Traditional Chinese medicine composition as well as preparation thereof and construction method of HPLC (High Performance Liquid Chromatography) specific chromatogram thereof

Abstract

The invention belongs to the technical field of medicines, particularly relates to a traditional Chinese medicine composition and a preparation thereof, and provides a preparation method. The traditional Chinese medicine composition preparation provided by the invention consists of a traditional Chinese medicine extract and pharmaceutically acceptable pharmaceutic adjuvants, wherein the traditional Chinese medicine extract is prepared by extracting 10-20 parts of wild buckwheat rhizome, 3-8 parts of honey stemona root, 3-8 parts of honey aster, 3-8 parts of scalded bitter apricot kernel, 2-5 parts of scutellaria baicalensis, 3-8 parts of loquat leaf, 3-8 parts of rhizoma anemarrhenae and 5-15 parts of gypsum. The invention also provides a method for establishing the HPLC characteristic chromatogram of the traditional Chinese medicine composition and the preparation thereof, and the method is established by adopting a high performance liquid chromatography. Chromatographic conditions are as follows: a chromatographic column takes octadecylsilane chemically bonded silica as a filler; acetonitrile is used as a mobile phase A, a phosphoric acid solution is used as a mobile phase B, and gradient elution is carried out. The quality levels of the traditional Chinese medicine composition and the preparation thereof can be comprehensively and effectively controlled.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a traditional Chinese medicine composition and its preparation, and provides a preparation method and a method for constructing HPLC characteristic chromatograms. Using this invention, the quality level of the traditional Chinese medicine composition and its preparation can be comprehensively and effectively controlled. Background Technology

[0002] Coughing is a protective reflex, but excessively frequent coughing can cause discomfort. A cough lasting more than three weeks without obvious evidence of lung disease is generally defined as chronic cough. Due to its multiple causes, unclear pathogenesis, and the fact that some diseases only manifest as coughing, the diagnosis and treatment of chronic cough can sometimes be quite difficult. Since the Irwin Anatomical Diagnostic Procedure for Chronic Cough, proposed in 1981 and revised in 1990, significant progress has been made in the diagnosis and treatment of chronic cough. Post-cold cough is one of the causes of chronic cough; chronic cough following an upper respiratory tract infection can occur in 12%-15% of cases. Currently, it is believed that although cold symptoms may subside after an upper respiratory tract infection, viruses and bacteria damage the integrity of the respiratory mucosal epithelium, reducing the respiratory tract's defense capabilities and causing pathological damage to the bronchial wall mucosa, often leading to a persistent cough.

[0003] Post-cold cough is also a common cause of chronic cough in children, referring to a persistent cough that continues even after the acute symptoms of a cold have subsided. Besides respiratory viruses, other respiratory infections can also cause this type of cough. Children with this condition often experience an irritating dry cough or cough up small amounts of white, mucous sputum, which can last for 3-8 weeks or even longer. Chest X-rays are normal, and antibiotic treatment is ineffective. Scholars both domestically and internationally have found that these children with post-cold cough may be suffering from allergic cough, hence the clinical term "cough variant asthma" (CVA).

[0004] Chinese patent CN112843192A discloses a traditional Chinese medicine composition for relieving cough, resolving phlegm, and relieving asthma, and its preparation method. It also discloses a clinically experienced formula for post-cold cough and cough-variant asthma. The formula consists of buckwheat, honey-processed stemona root, honey-processed aster root, roasted bitter almond, scutellaria root, loquat leaf, anemarrhena rhizome, and gypsum. This product has the effects of clearing the lungs and resolving phlegm, relieving cough, and promoting lung function. Clinically, it is used for post-cold cough and cough-variant asthma belonging to the wind-heat invading the lung syndrome, characterized by cough, itchy throat, coughing when itchy, or paroxysmal choking cough, shortness of breath, sudden onset or aggravation upon exposure to cold air, odors, etc., or severe cough at night and upon waking, often recurring, dry cough with little or no phlegm, and a thin white tongue coating.

[0005] The main active ingredients of this traditional Chinese medicine composition are alkaloids, non-alkaloids, terpenes and their glycosides, flavonoids and their glycosides, organic acids, volatile oils, saponins, amino acids and other substances.

[0006] The decoction, alcohol extract, and alcoholic extract of Stemona japonica have significant inhibitory effects on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, and are one of the main active ingredients in Ganke Granules. Modern research shows that Stemona japonica alkaloids can reduce the excitability of the respiratory center in animals and inhibit the cough reflex. Some scholars have conducted pharmacological studies on the alkaloids of raw and honey-processed Stemona japonica. The results show that honey-processed Stemona japonica has a significantly enhanced antitussive effect and reduced toxicity. This indicates that honey-processing of Stemona japonica may generate new compounds with strong antitussive effects, or increase the original effective antitussive components while reducing the content of toxic components. It reduces the slightly toxic and stomach-irritating components, ultimately resulting in a decrease in the total alkaloid content of honey-processed Stemona japonica, but with enhanced antitussive effect and reduced toxicity.

[0007] Chinese patent CN112843192A only discloses the traditional Chinese medicine composition, its preparation method, and its uses, but does not disclose the specific preparation method of the formulation and its granule dosage form, nor the quality control method of the composition.

[0008] Granules offer advantages such as portability and high patient compliance. However, the taste of traditional Chinese medicine granules is often unacceptable to patients, especially children, leading to difficulties in medication administration. Therefore, this invention investigates the formulation process of this traditional Chinese medicine composition to improve its palatability, particularly by reducing bitterness, which is expected to significantly improve patient compliance in children. Selecting a suitable formulation method and establishing a preparation method suitable for commercial production will provide a product with excellent stability, possessing significant clinical and commercial value. Furthermore, since traditional Chinese medicine and its compound preparations are complex multi-component systems, quality evaluation should utilize detection methods that provide rich identification information. However, current methods such as microscopic identification and content determination are insufficient to address this issue, and existing technologies lack effective means for quality control related to cough granules. To more comprehensively and effectively control the quality level of this traditional Chinese medicine composition and its cough granule preparation, ensuring greater safety and efficacy in clinical use, an effective quality control method needs to be established. Summary of the Invention

[0009] The purpose of this invention is to provide a traditional Chinese medicine composition preparation with the effects of relieving cough, resolving phlegm, and relieving asthma.

[0010] Another objective of this invention is to provide a traditional Chinese medicine composition granule with antitussive, expectorant, and asthma-relieving effects.

[0011] Another objective of this invention is to provide a method for preparing a traditional Chinese medicine composition granule with antitussive, expectorant, and antiasthmatic effects.

[0012] Another objective of this invention is to provide a method for constructing HPLC characteristic chromatograms of traditional Chinese medicine compositions and their preparations.

[0013] The present invention discloses a traditional Chinese medicine composition preparation with antitussive, expectorant, and antiasthmatic effects, which is composed of a traditional Chinese medicine extract prepared by extracting 10-20 parts of buckwheat, 3-8 parts of honey-processed stemona root, 3-8 parts of honey-processed aster root, 3-8 parts of bitter almond, 2-5 parts of scutellaria root, 3-8 parts of loquat leaf, 3-8 parts of anemarrhena rhizome, and 5-15 parts of gypsum, and pharmaceutically acceptable excipients.

[0014] Preferably, the traditional Chinese medicine composition preparation is prepared from the following raw materials in parts by weight: 15 parts of buckwheat, 5 parts of honey-processed stemona root, 5 parts of honey-processed aster root, 5 parts of roasted bitter almond, 3 parts of scutellaria root, 5 parts of loquat leaf, 5 parts of anemarrhena rhizome, and 10 parts of gypsum.

[0015] Preferably, the traditional Chinese medicine composition preparation is prepared from the following raw materials in parts by weight: 15 parts of buckwheat, 4 parts of honey-processed stemona root, 4 parts of honey-processed aster root, 4 parts of roasted bitter almond, 2 parts of scutellaria root, 4 parts of loquat leaf, 4 parts of anemarrhena rhizome, and 8 parts of gypsum.

[0016] Preferably, the traditional Chinese medicine composition preparation is prepared from the following raw materials in parts by weight: 15 parts of buckwheat, 6 parts of honey-processed stemona root, 6 parts of honey-processed aster root, 6 parts of roasted bitter almond, 4 parts of scutellaria root, 6 parts of loquat leaf, 6 parts of anemarrhena rhizome, and 12 parts of gypsum.

[0017] Pharmaceutically acceptable excipients may include diluents, disintegrants, excipients, binders, lubricants, surfactants, fillers, preservatives, stabilizers, flavoring agents, thickeners, and flow aids.

[0018] Commonly used excipients include starch, lactose, dextrin, powdered sugar, microcrystalline cellulose, mannitol, xylitol, polyethylene glycol, calcium sulfate, dicalcium phosphate, calcium carbonate, modified starch, sorbitol, polyvinylpyrrolidone, heavy magnesium carbonate, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, sodium carboxymethyl starch, hydroxypropyl cellulose, povidone K30, kaolin, pregelatinized starch, magnesium stearate, talc, micronized silica gel, stevioside, betaine, aspartame, glycyrrhizin, sodium saccharin, citric acid, sorbic acid, potassium sorbate, ethylparaben, sucrose, starch paste, syrup, guar gum, steviol glycosides, sodium alginate, maltose, citric acid, malic acid, sucralose, menthol, coffee powder, monoglycerides, magnesium dodecyl sulfate, beta-cyclodextrin, etc.

