Granules capable of relieving sore-throat and detoxifying and preparation method thereof

Abstract

The invention provides a sore-throat relieving and detoxification granule and a preparation method thereof, and belongs to the technical field of medicines, the sore-throat relieving and detoxification granule comprises the following components: mint volatile oil, beta-cyclodextrin, a sore-throat relieving and detoxification extract, a filler and sucralose, meanwhile, the mint volatile oil and the beta-cyclodextrin are prepared into an inclusion compound, the inclusion compound and other raw materials are mixed and granulated, and the sore-throat relieving and detoxification granule is obtained. According to the sore-throat-relieving and detoxifying granules and the preparation method thereof, the stability of mint volatile oil in the sore-throat-relieving and detoxifying granules is improved, and the antipyretic and anti-inflammatory effects of the sore-throat-relieving and detoxifying granules are enhanced.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a throat-soothing and detoxifying granule and its preparation method. Background Technology

[0002] According to pages 1038-1039 of Part I of the 2020 edition of the Chinese Pharmacopoeia, the formula for relieving sore throat and detoxifying consists of sixteen herbs: Isatis root, honeysuckle, forsythia, peppermint, burdock seed (fried), hawthorn (charred), platycodon root, indigo leaf, silkworm, scrophularia root, scutellaria root, rehmannia root, trichosanthes root, rhubarb, fritillaria bulb, and ophiopogon root. It has the effects of clearing the lungs and relieving sore throat, detoxifying and reducing fever. It is used for symptoms such as sore throat, dry throat, red and swollen tonsils, fever and chills caused by exogenous wind-heat; acute tonsillitis, acute pharyngitis, etc.

[0003] The preparation method of the throat-soothing and detoxifying granules includes: extracting volatile oil from the above sixteen ingredients, collecting the distilled aqueous solution separately, decocting the dregs with the remaining fifteen ingredients such as honeysuckle twice with water, each time for 1.5 hours, filtering, combining the filtrate with the above distilled aqueous solution, concentrating to a relative density of 1.38~1.40 (80℃), adding appropriate amounts of sucrose, starch or dextrin, making granules, drying, adding volatile oil, mixing well, and making 1000g; or adding appropriate amounts of dextrin and aspartame, making granules, drying, adding volatile oil, mixing well, and making 300g (sugar-free), which is the final product.

[0004] Peppermint volatile oil plays a very important role in throat-soothing and detoxifying formulas, including dispelling wind, clearing heat, and treating exogenous wind-heat, headache, red eyes, sore throat, toothache, and itchy skin. However, it has been previously discovered that the peppermint volatile oil in throat-soothing and detoxifying granules is lost to some extent during long-term storage, resulting in insufficient product stability. Summary of the Invention

[0005] In view of this, the present invention provides a throat-soothing and detoxifying granule and its preparation method, which increases the stability of peppermint volatile oil in the throat-soothing and detoxifying granule.

[0006] To achieve the above objectives, the present invention provides a throat-soothing and detoxifying granule, comprising the following components: peppermint volatile oil, β-cyclodextrin, throat-soothing and detoxifying extract, filler, and sucralose.

[0007] Optionally, the raw materials for the throat-soothing and detoxifying extract are Isatis root, honeysuckle, forsythia, peppermint, fried burdock seed, charred hawthorn, platycodon, indigo leaf, silkworm, scrophularia, scutellaria, rehmannia, trichosanthes root, rhubarb, fritillaria thunbergii, and ophiopogon japonicus.

[0008] Optionally, the throat-soothing and detoxifying extract is a thick throat-soothing and detoxifying extract, and the fillers are sucrose and dextrin; the mass ratio of the thick throat-soothing and detoxifying extract, peppermint volatile oil, β-cyclodextrin, sucrose, dextrin and sucralose is (350.0~465.0):(0.1~0.39):(1.0~3.9):(305.0~350.0):(305.0~350.0):(2~3).

[0009] Optionally, the dextrin is passed through a 100-mesh sieve, and the sucrose is pulverized and then passed through a 100-mesh sieve.

[0010] Optionally, the throat-soothing and detoxifying extract is a throat-soothing and detoxifying dry extract powder, and the filler is lactose; the mass ratio of the throat-soothing and detoxifying dry extract powder, peppermint volatile oil, β-cyclodextrin, lactose, and sucralose is (2517.50~3344.68): (1.43~5.57): (14.3~55.7): (1084.37~1960.56): (9.5~10.5).

[0011] Optionally, the lactose is passed through a 100-mesh sieve.

[0012] To achieve the above objectives, the present invention also provides a method for preparing throat-soothing and detoxifying granules, comprising the following steps: encapsulating peppermint volatile oil with β-cyclodextrin to obtain an inclusion complex; after dehydration, drying, and pulverization, the inclusion complex is mixed with a filler, sucralose, and throat-soothing and detoxifying extract for granulation; and then granulated and mixed to obtain throat-soothing and detoxifying granules.

[0013] Optionally, the granulation is performed using a screening machine, wherein the upper layer of the screening machine is a 10-mesh stainless steel screen and the lower layer of the screening machine is an 80-mesh stainless steel screen.

[0014] Optionally, the total mixing is performed using a mixer, the operating parameters of which are a frequency of 50Hz and a time of 20min.

[0015] Optionally, the inclusion complex obtained by combining the peppermint volatile oil with β-cyclodextrin is obtained by one of the following methods: saturated aqueous solution method, grinding method, and ultrasonic method.

