, dry paste yield and precipitation amount, so the results of the alcohol precipitation orthogonal test are mainly analyzed using the polysaccharide transfer rate and the precipitation amount that more intuitively reflects the impurity removal rate.

[0145] The results of the alcohol precipitation orthogonal test - polysaccharide transfer rate are shown in Table 15. The variance analysis table of the alcohol precipitation orthogonal test - polysaccharide transfer rate is shown in Table 16.

[0146] Table 15

[0147]

[0148]

[0149] Table 16

[0150] Sources of variance A B C D Error E Sum of Squares of Deviations 355.57 1873.01 104.61 6.73 6.73 Degrees of Freedom 2.00 2.00 2.00 2.00 2.00 Mean square (MS) 177.79 936.51 52.31 3.36 3.36 F-number 52.85 278.38 15.55 1.00 F critical value F0.01(1,2)＝ 99 F0.05(1,2)＝ 19

[0151] It can be seen from Tables 15-16 above that factors A and B are significant, and the influence of each factor is: B>A>C>D. From the sum and difference, it can be seen that to remove more polysaccharides (lowest transfer rate), the better factor combination is A3B3C1, that is: the relative density of the solution is 1.15, the alcohol content of the solution is 75%, and the standing time is 12 hours.

[0152] The results table of alcohol precipitation orthogonal test - precipitation amount is shown in Table 17 below, and the variance analysis table of alcohol precipitation orthogonal test - polysaccharide transfer rate is shown in Table 18 below.

[0153] Table 17

[0154]

[0155]

[0156] Table 18

[0157]

[0158]

[0159] From Table 17-18 above, we can see that factors A and B are significant, and the influence of each factor is: B>A>C>D. From the sum and difference, we can see that to remove more impurities, the better factor combination is A3B3C2, that is, the relative density of the alcohol-precipitated clear paste is 1.15, the alcohol content of the alcohol precipitation solution is 75%, and the standing time is 18 hours. Because the standing time of factor C has no significant significance, and factor A is within a certain range, the greater the relative density of the alcohol-precipitated clear paste, the better the alcohol precipitation effect. Considering the operability and production efficiency of workshop production, the relative density of the alcohol-precipitated clear paste is set to 1.15-1.18, and the alcohol precipitation standing time is set to 12-18 hours.

[0160] In summary, in the alcohol precipitation process, the effect is better when the relative density of the alcohol precipitated paste is 1.15-1.18 (60°C), the alcohol content of the supernatant is 75%, and the standing time is 12-18h.

[0161] Example 7

[0162] The type and amount of the solubilizing agent for dissolving menthol in Example 1 were screened.

[0163] 1) Screening of solubilizer types:

[0164] Take equal amounts of alcohol-precipitated cream, add menthol solution dissolved by the solubilizing auxiliary material in Table 19, make up to the same volume, put into a high-density polyethylene spray bottle, place at room temperature, and observe continuously for 30 days (d). During the observation, pour the solution into a clean transparent glass test bottle and observe it under a fluorescent light. At the same time, observe the drug deposition in the spray bottle. The research results are shown in Table 19.

[0165] Table 19

[0166]

[0167]

[0168] As can be seen from Table 19 above, when polysorbate 80+poloxamer 188, polysorbate 80+sodium citrate and glycerol are used as solubilizers, the solution is clear, drug deposition is not obvious, and the solubilization effect is better than that of other groups, among which the polysorbate 80+poloxamer 188 group is better.

[0169] 2) Amount of solubilizer

[0170] Take an equal amount of alcohol-precipitated clear paste, add menthol solution dissolved by the solubilizing auxiliary materials in Table 20 below, adjust the volume to the same volume, and put it into a high-density polyethylene spray bottle. Use a high-low temperature cycle test to observe the stability of the solution and evaluate the quality of the prescription. The sample placement conditions for the high-low temperature cycle test are: 2 days at room temperature, 2 days at 2-8°C, 2 days at room temperature, 2 days at 40°C, 3 days at 2-8°C, 11 days at 60°C, and finally 3 days at 40°C. Take a sample to observe the state of the solution each time the temperature is changed. The results are shown in Table 20 below.

