A preparation method and quality control method of Polygonatum odoratum formula granules

Abstract

The invention belongs to the technical field of traditional Chinese medicine detection, and specifically provides a preparation method and quality control method of yuzhu formula granules, comprising: mixing dextrin and silicon dioxide into yuzhu extract before drying, adding or not adding auxiliary materials after drying, and granulating to obtain yuzhu formula granules. Dextrin and silicon dioxide can be mixed with yuzhu extract before drying to play a synergistic role in improving the quality of yuzhu formula granules and significantly improving the powder collection rate of yuzhu formula granules. The obtained yuzhu formula granules have low hygroscopicity and good formability and fluidity.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine detection, and particularly relates to a preparation method and a quality control method of polygonatum odoratum formula granules. Background Art

[0002] Polygonatum odoratum is the dried rhizome of Polygonatum odoratum (Mill.) Druce, a plant of the Liliaceae family. It is a commonly used Chinese medicinal material in my country, with a long history of application, extensive cultivation, and very rich resources. It was first recorded in the Shennong's Herbal Classic as a top-grade herb. It is mild in nature and sweet in taste. It has the effects of nourishing yin and moistening dryness, promoting body fluid and quenching thirst. It is used for dry mouth and throat due to fever, dry cough, restlessness, palpitations, diabetes, etc. According to modern research, the chemical components contained in Polygonatum odoratum mainly include Polygonatum odoratum polysaccharides, steroidal saponins, flavonoids, volatile oils, etc., which have the effects of coronary dilation, lowering blood lipids, lowering blood sugar, treating diabetes, and enhancing immunity. Its comprehensive utilization and economic value are gradually attracting people's attention.

[0003] Polygonatum odoratum is a commonly used Chinese medicinal material in clinical practice, but there is no clear report on the preparation method of its formula granules. Due to its properties, the total sugar content in Polygonatum odoratum is relatively high. When the formula granules are prepared by conventional processes, the dry powder is sticky and easy to absorb moisture, making the preparation difficult, resulting in increased production costs and reduced powder recovery rate. Summary of the invention

[0004] Therefore, the technical problem to be solved by the present invention is to overcome the problem of low powder recovery rate in the preparation method of the yuzhu formula granules in the prior art, thereby providing a preparation method of the yuzhu formula granules.

[0005] To this end, the present invention provides a method for preparing radix polygonatum formula granules, comprising: mixing dextrin and silicon dioxide into radix polygonatum extract before drying, adding or not adding auxiliary materials after drying, and granulating to obtain radix polygonatum formula granules.

[0006] Furthermore, the mass ratio of dextrin to silicon dioxide is 1:1-9:1, preferably 9:1.

[0007] Furthermore, the total mass of the dextrin and silicon dioxide accounts for 10%-20% of the raw material amount of the Polygonatum odoratum extract slices, preferably 20%.

[0008] The amount of raw materials used refers to the quality of the Polygonatum odoratum raw materials used in the production process of Polygonatum odoratum extract.

[0009] Furthermore, the polygonatum odoratum extract is a clear paste obtained by water extraction and concentration of polygonatum odoratum slices; and / or the drying is spray drying; and / or the auxiliary material is selected from dextrin and / or silicon dioxide.

[0010] Furthermore, the extraction is carried out by decoction in water, the number of extractions is 1 to 3 times, preferably 2 times, the extraction time is 0.5 to 3 hours, preferably 1 to 2 hours, and the amount of water used is 8 to 20 times the mass of the Polygonatum odoratum slices, preferably 10 to 15 times.

[0011] Further, the mixture is concentrated under reduced pressure at a vacuum degree of -0.07 to -0.09 MPa to a clear paste having a relative density of 1.05 to 1.15 (60° C.).

[0012] Furthermore, after the extraction, the method further includes the steps of filtering and collecting the extract.

[0013] The extract can also be placed in a water bath before reduced pressure concentration, with a water bath temperature of 50 to 100° C., preferably 50 to 80° C., and a water bath time of 0 to 24 hours, preferably 0 to 12 hours.

[0014] Furthermore, during the spray drying process, the spray tower inlet air temperature is controlled to be 150-160°C, the outlet air temperature is controlled to be 65-80°C, the atomizer frequency is controlled to be 200-300Hz; and the feed pump frequency is controlled to be 0-50Hz.

[0015] Furthermore, dry granulation is adopted, and 0%-15% of auxiliary materials by weight of the decoction pieces can be added before granulation. The auxiliary materials can be dextrin and / or silicon dioxide.

[0016] In certain preferred embodiments, the method for preparing the Polygonatum odoratum particles comprises the following steps:

[0017] Take the radix polygonati officinalis slices, add 10-15 times the weight of water, extract for 1-3 hours, i.e., first decoction; add 5-10 times the weight of the radix polygonati officinalis slices of water to the residue after the first decoction, extract for 1-3 hours, i.e., second decoction; combine the two decoctions, reduce pressure and concentrate to a clear paste with a relative density of 1.00-1.15; add dextrin and silicon dioxide to the clear paste, mix evenly, preheat the liquid with stirring and heat to 50-80°C, spray dry, spray tower inlet temperature: 150-160°C, outlet temperature: 65-80°C, atomizer frequency: 200-300Hz; feed pump frequency: 0-50Hz. Granulation: add 0%-15% of the radix polygonati officinalis slices amount of auxiliary materials to the radix polygonati officinalis dry powder, put it in a mixer, mix for 30 minutes, granulate it with a dry granulator, and obtain 20-60 mesh particles.

[0018] The present invention also provides a quality control method for the Polygonatum odoratum formula granules, comprising one or more of the following methods:

[0019] (1) Quality control using infrared fingerprints includes the following steps:

[0020] The granules of Polygonatum odoratum were ground into powder and tested by potassium bromide direct tableting method. The testing method was to use Fourier transform infrared spectrometer with a measuring range of 4000cm -1-350cm -1 , DTGS detector, resolution 0.5cm -1 , scanning times 16 times;

[0021] (2) Quality control by high performance liquid chromatography, including the following steps:

[0022] Preparation of test solution;

[0023] The test solution was tested by high performance liquid chromatography, using HSS T3 bonded silica gel as filler, using phosphoric acid aqueous solution and acetonitrile as mobile phases for gradient elution, the gradient elution program included: 0→10min→15min→28min→40min→50min→55min→60min→65min→66min, the volume percentage of acetonitrile in the mobile phase was: 3%→8%→13%→25%→40%→65%→90%→100%→100%→3%, and the HPLC characteristic spectrum of the Yuzhu formula granules was obtained;

[0024] (3) High performance liquid chromatography (HPLC) is used for content determination, comprising the following steps:

[0025] Preparation of test solution;

[0026] Preparation of dioscin reference solution;

[0027] The test solution and the dioscin reference solution were detected by high performance liquid chromatography, using HSS T3 bonded silica gel as a filler, and using an aqueous solution containing phosphoric acid and acetonitrile as mobile phases for gradient elution. The gradient elution program included: 0→10min→15min→28min→40min→50min→55min→60min→65min→66min, and the volume percentage of acetonitrile in the mobile phase was: 3%→8%→13%→25%→40%→65%→90%→100%→100%→3%. According to the concentration of dioscin in the reference solution, the peak area of ​​the reference solution in the chromatogram and the peak area of ​​dioscin in the test solution in the chromatogram, the content of dioscin in the Polygonatum odoratum formula granules was calculated by the external standard method.