[0019] The pharmaceutical excipients account for 30%-80% of the weight of the formulation.

[0020] The present invention discloses a traditional Chinese medicine composition granule with antitussive, expectorant and antiasthmatic effects, which is composed of the above-mentioned traditional Chinese medicine extracts, fillers and flavoring agents.

[0021] More preferably, the pharmaceutical excipients account for 40%-70% of the weight of the formulation;

[0022] The filler accounts for 39.975% to 69.5% of the weight of the formulation; the flavoring agent accounts for 0.025% to 0.5% of the weight of the formulation; more preferably, the filler accounts for 39.95% to 69.95% of the weight of the formulation; and the flavoring agent accounts for 0.05% of the weight of the formulation.

[0023] The filler is maltodextrin, dextrin, maltodextrin-dextrin = 1:1, or soluble starch;

[0024] The filler is preferably maltodextrin;

[0025] The flavoring agent is one or more of sucralose, steviol glycosides, and aspartame.

[0026] The flavoring agent is preferably sucralose;

[0027] The preparation method of the traditional Chinese medicine composition formulation of the present invention includes the following steps:

[0028] Step 1: Pre-treatment process;

[0029] Step 2: Take 8 medicinal slices according to the prescription, add water and heat to extract, then filter;

[0030] Step 3: Concentrate the filtrate from Step 2 into a clear paste;

[0031] Step 4: Take the clear paste from Step 3 and dry it into a dry paste powder;

[0032] Step 5: Take the dry powder from Step 4, add excipients, and prepare the corresponding formulation.

[0033] Further optimization:

[0034] Step 1: Pre-processing step, take the blanched bitter almond slices and crush them.

[0035] Preferably, the crushing process in step 1 is carried out using a screen with an 8-10 mm aperture.

[0036] Preferably, the crushing process standard in step 1 is as follows: the crushed medicinal slices are subjected to a double sieving method, passing through 10mm and 0.85mm sieves respectively, so that both can pass through the 10mm sieve, and the fine powder passing through the 0.85mm sieve does not exceed 20%, and the crushing yield shall not be less than 95%.

[0037] Step 2: Take 10-20 parts of buckwheat, 3-8 parts of honey-processed stemona root, 3-8 parts of honey-processed aster root, 3-8 parts of roasted bitter almond (crushed), 2-5 parts of scutellaria root, 3-8 parts of loquat leaf, 3-8 parts of anemarrhena rhizome, and 5-15 parts of gypsum according to the prescription. Add water, heat and extract, filter, and the product is obtained.

[0038] Preferably, the amount of water added in step 2 can be 6 to 12 times;

[0039] Preferably, the extraction is performed 2-3 times in step 2;

[0040] Preferably, the heating and extraction time in step 2 can be 0.5 hours to 3 hours; more preferably 1 hour to 2 hours.

[0041] Preferably, the filtration mesh size of the extract in step 2 can be 80-300 mesh; more preferably 200-300 mesh.

[0042] More preferably, in step 2, 8-10 times the amount of water is added, and the extraction is performed twice for 1-2 hours; the extract is filtered through a 200-300 mesh filter, and the filtrates are combined to obtain the final product.

[0043] Step 3: Take the filtrate from Step 2 and concentrate it into a clear paste.

[0044] The concentration process in step 3 can be carried out using atmospheric pressure concentration or vacuum concentration.

[0045] In step 3, the vacuum concentration temperature is 60℃-80℃.

[0046] Preferably, the relative density of the extract in step 3 is in the range of 1.10 to 1.15 (60°C);

[0047] Step 4: Take the clear paste from Step 3 and dry it into a dry paste powder.

[0048] The drying method in step 4 is spray drying;

[0049] More preferably, the drying method in step 4 is spray drying, which has the advantages of rapid drying, reduced loss of heat-sensitive components during the process, high production efficiency, fewer operators, and high product quality. Compared with vacuum drying, which has a longer heating time and lower production efficiency, microwave drying has the characteristics of fast speed, high efficiency, greatly shortened drying cycle, and reduced energy consumption, but the effect of the drying process on the drug is unclear.

[0050] More preferably, during the spray drying process, the inlet air temperature is 160℃-180℃.

[0051] Step 5: Take the dry powder from Step 4, add excipients, and granulate.

[0052] Preferably, in step 5, the dry powder can be granulated using a dry or wet method, and the clear powder can be granulated using a one-step granulation method.

[0053] More preferably, the granulation method for the dry powder is dry granulation.

[0054] Preferably, the dry powder in step 4 is granulated by dry granulation, with the addition of fillers and flavoring agents, mixed evenly, and then granulated into 14-mesh / 65-mesh particles.

[0055] More preferably, the filler added during the dry granulation process is maltodextrin. Using maltodextrin as a filler results in good formability, non-sticking to the pressure roller, uniform granules, moderate hardness, uniform color, and a high one-time forming rate. Using dextrin as a filler results in granules with lower hardness, while using soluble starch as a filler leads to poor granule formability and sticking to the pressure roller. Therefore, maltodextrin is preferred as the filler.

[0056] The flavoring agent is one or more of sucralose, steviol glycosides, and aspartame.

[0057] More preferably, the proportion of sucralose, the flavoring agent added during the dry granulation process, is 0.05%. Compared with sucralose proportions of 0.1%, 0.2%, and 0.3%, 0.05% has the best taste, therefore, the preferred proportion of sucralose added is 0.05%.

[0058] More preferably, the granulation method in step 5 is dry granulation. Particles produced by dry granulation have good formability, do not stick to the pressure roller, are uniform in size, have moderate hardness, and uniform color. Particles produced by wet granulation have good formability, are uniform in size, and have moderate hardness, but are not uniform in color. Particles produced by one-step granulation have poor particle size and are not uniform in color. Therefore, dry granulation is preferred.

[0059] Step 6: Take the granules prepared in Step 5 and package them using a polyester / aluminum / polyethylene pharmaceutical composite film as the packaging material, according to the packaging formulation specifications.

[0060] Preferably, the packaging formulation in step 6 can be any specification from 6g / bag to 10g / bag.

[0061] More preferably, the packaging formulation has a specification of 8g / bag.

[0062] This invention provides a method for constructing HPLC characteristic chromatograms of traditional Chinese medicine compositions and their preparations, wherein the method employs high-performance liquid chromatography (HPLC).

[0063] (1) Chromatographic determination of characteristic chromatograms

[0064] This invention employs high-performance liquid chromatography (HPLC), and the chromatographic conditions are as follows:

[0065] Column: Packed with octadecylsilane-bonded silica gel;

[0066] Mobile phase: Gradient elution was performed using acetonitrile as mobile phase A and phosphoric acid solution as mobile phase B.

[0067] The gradient elution is as follows:

[0068] Gradient elution table

[0069]

[0070] According to the present invention, the method further includes the preparation and determination of the test solution.

[0071] According to the present invention, the test solution is prepared by: taking an appropriate amount of the traditional Chinese medicine composition or its preparation, Gan Ke Granules, grinding it finely, adding a suitable solvent, shaking well, filtering, and taking the filtrate.

[0072] The traditional Chinese medicine composition consists of buckwheat, honey-processed stemona root, honey-processed aster root, roasted bitter almond, scutellaria root, loquat leaf, anemarrhena rhizome, and gypsum; the cough granules are prepared from the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0073] According to the present invention, the determination method is as follows: the test solution is pipetted into a liquid chromatograph, measured, and the chromatogram is recorded to obtain the solution.

[0074] Preferably, according to the present invention, the preparation method of the test solution is as follows: take an appropriate amount of cough granules, grind them into a fine powder, take about 1g, weigh it accurately, place it in a stoppered conical flask, add 25ml of 50% methanol, seal tightly, weigh it, sonicate (power 250W, frequency 40kHz) for 30 minutes, cool it, weigh it again, make up the lost weight with 50% methanol, shake well, filter it, and the test solution is obtained.

[0075] According to the present invention, octadecylsilane-bonded silica gel is used as a filler;

[0076] Preferred: The column is packed with octadecylsilane-bonded silica gel, with a length of 250 mm, an inner diameter of 4.6 mm, and a particle size of 5 μm;

[0077] More preferred: Kromasil 100-5-C18 (4.6×250mm, 5μm); optional from: Kromasil 100-5-C18 (4.6×250mm, 5μm) SN: H229260, Kromasil 100-5-C18 (4.6×250mm, 5μm) SN: H227021, Kromasil 100-5-C18 (4.6×250mm, 5μm) SN: H229259, etc.

[0078] According to the present invention, the phosphoric acid solution contains a phosphoric acid volume fraction of 0.05%-0.15%.

[0079] Preferably, the volume fraction of phosphoric acid can be 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14 or 0.15%;

[0080] More preferably, the phosphoric acid solution has a phosphoric acid volume fraction of 0.1%.

[0081] Preferably, the mobile phase is a gradient elution of acetonitrile (A) and 0.1% phosphoric acid solution (B).

