Production process, product and application of callicarpa nudiflora particles

Abstract

The invention provides a production process, a product and application of callicarpa nudiflora granules, and belongs to the technical field of traditional Chinese medicine preparations. The production process of the callicarpa nudiflora comprises the following steps: S1, decocting callicarpa nudiflora with water, filtering, concentrating filtrate to obtain thick paste, and drying the thick paste to obtain dry callicarpa nudiflora extract; s2, mixing the callicarpa nudiflora dry extract obtained in the step S1 with auxiliary materials, granulating, and drying to obtain callicarpa nudiflora granules; wherein in the step S1, the filtration comprises screen filtration and ceramic membrane filtration, and the filtrate concentration comprises membrane concentration and vacuum concentration. Compared with the prior art, the process has the advantages that the energy consumption is effectively reduced and the production cost is reduced on the basis of ensuring that the solid content, the effective component content and the product quality of the product are not influenced.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine preparations, and relates to a production process, product and application of Callicarpa nudiflora Hook.&Arn. granules. Background Art

[0002] Callicarpa nudiflora Hook.&Arn, with the Latin name Callicarpa nudiflora Hook.&Arn, is a shrub to small tree in the family Lamiaceae, reaching a height of up to 7 meters; the old branches are glabrous and the lenticels are obvious, and the young branches, petioles and inflorescences are densely covered with grayish-brown branched pubescence. The leaves of Callicarpa nudiflora Hook.&Arn are used medicinally, with the effects of stopping bleeding and relieving pain, dispelling stasis and reducing swelling. It can treat traumatic bleeding, traumatic swelling and pain, rheumatic swelling and pain, hemoptysis due to pulmonary tuberculosis, gastrointestinal bleeding and other symptoms.

[0003] Chinese Patent Application CN110827995A provides a method for characterizing the chromatogram and mass spectrum fingerprints of the secondary metabolites of the genuine Callicarpa nudiflora Hook.&Arn. The UPLC is used to establish the fingerprint of all components of the genuine Callicarpa nudiflora Hook.&Arn, and the UPLC and DAD / QTOF MS / MS coupling technology is used for on-line rapid component qualitative analysis and compound identification of the fingerprint of all components of the genuine Callicarpa nudiflora Hook.&Arn, forming the best phenotype of chemical substances in the specific natural environment of the genuine Callicarpa nudiflora Hook.&Arn. The beneficial effects of this technology are as follows: the method for the fingerprint of all components of the genuine Callicarpa nudiflora Hook.&Arn is simple to operate, has a large peak capacity, and has good precision, reproducibility and stability. The chromatographic peaks have good separation, short analysis time, high analysis efficiency and sensitivity; the best phenotype of chemical substances in the specific natural environment of the genuine Callicarpa nudiflora Hook.&Arn is formed, which solves the problems such as the chaotic application of the Callicarpa nudiflora Hook.&Arn source in the market and the inability to characterize the genuine medicinal materials.

[0004] Chinese Patent Application CN115177677A provides a preparation process of Callicarpa nudiflora Hook.&Arn extract, including the following steps: (1) putting the Callicarpa nudiflora Hook.&Arn medicinal materials into an extraction tank, extracting twice with water, adding 10.5 - 11.5 times the weight of water for the first extraction for 1.8 - 2.2 hours, and adding 9.5 - 10.5 times the weight of water for the second extraction for 0.9 - 1.1 hours, and combining the extraction solutions; (2) performing vacuum concentration on the above extraction solution, controlling the vacuum degree: 0.03 - 0.04 MPa, temperature: 75 - 85 °C; steam pressure < 0.1 MPa to obtain the concentrated solution; (3) performing spray drying on the above concentrated solution, controlling the inlet air temperature at 120 - 130 °C and the outlet air temperature at 70 - 90 °C to obtain the Callicarpa nudiflora Hook.&Arn extract. Using this method, not only the transfer rate of luteoloside is improved, but also the transfer rate of acteoside is improved, effectively increasing the content of active ingredients in the Callicarpa nudiflora Hook.&Arn extract and making full use of the medicinal value of Callicarpa nudiflora Hook.&Arn.