[0028] Furthermore, the infrared fingerprint of the yuzhu formula granules has the following characteristics: at 1021.98 cm -1 There is a strongest peak at 2932.00cm -1 There is a secondary peak at 1636.68cm -1 There is a strong peak at 1419.99cm -1 , and 1374.22cm -1 , 1244.68cm -1 Forming a peak cluster; at 1734.49cm-1 、575.88cm -1 There is characteristic absorption at; and / or, the HPLC characteristic spectrum of the Polygonatum odoratum formula granules has 9 common characteristic peaks, the peak corresponding to the diosgenin reference substance peak is the S peak, and the relative retention time of each characteristic peak and the S peak is within the range of ±10% of the specified value; the specified values ​​are: 0.12 (peak 1), 0.13 (peak 2), 0.17 (peak 3), 0.18 (peak 4), 0.23 (peak 5), 0.35 (peak 6), 1.00 (peak 7), 1.08 (peak 8), 1.24 (peak 9); and / or, the content of diosgenin in each 1g of the Polygonatum odoratum formula granules is 1.14mg~2.13mg.

[0029] Furthermore, in the high performance liquid chromatography, the detection wavelength is 200-205 nm, the flow rate is 0.8-1.2 mL / min, and the column temperature is 25-35° C.; and / or, the chromatographic column is a Waters Xselect HSS T3 column; and / or, the concentration of phosphoric acid in the aqueous solution containing phosphoric acid is 0.05-0.2% (volume percentage).

[0030] Furthermore, the method for preparing the test solution includes extracting the test sample with a 40-95% methanol aqueous solution to obtain an extract, filtering, taking the liquid, drying, adding a 40-95% methanol aqueous solution to dissolve, and filtering to obtain the test solution.

[0031] Optionally, the volume ratio of the mass of the test sample to the 40-95% methanol aqueous solution is 0.1-0.5 g:100 ml.

[0032] Furthermore, the preparation method of the dioscin reference solution includes taking an appropriate amount of the dioscin reference, accurately weighing it, and adding 40-95% methanol to prepare a dioscin solution containing 0.05-1.0 mg of dioscin per 1 ml.

[0033] The technical solution of the present invention has the following advantages:

[0034] 1. The preparation method of the yuzhu formula granules provided by the present invention is as follows: dextrin and silicon dioxide are mixed into the yuzhu extract before drying, and after drying, auxiliary materials are added or not added, and granulation is performed to obtain the yuzhu formula granules. The dextrin and silicon dioxide are mixed with the yuzhu extract before drying to play a synergistic role in improving the quality of the yuzhu formula granules and significantly improving the powder collection rate of the yuzhu formula granules. The obtained yuzhu formula granules have low hygroscopicity and good formability and fluidity.

[0035] 2. The preparation method of the Polygonatum odoratum formula granules provided by the present invention can further improve the formability and flowability of the formula granules and further improve the powder recovery rate by controlling the mass ratio of the dextrin and silicon dioxide to 1:1-9:1, especially 9:1.

[0036] 3. The preparation method of the yuzhu formula granules provided by the present invention can further improve the powder recovery rate while maintaining the quality of the yuzhu granules by controlling the total mass of dextrin and silicon dioxide to account for 10%-20%, especially 20%, of the mass of the yuzhu decoction pieces used for the yuzhu extract.

[0037] 4. The quality control method of the Polygonatum odoratum formula granules provided by the present invention has established a quality control method for determining the content of dioscin, the main indicator component in the Polygonatum odoratum granules, by high performance liquid chromatography. It has the advantages of high precision, good stability, good repeatability and high accuracy. At the same time, it can monitor the quality of the finished product and ensure the consistency of the quality of the finished product between batches.

[0038] 5. The quality control method of the yuzhu formula granules provided by the present invention uses an infrared fingerprint method to control the quality of the yuzhu granules. The method is simple to operate, scientific, advanced, fast, and highly operable. It can quickly solve a primary problem in the macroscopic quality control of traditional Chinese medicines - the identification of the authenticity of traditional Chinese medicines.

[0039] 6. The quality control method of the yuzhu formula granules provided by the present invention adopts HSS T3 bonded silica gel as a filler, adopts a phosphoric acid-containing aqueous solution and acetonitrile as a mobile phase for gradient elution, and the gradient elution program includes: 0→10min→15min→28min→40min→50min→55min→60min→65min→66min, and the volume percentage of acetonitrile in the mobile phase is: 3%→8%→13%→25%→40%→65%→90%→100%→100%→3%, and the HPLC characteristic spectrum of the yuzhu formula granules is obtained; finally, 9 common characteristic peaks are obtained, and the effective separation of the 9 common characteristic peaks is achieved, and the obtained characteristic spectrum has a stable baseline, a good peak shape of the characteristic peak, and a short detection time, which provides a scientific basis for the comprehensive establishment of the quality control standard of the yuzhu formula granules. In addition, the peak position of diosgenin can be accurately located, fully reflecting the integrity and characteristic of the yuzhu formula granules.