[0082] According to the present invention, the detection wavelength is 200–360 nm;

[0083] Preferably, the detection wavelength can be 200nm, 210nm, 220nm, 230nm, 240nm, 250nm, 260nm, 270nm, 280nm, 290nm, 300nm, 310nm, 320nm, 330nm, 340nm, 350nm or 360nm;

[0084] More preferably, the detection wavelength is 300nm.

[0085] According to the present invention, the flow rate is 0.8, 0.9, or 1.0 ml / min.

[0086] According to the present invention, the column temperature is 20–30°C;

[0087] Preferably, the column temperature is 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30.

[0088] More preferably, the column temperature is 25°C.

[0089] According to the present invention, the injection volume is 10 μl.

[0090] The present invention also provides a feature map of cough-inducing particles constructed by the above-described construction method.

[0091] Compared with the prior art, the present invention has the following beneficial effects:

[0092] The method for preparing traditional Chinese medicine granules provided by this invention produces granules with uniform size, high molding rate, good solubility, low moisture absorption, easy storage, and good taste, which can be used for the large-scale industrial production of this traditional Chinese medicine granule.

[0093] This invention also provides the application of the characteristic chromatograms of the above-mentioned traditional Chinese medicine composition and its preparations, which can be used to identify the individual herbs in the traditional Chinese medicine composition or to evaluate the quality of the traditional Chinese medicine composition and preparations such as cough granules. Attached Figure Description

[0094] Figure 1 The feature map of Example 14;

[0095] Figure 2 The feature map of Comparative Example 1;

[0096] Figure 3 This is the feature map of Comparative Example 2;

[0097] Figure 4 A feature spectrum overlay diagram for wavelength selection experiments;

[0098] Figure 5 The HPLC chromatograms of Example 15, Comparative Example 3, Comparative Example 4, Comparative Example 5, and Comparative Example 6 are overlaid (a is Example 15; b is Comparative Example 3; c is Comparative Example 4; d is Comparative Example 5; e is Comparative Example 6).

[0099] Figure 6 The HPLC chromatograms are overlaid to indicate the medicinal properties of the herbs (a) the test solution; b) honey-processed Aster tataricus slices; c) Scutellaria baicalensis slices; d) scalded bitter almond slices; e) loquat leaf slices; f) buckwheat slices; g) honey-processed Stemona japonica slices; h) gypsum; i) Anemarrhena asphodeloides slices).

[0100] Figure 7 Overlay of HPLC chromatograms for localizing relevant components (a. test solution; b. blank solvent; c. baicalin; d. epicatechin; e. cryptochlorogenic acid; f. oleanolic acid; g. ursolic acid; h. asterone; i. amygdalin; j. chlorogenic acid; k. baicalin; l. baicalein; m. mangiferin; n. neochlorogenic acid);

[0101] Figure 8 To comprehensively examine the HPLC chromatogram overlay (a. reference solution; b. test solution; c. sucralose solution; d. maltodextrin solution; e. blank solvent);

[0102] Figure 9 This is an overlay of the precision results of the feature map (a precision 6; b precision 5; c precision 4; d precision 3; e precision 2; f precision 1);

[0103] Figure 10 This is a superimposed image of the stability results of the characteristic map (a49h; b35h; c28h; d14h e0h);

[0104] Figure 11 The feature map repeatability results are overlaid (a repeatability 6; b repeatability 5; c repeatability 4; d repeatability 3; e repeatability 2; f repeatability 1);

[0105] Figure 12A superimposed graph of test results at different flow rates (a 1.0 ml / min; b 0.8 ml / min; c 0.9 ml / min);

[0106] Figure 13 A superimposed graph of test results at different column temperatures (a 30℃; b 25℃; c 20℃);

[0107] Figure 14 To superimpose test results from different chromatographic columns Figure 1 (a Kromasil 100-5-C18 (4.6×250mm, 5μm) SN: H227021; b Welch Ultimate LP C18 (4.6×250mm, 5μm); c Inertsil ODS-4 (4.6×250mm5μm));

[0108] Figure 15 To superimpose test results from different chromatographic columns Figure 2 (a Kromasil 100-5-C18 (4.6×250mm, 5μm) SN: H229259; b Kromasil 100-5-C18 (4.6×250mm, 5μm) SN: H227021; c Kromasil 100-5-C18 (4.6×250mm, 5μm) SN: H229260);

[0109] Figure 16 Overlay plot of test results from instruments from different manufacturers (a) Shimadzu LC-20AD; b) Agilent 1260II;

[0110] Figure 17 This is a common pattern diagram for the characteristic spectra of 10 batches of test samples;

[0111] Figure 18 For comparison feature maps. Detailed Implementation

[0112] The present invention will be further described in detail below through embodiments. These embodiments are only used to illustrate the present invention and do not limit the scope of the present invention.

[0113] The prescription for Ganke Granules is as follows: 10-20 parts of buckwheat, 3-8 parts of stemona root, 3-8 parts of aster root, 3-8 parts of bitter almond, 2-5 parts of scutellaria root, 3-8 parts of loquat leaf, 3-8 parts of anemarrhena rhizome, and 5-15 parts of gypsum. All eight ingredients meet the corresponding medicinal material standards in the 2020 edition of the Chinese Pharmacopoeia and are prepared according to the methods specified for each ingredient.

[0114] Preparation of cough granules: Take gypsum, add water equivalent to 6-12 times the total weight of the eight medicinal materials, then add buckwheat, honey-processed stemona root, honey-processed aster root, roasted bitter almond, scutellaria root slices, loquat leaf, and anemarrhena rhizome. Extract for 0.5-3 hours, filter, and reserve the extract. Add water to the residue again and extract 1-2 times, each time adding water equivalent to 6-12 times the total weight of the eight medicinal materials, and each extraction time is 0.5-3 hours. Filter, combine the filtrate with the previous extract, concentrate to a clear paste, dry, pulverize into a fine powder, add excipients and mix well to form granules.

[0115] 1. The reagents, instruments, and apparatus of this invention:

[0116] Drug trials:

[0117]

[0118]

[0119] instrument:

[0120]

[0121] Reagents:

[0122] Example 1: Investigation of Crushing Process

[0123] 200 servings of roasted bitter almonds

[0124] The preparation method is as follows:

[0125] Crushing was carried out using crushers with 12mm, 10mm, 8mm, and 6mm screens respectively, so that all the powder passed through the 12mm, 10mm, 8mm, and 6mm screens, and then through a 0.85mm screen. The crushing process was preliminarily determined based on the yield and fine powder rate. The results are shown in Table 1.

[0126] Table 1. Investigation on the crushing of bitter almonds.

[0127]

[0128]

[0129] The above results indicate that when the crushing aperture is 12 mm, there are large, uncrushed particles. When the crushing screen aperture is 6 mm, 8 mm, and 10 mm, the yield is basically the same, with more fine powder at 6 mm. The next step is to determine the extraction rate of bitter almonds from screens with different crushing apertures and to determine the pretreatment method for bitter almond slices.

[0130] The traditional Chinese medicine composition in this embodiment is prepared from the following raw materials in parts by weight: 15 parts of buckwheat, 5 parts of honey-processed stemona root, 5 parts of honey-processed aster root, 5 parts of roasted bitter almond, 3 parts of scutellaria root, 5 parts of loquat leaf, 5 parts of anemarrhena rhizome, and 10 parts of gypsum.

[0131] The preparation method of the traditional Chinese medicine composition is as follows:

[0132] Take crushed bitter almonds and other seven medicinal slices such as buckwheat. Take 4 portions of the medicinal slices and divide them into two groups of two portions each. Each portion is twice the daily prescription. Two portions are added with crushed bitter almonds with a mesh size of 8 mm, and the other two portions are added with crushed bitter almonds with a mesh size of 10 mm. Add 8-10 times the amount of water to each portion and decoct 2-3 times, each time for 1-3 hours. Measure the content of amygdalin in the extract and calculate the total amount. The data results are shown in Table 2.

[0133] Table 2 Summary of Pretreatment Process Data

[0134]

[0135] The experimental results show that crushing bitter almonds using 8mm and 10mm mesh screens in a crusher has virtually no impact on the amygdalin extraction rate. The pretreatment process is determined as follows: Crushed bitter almond slices are passed through 10mm and 0.85mm screens, ensuring that both can pass through the 10mm screen, and that no more than 20% of the fine powder passes through the 0.85mm screen. The crushing yield must not be less than 95%.

[0136] Example 2: Examination of the number of extractions

[0137] The traditional Chinese medicine composition in this embodiment is prepared from the following raw materials in parts by weight: 15 parts of buckwheat, 5 parts of honey-processed stemona root, 5 parts of honey-processed aster root, 5 parts of roasted bitter almond, 3 parts of scutellaria root, 5 parts of loquat leaf, 5 parts of anemarrhena rhizome, and 10 parts of gypsum.

[0138] The preparation method of the traditional Chinese medicine composition is as follows:

[0139] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0140] (2) Take 8 portions of blanched bitter almonds (crushed) and the remaining seven medicinal slices, including buckwheat, and divide them into 4 groups of 2 portions each. Conduct an investigation experiment according to the design in Table 3, determine the baicalin content in the extract and calculate the total amount. The results are shown in Table 4 below.