[0005] Chinese Patent Application CN117839435A provides a ceramic membrane filtration process for the extraction solution of Callicarpa nudiflora. By adding an alkali during the extraction process of Callicarpa nudiflora to adjust the pH of the solution, and then adding an acid to reduce the extraction solution after the extraction is completed, the substances blocking the membrane pores can be complexed by changing the pH of the solution, thereby achieving the purpose of improving the membrane flux and separation efficiency and reducing the separation time; meanwhile, the total content and transmittance of the active ingredients caffeic acid, forsythoside B and acteoside remain unchanged.

[0006] However, the prior art has not yet been able to provide a production process for Callicarpa nudiflora granules that can reduce production energy consumption and costs without affecting product quality. Summary of the Invention

[0007] In view of this, aiming at the problem that the prior art has not yet been able to provide a production process for Callicarpa nudiflora granules that can reduce production energy consumption and costs without affecting product quality, the purpose of the present invention is to provide a production process, product and application of Callicarpa nudiflora granules.

[0008] To achieve the above-mentioned invention purpose, on the one hand, the present invention provides a production process for Callicarpa nudiflora granules, including the following steps:

[0009] S1. Decoct Callicarpa nudiflora with water, filter, concentrate the filtrate to obtain a thick paste, and dry the thick paste to obtain a dry extract of Callicarpa nudiflora; S2. Mix the dry extract of Callicarpa nudiflora obtained in step S1 with auxiliary materials, granulate, and dry to obtain Callicarpa nudiflora granules; wherein, in step S1, the filtration includes screen filtration and ceramic membrane filtration, and the concentration of the filtrate includes membrane concentration and vacuum concentration.

[0010] Preferably, in step S1, the screen filtration uses a filter with a 80-120 mesh screen. More preferably, and as an example of the present invention, in step S1, the screen filtration uses a filter with a 100 mesh screen.

[0011] Preferably, in step S1, the vacuum concentration uses a double-effect energy-saving concentrator. More preferably, and as an example of the present invention, in step S1, the vacuum concentration uses an EJZN-2500 double-effect energy-saving concentrator.

[0012] Preferably, in step S1, the ceramic membrane filtration uses a ceramic membrane filter with a pore size of 5-200 nm.

[0013] More preferably, in step S1, the ceramic membrane filtration uses a ceramic membrane filter with a pore size of 5 nm, 15 nm, 100 nm or 200 nm.

[0014] Still more preferably, and as an example of the present invention, in step S1, the ceramic membrane filtration uses a ceramic membrane filter with a pore size of 100 nm.

[0015] Preferably, in step S1, the material of the ceramic membrane filter used in the ceramic membrane filtration is alumina.

[0016] Preferably, in step S1, the membrane concentration uses a reverse osmosis organic membrane concentrator or a nanofiltration organic membrane concentrator.

[0017] More preferably, and as an example of the present invention, in step S1, the membrane concentration uses a reverse osmosis organic membrane concentrator.

[0018] Preferably, in step S1, the material of the membrane concentrator used in the membrane concentration is polyamide.

[0019] Preferably, in step S1, the concentration of the filtrate includes the following steps: the filtrate is concentrated by membrane to 5%-30% of the original volume, and then concentrated under reduced pressure at 75-85°C to a relative density of 1.30-1.35.

[0020] More preferably, and as an example of the present invention, the concentration of the filtrate includes the following steps: the filtrate is concentrated by membrane to 5%-25% (more preferably 10%-25%) of the original volume, and then concentrated under reduced pressure at 80°C to a relative density of 1.30-1.35.

[0021] Preferably, in step S2, the excipients are selected from one or more of dextrin, starch, lactose, lactose monohydrate, sucrose, mannitol, microcrystalline cellulose, pregelatinized starch, glucose, stevioside, microcrystalline cellulose, polyvinylpyrrolidone, mogroside, and xylitol.

[0022] More preferably, and as an example of the present invention, in step S2, the excipients are dextrin and stevioside.

[0023] Preferably, in step S2, the granulation is carried out using an aqueous ethanol solution.

[0024] More preferably, and as an example of the present invention, in step S2, the granulation is carried out using an aqueous ethanol solution with a weight concentration of 60%.