[0040] 7. The quality control method of the yuzhu formula granules provided by the present invention uses dioscin as the index component in each stage of the process research, and uses the content, characteristic spectrum and paste yield of 15 batches of yuzhu standard decoctions as evaluation indicators to ensure that the transfer rate of the index components of yuzhu in different process studies reaches the technical requirements of yuzhu standard decoction decoction. With dioscin as the index component, the quality standards of yuzhu raw materials, intermediates and finished granules are established, which can effectively achieve product quality control. Among them, the transfer rate of dioscin in 15 batches of yuzhu standard decoctions is 6.2% to 21.5%, and the paste yield is 22.2% to 30.0%; 20% of the auxiliary materials of the decoction piece can be added in the drying step, and the intermediate paste yield range is 42.2% to 50.0%. The fingerprint of the yuzhu standard decoction is established, and 9 common peaks are calibrated, and the similarity is greater than 0.9. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0042] Figure 1 This is the infrared fingerprint obtained in Example 4;

[0043] Figure 2 This is the characteristic spectrum of method 1 of experimental example 2;

[0044] Figure 3 This is the characteristic spectrum of Experimental Example 2 Method 2;

[0045] Figure 4 This is the characteristic spectrum of Experimental Example 2 Method 3;

[0046] Figure 5 Characteristic spectra obtained from different chromatographic columns in Experimental Example 2; from bottom to top, they are chromatographic column 3, chromatographic column 2, and chromatographic column 1;

[0047] Figure 6 It is a comparison chart of the test substance and the reference substance;

[0048] Figure 7 It is the comparative characteristic spectrum of 15 batches of freeze-dried powder of standard decoction of Polygonatum odoratum and 4 batches of formula granules;

[0049] Figure 8 To investigate the atlas for specificity;

[0050] Fig. 9 It is a linear relationship graph. DETAILED DESCRIPTION

[0051] The following examples are provided to better further understand the present invention, but are not limited to the best mode of implementation, and do not limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the enlightenment of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention. If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments used is not specified, they are all conventional reagent products that can be purchased commercially. Parts by weight refers to how many times the mass of the water added is the mass of the decoction piece.

[0052] Example 1

[0053] This embodiment provides a method for preparing Polygonatum odoratum particles, comprising the following steps:

[0054] Take the radix polygonati officinalis slices, add 12 times the weight of water, decoct and extract for 2 hours, i.e., the first decoction; add 10 times the weight of water of the radix polygonati officinalis slices to the residue after the first decoction, decoct and extract for 1.5 hours, i.e., the second decoction; combine the two decoction liquids, and reduce the pressure and concentrate to a clear paste with a relative density of 1.10 (60°C) under a vacuum degree of -0.07 to -0.09 MPa; add dextrin of 18% of the radix officinalis slice feed amount and 2% of silicon dioxide to the clear paste, mix evenly, preheat the liquid with stirring and heat to 60°C, and spray dry, the spray tower inlet temperature is 160°C, the outlet temperature is 70°C, the atomizer frequency is 250Hz; the feed pump frequency is 25Hz, and the radix polygonati officinalis spray-dried powder is obtained, and granulated by a dry granulator to obtain granules of 20 to 60 meshes.

[0055] Example 2

[0056] This embodiment provides a method for preparing Polygonatum odoratum particles, comprising the following steps:

[0057] Take the radix polygonatum decoction pieces, add 10 times the weight of water, decoct and extract for 2 hours, i.e., the first decoction; add 8 times the weight of water of the radix polygonatum decoction pieces to the residue after the first decoction, decoct and extract for 1.5 hours, i.e., the second decoction; combine the two decoction liquids, and reduce the pressure to concentrate to a clear paste with a relative density of 1.10 (60°C) under a vacuum degree of -0.07 to -0.09Mpa; add dextrin and 10% silicon dioxide in an amount of 10% of the decoction pieces to the clear paste, mix them evenly, preheat the liquid with stirring and heat to 60°C, and spray dry it, the spray tower inlet temperature is 160°C, the outlet temperature is 70°C, the atomizer frequency is 250Hz; the feeding pump frequency is 25Hz, and the radix polygonatum spray-dried powder is obtained, dextrin in an amount of 8% of the decoction pieces is added to the radix polygonatum dry powder, placed in a mixer, mixed for 30 minutes, and granulated with a dry granulator to obtain particles of 20 to 60 meshes.

[0058] Example 3

[0059] This embodiment provides a method for preparing Polygonatum odoratum particles, comprising the following steps:

[0060] Take the radix polygonatum decoction pieces, add 14 times the weight of water, decoct and extract for 2.5 hours, i.e., one decoction; add 11 times the weight of water of the radix polygonatum decoction pieces to the residue after the first decoction, decoct and extract for 2.5 hours, i.e., two decoctions; combine the two decoctions, and reduce the pressure to concentrate to a clear paste with a relative density of 1.10 (60°C) under a vacuum degree of -0.07 to -0.09 MPa; add 15% of dextrin and 5% of silicon dioxide to the clear paste, mix evenly, preheat the liquid with stirring and heat to 60°C, spray dry, the spray tower inlet temperature is 160°C, the outlet temperature is 65°C, the atomizer frequency is 250Hz; the feeding pump frequency is 25Hz, and the radix polygonatum spray-dried powder is obtained, 4% of dextrin and 10% of silicon dioxide in the amount of the decoction pieces are added to the radix polygonatum dry powder, placed in a mixer, mixed for 30 minutes, granulated with a dry granulator, and 20-60 mesh particles are obtained.

[0061] Example 4

[0062] This embodiment provides a quality control method for Polygonatum odoratum formula granules, which uses infrared fingerprint spectrum for quality control, including the following steps:

[0063] Take an appropriate amount of the Polygonatum odoratum granule sample obtained in Example 1, grind it into powder, pass it through a 60-100 mesh sieve, and grind it with potassium bromide powder (chromatographically pure) in an agate mortar at a mass ratio of 1:200. Take an appropriate amount and put it into a tableting mold, and press it into tablets on a tablet press.

[0064] The infrared fingerprint identification method is: using Fourier transform infrared spectrometer, the measurement range is 4000cm -1 -350cm -1 , DTGS (deuterated triglycine sulfate) detector, resolution 0.5cm -1 , scanning times 16 times, water and carbon dioxide interference were removed during scanning, relative humidity was lower than 60%, potassium bromide direct tableting method was used for detection; infrared fingerprint of Polygonatum odoratum is as follows Figure 1 , with the following characteristics: at 1021.98cm -1 There is a strongest peak at 2932.00cm -1 There is a secondary peak at 1636.68cm -1 There is a strong peak at 1419.99cm -1 , and 1374.22cm -1 , 1244.68cm -1 In addition to the above peaks, there is a peak cluster at 1734.49 cm -1 、575.88cm -1 There is characteristic absorption.

[0065] Example 5

[0066] This embodiment provides a quality control method for Polygonatum odoratum formula granules, which uses high performance liquid chromatography to construct a characteristic spectrum, including the following steps:

[0067] Preparation of test solution: Take an appropriate amount of the test sample, grind it into powder, take about 0.3g, weigh it accurately, put it in a conical flask, add 100ml of 90% methanol accurately, plug it tightly, weigh it, treat it ultrasonically (power 500W, frequency 40kHz) for 20 minutes, let it cool, weigh it again, make up the lost weight with 90% methanol, shake it well, filter it, take 50ml of the filtrate, evaporate it to dryness, dissolve it in a 5ml volumetric flask with 90% methanol, make up to volume, shake it well, filter it, and the filtrate is used as the test sample.