[0016] Optionally, the saturated aqueous solution method includes the following steps: S1. Mix β-cyclodextrin with purified water, heat and stir until fully dissolved to obtain a cyclodextrin solution, cool and keep warm for later use; S2. Mix peppermint volatile oil with anhydrous ethanol until homogeneous to obtain peppermint volatile oil solution. Add the peppermint volatile oil solution dropwise into the cyclodextrin solution while stirring to encapsulate the mixture. After encapsulation, refrigerate. S3. After refrigeration, perform vacuum filtration, wash the precipitate to obtain filter residue, and dry the filter residue to obtain peppermint volatile oil inclusion complex.

[0017] Optionally, the peppermint volatile oil is encapsulated with β-cyclodextrin in a ratio of 9-13g β-cyclodextrin to 1ml peppermint volatile oil; the mass ratio of β-cyclodextrin to purified water is 1:(8-10); the mass ratio of peppermint volatile oil to anhydrous ethanol is 1:(2-3); the heating and stirring in step S1 is carried out at a temperature of 58-60℃ and a stirring rate of 180-220r / min; the cooling and heat preservation is carried out at 55℃ for 0.5-1h.

[0018] Optionally, the process of adding the peppermint volatile oil solution to the cyclodextrin solution while stirring involves adding the peppermint volatile oil solution at a rate of 2-3 drops / second to the cyclodextrin solution, while simultaneously stirring at 450-550 rpm. Timing begins after all the peppermint volatile oil solution has been added to the cyclodextrin solution, with a stirring rate of 450-550 rpm and a stirring time of 1.5-2 hours. The refrigeration temperature is 4-10°C, and the time is 12-24 hours. The drying temperature of the filter residue is 40-55°C, and the time is 8-12 hours.

[0019] Optionally, in step S3, two layers of medium-speed qualitative filter paper are used for vacuum filtration.

[0020] Optionally, the granulation includes wet granulation and dry granulation, wherein the filler in wet granulation is sucrose and dextrin, and the filler in dry granulation is lactose.

[0021] Optionally, the dry granulation uses a dry granulator, the operating parameters of which are: pressure 5~5.5MPa, vertical rotation speed 10~20 r / min, pressure roller rotation speed 6~8 r / min, and granulation rotation speed 40~65 r / min.

[0022] The above-described technical solution of the present invention has at least the following beneficial effects: The technical solution provided by this invention significantly reduces the use of fillers by adjusting the ratio of raw materials. On the one hand, it reduces the amount of sucrose in the sucrose-containing throat-soothing and detoxifying granules, reducing the weight of each granule to 9g~13g, thus increasing the clinical suitability for patients. On the other hand, the sucrose-free throat-soothing and detoxifying granules use dry granulation, and by adjusting the parameter range, the preparation efficiency is improved, and the weight of each bag of sucrose-free throat-soothing and detoxifying granules is reduced to 4~5.5g.

[0023] The technical solution provided by this invention introduces peppermint volatile oil and β-cyclodextrin into the raw materials of throat-soothing and detoxifying granules, and provides a method for preparing throat-soothing and detoxifying granules. In this method, peppermint volatile oil is encapsulated with β-cyclodextrin and then mixed with the remaining raw materials for granulation. This improves the stability of peppermint volatile oil and increases the bioavailability of throat-soothing and detoxifying granules. Furthermore, Experiment 3 shows that the encapsulation of peppermint volatile oil enhances the anti-inflammatory and antipyretic effects of throat-soothing and detoxifying granules compared to the spraying method. Attached Figure Description

[0024] Figure 1 These are thin-layer chromatographic images of the throat-soothing and detoxifying granules prepared in the embodiments and comparative examples of the present invention.

[0025] Figure 1 Menthol was used as a control. Sugar-free packaging refers to the throat-soothing and detoxifying granules of Example 3. Sugar-free spray refers to the throat-soothing and detoxifying granules of Comparative Example 3. Sugar-packaged packaging refers to the throat-soothing and detoxifying granules of Example 6. Sugar-sprayed spray refers to the throat-soothing and detoxifying granules of Comparative Example 4. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the following will be described in conjunction with the accompanying drawings of the embodiments of the present invention. Figure 1 The technical solutions of the embodiments of the present invention will be clearly and completely described herein. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention are within the scope of protection of the present invention.

[0027] Pharmacopoeia prescription: Isatis root 91.8g, honeysuckle 91.8g, forsythia 30.6g, peppermint 30.6g, burdock seed (fried) 30.6g, hawthorn (charred) 91.8g, platycodon root 30.6g, indigo leaf 91.8g, silkworm 30.6g, scrophularia root 91.8g, scutellaria root 45.9g, rehmannia root 61.2g, trichosanthes root 61.2g, rhubarb 30.6g, fritillaria bulb 45.9g, ophiopogon root 91.8g.

[0028] Preparation method of soothing and detoxifying extract: Peppermint extract volatile oil with water, collect the volatile oil, filter the water extract, and set aside the filtrate and the dregs; boil the peppermint dregs and the other fifteen ingredients with water twice, each time for 1.5 hours, filter the decoction, combine the filtrates, add the water extract that was used for peppermint oil extraction, and concentrate to a relative density of 1.38~1.40 (80℃).

[0029] The throat-soothing and detoxifying extract of the present invention is prepared according to the pharmacopoeia prescription.