[0141] The main component of Scutellaria baicalensis is baicalin. The 2020 edition of the Chinese Pharmacopoeia includes a method for determining the content of baicalin in the quality standard of Scutellaria baicalensis, which requires that the content should not be less than 8.0%. Therefore, baicalin in Scutellaria baicalensis was selected as the evaluation index for process screening.

[0142] Table 3. Experimental Design for the Number of Extractions

[0143]

[0144] Table 4 Summary of Experimental Results Regarding the Number of Extractions

[0145]

[0146] The experimental results show that there is no significant difference between different extraction times. Based on actual production conditions, in order to save production costs and improve production efficiency, the optimal number of extraction times is 2-3.

[0147] Example 3: Investigation of Water Addition

[0148] The traditional Chinese medicine composition in this example is prepared from the following parts by weight of active pharmaceutical ingredient:

[0149] 15 parts of golden buckwheat, 6 parts of honey-processed stemona root, 6 parts of honey-processed aster root, 6 parts of roasted bitter almond, 4 parts of scutellaria root, 6 parts of loquat leaf, 6 parts of anemarrhena rhizome, and 12 parts of gypsum.

[0150] The preparation method is as follows:

[0151] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0152] (2) Take 10 portions of blanched bitter almonds (crushed) and the remaining seven medicinal slices, including buckwheat, and divide them into 5 groups of 2 portions each. Conduct an investigation experiment according to the design in Table 5, determine the baicalin content in the extract and calculate the total amount. The results are shown in Table 6 below.

[0153] Table 5. Experimental Design for Water Addition Quantity Investigation

[0154]

[0155] Table 6 Results of Water Addition Survey

[0156]

[0157] The above test results show that 6 times the amount of water results in the lowest total amount of baicalin, while the total amount of other baicalin extracts is basically the same with no significant difference. In order to save costs and ensure sufficient extraction, the preferred amount of water is 8-10 times the amount of water.

[0158] Example 4: Extraction Time Examination

[0159] The traditional Chinese medicine composition in this example is prepared from the following parts by weight of active pharmaceutical ingredient:

[0160] 15 parts of golden buckwheat, 6 parts of honey-processed stemona root, 6 parts of honey-processed aster root, 6 parts of roasted bitter almond, 4 parts of scutellaria root, 6 parts of loquat leaf, 6 parts of anemarrhena rhizome, and 12 parts of gypsum.

[0161] The preparation method is as follows:

[0162] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0163] (2) Take 8 portions of blanched bitter almonds (crushed) and the remaining seven medicinal slices, including buckwheat, and divide them into 4 groups of 2 portions each. Conduct an investigation experiment according to the design in Table 7, determine the baicalin content in the extract, and calculate the total amount. The results are shown in Table 8 below.

[0164] Table 7 Experimental Design for Extraction Time

[0165]

[0166] Table 8 Results of the Extraction Time Examination

[0167]

[0168] The above test results show that the total amount of astragaloside and the yield of extract are relatively small when decocted for 1 hour / 0.5 hours, while there is no significant difference in the total amount of baicalin extracted and the yield of extract when decocted for 1-2 hours. In order to save production costs and improve production efficiency, the extraction time of 1-2 hours is preferred.

[0169] Example 5: Study on Filtration Process

[0170] The traditional Chinese medicine composition in this embodiment is prepared from the following raw materials in parts by weight: 15 parts of buckwheat, 4 parts of honey-processed stemona root, 4 parts of honey-processed aster root, 4 parts of roasted bitter almond, 2 parts of scutellaria root, 4 parts of loquat leaf, 4 parts of anemarrhena rhizome, and 8 parts of gypsum.

[0171] The preparation method is as follows:

[0172] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0173] (2) Take the bitter almonds (crushed), add water to the remaining seven ingredients such as buckwheat and boil twice, each time for 2 hours.

[0174] (3) The above extract was filtered through 80 mesh, 100 mesh, 200 mesh and 300 mesh respectively. The clarity of the filtered liquid and after standing for a period of time were observed. The results are shown in Table 9.

[0175] Table 9. Results of Filtration Process Tests

[0176]

[0177]

[0178] The results above show that there is little difference in the clarity of the medicinal solution after filtration through 200 mesh and 300 mesh. To ensure the clarity and ease of use of the extract in production, the preferred filtration process is filtration through 200-300 mesh at atmospheric pressure.

[0179] Example 6: Study on Concentration Process Parameters

[0180] The traditional Chinese medicine composition in this embodiment is prepared from the following raw materials in parts by weight: 15 parts of buckwheat, 4 parts of honey-processed stemona root, 4 parts of honey-processed aster root, 4 parts of roasted bitter almond, 2 parts of scutellaria root, 4 parts of loquat leaf, 4 parts of anemarrhena rhizome, and 8 parts of gypsum.

[0181] The preparation method is as follows:

[0182] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0183] (2) Take the bitter almonds (crushed), add 10 times the amount of water to the remaining seven ingredients such as buckwheat and decoct twice, each time for 1 hour.

[0184] (3) Filter the above extract through a 300-mesh filter and combine the filtrates.

[0185] (4) The above filtrate was divided into 5 equal portions and concentrated under reduced pressure at concentration temperatures of 50℃, 60℃, 70℃, 80℃ and 90℃ respectively, until a clear extract with a relative density of 1.10~1.15 (60℃) was obtained. The concentration temperature was optimized based on the total amount of baicalin. The experimental results are shown in Table 10.

[0186] Table 10 Results of Experimental Study on Concentration Process

[0187]

[0188] The above test results show that when the concentration temperature is 50℃, 60℃, 70℃, or 80℃, there is no significant difference in the total amount of baicalin compared with the extract before concentration. When the concentration temperature is 90℃, the total amount of astragalin extracted is significantly reduced, indicating that the concentration temperature of 50℃, 60℃, 70℃, and 80℃ has little impact on the loss of sample components. However, when the concentration temperature is 50℃, the drying time is too long, which is not suitable for large-scale production. Therefore, the preferred concentration temperature is 60℃ to 80℃.

[0189] Example 7: Relative Density Investigation

[0190] The traditional Chinese medicine composition in this embodiment is prepared from the following raw materials in parts by weight: 15 parts of buckwheat, 5 parts of honey-processed stemona root, 5 parts of honey-processed aster root, 5 parts of roasted bitter almond, 3 parts of scutellaria root, 5 parts of loquat leaf, 5 parts of anemarrhena rhizome, and 10 parts of gypsum.

[0191] The preparation method is as follows:

[0192] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0193] (2) Take the bitter almonds (crushed), add 10 times the amount of water to the remaining seven ingredients such as buckwheat and decoct twice, each time for 1 hour.

[0194] (3) Filter the above extract through a 300-mesh filter and combine the filtrates.

[0195] (4) The above filtrate was concentrated under reduced pressure to relative densities of 1.10 (60℃), 1.15 (60℃), and 1.20 (60℃). Spray drying was carried out under the conditions of inlet air temperature of 160-170℃, outlet air temperature of 90-100℃, and separator pressure difference of 0.5-0.6 kPa. The density of the concentrate before spray drying was determined by the drying conditions, powder recovery rate, moisture content of the dry powder, and hygroscopicity after 24 hours. The results are shown in Table 11.

[0196] Table 11 Results of the relative density test of the concentrate

[0197]

[0198] Based on experimental observations, when the relative density of the concentrate is 1.10–1.15 (60℃), the drying state inside the tower is good, the dry powder can be easily swept off, the dry powder in the tank is relatively loose and easy to collect, and the spray drying state is good. When the relative density of the concentrate is 1.198 (60℃), the atomization effect is poor, and it is still droplets that stick to the tower. Therefore, the preferred relative density of the concentrate before spray drying is 1.10–1.15 (60℃).

[0199] Example 8: Inlet Air Temperature Investigation

[0200] Three portions of the concentrated liquid from Example 7, which had been concentrated to a relative density of 1.110 (60°C), were used for spray drying studies. According to the parameters in Table 10, the inlet air temperature was set to 160°C, 170°C, and 180°C, the outlet air temperature to 90–100°C, and the separator pressure difference to 0.5–0.6 kPa. Spray drying was performed, the spray drying status was monitored, the powder was collected, the powder collection rate and the paste yield were calculated, and the moisture content, 24-hour hygroscopicity, and baicalin content were measured. The total amount of baicalin was calculated. The results are shown in Table 12 below.

[0201] Table 12 Inlet Air Temperature Investigation

[0202]

[0203] The moisture content of the three dry powders was similar, their drying conditions were all good, and the powder recovery rate was greater than 90%. There were no significant differences in the indicators of the three samples. Therefore, the preferred air inlet temperature for spray drying is 160-180℃.

[0204] Example 9: Investigation of Granulation Methods for Granulation Formulation

[0205] Two portions of the dry powder from Example 8 were granulated using both dry and wet methods.

[0206] Dry granulation: Add dextrin to the specified amount, mix evenly, and perform dry granulation according to the commonly used dry granulation parameters, i.e., roller spacing: 0.2-0.4 mm; roller speed: 6 rpm, to produce granules with a mesh size of 14 mesh / 65 mesh.