[0068] Take 10 μl of the test solution and detect it by high performance liquid chromatography. The chromatographic conditions are as follows: use a chromatographic column WatersXselect HSS T3 (column length is 250 mm, inner diameter is 4.6 mm, particle size is 5 μm); use acetonitrile as mobile phase A, use 0.1% phosphoric acid as mobile phase B, and perform gradient elution according to the provisions in the following table; flow rate is 1 ml per minute; column temperature is 30°C; detection wavelength is 203 nm; theoretical plate number should be not less than 10000 calculated based on reference peak. The HPLC characteristic spectrum of the Polygonatum odoratum formula granules is obtained.

[0069]

[0070] Example 6

[0071] This embodiment provides a quality control method for Polygonatum odoratum formula granules, which uses high performance liquid chromatography to perform content determination, comprising the following steps:

[0072] The chromatographic conditions and system suitability test used a chromatographic column Waters Xselect HSS T3 (column length: 250 mm, inner diameter: 4.6 mm, particle size: 5 μm); acetonitrile was used as mobile phase A, 0.1% phosphoric acid was used as mobile phase B, and gradient elution was performed as specified in the following table; the flow rate was 1 ml per minute; the column temperature was 30° C.; the detection wavelength was 203 nm; and the number of theoretical plates calculated based on the reference peak should be no less than 10,000.

[0073]

[0074] Preparation of reference solution: Take appropriate amount of dioscin reference substance, weigh accurately, add 70% methanol to prepare a solution containing 0.2 mg of dioscin per 1 ml.

[0075] Preparation of test sample solution Take an appropriate amount of the test sample, grind it into powder, take about 0.3 g, weigh it accurately, put it in a conical flask, accurately add 100 ml of 90% methanol, plug it tightly, weigh it, treat it with ultrasound (power 500 W, frequency 40 kHz) for 20 minutes, let it cool, weigh it again, make up the lost weight with 90% methanol, shake it well, filter it, take 50 ml of the filtrate, evaporate it to dryness, dissolve it in a 5 ml volumetric flask with 90% methanol, make up to volume, shake it well, filter it, and the filtrate is used as the test sample.

[0076] Determination method: Accurately pipette 10 μl of the reference solution and the test solution respectively, inject them into the liquid chromatograph for determination, and calculate the content of dioscin in the Polygonatum odoratum formula granules by the external standard method based on the concentration of dioscin in the reference solution, the peak area of ​​the reference solution in the chromatogram and the peak area of ​​dioscin in the test solution in the chromatogram.

[0077] Example 7

[0078] This embodiment provides a quality control method for Polygonatum odoratum formula granules, which uses high performance liquid chromatography to determine the content and construct a characteristic spectrum, including the following steps:

[0079] Preparation of test solution: Take an appropriate amount of the test sample, grind it into powder, take about 0.3g, weigh it accurately, put it in a conical flask, add 100ml of 90% methanol accurately, plug it tightly, weigh it, treat it with ultrasound (power 500W, frequency 40kHz) for 20 minutes, let it cool, weigh it again, make up the lost weight with 90% methanol, shake it well, filter it, take 50ml of the filtrate, evaporate it to dryness, dissolve it in a 5ml volumetric flask with 90% methanol, make up to volume, shake it well, filter it as the test sample.

[0080] Preparation of reference solution: Take appropriate amount of dioscin reference substance, weigh accurately, add 70% methanol to prepare a solution containing 0.2 mg of dioscin per 1 ml.

[0081] Accurately pipette 10 μl of the reference solution and the test solution respectively, and detect by high performance liquid chromatography. The chromatographic conditions are as follows: use a chromatographic column Waters Xselect HSS T3 (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, and gradient elution is performed according to the regulations in the following table; the flow rate is 1 ml per minute; the column temperature is 30°C; the detection wavelength is 203 nm; the number of theoretical plates calculated based on the reference peak should not be less than 10000.

[0082]

[0083] The HPLC characteristic spectrum of the Yuzhu Formula Granule and the reference substance chromatogram are obtained. The content of dioscin in the Yuzhu Formula Granule is calculated by the external standard method according to the concentration of dioscin in the reference substance solution, the peak area of ​​the reference substance solution in the chromatogram, and the peak area of ​​dioscin in the test solution in the chromatogram.

[0084] Comparative Example 1

[0085] This comparative example provides a method for preparing Polygonatum odoratum granules, which is basically the same as that of Example 1, except that no dextrin and silicon dioxide are added to the clear paste before spray drying, and the other process conditions are the same as those of Example 1.

[0086] Comparative Example 2

[0087] This comparative example provides a preparation method of Polygonatum odoratum granules, which is basically the same as Example 1, except that 20% of dextrin is added to the clear paste before spray drying and mixed evenly, and the other process conditions are the same as Example 1.

[0088] Comparative Example 3

[0089] This comparative example provides a preparation method of Polygonatum odoratum granules, which is basically the same as Example 1, except that 15% dextrin and 5% magnesium stearate are added to the clear paste before spray drying and mixed evenly, and the other process conditions are the same as Example 1.

[0090] Comparative Example 4

[0091] This comparative example provides a preparation method of Polygonatum odoratum granules, which is basically the same as Example 1, except that 15% of dextrin is added to the clear paste before spray drying and mixed evenly, and the other process conditions are the same as Example 1.

[0092] Comparative Example 5

[0093] This comparative example provides a method for preparing Polygonatum odoratum particles, which is basically the same as Example 1, except that 5% of silicon dioxide is added to the clear paste before spray drying and mixed evenly, and the other process conditions are the same as Example 1.

[0094] Experimental Example 1

[0095] The yuzhu formula granules were prepared according to the methods of each embodiment and the comparative example, and the content of dioscin in the yuzhu spray-dried powder obtained in the preparation process of each group of yuzhu formula granules was determined by the high performance liquid chromatography method of Example 6, and the powder recovery rate (%) after spray drying was calculated according to the following formula, powder recovery rate = weight of spray-dried powder (g) / (weight of clear paste (g) × solid content (%) + weight of auxiliary materials added before spray drying (g) × 100%, wherein the solid content was tested according to the following method: in the preparation process of each group of yuzhu formula granules, 3g of clear paste was taken, accurately weighed W2, put into a weighing bottle W1 with a constant weight, opened the cover and put it in a microwave oven and heated repeatedly several times, taken out, covered, moved to a dryer, left at room temperature for 30min, weighed, and then heated several times under the above conditions, moved to a dryer, left at room temperature for 30min, and weighed W3, until the difference between two consecutive weighings was no more than 5mg. Solid content (%) = (W3-W1) / W2*100. Calculate the RSD value of the powder collection rate of Example 1, Comparative Example 2 and Comparative Example 3 (recorded as RSD-1), calculate the RSD value of the powder collection rate of Example 3 and Comparative Examples 1-5 (recorded as RSD-2), calculate the RSD value of the powder collection rate of Examples 1-3 (recorded as RSD-3), and the results are shown in the table below.