[0030] Example 1 This invention provides a throat-soothing and detoxifying granule (containing sucrose), comprising the following components: peppermint volatile oil, β-cyclodextrin, throat-soothing and detoxifying extract, filler, and sucralose. The throat-soothing and detoxifying extract is a thick throat-soothing and detoxifying extract, and the filler is sucrose and dextrin. The weights of each raw material are shown in Table 1.

[0031] Table 1. Weight of each raw material in sucrose-containing throat-soothing and detoxifying granules (commercial batch of 70,000 bags)

[0032] Comparative Example 1 Compared with Example 1, the only differences are that it does not contain β-cyclodextrin and sucralose, and the weights of each ingredient are shown in Table 2 below: Table 2. Weight of raw materials for existing prescription sucrose-containing throat-soothing and detoxifying granules (commercial batch of 70,000 bags).

[0033] The quality of the sucrose-containing throat-soothing and detoxifying granules prepared in Example 1 and Comparative Example 1 was compared, and the results are shown in Table 3 below.

[0034] Table 3. Comparison of the quality of throat-soothing and detoxifying granules in Example 1 and Comparative Example 1

[0035] As shown in Table 3, the throat-soothing and detoxifying granules containing sucrose prepared in Example 1, compared with those prepared in Comparative Example 1, have a less sweet taste, improve patient tolerance to medication, and reduce the amount of sucrose used, thus reducing costs.

[0036] Example 2 This invention provides a throat-soothing and detoxifying granule (sugar-free), comprising the following components: peppermint volatile oil, β-cyclodextrin, throat-soothing and detoxifying extract, filler, and sucralose. The throat-soothing and detoxifying extract is a throat-soothing and detoxifying dry powder, and the filler is lactose. The weights of each raw material are shown in Table 4.

[0037] Table 4. Weight of each ingredient in sugar-free throat-soothing and detoxifying granules (commercial batch of 210,000 bags)

[0038] Comparative Example 2 The difference from Example 2 is that it does not contain lactose and β-cyclodextrin, but it does contain aspartame. The weights of each ingredient are shown in Table 5 below.

[0039] Table 5. Weight of each ingredient in sugar-free throat-soothing and detoxifying granules (commercial batch of 70,000 bags)

[0040] The quality of the sucrose-free throat-soothing and detoxifying granules prepared in Example 2 and Comparative Example 2 was compared, and the results are shown in Table 6 below.

[0041] Table 6. Comparison of the quality of throat-soothing and detoxifying granules in Example 2 and Comparative Example 2

[0042] As shown in Table 6, the sucrose-free throat-soothing and detoxifying granules prepared in Example 2 have a less cloyingly sweet taste compared to the sucrose-free throat-soothing and detoxifying granules prepared in Comparative Example 2.

[0043] Example 3 This invention provides a method for preparing throat-soothing and detoxifying granules (sugar-free), comprising the following steps: Inclusion of peppermint volatile oil and β-cyclodextrin using a saturated aqueous solution method to obtain an inclusion complex; that is, 20g of β-cyclodextrin is mixed with purified water at a mass ratio of 1:10, heated to 60℃, and stirred at a low speed of 200r / min during heating to ensure complete dissolution. After cooling to 55℃, the cyclodextrin solution is kept at this temperature for 0.5h for later use. 2ml of peppermint volatile oil is mixed with anhydrous ethanol at a volume ratio of 1:2 to obtain a peppermint volatile oil solution. The peppermint volatile oil solution is added dropwise to the cyclodextrin solution at a rate of 2-3 drops / second, and stirred at 500r / min. After all the volatile oil has been added, timing begins, and stirring continues at 500r / min for 2h. The inclusion complex is obtained after inclusion is complete. The inclusion complex is refrigerated at 8℃ for 12h, filtered through two layers of filter paper, and the precipitate is washed twice with purified water. The filter residue was dried in a 40℃ oven for 10 hours, turning it once during the process, to obtain the peppermint volatile oil inclusion complex.

[0044] Peppermint volatile oil inclusion complexes were dehydrated, dried, and pulverized, then mixed with lactose, sucralose, and throat-soothing and detoxifying dry granule powder. Dry granulation was then performed. Lactose and dextrin were sieved through a 100-mesh sieve, and sucrose was pulverized and sieved through a 100-mesh sieve. Dry granulation was conducted using a dry granulator with the following operating parameters: pressure 5.5 MPa, vertical rotation speed 15 r / min, pressure roller speed 8 r / min, and granulation speed 40 r / min. After granulation and mixing, throat-soothing and detoxifying granules were obtained. Granulation was performed using a sieving machine with a 10-mesh stainless steel screen on the upper layer and an 80-mesh stainless steel screen on the lower layer. Mixing was performed using a mixer with the following operating parameters: frequency 50 Hz and time 20 min.

[0045] Example 4 The difference from Example 3 lies only in the use of a grinding method to encapsulate peppermint volatile oil with β-cyclodextrin to obtain an inclusion complex. The grinding method includes the following steps: 20g of β-cyclodextrin is mixed with purified water at a mass ratio of 1:3 to obtain a cyclodextrin solution. 2ml of peppermint volatile oil is mixed with anhydrous ethanol at a volume ratio of 1:2 to obtain a peppermint volatile oil solution. The cyclodextrin solution and peppermint volatile oil solution are mixed and poured into a mortar. The mixture is ground 8 times, 10 minutes each time. After encapsulation, the mixture is refrigerated at 4-10℃ for 12-24 hours, filtered through two layers of filter paper, and the precipitate is washed twice with purified water. The filter residue is placed in a 40℃ oven and dried for 10 hours, turning it once during the drying process, to obtain the peppermint volatile oil inclusion complex.