[0171] Table 20

[0172]

[0173]

[0174] It can be seen from Table 20 above that when polysorbate 80 + poloxamer 188 are used as solubilizers, under high and low temperature cycle conditions, the solution is clear and has no precipitation, and the stability is optimal; when glycerol is used as a solubilizer, at the end of the test, the inner wall of the bottle is obviously stained after the drug solution is washed with purified water, and the inner packaging material may have a certain adsorption on the prescription; in order to ensure the stability of the solution while taking into account the production cost, it is better to choose 28 parts of polysorbate 80 + 28 parts of poloxamer 188 as menthol solubilizing excipients.

[0175] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0176] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A Huang's sound spray, characterized in that: include: Sterculia lychnophora, Platycodon grandiflorum, Periostracum cicadae, licorice, Forsythia suspensa, rhubarb, Chuanxiong, Terminalia chebula, Fritillaria thunbergii, mint, Fangcacha, menthol, polysorbate 80 and poloxamer-188; the dosage of Sterculia lychnophora is 1-50 parts, the dosage of Platycodon grandiflorum is 10-200 parts, the dosage of Periostracum cicadae is 5-100 parts, the dosage of Licorice is 10-200 parts, the dosage of Forsythia suspensa is 10-200 parts, the dosage of Rhubarb is 5 -100 parts, the amount of Chuanxiong is 5-100 parts, the amount of Terminalia chebula is 5-100 parts, the amount of Fritillaria thunbergii is 15-250 parts, the amount of mint is 10-200 parts, the amount of Fangcaicae catechu is 10-200 parts, the amount of menthol is 0.1-10 parts, the amount of polysorbate 80 is 10-50 parts and the amount of poloxamer-188 is 10-50 parts; The Huang's sound spray is prepared by the following method: 1) extracting Sterculia lychnophora, Platycodon grandiflorum, Periostracum Cicadae, Licorice, Fructus Forsythiae, Rhubarb, Rhizoma Chuanxiong, Fructus Terminaliae Terminaliae, Fritillaria thunbergii, Mentha, and Rhizoma Cibotii with water, and filtering to obtain a mother liquor for impurity removal; 2) subjecting the impurity-removing mother liquor to an impurity-removing treatment under the condition that the impurity-removing agent is ZTC1+1ⅡB and ZTC1+1ⅡA; 3) subjecting the product obtained after the impurity removal treatment in step 2) to alcohol precipitation treatment to obtain an alcohol-precipitated clear paste; 4) mixing the alcohol-precipitated clear paste with menthol to obtain Huang's sound spray; Wherein, the concentrations of the ZTC1+1ⅡB component solution and the ZTC1+1ⅡA component solution are both 0.5%-5%; the dosage of the ZTC1+1ⅡB component solution is 10%-40% of the dosage of the impurity removal mother solution, and the dosage of the ZTC1+1ⅡA component solution is 5%-20% of the dosage of the impurity removal mother solution; Wherein, the material-liquid ratio of the impurity removal mother liquor is 1:8-1:10; After the impurity removal treatment and before the alcohol precipitation treatment, the product after the impurity removal treatment is further filtered to obtain a filtrate, and the filtrate is concentrated at a temperature of 60° C. to a relative density of 1.15-1.18; The alcohol precipitation treatment is performed until the alcohol content of the supernatant is 75%; The alcohol precipitation treatment time is 12 to 18 hours; The menthol is preliminarily dissolved; the dissolution is carried out under the condition that the solubilizer is polysorbate 80 and poloxamer-188 and the solvent is water.