[0207] Wet granulation: Add dextrin to the specified amount, mix evenly, add 75% ethanol as a wetting agent to make a soft mass, put it into an automatic granulator for granulation, dry at 65℃, and granulate through a 14-mesh / 65-mesh sieve to obtain the final product.

[0208] Take the concentrate from Example 8 and granulate it using a one-step granulation method. The inlet air temperature is set to 100-110℃, the fan frequency is 35-45Hz, the material temperature is 65-75℃, the liquid inlet rate is 10r / min, and the atomization pressure is 0.20MPa. A mixture of dextrin and microcrystalline cellulose powder is used as the base material and sprayed into the concentrate to obtain granules.

[0209] The granulation process and particle characteristics were compared as evaluation indicators, and the results are shown in Table 13.

[0210] Pellet produced by dry granulation has good formability, does not stick to the pressure roller, is uniform in size, has moderate hardness, and uniform color; pellets produced by wet granulation have good formability, are uniform in size, and have moderate hardness, but are uneven in color; pellets produced by one-step granulation have poor particle size and uneven color. Therefore, dry granulation is preferred.

[0211] Table 13 Results of Granulation Method Investigation

[0212] Example 10: Investigation of Filler Types

[0213] The dry granule powder from Example 8 was used for research. Five portions of the powder were taken and mixed with maltodextrin, dextrin, soluble starch, maltodextrin-dextrin (1:1 ratio), sucrose, and other additives until the specified amount was reached. The mixture was then granulated using common dry granulation parameters: roller spacing 0.2–0.4 mm; roller speed 6 rpm. The granulation mesh size was 14 mesh / 65 mesh. Granulation performance, particle shape, one-time molding rate, and 24-hour hygroscopicity were used as evaluation indicators to screen fillers. The results are shown in Table 14.

[0214] Table 14 Results of the Investigation on Filler Types

[0215]

[0216]

[0217] The granulation results show that maltodextrin as a filler exhibits good formability, does not stick to the pressure roller, produces uniform granules with moderate hardness and color, and has a high one-time forming rate. When dextrin is used as a filler, the granules have lower hardness, while when soluble starch is used as a filler, the granules have poor formability and stick to the pressure roller. Therefore, maltodextrin is the preferred filler.

[0218] Example 11 Drug Loading Assessment

[0219] The dry extract powder from Example 8 was used for research. The extract powder was mixed evenly with the filler maltodextrin at drug loadings of 30%, 40%, 50%, 60%, 70%, and 80% of the product weight, respectively, and then dry-granulated to a mesh size of 14 mesh / 65 mesh. Granulation conditions, particle characteristics, one-time molding rate, and 24-hour hygroscopicity were used as evaluation indicators. The results are shown in Table 15.

[0220] Table 15 Results of the Examination of Formulation Specifications

[0221]

[0222] When the drug loading was 40%, 50%, 60%, and 70%, there was no sticking to the granulation wheel during the granulation process, and there were no significant differences in dry granulation state, particle characteristics, one-time molding rate, and 24-hour hygroscopicity. Considering the fluctuations in dosage and batch-to-batch yield, a drug loading of 40%-70% was preferred.

[0223] Example 12: Investigation of Flavoring Agents

[0224] Because the granules themselves have poor palatability, a certain amount of flavoring agents need to be added to improve the taste and make it easier for patients to accept. Commonly used flavoring agents include aspartame, steviol glycosides, and sucralose. Sucralose has a relatively high safety profile. This product uses sucralose, aspartame, and steviol glycosides as flavoring agents, and the dosage was investigated. The dry extract powder from Example 8 was used for the study. Different proportions of flavoring agents were added to the dry extract powder and maltodextrin, and the taste was used as the evaluation index. The results are shown in Table 16.

[0225] Table 16 Results of the Investigation on the Dosage of Flavoring Agents

[0226]

[0227] The best taste is achieved when 0.05% sucralose, 0.3% aspartame, and 0.3% steviol glycosides are added. To reduce the amount of flavoring agents needed and make it easier to take, it is preferable to add 0.05% sucralose for flavoring.

[0228] 2. Selection of chromatographic conditions for characteristic spectra

[0229] Selection of gradient elution program

[0230] Example 13: Preparation of cough granules:

[0231] Take 80g of gypsum, add water equivalent to 6 times the total weight of the eight medicinal materials, and extract for 3 hours. Then add 150g of buckwheat, 40g of honey-processed stemona root, 40g of honey-processed aster root, 40g of bitter almond, 20g of scutellaria root slices, 40g of loquat leaf, and 40g of anemarrhena rhizome, and continue extraction for 2 hours. Filter and reserve the extract. Add water to the residue twice more, each time adding water equivalent to 6 times the total weight of the eight medicinal materials, and extract for 2 hours each time. Filter and combine the filtrate with the previous extract. Concentrate to a clear paste with a relative density of 1.20-1.30 at 60-70℃. Dry, pulverize into a fine powder, add appropriate amounts of sucralose and maltodextrin, mix well, and granulate to obtain the final product.

[0232] Example 14

[0233] (1) Preparation of test solution: Take the cough granules from Example 13, grind them into a fine powder, take 1g, add 25ml of 50% methanol, sonicate for 30 minutes, filter out and cool, weigh, add 50% methanol to make up the lost weight, shake well, filter, and take the filtrate.

[0234] (2) Determination method: Accurately pipette 10 μl of the test solution, inject it into the liquid chromatograph, determine and record the chromatogram.

[0235] (3) Chromatographic conditions are as follows

[0236] Chromatographic column: octadecylsilane-bonded silica gel as packing material (column length 250 mm, inner diameter 4.6 mm, particle size 5 μm); acetonitrile as mobile phase A, 0.1% phosphoric acid as mobile phase B, flow rate 1.0 ml / min, column temperature 25℃, gradient elution according to the table below.

[0237] Table 17 Gradient Elution Table

[0238]

[0239] Chromatogram (see) Figure 1 .

[0240] Comparative Example 1

[0241] The difference from Example 14 is that the chromatographic column is packed with octadecylsilane-bonded silica gel (column length 250 mm, inner diameter 4.6 mm, particle size 5 μm); acetonitrile is used as mobile phase A, 0.1% phosphoric acid is used as mobile phase B, the flow rate is 1.0 ml per minute, the column temperature is 35°C, and gradient elution is performed according to the table below.

[0242] Table 18 Gradient Elution Table

[0243]

[0244] Chromatogram (see) Figure 2 .

[0245] Comparative Example 2

[0246] The difference from Example 14 is that the mobile phase system remains the same, the elution gradient is adjusted as shown in the table below, and everything else remains unchanged.

[0247] Table 19 Gradient Elution Table

[0248]

[0249]

[0250] Chromatogram (see) Figure 3 .

[0251] Results analysis: By comparing three different chromatographic conditions, the chromatographic peaks at 25-40 minutes in the chromatogram of Comparative Example 1 did not achieve baseline separation, and the chromatographic peaks at around 60 minutes in the chromatogram of Comparative Example 2 did not have good separation. It was determined that the baseline was relatively stable, the amount of information was large, the peak separation was good, and the peak identification information was abundant under the conditions of Example 14.

[0252] b. Selection of detection wavelength

[0253] A diode array detector was used to scan the test solution at wavelengths of 190–400 nm. Results showed that the chromatographic peak response was moderate and the baseline was relatively stable within the wavelength range of 270–300 nm. Analysis was performed in this wavelength range (see...). Figure 4 Chromatograms were extracted at wavelengths of 200nm, 220nm, 230nm, 240nm, 250nm, 270nm, 280nm, 300nm, 320nm, and 360nm. The results showed that the information content was greater at the wavelength of 300nm, the chromatographic peak response value was moderate, and the baseline was more stable. Therefore, 300nm was selected as the detection wavelength.

[0254] 3. Investigation of the preparation method of the test solution

[0255] Example 15

[0256] The test solution is prepared by the following steps:

[0257] Take the cough granules from Example 13, grind them into a fine powder, weigh about 1g accurately, place them in a stoppered conical flask, add 25ml of 50% methanol, seal tightly, weigh, sonicate (power 250W, frequency 40kHz) for 30 minutes, cool, weigh again, replenish the lost weight with 50% methanol, shake well, filter, and the product is obtained.

[0258] Comparative Example 3

[0259] The test solution is prepared by the following steps:

[0260] Take the cough granules from Example 13, grind them into a fine powder, weigh about 1g accurately, place them in a stoppered conical flask, add 25ml of 70% methanol, seal tightly, weigh, sonicate (power 250W, frequency 40kHz) for 30 minutes, cool, weigh again, replenish the lost weight with 70% methanol, shake well, filter, and the product is obtained.

[0261] Comparative Example 4

[0262] The test solution is prepared by the following steps:

[0263] Take the cough granules from Example 13, grind them into a fine powder, weigh about 1g accurately, place them in a stoppered conical flask, add 25ml of methanol, seal tightly, weigh, sonicate (power 250W, frequency 40kHz) for 30 minutes, cool, weigh again, replenish the lost weight with methanol, shake well, filter, and the product is obtained.