[0046] Example 5 The difference from Example 3 lies only in the use of an ultrasonic method to encapsulate peppermint volatile oil with β-cyclodextrin to obtain an inclusion complex. The ultrasonic method includes the following steps: 20g of β-cyclodextrin and purified water are mixed at a mass ratio of 1:10, heated to 60℃, and stirred at a low speed of 200r / min during heating to ensure complete dissolution. After cooling to 55℃, the cyclodextrin solution is kept at this temperature for 0.5h. 2ml of peppermint volatile oil and anhydrous ethanol are mixed evenly at a volume ratio of 1:2 to obtain a peppermint volatile oil solution. The peppermint volatile oil solution is added dropwise to the cyclodextrin solution at a rate of 2-3 drops / second, while simultaneously sonicating at a frequency of 30Hz. Once all the volatile oil has been added, timing begins, and sonication continues at 30Hz for 2h. After inclusion, the mixture is refrigerated at 4-10℃ for 12-24h, filtered through two layers of filter paper, and the precipitate is washed twice with purified water. The filter residue is dried in a 40℃ oven for 10h, turning it once during the drying process, to obtain the peppermint volatile oil inclusion complex.

[0047] The inclusion rates of volatile oils were calculated for the inclusion compounds prepared in Examples 3-5, as shown in Table 7.

[0048] The calculation formula is: Inclusion yield (%) = mass of inclusion compound / (mass of inclusion material + mass of volatile oil) * 100%; Oil content (%) = Volatile oil content in the inclusion compound / Blank recovery rate / Mass of the inclusion compound * 100%; Volatile oil inclusion rate (%) = Amount of volatile oil in the inclusion compound / Amount of volatile oil added * 100%.

[0049] Table 7. Inclusion rates of volatile oils in the inclusion compounds prepared in Examples 3-5

[0050] Example 6 This invention provides a method for preparing throat-soothing and detoxifying granules, comprising the following steps: Peppermint volatile oil and β-cyclodextrin are encapsulated using a saturated aqueous solution method to obtain an inclusion complex. Specifically, 18g of β-cyclodextrin is mixed with purified water at a mass ratio of 1:8, heated to 58℃, and stirred at a low speed of 220r / min during heating to ensure complete dissolution. The solution is then cooled to 55℃ and kept warm for 1 hour. 2ml of peppermint volatile oil is mixed with anhydrous ethanol at a volume ratio of 1:3 to obtain a peppermint volatile oil solution. This solution is added dropwise to the cyclodextrin solution at a rate of 2 drops / second, while stirring at 450r / min. After all the volatile oil has been added, the mixture is stirred at 550r / min for 1.5 hours. The inclusion complex is then obtained. The inclusion complex is refrigerated at 4℃ for 24 hours, filtered through two layers of filter paper, and the precipitate is washed three times with purified water. The filter residue is dried in a 55℃ oven for 8 hours, turning it once during the drying process, to obtain the peppermint volatile oil inclusion complex.

[0051] Peppermint volatile oil inclusion complex is dehydrated, dried, and pulverized, then mixed with sucrose, dextrin, sucralose, and a throat-soothing and detoxifying thick extract for granulation. After drying, granulation, and final mixing, throat-soothing and detoxifying granules are obtained. Granulation is performed using a sieving machine with a 10-mesh stainless steel screen on the upper layer and an 80-mesh stainless steel screen on the lower layer. Final mixing is performed using a mixer with a frequency of 50Hz and a time of 20min.

[0052] Comparative Example 3 Compared with Example 3, the only difference is that instead of preparing peppermint volatile oil and β-cyclodextrin into an inclusion complex, peppermint volatile oil is directly sprayed into the throat-soothing and detoxifying granules to obtain sucrose-free throat-soothing and detoxifying granules.

[0053] Comparative Example 4 Compared with Example 6, the only difference is that instead of preparing a complex of peppermint volatile oil and β-cyclodextrin, peppermint volatile oil is directly sprayed into the throat-soothing and detoxifying granules to obtain sucrose-containing throat-soothing and detoxifying granules.

[0054] The throat-soothing and detoxifying granules prepared in Examples 3 and 6, as well as Comparative Examples 3 and 4, were tested for stability using thin-layer chromatography of peppermint volatile oil. Figure 1 .

[0055] Experimental Method: Take 10g of sugar-free and 20g of sugar-containing granules for sore throat and detoxification, grind them finely, add 250ml of water, shake well, connect to the volatile oil analyzer, add 2ml of water from the top of the analyzer, then add 1ml of ethyl acetate, heat under reflux for 2 hours, and take the ethyl acetate solution as the test solution. Separately, take menthol reference standard, add ethyl acetate to prepare a solution containing 1mg per ml, as the reference solution. Perform thin-layer chromatography (General Rule 0502), take 5μl of each of the above solutions, spot them separately on the same silica gel G thin-layer plate, use cyclohexane-ethyl acetate (17:3) as the developing solvent, develop, remove, air dry, spray with 0.5% vanillin-sulfuric acid-ethanol (2:8) mixed solution, heat at 105℃ until the spots are clearly visible, and examine under sunlight. In the chromatogram of the test sample, spots of the same color appear at the corresponding positions as in the chromatogram of the reference standard.