[0096] Table 1 Test results

[0097]

[0098] The results showed that the type of auxiliary materials added before drying slightly increased the content of diosgenin, but had a greater impact on the powder yield. Compared with comparative examples 1-5, dextrin and silicon dioxide in examples 1-3 of the present invention played a synergistic role and significantly increased the powder yield of Polygonatum odoratum granules.

[0099] The hygroscopicity, formability, angle of repose, bulk density and solubility of each group of granule samples were tested, and the RSD values ​​of the six groups of Example 3 and Comparative Examples 1-5 (recorded as RSD-1) were calculated, and the RSD values ​​of the three groups of Examples 1-3 (recorded as RSD-2) were calculated. The results are shown in the table below.

[0100] The test method is as follows: Bulk density: Place the sample in a dry 50ml measuring cylinder (other specifications of measuring cylinders can be used, but 50%-90% of the total capacity must be filled). Record the sample volume, weigh the total weight and record it, and calculate the bulk density. Do this three times and calculate the average value. Bulk density = dry powder mass / dry powder volume.

[0101] Angle of repose: Use the fixed funnel method to connect and fix three funnels in series, ensuring that the distance between the lower end of the funnel and the horizontally placed coordinate paper is 1 cm (H value). Carefully pour the sample along the funnel wall into the top funnel until the tip of the sample cone formed on the coordinate paper touches the funnel mouth. Measure the diameter of the cone bottom (2R) from the coordinate paper and calculate the radius (R). Do this five times and calculate the average value. Angle of repose tanα = H / R.

[0102] Solubility: Take 5g of sample, add 100ml of hot water, stir for 5 minutes, and observe immediately. If it is not completely dissolved, identify the insoluble matter and determine its source.

[0103] Hygroscopicity: Take the dry sample and spread it in a weighing bottle with constant weight to a thickness of about 2mm (about 1-2g), put it in a 30℃ blast drying oven to dry for a certain period of time, weigh it, and place it in an environment with a temperature of 25℃ and a relative humidity of 75% to constant weight. Place it in the above environment (open the lid) for 24 hours, take it out and weigh it at 0.5h, 1h, 2h, 4h, 8h, 16h, and 24h, calculate the moisture absorption rate, and draw a moisture absorption curve. Do 2 groups in total and calculate the average value. Moisture absorption rate = (constant weight - empty bottle weight) / sample weight * 100%.

[0104] Table 2 Test results

[0105] name Hygroscopicity (%) Formability (%) Angle of repose Bulk density (g / ml) Solubility Example 1 17.0％ 91.2％ 32.15° 0.73 All melted Example 2 16.2％ 93.1％ 30.08° 0.73 All melted Example 3 17.9％ 91.2％ 32.32° 0.73 All melted Comparative Example 1 23.0％ 58.0％ 37.7° 0.71 All melted Comparative Example 2 20.2％ 75.6％ 35.58° 0.71 All melted Comparative Example 3 18.50％ 90.20％ 32.65° 0.74 All melted Comparative Example 4 20.3％ 75.0％ 36.75° 0.71 All melted Comparative Example 5 18.0％ 80.0％ 33.15° 0.71 All melted RSD-1(%) 9.93 15.54 6.60 2.02 RSD-2(%) 4.99 1.19 3.96 0.00

[0106] The results show that the type of auxiliary materials added before drying has a great influence on the hygroscopicity, formability and fluidity of the yuzhu formula granules (RSD>5%), and has no significant effect on bulk density and solubility. Compared with comparative examples 1-2 and comparative examples 4-5, the hygroscopicity, formability and fluidity of the yuzhu granules prepared by examples 1-3 of the present invention are significantly improved.

[0107] Experimental Example 2 Construction of characteristic spectrum of formula particles

[0108] 1. Instruments, reagents and test drugs

[0109] Instruments and materials: Instruments: Waters high performance liquid chromatograph (UV detector), electronic balance (ML204T, Mettler Toledo Instrument Co., Ltd.), electronic balance (JJ500, Changshu Shuangjie Testing Instrument Factory), ultrasonic cleaner (KQ-100DE, Kunshan Ultrasonic Instrument Co., Ltd.), chromatographic column: Waters Xselect HSS T3 (4.6*250mm, 5μm);

[0110] Test drugs: Polygonatum odoratum slices (batch numbers: B19041-Y079-201903-001 to B19041-Y079-201903-015), Polygonatum odoratum formula granules: 21035002, 21035022, 21035042, 21035051, which were prepared according to the method of Example 1 respectively.

[0111] Reagents: Acetonitrile (Merck) was of chromatographic grade; phosphoric acid (Thermo) was of chromatographic grade; water was distilled water (Watsons); other reagents were of analytical grade.

[0112] The freeze-dried powder of standard decoction of Polygonatum odoratum can be prepared by conventional methods in the art. For example, the present invention is prepared according to the following steps: take Polygonatum odoratum decoction pieces, put them in a casserole, soak them for 30 minutes, add 12 times the amount of water of the decoction pieces for the first decoction, boil them over high heat, simmer for 30 minutes over low heat, filter them while hot, cool them quickly and set them aside; add 10 times the amount of water of the decoction pieces for the second decoction, boil them over high heat, simmer for 20 minutes over low heat, filter them while hot, cool them quickly and set them aside; combine the filtrate, concentrate (60°C), concentrate to a solid-liquid ratio of about 1:1 (relative density is 1.05-1.10 (50°C)), and freeze-dry to obtain the product.

[0113] My plan number

[0114] 2. Preparation of test solution

[0115] Take an appropriate amount of formula granules, grind them into powder, take about 0.3g, weigh it accurately, put it in a conical flask, add 100ml of 90% methanol accurately, plug it tightly, weigh it, treat it with ultrasound (power 500W, frequency 40kHz) for 20 minutes, let it cool, weigh it again, make up the lost weight with 90% methanol, shake it well, filter it, take 50ml of the filtrate, evaporate it to dryness, dissolve it in a 5ml volumetric flask with 90% methanol, make up to volume, shake it well, filter it, and use the filtrate as the test sample.

[0116] 3. Optimization of chromatographic conditions

[0117] (1) Mobile phase gradient optimization experiment

[0118] Take 10 μl of the test solution prepared in Item 2 of this Experimental Example and detect it by high performance liquid chromatography using the following chromatographic conditions.