[0025] Preferably, in step S2, the weight ratio of the dry extract of Callicarpa nudiflora to the Callicarpa nudiflora granules is 4:15.

[0026] On the other hand, the present invention provides a Callicarpa nudiflora granule produced by the above production process.

[0027] On yet another aspect, the present invention provides the application of the above production process in the production of Callicarpa nudiflora granules.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] Based on the existing production process of Callicarpa nudiflora Hook. et Arn. granules, through the process improvement of the filtration and concentration steps, on the premise that there is no obvious difference in the product quality provided by the existing process, the filtration effect is effectively improved, and the energy consumption and cost of the entire production process of Callicarpa nudiflora Hook. et Arn. granules are reduced. Detailed implementation mode

[0030] Terms and declarations of the present invention:

[0031] 1. Articles "a", "an" and "the": Unless otherwise explicitly limited to one (kind) of object, it includes plural objects.

[0032] 2. Numerical range: Unless otherwise explicitly indicated, all ranges or ratios disclosed herein will be understood to include any and all sub-ranges or sub-ratios contained therein. For example, the stated range or ratio of 1 to 30 should be considered to be included between the minimum value of 1 and the maximum value of 30, and any sub-range or sub-ratio, integer, decimal, or sub-range or sub-ratio composed of integers or decimals including the endpoints.

[0033] The following non-limiting examples can enable those of ordinary skill in the art to more comprehensively understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary illustration of the scope claimed by the present invention. Those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and it should also fall within the scope claimed by the present invention.

[0034] The present invention will be further described below by way of specific examples. All kinds of chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are mass contents. Unless otherwise specified, it is understood to be carried out at room temperature.

[0035] Example 1

[0036] An optimized production process of Callicarpa nudiflora Hook. et Arn. granules.

[0037] Take Callicarpa nudiflora and decoct it with water. The way of decocting with water is the same as that recorded in the [Preparation Method] of the dry extract of Callicarpa nudiflora under the item of Callicarpa nudiflora Tablets in Part I of the Chinese Pharmacopoeia 2020 Edition, that is: decoct with water twice, 2 hours for the first time and 1 hour for the second time, and combine the decoction liquids. Filter with a 100-mesh sieve (double-filter of 100-mesh sieve with Φ230×750 DN50), and then filter through a 100-nm ceramic membrane (JSMST-MF100-23-2 ceramic membrane filter with a flow rate of 2000 kg / h). After the filtrate is concentrated to 10% of the original volume by a reverse osmosis organic membrane (JSMST-RO-8040-12 reverse osmosis membrane concentrator with a flow rate of 2000 kg / h), continue to concentrate under reduced pressure (EJZN-2500 double-effect energy-saving concentrator with a flow rate of 2500 kg / h) to a thick paste with a relative density of 1.30 - 1.35 (80°C). The thick paste is vacuum-dried at 75 - 85°C to obtain the dry extract of Callicarpa nudiflora. Crush the dry extract of Callicarpa nudiflora into fine powder and pass through a 60-mesh sieve.

[0038] Take 266.7 g of the fine powder of the dry extract of Callicarpa nudiflora, add 725.3 g of dextrin and 8 g of stevioside, mix evenly, make granules with 60% ethanol, dry and size the granules to obtain 1000 g of Callicarpa nudiflora granules.

[0039] The produced Callicarpa nudiflora granules can be further mixed for 30 minutes, packed in an aluminum-plastic composite film, and externally packaged according to the packaging specifications to obtain the packaged Callicarpa nudiflora granule product.

[0040] Example 2

[0041] Compared with Example 1, the 100-nm ceramic membrane is changed to a 200-nm ceramic membrane, and the rest are the same.

[0042] Example 3

[0043] Compared with Example 1, the 100-nm ceramic membrane is changed to a 15-nm ceramic membrane, and the rest are the same.

[0044] Example 4

[0045] Compared with Example 1, the 100-nm ceramic membrane is changed to a 5-nm ceramic membrane, and the rest are the same.

[0046] Example 5

[0047] Compared with Example 1, the reverse osmosis organic membrane is changed to a nanofiltration organic membrane, and the rest are the same.