2. Huang's sound spray according to claim 1, characterized in that: The dosage of Sterculia lychnophora is 5 parts, the dosage of Platycodon grandiflorum is 50 parts, the dosage of Periostracum cicadae is 20 parts, the dosage of licorice is 50 parts, the dosage of Forsythia suspensa is 50 parts, the dosage of Rhubarb is 20 parts, the dosage of Ligusticum chuanxiong is 20 parts, the dosage of Terminalia chebula is 20 parts, the dosage of Fritillaria thunbergii is 60 parts, the dosage of mint is 40 parts, the dosage of Rhizoma Anemarrhenae is 40 parts, the dosage of menthol is 1 part, the dosage of Polysorbate 80 is 28 parts and the dosage of Poloxamer-188 is 28 parts.

3. A method for preparing the Huang's sound spray as claimed in claim 1, characterized in that: include: 1) extracting Sterculia lychnophora, Platycodon grandiflorum, Periostracum Cicadae, Licorice, Fructus Forsythiae, Rhubarb, Rhizoma Chuanxiong, Fructus Terminaliae Terminaliae, Fritillaria thunbergii, Mentha, and Rhizoma Cibotii with water, and filtering to obtain a mother liquor for impurity removal; 2) subjecting the impurity-removing mother liquor to an impurity-removing treatment under the condition that the impurity-removing agent is ZTC1+1ⅡB and ZTC1+1ⅡA; 3) subjecting the product obtained after the impurity removal treatment in step 2) to alcohol precipitation treatment to obtain an alcohol-precipitated clear paste; 4) mixing the alcohol-precipitated clear paste with menthol to obtain Huang's sound spray; Wherein, the concentrations of the ZTC1+1ⅡB component solution and the ZTC1+1ⅡA component solution are both 0.5%-5%; the dosage of the ZTC1+1ⅡB component solution is 10%-40% of the dosage of the impurity removal mother solution, and the dosage of the ZTC1+1ⅡA component solution is 5%-20% of the dosage of the impurity removal mother solution; Wherein, the material-liquid ratio of the impurity removal mother liquor is 1:8-1:10; After the impurity removal treatment and before the alcohol precipitation treatment, the product after the impurity removal treatment is further filtered to obtain a filtrate, and the filtrate is concentrated at a temperature of 60° C. to a relative density of 1.15-1.18; The alcohol precipitation treatment is performed until the alcohol content of the supernatant is 75%; The alcohol precipitation treatment time is 12 to 18 hours; The menthol is preliminarily dissolved; the dissolution is carried out under the condition that the solubilizer is polysorbate 80 and poloxamer-188 and the solvent is water.

4. The preparation method according to claim 3, characterized in that: Before the water extraction treatment, the Sterculia lychnophora, Platycodon grandiflorum, Periostracum cicadae, Licorice root, Forsythia suspensa, Rhubarb, Ligusticum chuanxiong, Terminalia chebula, Fritillaria thunbergii, Mentha, and Rhizoma Ceratitis are soaked in 10 times the amount of water for 1 hour.

5. The preparation method according to claim 3, characterized in that: The water extraction treatment was carried out at a temperature of 100° C. for 1.5 hours.

6. The preparation method according to claim 3, characterized in that: The water extraction treatment was performed twice.

7. The preparation method according to claim 3, characterized in that: After the water extraction treatment, the filtrate obtained after filtering in step 1) is further concentrated under reduced pressure at a temperature of 60° C. to 80° C.

8. The preparation method according to claim 3, characterized in that: The solid-to-liquid ratio of the impurity-removing mother liquor is 1:

8.

9. The preparation method according to claim 3, characterized in that: The impurity removal treatment is carried out at a temperature of 50°C to 70°C.

10. The preparation method according to claim 3, characterized in that: The concentration of the ZTC1+1ⅡB component solution is 1%.

11. The preparation method according to claim 3, characterized in that: The concentration of the ZTC1+1ⅡA component solution is 1%.

12. The preparation method according to claim 3, characterized in that: The amount of the ZTC1+1ⅡB component solution used is 25% of the amount of the impurity removal mother solution used.