[0119] Method 1: Reference: Agilent Zorbax XDB C8 (4.6×150 mm, 5 μm) was used as the chromatographic column, acetonitrile was used as the mobile phase A, 0.1% phosphoric acid water was used as the mobile phase B, and gradient elution was performed according to the table below; the detection wavelength was 203 nm, the column temperature was 30° C., and the flow rate was 1.0 ml / min.

[0120] Table 3 Gradient elution table

[0121]

[0122] Summary: Figure 2 As shown in the chromatogram obtained by this method, all the chromatographic peaks are relatively wide and the baseline is not flat, so other types of chromatographic columns are replaced to try separation.

[0123] Method 2: The chromatographic column was Waters Xselect HSS T3 (4.6×250mm, 5μm), acetonitrile was used as mobile phase A, 0.1% phosphoric acid water was used as mobile phase B, and gradient elution was performed according to the table below; the detection wavelength was 203nm, the column temperature was 30°C, the flow rate was 1.0ml / min, and the injection volume was 10μl.

[0124] Table 4 Gradient elution table

[0125]

[0126] Summary: Figure 3 As shown in the figure, after replacing the chromatographic column, the shape of the chromatographic peak was significantly improved, but the baseline was not stable from 15 to 38 minutes, and some chromatographic peaks were slightly disturbed. The elution speed was reduced and optimization was continued.

[0127] Method 3: The chromatographic column was Waters Xselect HSS T3 (4.6×250mm, 5μm), acetonitrile was used as mobile phase A, 0.1% phosphoric acid was used as mobile phase B, and gradient elution was performed according to the table below; the detection wavelength was 203nm, the column temperature was 30°C, the flow rate was 1.0ml / min, and the injection volume was 10μl.

[0128] Table 5 Gradient elution table

[0129]

[0130] Table 6 Peak information table of the chromatogram of the test solution in method 3

[0131]

[0132] Summary: Figure 4 As shown in the figure, the optimized method 3 has more chromatographic information, good peak shape and separation effect, and the chromatographic peak is small within 12-50 minutes. Considering the correlation between medicinal materials and particles in the later study and the difference in peak area between different batches, this part of the elution method is retained. Method 3 is used as the characteristic chromatographic method of Polygonatum odoratum.

[0133] (2) Chromatographic column investigation experiment

[0134] The test solution of the Polygonatum formula granules was prepared according to the method under item 2 of this experimental example. The test solution of the Polygonatum formula granules was detected using the chromatographic conditions of method 3 under item 3(1) of this experimental example, the only difference being the different chromatographic columns. The effects of different chromatographic columns on the durability of the characteristic spectrum of the Polygonatum formula granules were compared. Different brands of octadecylsilane bonded silica gel chromatographic columns (chromatographic column 1: Waters Xselect HSS T3 (4.6*250mm, 5μm) chromatographic column; chromatographic column 2: Agilent Zorbax Bonus-RP (4.6*250mm, 5μm); chromatographic column 3: Ultimate LP-C18 (4.6*250mm, 5μm) were used.

[0135] The results show that the characteristic peaks in column 3 are quite different and cannot be identified; the order of characteristic peaks in columns 2 and 1 is close, but column 1 has better separation effect of 5-9min chromatographic peaks. It is recommended to specify the chromatographic column as WatersXselect HSS T3 (4.6*250mm, 5μm) column.

[0136] 4. Identification of characteristic peaks

[0137] Take an appropriate amount of dioscin reference substance, weigh accurately, and add 70% methanol to prepare a reference substance solution containing 0.2 mg of reference substance per 1 ml.

[0138] The test solution and the reference solution of the Polygonatum odoratum formula granules were tested and compared according to the chromatographic conditions of Method 3 under Item 3(1) of this Experimental Example. The results are as follows: Figure 6 From bottom to top are the chromatograms of the diosgenin reference solution and the Polygonatum odoratum formula granule test solution.

[0139] Summary: The retention time of Peak 7 in the chromatogram of the test sample of Polygonatum odoratum formula granules is consistent with that of the chromatographic peak of Dioscorea saponin, which confirms that Peak 7 is Dioscorea saponin.

[0140] 5. Determination of characteristic peaks and establishment of reference spectrum

[0141] (1) Construction method

[0142] Take about 0.6g of Polygonatum odoratum reference medicinal material (passed through No. 3 sieve), weigh it, add 50ml of water, soak for 30min, then boil for 40min, filter, evaporate the filtrate to dryness, dissolve it in a 5ml volumetric flask with 90% methanol, make up to volume, shake well, and filter as the reference solution of the reference medicinal material.

[0143] Take 15 batches of freeze-dried powder of standard decoction of Polygonatum odoratum and 4 batches of formula granules to prepare test sample solutions according to the following method: take an appropriate amount of the test sample, grind it into powder, take about 0.3g, weigh it accurately, put it in a conical flask, accurately add 100ml of 90% methanol, plug it tightly, weigh it, treat it with ultrasound (power 500W, frequency 40kHz) for 20 minutes, let it cool, weigh it again, make up the lost weight with 90% methanol, shake it well, filter it, take 50ml of the filtrate, evaporate it to dryness, dissolve it in a 5ml volumetric flask with 90% methanol, make up to volume, shake it well, filter it, and the filtrate is used as the test sample.

[0144] The test sample solution and the control medicinal material reference solution were respectively detected by high performance liquid chromatography: HSS T3 bonded silica gel was used as the filler (column length was 250 mm, inner diameter was 4.6 mm, particle size was 5 μm); acetonitrile was used as mobile phase A, 0.1% phosphoric acid was used as mobile phase B, and gradient elution was performed according to the provisions in the following table; the flow rate was 1 ml per minute; the column temperature was 30°C; the detection wavelength was 203 nm; the column temperature was 30°C, and the flow rate was 1.0 ml / min; the theoretical plate number calculated based on the reference peak should not be less than 10,000.

[0145] Table 7 Gradient elution program

[0146]

[0147] (2) Use the "Chinese Herbal Medicine Chromatographic Characteristic Spectrum Similarity Evaluation System" (2012.1 version) to mark the common peaks, and use S1 as the reference spectrum, calculate the median, and obtain the reference spectrum. Calculate the similarity between each batch of Polygonatum odoratum formula granules and the reference spectrum to determine the acceptable range of similarity. According to the characteristics of each chromatographic peak and the active ingredients in Polygonatum odoratum, the retention time and peak area of ​​each common peak are counted, and the acceptability of the retention time of each common peak is clarified, see Figure 6 shown.