[0264] Comparative Example 5

[0265] The test solution is prepared by the following steps:

[0266] Take the cough granules from Example 13, grind them into a fine powder, weigh about 1g accurately, place them in a stoppered conical flask, add 20ml of water to dissolve them, extract twice with water-saturated n-butanol, 40ml each time, collect the n-butanol layer, evaporate to dryness, add 25ml of methanol to dissolve the residue, transfer it to a 25ml volumetric flask, add methanol to make up to the mark, shake well, filter, and take the filtrate to obtain the final product.

[0267] Comparative Example 6

[0268] The test solution is prepared by the following steps:

[0269] Take the cough granules from Example 13, grind them into a fine powder, weigh about 1g accurately, place them in a stoppered conical flask, add 20ml of water to dissolve them, extract twice with ethyl acetate, 40ml each time, collect the ethyl acetate layer, evaporate to dryness, add 25ml of methanol to dissolve the residue, transfer it to a 25ml volumetric flask, add methanol to make up to the mark, shake well, filter, and take the filtrate to obtain the final product.

[0270] For the assay, accurately pipette 10 μl of each of the test solutions from Example 15 and Comparative Examples 3-6, inject them into the liquid chromatograph, and determine the chromatograms under the chromatographic conditions of Example 13. Record the chromatograms of the test solutions extracted with different solvents. See the chromatograms for details. Figure 5 .

[0271] The results showed that, compared with Comparative Example 6, the chromatogram of Example 15 contained less information about the number of chromatographic peaks and had a lower response value. Compared with Comparative Examples 3, 4, and 5, there was no significant difference in the number of chromatographic peaks in the chromatograms of Example 15. However, Example 15 showed a higher peak response value and a more uniform peak distribution. Therefore, the preparation method of the test sample in Example 15 was ultimately selected as the appropriate method, as follows:

[0272] Take about 1g of the cough granules, grind them into a fine powder, place them in a stoppered conical flask, add 25ml of 50% methanol, seal tightly, weigh, sonicate (power 250W, frequency 40kHz) for 30 minutes, cool, weigh again, replenish the lost weight with 50% methanol, shake well, filter, and the product is ready.

[0273] 4. Selection of reference points and peak assignment

[0274] Example 16

[0275] A. Medicinal Flavor Peak

[0276] The preparation methods for single-herb decoction solutions of buckwheat, honey-processed stemona root, honey-processed aster root, roasted bitter almond, scutellaria root, loquat leaf, anemarrhena rhizome, and gypsum are as follows:

[0277] (1) Weigh 0.2g each of honey-processed Stemona japonica, honey-processed Aster tataricus, roasted bitter almond, loquat leaf, and Anemarrhena asphodeloides slices, 0.4g of gypsum, and 0.6g of buckwheat. Add 50ml of water to each ingredient, decoct for 20 minutes, filter, evaporate to dryness, wash with 50% methanol in several batches, transfer to a 25ml volumetric flask, sonicate for 30 minutes, remove, cool, dilute with 50% methanol to the mark, shake well, filter, and obtain the product.

[0278] (2) Weigh 0.1g of Scutellaria baicalensis slices, add 50ml of water, decoct for 20 minutes, filter, evaporate to dryness, wash with 50% methanol in several batches, transfer to a 50ml volumetric flask, sonicate for 30 minutes, take out, cool, dilute with 50% methanol to the mark, shake well, filter, and obtain.

[0279] The preparation method of the test solution is as follows:

[0280] After preparing the corresponding test solutions according to the test sample preparation method determined in Example 15, the chromatographic conditions determined in Example 14 were used to determine the attribution of each medicinal peak in the characteristic chromatogram of the compound preparation. The results are shown in [Figure 14]. Figure 6 See Table 20.

[0281] Table 20 Classification of Single Herbs

[0282]

[0283]

[0284] from Figure 6 As can be seen from the results in Table 20, all six herbs in Gan Ke Granules—bitter apricot kernel, honey-processed aster, honey-processed stemona, buckwheat, anemarrhena, scutellaria, and loquat leaf—can be identified in the characteristic spectrum disclosed in this invention, indicating that the characteristic spectrum disclosed in this invention can be used for the quality control of Gan Ke Granules.

[0285] B-chromatographic peak identification

[0286] The relevant chemical components of each ingredient in the prescription were reviewed, and the inferred possible components were identified using known reference standards. The results are shown below. Figure 7 See Table 21.

[0287] Table 21 Chromatographic Peak Identification

[0288]

[0289] from Figure 7 As can be seen from the results in Table 21, the characteristic spectrum disclosed in this invention has four identifiable characteristic peaks, among which chlorogenic acid, neochlorogenic acid, and cryptochlorogenic acid have been identified, thereby improving the accuracy and comprehensiveness of the characteristic spectrum evaluation.

[0290] C. Selection of Reference Frame

[0291] Reference Figure 7 The chromatogram showed that the chlorogenic acid peak had good resolution, good peak shape, and moderate retention time, so it was labeled as peak S. Chlorogenic acid standard was used as a reference.

[0292] 5. Methodological Examination

[0293] Example 17

[0294] A. Specificity Testing and Holistic Examination

[0295] Test solution: Take about 1g of finely ground cough granules from Example 13, accurately weigh it, place it in a stoppered conical flask, add 25ml of 50% methanol, seal tightly, weigh, sonicate (power 250W, frequency 40kHz) for 30 minutes, cool, weigh again, replenish the lost weight with 50% methanol, shake well, filter, and the test solution is obtained.

[0296] Reference solution: Weigh an appropriate amount of chlorogenic acid reference standard accurately, add 50% methanol to prepare a solution containing 15 μg per ml.

[0297] Blank solution: 50% methanol as the solvent for the test sample.

[0298] Excipient solution:

[0299] (1) Sucralose: Take sucralose and prepare it according to the same method as the test sample.

[0300] (2) Maltodextrin: Take maltodextrin and prepare it according to the same method as the test sample.

[0301] Inject the test solution, reference solution, and blank solvent into the liquid chromatograph, record the chromatograms, and examine the integrity of the test sample.

[0302] Chromatographic conditions and system suitability tests were conducted using octadecylsilane-bonded silica gel as the stationary phase; acetonitrile as mobile phase A and 0.1% phosphoric acid solution as mobile phase B, with gradient elution performed according to the specifications in the table below; column temperature was 25℃; detection wavelength was 300nm. The theoretical plate number, calculated based on chlorogenic acid, should not be less than 10,000.

[0303]

[0304] See results Figure 8

[0305] from Figure 8 The results show that the chromatographic peaks were basically collected after 100 minutes, and the chromatographic conditions have reached the maximum information collection. Therefore, setting the collection time to 100 minutes is reasonable.

[0306] B. Instrument precision test

[0307] Take an appropriate amount of cough granules, grind them into a fine powder, and accurately weigh about 1g. Follow the preparation and determination methods for the test solution in Example 15, and inject the sample six times consecutively. Using the S peak as a reference, calculate the relative retention time. See the detailed determination results below. Figure 9 Table 22.

[0308] Table 22 Relative retention time results of instrument precision test (n=6)

[0309]

[0310] The test results show that the relative retention times are basically consistent, the RSD is less than 2.0%, and the instrument precision is good.

[0311] C. Stability test

[0312] Take an appropriate amount of cough granules, grind them into a fine powder, and accurately weigh about 1g. Follow the preparation and determination methods for the test solution in Example 15. Inject the sample at 0, 14, 28, 35, and 49 hours. Calculate the relative retention time using the S peak as a reference. See the detailed results below. Figure 10 Table 23.

[0313] Table 23 Results of relative retention times in stability tests of test samples

[0314]

[0315]

[0316] The test results showed that the relative retention times were basically consistent, and the RSDs were all less than 2.0%, indicating that the test solution had good stability within 49 hours.

[0317] D. Repeatability test

[0318] Take an appropriate amount of cough granules, grind them into a fine powder, and accurately weigh about 1g. Prepare 6 portions according to the test solution preparation method and determination method in Example 15. Calculate the relative retention time using the S peak as a reference. See the specific determination results below. Figure 11 Table 24.

[0319] Table 24 Results of Relative Retention Time in Repeatability Tests

[0320]

[0321]

[0322] The experimental results show that the relative retention times are basically consistent, and the RSD is less than 2.0%, indicating that the reproducibility of this method is good.

[0323] E. Durability test

[0324] Three different flow rates (0.8 ml / min, 0.9 ml / min, 1.0 ml / min), three different column temperatures (20℃, 25℃, 30℃), and three different brands of columns were investigated: Kromasil 100-5-C18 (4.6×250 mm, 5 μm) SN: H227021, Welch Ultimate LP C18 (4.6×250 mm, 5 μm), and Inertsil ODS-4 (4.6×250 mm, 5 μm). The results showed that the separation of peaks 9, 10, and 11 was poor on the second and third columns. Therefore, columns of the same brand but with different SN numbers, Kromasil 100-5-C18 (4.6×250 mm, 5 μm) SN: H229260 and Kromasil, were also investigated. The robustness of two instruments from different manufacturers (Shimadzu and Agilent) to these chromatographic conditions was tested. The relative retention times of the remaining peaks were calculated using the S peak as a reference. Specific results are shown in Tables 25-28. Figures 12-16 .