13. The preparation method according to claim 3, characterized in that: The amount of the ZTC1+1ⅡA component solution used is 12.5% ​​of the amount of the impurity removal mother solution used.

14. The preparation method according to claim 3, characterized in that: The alcohol precipitation treatment is performed when the solvent used is ethanol.

15. The preparation method according to claim 3, characterized in that: Under the condition of a temperature of 50° C.-70° C., the relative density of the alcohol precipitation paste is 1.15-1.

20.

16. A method for preparing the Huang's sound spray as claimed in claim 1, characterized in that: include: 1) crushing Fritillaria thunbergii, and extracting with Sterculia lychnophora, Platycodon grandiflorum, Periostracum cicadae, Licorice, Forsythia suspensa, Rhubarb, Rhizoma Chuanxiong, Terminalia chebulae, Mentha, and Rhizoma Cibotii, wherein the extracting step is to soak the mixture in 10 times the amount of water for 1 hour, extract the mixture twice in 10 times the amount of water, filter the mixture, and concentrate the mixture under reduced pressure at a temperature of 60° C. to a liquid-to-drug ratio of 1:8 to obtain a mother liquor having been decontaminated; 2) adding ZTC1+1ⅡB component solution to the impurity removal mother liquor at a temperature of 50°C to 70°C, wherein the amount of the ZTC1+1ⅡB component solution is 25% of the amount of the impurity removal mother liquor, and the concentration of the ZTC1+1ⅡB component solution is 1%, stirring for 10 minutes, keeping warm and standing for 30 minutes, then adding ZTC1+1ⅡA component solution, wherein the amount of the ZTC1+1ⅡA component solution is 12.5% ​​of the amount of the impurity removal mother liquor, and the concentration of the ZTC1+1ⅡA component solution is 1%, stirring for 10 minutes, keeping warm and standing for 30 minutes, and then letting it stand for 12 hours to 24 hours to obtain a liquid after impurity removal; 3) centrifugally filtering the impurity-removed liquid to obtain a filtrate, concentrating the filtrate under reduced pressure to a relative density of 1.15 to 1.18, adding ethanol to precipitate until the supernatant contains 75% alcohol, leaving the precipitate to stand for 12 to 18 hours, filtering, and concentrating the filtrate under reduced pressure at a temperature of 50° C. to 70° C. to a relative density of 1.15 to 1.20 to obtain an alcohol-precipitated clear paste; 4) mixing the alcohol-precipitated clear paste with menthol to obtain Huang's sound spray; The menthol is preliminarily dissolved; the dissolution is carried out under the condition that the solubilizer is polysorbate 80 and poloxamer-188 and the solvent is water.

17. The preparation method according to claim 3 or 16, characterized in that: The amount of Sterculia lychnophora is 5 parts, the amount of Platycodon grandiflorum is 50 parts, the amount of Periostracum cicadae is 20 parts, the amount of licorice is 50 parts, the amount of Forsythia suspensa is 50 parts, the amount of Rhubarb is 20 parts, the amount of Ligusticum chuanxiong is 20 parts, the amount of Terminalia chebula is 20 parts, the amount of Fritillaria thunbergii is 60 parts, the amount of mint is 40 parts, the amount of Rhizoma Catechu is 40 parts, and the amount of menthol is 1 part.

18. The preparation method according to claim 3 or 16, characterized in that: The dissolution treatment is carried out at a temperature of 50°C to 60°C.

19. The preparation method according to claim 3 or 16, characterized in that: The amount of water used in the dissolution treatment is 300-800 parts.

20. The preparation method according to claim 3 or 16, characterized in that: The usage of the polysorbate 80 is 28 parts.

21. The preparation method according to claim 3 or 16, characterized in that: The amount of Poloxamer-188 is 28 parts.

22. The preparation method according to claim 19, characterized in that: The amount of water used in the dissolution treatment was 500 parts.

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