[0148] A total of 9 peaks were selected as characteristic peaks. Peak 7 is the reference peak of diosgenin reference substance (S peak). The relative retention times of the characteristic peaks and the S peak are 0.12 (peak 1), 0.13 (peak 2), 0.17 (peak 3), 0.18 (peak 4), 0.23 (peak 5), 0.35 (peak 6), 1.00 [peak 7 (S)], 1.08 (peak 8), and 1.24 (peak 9). The retention time should be within ±10% of the specified value. However, the difference in peak area is large, with an RSD value of 3.47% to 7.36%, so the peak area is not included in the standard. The similarity between the characteristic spectra of the four batches of Polygonatum odoratum formula granules and the reference spectra is between 0.998 and 1.000, all greater than 0.9.

[0149] Table 8 Relative retention time of 15 batches of Polygonatum odoratum standard decoction freeze-dried powder

[0150]

[0151]

[0152] Table 9 Relative peak areas of 15 batches of Polygonatum odoratum standard decoction freeze-dried powder

[0153]

[0154] Table 10 Similarity of characteristic spectra of four batches of Polygonatum odoratum formula granules

[0155]

[0156] Table 11 Characteristic spectrum information of 4 batches of Polygonatum odoratum formula granules

[0157]

[0158]

[0159] Experimental Example 3 Methodological Verification

[0160] 1. Instruments, reagents and test drugs

[0161] The instruments and reagents are the same as those in Experiment 2.

[0162] Test drug: Polygonatum odoratum formula granules were prepared according to the method of Example 1, and the batch numbers were 21035002, 21035022, 21035042, and 21035051, respectively.

[0163] Dioscin (China Food and Drug Administration, 111707-201703, purity 96.1%)

[0164] 2. Methodological verification of feature map construction

[0165] (1) Instrument precision

[0166] Take Polygonatum odoratum formula granules (batch number: 21035042) to prepare a test solution according to the method of Example 5. Take 6 portions of the test solution and test it under the chromatographic conditions of Method 3 of Experimental Example 2, Part 3 (1). Repeat the injection 6 times and calculate the RSD of the relative retention time of 9 characteristic peaks to be 0.00-0.14%. The results show that the instrument has good precision.

[0167] (2) Repeatability

[0168] A sample of Polygonatum odoratum formula granules (batch number: 21035042) was taken, and 6 test solutions were prepared in parallel according to the method of Example 5 and measured under the chromatographic conditions of Method 3 of Experimental Example 2, Part 3 (1). The RSD of the relative retention time of the 9 characteristic peaks was calculated to be 0.00-0.14%. The results showed that the method had good repeatability.

[0169] (3) Intermediate precision (personnel)

[0170] Three experimenters prepared the test solution of Polygonatum odoratum formula granules (batch number: 21035042) according to the method of Example 5 and measured it under the chromatographic conditions of Method 3 of Experimental Example 2, Part 3 (1). The RSD of the relative retention time of the 9 characteristic peaks was calculated to be 0.00-0.66%, and the intermediate precision was good.

[0171] (4) Stability test

[0172] The test solution was prepared by the method of Example 5 using Polygonatum odoratum formula granules (batch number: 21035042), and the HPLC test was performed under the chromatographic conditions of Method 3 of Experimental Example 2, Part 3 (1) at 0 h, 2 h, 4 h, 8 h, 12 h, and 24 h, respectively. The RSD of the relative retention time of the 9 characteristic peaks was calculated to be 0.00-0.20%. The results showed that the test solution was stable within 24 h and met the determination requirements.

[0173] (5) Investigation of different column temperatures

[0174] Take Yuzhu Granule (batch number: 21035042), prepare the test solution according to the method of Example 5, and measure it at different column temperatures (28°C, 30°C and 32°C) according to the method of Example 5 to investigate the durability of the experimental method for column temperature. The chromatograms obtained at different column temperatures, the RSD of the relative retention time of the 9 characteristic peaks calculated was 0.13-3.42%. The results show that this method has good durability for column temperature.

[0175] (6) Investigation of different flow rates

[0176] Take Yuzhu Granule (batch number: 21035042), prepare the test solution according to the method of Example 5, and measure it under different flow rates (0.95ml / min, 1.00ml / min and 1.05ml / min) according to the chromatographic conditions of Example 5 to investigate the durability of the experimental method for flow rate. The chromatograms obtained at different flow rates, the RSD of the relative retention time of the 9 characteristic peaks calculated was 0.65-4.93%, indicating that the method has good durability for flow rate.

[0177] 3. Methodological validation of content determination

[0178] (1) Exclusivity

[0179] Take an appropriate amount of the auxiliary materials used in the Yuzhu granule formula granules (18% dextrin and 2% silicon dioxide in the decoction piece feeding amount) and prepare a negative control solution according to the preparation method of the test solution in Example 6; the chromatograms of the Yuzhu formula granule test solution, dioscin reference solution, and negative control solution are obtained according to the method of Example 6, and the results are shown in Figure 8 .like Figure 8 From bottom to top, they are the test solution of Polygonatum odoratum formula granules, the diosgenin reference solution, and the negative control solution, with good specificity.

[0180] (2) Linear

[0181] Take an appropriate amount of diosgenin reference substance, accurately weigh it, add 70% methanol to prepare 90.16 μg diosgenin per 1 ml as linear 5 solution; then accurately pipette 5 ml, 2 ml, 1 ml, and 0.5 ml from linear 5 into a 10 ml volumetric flask, add 70% methanol to make it up to scale, numbered 4, 3, 2, and 1, and then accurately pipette 10 μl of the subsequent filtrate, inject it into a high performance liquid chromatograph, determine the peak area of ​​the chromatographic peak according to the method in the text, use the peak area of ​​the chromatographic peak as the ordinate and the concentration as the abscissa, observe whether it is linear, and then use the least squares method to perform linear regression, and the regression equation is y=1E+06x+1236.1, R 2 =0.9999, and its linear range is 0.004508051-0.09016102mg / ml.

[0182] Table 12 Dioscin standard curve

[0183]

[0184] (3) Accuracy

[0185] Take an appropriate amount of dioscin reference substance, accurately weigh it, and add 70% methanol to make a reference substance solution containing 0.001846 mg per 1 ml. Take 6 portions of this product powder with a known content (batch number: 21035042, dioscin content is 1.21 mg / g), each about 0.15 g, accurately weigh it, and add the reference substance to the sample (n=6) according to the ratio of the reference substance amount to the amount of the component to be determined in the test sample of 1:1, prepare the test sample, and the rest of the operation is the same as the method in the text. Calculate the recovery rate according to the following formula. The results are shown in Table 13.

[0186]

[0187] Table 13 Recovery rate experimental results

[0188]

[0189] The recovery rate of dioscin measured in the recovery test ranged from 100.77% to 104.49%, with an average recovery rate of 101.97% and an RSD value of 1.41%, which met the recovery rate requirements of the methodology validation, indicating that the results measured using this method are accurate.