[0056] Thin-layer chromatograms were obtained for 0 months, long-term (3 months), accelerated (3 months), long-term (6 months), and accelerated (6 months). Results are shown below. Figure 1 , Figure 1 Menthol was used as a control. Sugar-free packaging refers to the throat-soothing and detoxifying granules of Example 3. Sugar-free spray refers to the throat-soothing and detoxifying granules of Comparative Example 3. Sugar-packaged packaging refers to the throat-soothing and detoxifying granules of Example 6. Sugar-sprayed spray refers to the throat-soothing and detoxifying granules of Comparative Example 4.

[0057] Depend on Figure 1It can be seen that the volatile oil stability of the throat-soothing and detoxifying granules prepared in Examples 3 and 6 of the present invention is stronger than that of the throat-soothing and detoxifying granules prepared in Comparative Examples 3 and 4.

[0058] Example 7 This invention provides a throat-soothing and detoxifying granule (containing sucrose), with each bag containing 9-13g.

[0059] Example 8 This invention provides a throat-soothing and detoxifying granule (sugar-free), with each bag containing 4-5.5g.

[0060] Experimental Example I. The effect of dry granulation parameters on throat-soothing and detoxifying granules.

[0061] 1. The effect of pressure on throat-soothing and detoxifying granules The dry pellet mill parameters were set as follows: vertical rotation speed 10 rpm, pressure roller speed 5.0 rpm, and pelletizing speed 40.0 rpm. Pressures were set at 4.5, 5.0, 5.5, 6.0, 8.0, and 10 MPa, with 2 kg of material fed into the dry pellet mill each time. The results are shown in Table 8 below.

[0062] Table 8. Effects of pressure on throat-soothing and detoxifying granules

[0063] As shown in Table 8, the higher the pressure, the higher the one-time molding rate. However, when the pressure is less than 5 MPa, sticking occurs, and when the pressure is higher than 6.0 MPa, the color of the particles varies. Therefore, the pressure range is selected as 5~5.5 MPa.

[0064] 2. The effect of pressure roller speed on throat-soothing and detoxifying granules The dry pellet mill parameters were set as follows: pressure 5.5 MPa, vertical rotation speed 10 rpm, and pelletizing speed 40.0 rpm. The pressure roller speeds were set to 6, 7, 8, 9, and 10 rpm, with 2 kg of material fed into the dry pellet mill each time. The results are shown in Table 9 below.

[0065] Table 9. Effect of roller speed on throat-soothing and detoxifying granules

[0066] As shown in Table 9, the roller speed has a relatively small impact on the one-time forming rate. However, when the roller speed exceeds 9 rpm, the particle color varies. Therefore, the roller speed range is 6~8 rpm.

[0067] 3. The effect of granulation speed on throat-soothing and detoxifying granules The dry pellet mill parameters were set as follows: pressure 5.5 MPa, pressure roller speed 8 rpm, and vertical speed 10 rpm. The pelletizing speeds were set to 40, 45, 55, and 65 rpm, with 2 kg of material fed into the dry pellet mill each time. The results are shown in Table 10 below.

[0068] Table 10 Effect of Granulation Rotation Speed ​​on Throat-Soothing and Detoxifying Granules

[0069] As shown in Table 10, the pelletizing speed has little effect on the one-time forming rate and pellet color. The higher the pelletizing speed, the larger the angle of repose. Therefore, the pelletizing speed range is 40~65 rpm.

[0070] 4. The effect of vertical feeding speed on throat-soothing and detoxifying granules The dry pellet mill parameters were set as follows: pressure 5.5 MPa, pressure roller speed 8 rpm, and pelletizing speed 40.0 rpm. Vertical feeding speeds were set to 10 and 20 rpm respectively, with 2 kg of material fed into the dry pellet mill each time. The results are shown in Table 11.

[0071] Table 11 Effect of Vertical Feeding Speed ​​on Throat-Soothing and Detoxifying Granules

[0072] As shown in Table 11, the vertical rotational speed range is 10~20 rpm.

[0073] II. Influence of relevant parameters on the preparation of peppermint volatile oil inclusion complexes by saturated aqueous solution method 1. Effect of the mass ratio of β-cyclodextrin to water 20g of β-cyclodextrin was mixed with purified water at mass ratios of (1:8), (1:10), and (1:15), respectively, and heated to 60℃ with stirring at a low speed of 200r / min during heating to ensure complete dissolution. After cooling to 55℃, the cyclodextrin solution was kept at this temperature for 0.5h. 2ml of peppermint volatile oil was mixed with anhydrous ethanol at a volume ratio of 1:2 to obtain a peppermint volatile oil solution. The peppermint volatile oil solution was added dropwise to the cyclodextrin solution at 2-3 drops / second, while stirring at 500r / min. Timing was started after all the volatile oil was added, and stirring was continued at 500r / min for 2h. After inclusion, the mixture was refrigerated at 4-10℃ for 12-24h, filtered through two layers of filter paper, and the precipitate was washed twice with purified water. The filter residue was dried in a 40℃ oven for 10h, turning it once during the drying process, to obtain the peppermint volatile oil inclusion complex. The results are shown in Table 12.

[0074] Table 12 Effect of the mass ratio of β-cyclodextrin to water on volatile oil inclusion complexes

[0075] As shown in Table 12, the higher the water content, the more β-cyclodextrin dissolves, and the more volatile oil cannot be completely encapsulated. Therefore, the inclusion complex yield is highest at a ratio of 1:8. When the ratio of β-cyclodextrin to water is 1:(8~10), the inclusion complex yield and volatile oil encapsulation rate are relatively high. Therefore, the mass ratio of β-cyclodextrin to purified water is 1:(8~10).