[0325] Table 25 Relative retention time results for tests at different flow rates

[0326]

[0327]

[0328] Table 26 Relative retention times at different column temperatures.

[0329]

[0330] Table 27 Relative retention times of different SN columns.

[0331]

[0332] Table 28 Relative retention time results from tests using different instruments

[0333]

[0334]

[0335] The results showed that the determination results were basically consistent under different flow rates, column temperatures, different SN numbers of the same brand of chromatographic columns, and different instrument conditions. The main common chromatographic peaks in the chromatograms were sharp, symmetrical, and well separated. This indicates that the relative retention times of this method under different column temperatures, different flow rates, different SN numbers of the same brand of chromatographic columns, and different instrument conditions were all within a reasonable range, indicating that the method has good robustness.

[0336] 6. Establishment of Feature Maps

[0337] A. The characteristic chromatograms of 10 batches of cough granules were determined using this method, and the chromatograms were recorded. The obtained characteristic chromatograms were analyzed, and the chromatographic peaks with good stability and suitable response values ​​from the 10 batches of samples were selected as common peaks. A total of 13 common peaks were identified. See details below. Figure 17 .

[0338] B. Using the "Similarity Evaluation Software System for Chromatographic Fingerprints of Traditional Chinese Medicine (2012 Edition)" issued by the National Pharmacopoeia Commission, the chromatographic peaks of 10 batches of Gan Ke Granules were automatically matched to form a common pattern chromatogram, and a control chromatogram was established. The results are shown in [Figure Number]. Figure 18 .

[0339] C. Peak 7 in the common peaks of the 10 batches of samples had the same retention time as its corresponding reference peak. The results showed that the retention times of the 10 batches of samples were basically consistent with the retention times of their corresponding reference peaks. The results are shown in Table 29.

[0340] Table 29. Results of relative retention time of 10 batches of cough granules

[0341]

[0342]

[0343] The chromatogram of the test sample should show 13 characteristic peaks. The peak corresponding to the retention time of the reference peak is called the S peak. The relative retention time of each characteristic peak and the S peak should be calculated and should be within ±10% of the specified value. The specified retention time values ​​are 0.31 (peak 1), 0.53 (peak 2), 0.64 (peak 3), 0.70 (peak 4), 0.90 (peak 5), 0.94 (peak 6), 1.00 [peak 7 (S)], 1.18 (peak 8), 1.50 (peak 9), 1.54 (peak 10), 1.62 (peak 11), 2.18 (peak 12), and 2.29 (peak 13).

[0344] Example 18 Preparation of cough granules

[0345] In this embodiment, the granule preparation of the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of buckwheat, 4 parts of honey-processed stemona root, 4 parts of honey-processed aster root, 4 parts of roasted bitter almond, 2 parts of scutellaria root, 4 parts of loquat leaf, 4 parts of anemarrhena rhizome, and 8 parts of gypsum.

[0346] The method for preparing granules of traditional Chinese medicine composition is as follows:

[0347] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0348] (2) Take the bitter almonds (crushed), add water to the remaining seven ingredients such as buckwheat and boil twice. Boil for 2 hours the first time and 1 hour the second time.

[0349] (3) Filter the above extract through a 300-mesh filter and combine the filtrates.

[0350] (4) Take the above filtrate and concentrate it under reduced pressure at a temperature of 60°C until it becomes a clear paste with a relative density of 1.10 (60°C).

[0351] (5) Take the above-mentioned clear paste and spray dry it under the conditions of inlet air temperature of 160℃, outlet air temperature of 90~100℃, and separator pressure difference of 0.5~0.6kPa to obtain dry paste powder.

[0352] (6) Take the above dry powder, add 0.05% sucralose and 49.95% maltodextrin, mix the powder and maltodextrin evenly, granulate by dry method, and granulate with a mesh size of 14 mesh / 65 mesh to obtain cough granules.

[0353] Example 19 Preparation of Cough Granules

[0354] In this embodiment, the granule preparation of the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of buckwheat, 5 parts of honey-processed stemona root, 5 parts of honey-processed aster root, 5 parts of roasted bitter almond, 3 parts of scutellaria root, 5 parts of loquat leaf, 5 parts of anemarrhena rhizome, and 10 parts of gypsum.

[0355] The method for preparing granules of traditional Chinese medicine composition is as follows:

[0356] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0357] (2) Take the bitter almonds (crushed), add 10 times the amount of water to the other seven ingredients such as buckwheat and decoct once for 3 hours.

[0358] (3) Filter the above extract through a 300-mesh filter and combine the filtrates.

[0359] (4) Take the above filtrate and concentrate it under reduced pressure at a concentration temperature of 70°C until the relative density is 1.12°C to obtain a clear paste.

[0360] (5) Take the above-mentioned clear paste and spray dry it under the conditions of inlet air temperature of 160℃, outlet air temperature of 90~100℃, and separator pressure difference of 0.5~0.6kPa to obtain dry paste powder.

[0361] (6) Take the above dry powder, add 0.05% sucralose and 49.95% dextrin, mix the powder and dextrin evenly, granulate by dry method, and granulate with a mesh size of 14 mesh / 65 mesh to obtain cough granules.

[0362] Example 20: Preparation of Cough Granules

[0363] In this embodiment, the granule preparation of the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of buckwheat, 5 parts of honey-processed stemona root, 5 parts of honey-processed aster root, 5 parts of roasted bitter almond, 3 parts of scutellaria root, 5 parts of loquat leaf, 5 parts of anemarrhena rhizome, and 10 parts of gypsum.

[0364] The method for preparing granules of traditional Chinese medicine composition is as follows:

[0365] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0366] (2) Take the bitter almonds (crushed), add water to the remaining seven ingredients such as buckwheat and boil twice, each time for 2 hours.

[0367] (3) Filter the above extract through a 300-mesh filter and combine the filtrates.

[0368] (4) Take the above filtrate and concentrate it under reduced pressure at a temperature of 80°C until the relative density is 1.15°C to obtain a clear paste.

[0369] (5) Take the above-mentioned clear paste and spray dry it under the conditions of inlet air temperature of 160℃, outlet air temperature of 90~100℃, and separator pressure difference of 0.5~0.6kPa to obtain dry paste powder.

[0370] (6) Take the above dry powder, add 0.05% sucralose and 49.95% maltodextrin, mix the powder and maltodextrin evenly, granulate by dry method, and granulate with a mesh size of 14 mesh / 65 mesh to obtain cough granules.

[0371] Example 21 Preparation of cough granules

[0372] In this embodiment, the granule preparation of the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of buckwheat, 6 parts of honey-processed stemona root, 6 parts of honey-processed aster root, 6 parts of roasted bitter almond, 4 parts of scutellaria root, 6 parts of loquat leaf, 6 parts of anemarrhena rhizome, and 12 parts of gypsum.

[0373] The method for preparing granules of traditional Chinese medicine composition is as follows:

[0374] (1) Take the bitter almond slices and crush them. Use a double sieve method to pass them through 10mm and 0.85mm sieves respectively, so that they can both pass through the 10mm sieve and the fine powder passing through the 0.85mm sieve does not exceed 20%. The crushing yield should not be less than 95%.

[0375] (2) Take the bitter almonds (crushed), add 10 times the amount of water to the remaining seven ingredients such as buckwheat and decoct three times, each time for 1 hour.

[0376] (3) Filter the above extract through a 300-mesh filter and combine the filtrates.

[0377] (4) Take the above filtrate and concentrate it under reduced pressure at a temperature of 80°C until it becomes a clear paste with a relative density of 1.13 (°C).

[0378] (5) Take the above-mentioned clear paste and spray dry it under the conditions of inlet air temperature of 170℃, outlet air temperature of 90~100℃, and separator pressure difference of 0.5~0.6kPa to obtain dry paste powder.

[0379] (6) Take the above-mentioned dry powder, add 0.05% sucralose and 29.95% dextrin by weight, mix the powder and dextrin evenly, and granulate by dry method to obtain cough granules with a granulation mesh size of 14 mesh / 65 mesh. Example 22 Stability test of cough granules

[0380] The cough granules prepared in Examples 18-21 were placed in a long-term stability test chamber and subjected to long-term stability testing at a temperature of 25°C and a relative humidity of 60%, in accordance with the standards of the Chinese Pharmacopoeia. The results are shown in Table 30.

[0381] Table 30 Results of the stability study of Gan Ke Granules

[0382]

[0383] The four batches of cough granules obtained through formulation and process screening showed excellent long-term stability, indicating that the final formulation and process selected in this invention are reasonable and can produce a product that meets pharmacopoeia requirements. This provides a preparation method suitable for commercial production, possessing significant clinical and commercial value.

Claims

1. A traditional Chinese medicine composition preparation, characterized in that, A traditional Chinese medicine extract and pharmaceutically acceptable pharmaceutical excipients are prepared from 10-20 parts of Fagopyrum cymosum, 3-8 parts of Oxytropis fischeri Bunge, 3-8 parts of Echiuim acutum, 3-8 parts of Bitter apricot kernel, 2-5 parts of Scutellaria baicalensis, 3-8 parts of Eriobotrya japonica, 3-8 parts of Anemarrhena asphodeloides, and 5-15 parts of Gypsum fibrosum; the weight percentage of the pharmaceutical excipients in the preparation is 30%-80%.