[0190] (4) Repeatability

[0191] Six portions of Yuzhu Granules (batch number: 21035042) were taken and measured according to the method of Example 6. The results showed that the dioscin content in the Yuzhu Formula Granules measured by the repeatability test was 1.21 mg / g, and the RSD was 1.0%, which met the repeatability requirements of the methodology verification.

[0192] (5) Intermediate precision

[0193] Different analysts used different liquid chromatographs (TUV detectors) at different times to conduct intermediate precision tests. Six portions of Yuzhu Granules (batch number: 21035042) were taken and measured according to the method of Example 6. The results showed that the dioscin content in the Yuzhu Formula Granules measured by the intermediate precision test was 1.18, with an RSD value of 1.1%, and the RSD value of the test result of the repeatability test was 2.7%, which met the precision requirements of the method validation; met the precision requirements of the method validation.

[0194] (6) Durability

[0195] Stability test

[0196] Take 6 portions of Yuzhu Granules (Batch No.: 21035042) and measure them according to the method of Example 6 at 0h, 2h, 4h, 8h, 12h and 24h, and record the change of diosgenin peak area. The results show that the RSD value of diosgenin peak area within 24 hours is 0.4%, which meets the requirements of system suitability test.

[0197] Investigation of different column temperatures

[0198] Six portions of Yuzhu Granules (batch number: 21035042) were taken and measured at different column temperatures (28°C, 30°C and 32°C) according to the method of Example 6 to investigate the durability of the experimental method for column temperature. Results: The chromatograms obtained at different column temperatures, the theoretical plate number, tailing factor and separation degree of dioscin all met the system suitability requirements; the average dioscin content was measured to be 1.21 mg / g, and the RSD value was 1.0%, which met the system suitability requirements. This shows that the method has good durability for column temperature.

[0199] Different flow rate investigation

[0200] Take Yuzhu Granule (batch number: 21035042) and measure it under different flow rates (0.95ml / min, 1.00ml / min and 1.05ml / min) according to the chromatographic conditions of Example 6 to investigate the durability of the experimental method for flow rate. Results: The chromatograms obtained at different flow rates, the theoretical plate number, tailing factor and separation degree of diosgenin all meet the system suitability requirements; the average diosgenin content was measured to be 1.20mg / g, and the RSD value was 0.80%, which met the system suitability requirements. This shows that the method has good durability for flow rate.

[0201] (7) Results of determination of diosgenin content in 4 batches of Yuzhu granules

[0202] Four batches of Yuzhu granules were taken and the dioscin content was determined according to the method of Example 6. The results are shown in the table below.

[0203]

[0204] The content range of dioscin in different batches of Yuzhu Granules was analyzed, and the mean value was 1.64 mg / g, and the range of mean ± 30% SD was 1.14-2.13 mg / g. Based on the above determination results, the content of dioscin (C 45 H 72 O 16 ) content range should be 1.14mg~2.13mg.

[0205] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. A quality control method for Polygonatum odoratum formula granules, characterized in that: The methods include the following (1) to (3): (1) Quality control using infrared fingerprints includes the following steps: The granules of Polygonatum odoratum were ground into powder and tested by potassium bromide direct tableting method. The testing method was to use Fourier transform infrared spectrometer with a measuring range of 4000cm -1 -350cm -1 , DTGS detector, resolution 0.5cm -1 , scan times 16 times; (2) The construction of characteristic spectrum by high performance liquid chromatography includes the following steps: Preparation of test solution; The test solution was tested by high performance liquid chromatography, using HSS T3 bonded silica gel as filler, using phosphoric acid aqueous solution and acetonitrile as mobile phases for gradient elution, the gradient elution program included: 0→10min→15min→28min→40min→50min→55min→60min→65min→66min, the volume percentage of acetonitrile in the mobile phase was: 3%→8%→13%→25%→40%→65%→90%→100%→100%→3%, and the HPLC characteristic spectrum of the Yuzhu formula granules was obtained; (3) High performance liquid chromatography (HPLC) is used for content determination, including the following steps: Preparation of test solution; Preparation of dioscin reference solution; The test solution and dioscin reference solution were tested by high performance liquid chromatography using HSS T3 bonded silica gel is used as a filler, and a phosphoric acid-containing aqueous solution and acetonitrile are used as mobile phases for gradient elution. The gradient elution program includes: 0→10min→15min→28min→40min→50min→55min→60min→65min→66min, and the volume percentage of acetonitrile in the mobile phase is: 3%→8%→13%→25%→40%→65%→90%→100%→100%→3%; according to the concentration of dioscin in the reference solution, the peak area of ​​the reference solution in the chromatogram, and the peak area of ​​dioscin in the test solution in the chromatogram, the content of dioscin in the Polygonatum odoratum formula granules is calculated by an external standard method. The test solution preparation method includes: extracting the test sample with a 40-95% methanol aqueous solution to obtain an extract, filtering, taking the liquid, drying, adding a 40-95% methanol aqueous solution to dissolve, and filtering to obtain the test solution.

2. The quality control method of the Polygonatum odoratum formula granules according to claim 1, characterized in that, The infrared fingerprint spectrum of the Polygonatum odoratum formula granules has the following characteristics: at 1021.98 cm -1 There is a strongest peak at 2932.00cm -1 There is a secondary peak at 1636.68cm -1 There is a strong peak at 1419.99cm -1 , and 1374.22cm -1 , 1244.68cm -1 Forming a peak cluster; at 1734.49cm -1 、575.88cm -1 There is characteristic absorption at; and / or, the HPLC characteristic spectrum of the Polygonatum odoratum formula granules has 9 common characteristic peaks, the peak corresponding to the diosgenin reference substance peak is the S peak, and the relative retention time of each characteristic peak and the S peak is within the range of ±10% of the specified value; the specified value is: peak 1 corresponds to 0.12, peak 2 corresponds to 0.13, peak 3 corresponds to 0.17, peak 4 corresponds to 0.18, peak 5 corresponds to 0.23, peak 6 corresponds to 0.35, peak 7 corresponds to 1.00, peak 8 corresponds to 1.08, peak 9 corresponds to 1.24; and / or, the content of diosgenin in each 1g of the Polygonatum odoratum formula granules is 1.14mg~2.13mg.

3. The quality control method of the Polygonatum odoratum formula granules according to claim 1 or 2, characterized in that, In the high performance liquid chromatography method, the detection wavelength is 200-205 nm, the flow rate is 0.8-1.2 mL / min, and the column temperature is 25-35° C.; and / or, the chromatographic column is a Waters Xselect HSS T3 column; and / or, the concentration of phosphoric acid in the aqueous solution containing phosphoric acid is 0.05-0.2%.

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