[0076] 2. Effect of the volume-to-mass ratio of peppermint volatile oil to cyclodextrin The inclusion complex of peppermint volatile oil was performed using a saturated aqueous solution method. First, 14g, 20g, and 26g of β-cyclodextrin were weighed and mixed with purified water at a mass ratio of 1:8, and heated to 60℃ with low-speed stirring at 200 rpm to ensure complete dissolution. After cooling to 55℃, the cyclodextrin solution was kept at this temperature for 0.5 hours. 2ml of peppermint volatile oil was mixed with anhydrous ethanol at a volume ratio of 1:2 to obtain a peppermint volatile oil solution. The peppermint volatile oil solution was added dropwise to the cyclodextrin solution at 2-3 drops / second, while stirring at 500 rpm. After all the volatile oil was added, the mixture was stirred at 500 rpm for 2 hours. After inclusion complexation, the mixture was refrigerated at 4-10℃ for 12-24 hours, filtered through two layers of filter paper, and the precipitate was washed twice with purified water. The filter residue was dried in a 40℃ oven for 10 hours, turning it once during the drying process, to obtain the peppermint volatile oil inclusion complex. The results are shown in Table 13.

[0077] Table 13 Effect of the volume-to-mass ratio of peppermint volatile oil to cyclodextrin on the inclusion complex of volatile oil.

[0078] As shown in Table 13, when the ratio of volatile oil to β-cyclodextrin is 1:7, the inclusion rate of volatile oil is low, and the volatile oil cannot be completely included. When the ratio of volatile oil to β-cyclodextrin is 1:10, the volatile oil is completely included. Therefore, the volume-mass ratio of peppermint volatile oil to β-cyclodextrin should be between 1:7 and 10. The inclusion rate of volatile oil increases while the yield of inclusion complex decreases. Taking all factors into consideration, the volume-mass ratio of peppermint volatile oil to β-cyclodextrin should be between 1:9 and 13.

[0079] 3. The effect of refrigeration temperature The inclusion complex of peppermint volatile oil was prepared using a saturated aqueous solution method. First, 40g of β-cyclodextrin and purified water were weighed and mixed at a mass ratio of 1:8. The mixture was heated to 60℃ with low-speed stirring at 200 rpm to ensure complete dissolution. After cooling to 55℃, the cyclodextrin solution was kept at this temperature for 0.5 hours. Then, 4ml of peppermint volatile oil was mixed with anhydrous ethanol at a volume ratio of 1:2 to obtain a peppermint volatile oil solution. This solution was then added dropwise to the cyclodextrin solution at a rate of 2-3 drops / second, while stirring at 500 rpm. Once all the volatile oil had been added, the mixture was stirred at 500 rpm for 2 hours. After inclusion, the mixture was divided into two portions and refrigerated at 25℃ and 4-10℃ respectively for 12-24 hours. The samples were filtered through two layers of filter paper, and the precipitate was washed twice with purified water. The filter residue was dried in a 40℃ oven for 10 hours, turning it once during the drying process. The peppermint volatile oil inclusion complex was obtained. The results are shown in Table 14.

[0080] Table 14 Effect of Refrigeration Temperature on Volatile Oil Inclusion Compounds

[0081] Table 14 shows that the inclusion rates of volatile oils are similar at 25℃ and 4~10℃. However, lower temperatures are more conducive to the precipitation of inclusion compounds and increase their yield. Therefore, the optimal refrigeration temperature is 4~10℃.

[0082] 4. Effect of drying temperature The inclusion complex of peppermint volatile oil was performed using a saturated aqueous solution method. First, 60g of β-cyclodextrin and purified water were weighed and mixed at a mass ratio of 1:8. The mixture was heated to 60℃ with low-speed stirring at 200 rpm to ensure complete dissolution. After cooling to 55℃, the cyclodextrin solution was kept at this temperature for 0.5 hours. 6ml of peppermint volatile oil was then mixed with anhydrous ethanol at a volume ratio of 1:2 to obtain a peppermint volatile oil solution. This solution was added dropwise to the cyclodextrin solution at a rate of 2-3 drops / second, while stirring at 500 rpm. Once all the volatile oil had been added, the mixture was stirred at 500 rpm for 2 hours. After inclusion, the mixture was refrigerated at 4-10℃ for 12-24 hours, filtered through two layers of filter paper, and the precipitate was washed twice with purified water. The filter residue was divided into three equal portions and dried in ovens at 40℃, 55℃, and 70℃ respectively, turning once during the drying process. These were the peppermint volatile oil inclusion complexes. The results are shown in Table 15.

[0083] Table 15 Effect of drying temperature on volatile oil inclusion compounds

[0084] As can be seen from Table 15, the higher the drying temperature, the lower the essential oil yield and the inclusion rate of essential oil show a downward trend. At drying temperatures of 40°C and 55°C, there is no obvious volatilization of the essential oil. Therefore, the drying temperature is 40 - 55°C. In addition, drying at 55°C can significantly reduce the drying time. Therefore, the preferred drying temperature is 55°C.

[0085] III. Influence of the addition method of peppermint essential oil on the efficacy of Liyan Jiedu Granules 1. Influence of the addition method of peppermint essential oil in Liyan Jiedu Granules on antipyretic effect 1.1 Experimental animals 60 SPF - level male SD rats (weighing 220 - 250 g) were purchased from Beijing Spearf Bio Co., Ltd. Production License: SCXK (Beijing) 2019 - 0010.