2. The preparation of traditional Chinese medicine composition according to claim 1, characterized in that, The pharmaceutically acceptable pharmaceutical excipients are selected from one or more of diluents, disintegrants, excipients, binders, lubricants, surfactants, fillers, surfactants, diluents, preservatives, stabilizers, flavoring agents, thickening agents, and glidants.

3. The preparation of traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition preparation is prepared from the following raw materials: Fagopyrum cymosum 15 parts, Oxytropis fischeri Bunge 5 parts, Echiuim acutum 5 parts, Bitter apricot kernel 5 parts, Scutellaria baicalensis 3 parts, Eriobotrya japonica 5 parts, Anemarrhena asphodeloides 5 parts, and Gypsum fibrosum 10 parts; Fagopyrum cymosum 15 parts, Oxytropis fischeri Bunge 4 parts, Echiuim acutum 4 parts, Bitter apricot kernel 4 parts, Scutellaria baicalensis 2 parts, Eriobotrya japonica 4 parts, Anemarrhena asphodeloides 4 parts, and Gypsum fibrosum 8 parts; Fagopyrum cymosum 15 parts, Oxytropis fischeri Bunge 6 parts, Echiuim acutum 6 parts, Bitter apricot kernel 6 parts, Scutellaria baicalensis 4 parts, Eriobotrya japonica 6 parts, Anemarrhena asphodeloides 6 parts, and Gypsum fibrosum 12 parts.

4. The traditional Chinese medicine composition preparation according to any one of claims 1-3, characterized in that, The preparation is a granule; the pharmaceutically acceptable pharmaceutical excipients include fillers and flavoring agents; the weight percentage of the pharmaceutical excipients in the preparation is 40%-70%; the weight percentage of the fillers in the preparation is 39.975%-69.5%; and the weight percentage of the flavoring agents in the preparation is 0.025%-0.5%.

5. The preparation of traditional Chinese medicine composition according to claim 4, characterized in that, The weight percentage of the fillers in the preparation is 39.95%-69.95%; and the weight percentage of the flavoring agents in the preparation is 0.05%.

6. The preparation of traditional Chinese medicine composition according to claim 4, characterized in that, The fillers are selected from malt dextrin, dextrin, malt dextrin-dextrin = 1:1, and soluble starch; further preferably, the fillers are malt dextrin-dextrin = 1:1, malt dextrin, and dextrin; and more preferably, the fillers are malt dextrin.

7. The preparation of traditional Chinese medicine composition according to claim 4, characterized in that, The flavoring agents are selected from one or more of sucralose, steviol glycoside, and aspartame; preferably, the flavoring agents are sucralose.

8. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The method comprises the following steps: Step 1: pretreatment process; Step 2: taking 8 pieces of decoction pieces according to the prescription, adding water and heating for extraction, and filtering; Step 3: taking the filtrate in step 2 to concentrate into a clear paste; Step 4: taking the clear paste in step 3 to dry into a dry paste powder; Step 5: taking the dry paste powder in step 4, adding excipients, and preparing the corresponding preparation.

9. The preparation method of the traditional Chinese medicine composition according to claim 8, characterized in that, The method comprises the following steps: Step 1: pretreatment process, taking Bitter apricot kernel decoction pieces and performing crushing treatment; the crushing treatment process is performed with a screen mesh with a pore size of 8-10 mm; Step 2: taking 8 pieces of decoction pieces according to the prescription, adding water and heating for extraction, and filtering; the water addition multiple in step 2 is 6-12 times; the extraction times in step 2 is 2-3 times; the heating extraction time in step 2 is 0.5-3 hours; and the extraction liquid filtration mesh number in step 2 can be 80-300; Step 3: taking the filtrate in step 2 to concentrate into a clear paste; the concentration process can adopt normal pressure concentration or reduced pressure concentration; Step 4: taking the clear paste in step 3 to dry into a dry paste powder; the drying method is spray drying; Step 5: taking the dry paste powder in step 4, adding excipients, and preparing the preparation.

10. The preparation method of the traditional Chinese medicine composition according to claim 8, characterized in that, The method comprises the following steps: Step 1: pretreatment process, taking bitter apricot kernel decoction pieces, crushing treatment; the crushing treatment process is crushed with a screen mesh of 8-10 mm aperture; the crushing process standard: after crushing, the decoction pieces are sieved with double sieves, respectively passing through 10 mm and 0.85 mm screen meshes, so that they can pass through the 10 mm screen mesh, and the fine powder passing through the 0.85 mm screen mesh is not more than 20%, and the crushing yield is not less than 95%; Step 2: according to the prescription, 8 kinds of decoction pieces are taken, water is added for extraction, and filtration; the water addition multiple in step 2 is 8-10 times; the extraction times in step 2 is 2-3 times; the heating extraction time in step 2 is 1-2 hours; the extraction liquid filtration mesh number in step 2 is 200-300; Step 3: taking the filtrate in step 2 to concentrate into clear paste; the concentration process is reduced pressure concentration, and the reduced pressure concentration temperature is 60-80℃; the relative density range of the clear paste is 1.10-1.15 (60℃); Step 4: taking the clear paste in step 3 to dry into dry paste powder; the drying method is spray drying; when the spray drying, the inlet air temperature is 160-180℃; Step 5: taking the dry paste powder in step 4, using dry granulation, adding filler and flavoring agent, mixing uniformly, 14 mesh / 65 mesh whole granulation, mixing uniformly, to prepare granules.

11. A traditional Chinese medicine composition and a method for constructing an HPLC characteristic chromatogram of a preparation thereof, the traditional Chinese medicine composition consisting of Fagopyrum cymosum, Stemona tuberosa, Radix Asiatic Paridiae, Amygdala amara, Radix Scophulariae, Folium Eriobotryae, Rhizoma Anemarrhenae, Gypsum Fibrosum, characterized in that, The method adopts high performance liquid chromatography; The chromatographic conditions are as follows: chromatographic column: octadecylsilane bonded silica gel as filler; Mobile phase: acetonitrile as mobile phase A, phosphoric acid solution as mobile phase B, gradient elution; The gradient elution conditions are as follows:

12. The method for constructing HPLC characteristic chromatogram of a traditional Chinese medicine composition and its preparation according to claim 11, characterized in that, The chromatographic conditions are as follows: Chromatographic column: octadecylsilane bonded silica gel as filler, chromatographic column length is 250 mm, inner diameter is 4.6 mm, particle size is 5 μm; Mobile phase: acetonitrile as mobile phase A, phosphoric acid solution as mobile phase B, the volume fraction of phosphoric acid is 0.05%-0.15%; gradient elution is carried out; Detection wavelength: 200-360 nm Column temperature: 20-30℃.

13. The method for constructing HPLC characteristic chromatogram of traditional Chinese medicine composition and its preparation according to claim 11 or 12, characterized in that, The chromatographic conditions are as follows: Chromatographic column: Kromasil 100-5-C18 (4.6x250mm, 5μm); Mobile phase: acetonitrile (A)-0.1% phosphoric acid solution (B); gradient elution is carried out; Detection wavelength: 300 nm; Column temperature: 25℃; Injection volume is 10 μl.

14. The method for constructing HPLC characteristic fingerprint of traditional Chinese medicine composition and its preparation according to claim 11 or 12, characterized in that, The method further includes preparation and determination of test sample solution; the preparation of test sample solution is as follows: taking a proper amount of traditional Chinese medicine composition or its preparation, adding suitable solvent, shaking, filtering, taking the filtered solution, and obtaining; The determination method is as follows: taking the test sample solution, injecting into liquid chromatograph, determining, and recording chromatogram.

15. The method for constructing HPLC characteristic chromatogram of a traditional Chinese medicine composition and its preparation according to claim 14, characterized in that, The preparation method of test sample solution is as follows: taking Ganqi granules, grinding, taking about 1 g, accurately weighing, placing in a conical flask with plug, tightly sealing, weighing, ultrasonic treatment, cooling, weighing again, supplementing the weight loss with 50% methanol, shaking, filtering, and obtaining.

16. The method for constructing HPLC characteristic chromatogram of a traditional Chinese medicine composition and its preparation according to claim 15, characterized in that, The ultrasonic treatment power is 250 W, the frequency is 40 kHz, and the ultrasonic time is 30 minutes.

17. The method for constructing HPLC characteristic chromatogram of a traditional Chinese medicine composition and its preparation according to claim 11 or 12, characterized in that, The characteristic spectrum has 13 characteristic peaks.

18. The method for constructing HPLC characteristic chromatogram of a traditional Chinese medicine composition and its preparation according to claim 11 or 12, characterized in that, The retention time of the 13 common characteristic peaks is respectively 0.31 for peak 1, 0.53 for peak 2, 0.64 for peak 3, 0.70 for peak 4, 0.90 for peak 5, 0.94 for peak 6, 1.00 for peak 7, 1.18 for peak 8, 1.50 for peak 9, 1.54 for peak 10, 1.62 for peak 11, 2.18 for peak 12, and 2.29 for peak 13.

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