[0086] Feeding conditions: temperature 22 - 25°C, humidity 40 - 60%, 12 h / 12 h light - dark cycle, free diet and water, and bedding and cages were replaced regularly.

[0087] 1.2 Experimental materials and instruments Liyan Jiedu Granules (Hebei Yongfeng Pharmaceutical Co., Ltd.), lipopolysaccharide (Sigma, USA), 0.9% sodium chloride injection (Shijiazhuang No. 4 Pharmaceutical Co., Ltd.), MC - 347 electronic thermometer (Omron Co., Ltd.).

[0088] 1.3 Experimental methods Before the experiment, the rats were adaptively fed for one week. The rectal temperature of the rats was measured at 9:00 am every day to make them adapt to rectal temperature measurement. Experimental rats with rectal temperature > 38°C or a difference in adjacent two measurements > 0.5°C were excluded. The qualified rats were randomly divided into 6 groups, with 10 rats in each group, namely the blank group, the model group, the inclusion group of essential oil of Liyan Jiedu Granules with sucrose (abbreviated as "sucrose inclusion group"), the spraying group of essential oil of Liyan Jiedu Granules with sucrose (abbreviated as "sucrose spraying group"), the inclusion group of essential oil of Liyan Jiedu Granules without sucrose (abbreviated as "no - sucrose inclusion group"), and the spraying group of essential oil of Liyan Jiedu Granules without sucrose (abbreviated as "no - sucrose spraying group").

[0089] Two days before modeling, after measuring the rectal temperature, the experimental groups were gavaged with Liyan Jiedu Granules, and the blank group and the model group were gavaged with 0.9% sodium chloride injection. The gavage volume was 2.5 ml once a day for three consecutive days. According to the rat dose conversion, the dosage of Liyan Jiedu Granules was calculated, as shown in Table 16 below. After the last administration, the experimental groups and the model group were intraperitoneally injected with LPS (20 μg / kg) freshly prepared with 0.9% sodium chloride injection, and the blank group was injected with 0.9% sodium chloride injection. The injection volume was 0.2 ml. The rectal temperature was measured at 1, 2, 3, 4, and 5 h after modeling, and the data were recorded, as shown in Table 17.

[0090] Table 16 Rat dosing doses

[0091] Note: The adult body weight is calculated as 70 kg, and the rat body weight is calculated as 0.2 kg.

[0092] 1.4 Experimental results Table 17 Results table of the effect of the addition method of menthol volatile oil in Liyan Jiedu Granules on antipyretic effect

[0093] Note: The results are mean ± standard deviation. Compared with the model group, aP < 0.05.

[0094] As can be seen from Table 17, at 1, 2, 3, 4, and 5 h after modeling, the anal temperature of the experimental group was significantly lower than that of the model group (P < 0.05). Adding menthol volatile oil to the extract of Liyan Jiedu Granules by spraying or inclusion can obtain better antipyretic effects. Although there is no significant difference in temperature changes between the inclusion group and the spraying group statistically, it can still be seen from the average value that the inclusion of menthol oil can enhance the antipyretic effect of Liyan Jiedu Granules compared with spraying.

[0095] 2. Effect of the addition method of menthol volatile oil in Liyan Jiedu Granules on anti-inflammatory effect 2.1 Experimental animals 60 SPF-grade male SD rats (body weight 220 - 250 g) were purchased from Beijing SPF Biotechnology Co., Ltd. Production license: SCXK (Beijing) 2019 - 0010.

[0096] Feeding conditions: Temperature 22 - 25 °C, humidity 40 - 60%, 12 h / 12 h light-dark cycle, free diet and water, regularly change bedding and cages.

[0097] 2.2 Experimental materials and instruments Liyan Jiedu Granules (Hebei Yongfeng Pharmaceutical Co., Ltd.), carrageenan (Sigma, USA), 0.9% sodium chloride injection (Shijiazhuang No. 4 Pharmaceutical Co., Ltd.), PV-200 type toe volume measuring instrument (Chengdu Taimeng Technology Co., Ltd.), electronic balance [Mettler Toledo Instruments (Shanghai) Co., Ltd.].

[0098] 2.3 Experimental methods Before the experiment, the rats were acclimatized for one week. The rats were randomly divided into 6 groups of 10 rats each: blank group, model group, group containing sucrose-containing throat-soothing and detoxifying granules with volatile oil (hereinafter referred to as "sucrose-containing group"), group containing sucrose-containing throat-soothing and detoxifying granules with volatile oil sprayed (hereinafter referred to as "sucrose-sprayed group"), group without sucrose-containing throat-soothing and detoxifying granules with volatile oil (hereinafter referred to as "sucrose-free group"), and group without sucrose-containing throat-soothing and detoxifying granules with volatile oil sprayed (hereinafter referred to as "sucrose-free group").

[0099] Normal paw volume determination: Before administration, a mark was made on the upper part of the ankle joint on the front of the rat's right hind paw, where the hair ends, and the normal right hind paw volume was measured. Two days before modeling, the experimental group was administered Liyan Jiedu granules by gavage, while the blank group and model group were administered 0.9% sodium chloride injection by gavage. The gavage volume was 2.5 ml for all groups, once daily for three consecutive days. The dosage of Liyan Jiedu granules was calculated based on the rat dosage conversion, as shown in Table 18 below. Thirty minutes after the last administration, 1% carrageenan was injected subcutaneously into the right hind paw of both the experimental and model groups, with an injection volume of 0.1 ml. The right hind paw volume was measured at 1, 2, 3, 4, and 5 hours after modeling, and the data were recorded, as shown in Table 19.

[0100] Calculation formula: Foot swelling rate (%) = (Foot volume of rats after inflammation - Foot volume of rats before inflammation) / Foot volume of rats before inflammation * 100%.

[0101] Table 18 Dosage for Rats

[0102] Note: Adult weight is 70kg, and rat weight is 0.2kg.

[0103] 2.4 Experimental Results Table 19. Effects of the method of adding peppermint oil to throat-soothing and detoxifying granules on their anti-inflammatory effects.

[0104] Note: Results are mean ± standard deviation. Compared with the model group, a P < 0.05.

[0105] Table 19 shows that, after modeling, foot swelling in the model group initially increased and then decreased at 1, 2, 3, 4, and 5 hours, peaking at 3 hours after inflammation induction. The swelling in the experimental group was significantly lower than that in the model group (P < 0.05). The peppermint oil in the Liyan Jiedu granules, whether added via spraying or encapsulation, exhibits certain anti-inflammatory effects. Although there was no statistically significant difference in temperature changes between the encapsulation and spraying groups, the average values ​​still indicate that peppermint oil encapsulation enhances the anti-inflammatory effect of the Liyan Jiedu granules compared to spraying.

[0106] The above are preferred embodiments of the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A throat-soothing and detoxifying granule, characterized in that, It includes the following components: peppermint volatile oil, β-cyclodextrin, throat-soothing and detoxifying extract, filler, and sucralose.

2. The throat-soothing and detoxifying granules according to claim 1, characterized in that, The throat-soothing and detoxifying extract is a thick throat-soothing and detoxifying extract, and the fillers are sucrose and dextrin; the mass ratio of the thick throat-soothing and detoxifying extract, peppermint volatile oil, β-cyclodextrin, sucrose, dextrin and sucralose is (350.0~465.0): (0.1~0.39): (1.0~3.9): (305.0~350.0): (305.0~350.0): (2~3).

3. The throat-soothing and detoxifying granules according to claim 1, characterized in that, The throat-soothing and detoxifying extract is a throat-soothing and detoxifying dry powder, and the filler is lactose; the mass ratio of the throat-soothing and detoxifying dry powder, peppermint volatile oil, β-cyclodextrin, lactose and sucralose is (2517.50~3344.68): (1.43~5.57): (14.3~55.7): (1084.37~1960.56): (9.5~10.5).

4. The method for preparing the throat-soothing and detoxifying granules as described in claim 1, characterized in that, Includes the following steps: Peppermint volatile oil was encapsulated with β-cyclodextrin to obtain an inclusion complex. The inclusion complex was dehydrated, dried, pulverized, and then mixed with a filler, sucralose, and a throat-soothing and detoxifying extract for granulation. After granulation and mixing, throat-soothing and detoxifying granules were obtained.

5. The method for preparing the throat-soothing and detoxifying granules according to claim 4, characterized in that, The inclusion complex obtained by combining peppermint volatile oil with β-cyclodextrin is obtained by one of the following methods: saturated aqueous solution method, grinding method, and ultrasonic method.

6. The method for preparing the throat-soothing and detoxifying granules according to claim 5, characterized in that, The saturated aqueous solution method includes the following steps: S1. Mix β-cyclodextrin with purified water, heat and stir until fully dissolved to obtain a cyclodextrin solution, cool and keep warm for later use; S2. Mix peppermint volatile oil with anhydrous ethanol until homogeneous to obtain peppermint volatile oil solution. Add the peppermint volatile oil solution dropwise into the cyclodextrin solution while stirring to encapsulate the mixture. After encapsulation, refrigerate. S3. After refrigeration, perform vacuum filtration, wash the precipitate to obtain filter residue, and dry the filter residue to obtain peppermint volatile oil inclusion complex.

7. The method for preparing the throat-soothing and detoxifying granules according to claim 6, characterized in that, The peppermint volatile oil is encapsulated with β-cyclodextrin at a ratio of 9-13g β-cyclodextrin to 1ml peppermint volatile oil; the mass ratio of β-cyclodextrin to purified water is 1:(8-10); the mass ratio of peppermint volatile oil to anhydrous ethanol is 1:(2-3); in step S1, the heating and stirring are carried out at a temperature of 58-60℃ and a stirring rate of 180-220r / min; the cooling and heat preservation are carried out at 55℃ for 0.5-1h.

8. The method for preparing the throat-soothing and detoxifying granules according to claim 6, characterized in that, The process of adding peppermint volatile oil solution dropwise into cyclodextrin solution while stirring involves adding the peppermint volatile oil solution at a rate of 2-3 drops / second while stirring at 450-550 rpm. Timing begins after all the peppermint volatile oil solution has been added to the cyclodextrin solution, with a stirring rate of 450-550 rpm and a stirring time of 1.5-2 hours. The refrigeration temperature is 4-10°C for 12-24 hours. The filter residue is dried at 40-55°C for 8-12 hours.

9. The method for preparing the throat-soothing and detoxifying granules according to claim 4, characterized in that, The granulation process includes wet granulation and dry granulation. The filler used in wet granulation is sucrose, and the filler used in dry granulation is lactose.

10. The method for preparing the throat-soothing and detoxifying granules according to claim 9, characterized in that, The dry granulation process uses a dry granulator, whose operating parameters are: pressure 5~5.5MPa, vertical rotation speed 10~20 r / min, pressure roller rotation speed 6~8 r / min, and granulation rotation speed 40~65 r / min.

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