[0048] Example 6

[0049] Compared with Example 1, after the filtrate is concentrated to 5% of the original volume by a reverse osmosis organic membrane, continue to concentrate under reduced pressure, and the rest are the same.

[0050] Example 7

[0051] Compared with Example 1, after the filtrate was concentrated to 25% of the original volume by the reverse osmosis organic membrane, it was continuously concentrated under reduced pressure, and the rest was the same.

[0052] Comparative Example 1

[0053] A production process of Callicarpa nudiflora Hook. ex W. T. Aiton granules. Compared with Example 1, ceramic membrane filtration and membrane concentration were omitted, and the rest was the same.

[0054] Take Callicarpa nudiflora Hook. ex W. T. Aiton, decoct it twice with water, 2 hours for the first time and 1 hour for the second time, and combine the decoctions. Filter with a 100-mesh sieve (double-filter with a 100-mesh sieve of Φ230×750 DN50), and concentrate the filtrate under reduced pressure (EJZN-2500 double-effect energy-saving concentrator with 2500 kg / h) to a thick paste with a relative density of 1.30 - 1.35 (80 °C). The thick paste was vacuum dried at 75 - 85 °C to obtain Callicarpa nudiflora Hook. ex W. T. Aiton dry extract. Crush the Callicarpa nudiflora Hook. ex W. T. Aiton dry extract into fine powder and pass through a 60-mesh sieve.

[0055] Take 266.7 g of the fine powder of Callicarpa nudiflora Hook. ex W. T. Aiton dry extract, add appropriate amounts of dextrin and stevioside, mix well, make granules with 60% ethanol, dry and size the granules to obtain 1000 g of Callicarpa nudiflora Hook. ex W. T. Aiton granules.

[0056] Comparative Example 2

[0057] A production process of Callicarpa nudiflora Hook. ex W. T. Aiton granules.

[0058] Prepare Callicarpa nudiflora Hook. ex W. T. Aiton dry extract (Callicarpa nudiflora Hook. ex W. T. Aiton extract) by the method described in Example 3 of Chinese Patent Application CN117839435A. The remaining steps are the same as those in Example 1.

[0059] Comparative Example 3

[0060] A production process of Callicarpa nudiflora Hook. ex W. T. Aiton granules. Compared with Example 1, membrane concentration was omitted, and the rest was the same.

[0061] Take Callicarpa nudiflora Hook. ex W. T. Aiton, decoct it twice with water, 2 hours for the first time and 1 hour for the second time, and combine the decoctions. Filter with a 100-mesh sieve (double-filter with a 100-mesh sieve of Φ230×750 DN50), and then filter through a 100 nm ceramic membrane (JSMST-MF100-23-2 ceramic membrane filter with 2000 kg / h). Concentrate the filtrate under reduced pressure (EJZN-2500 double-effect energy-saving concentrator with 2500 kg / h) to a thick paste with a relative density of 1.30 - 1.35 (80 °C). The thick paste was vacuum dried at 75 - 85 °C to obtain Callicarpa nudiflora Hook. ex W. T. Aiton dry extract. Crush the Callicarpa nudiflora Hook. ex W. T. Aiton dry extract into fine powder and pass through a 60-mesh sieve.

[0062] Take 266.7 g of the fine powder of Callicarpa nudiflora dry extract, add appropriate amounts of dextrin and stevioside, mix well, make granules with 60% ethanol, dry and size the granules to obtain 1000 g of Callicarpa nudiflora granules.

[0063] The produced Callicarpa nudiflora granules can be further mixed for 30 minutes, packed in aluminum-plastic composite film, and externally packaged according to the packaging specifications to obtain the packaged Callicarpa nudiflora granule product.

[0064] Comparative Example 4

[0065] A production process of Callicarpa nudiflora granules. Compared with Example 1, vacuum concentration is omitted, and the rest are the same.

[0066] Take Callicarpa nudiflora, decoct it twice with water, 2 hours for the first time and 1 hour for the second time, and combine the decoction. Filter it through a 100-mesh sieve (a double-filter of 100-mesh sieve with Φ230×750 DN50), and then filter it through a 100-nm ceramic membrane (a JSMST-MF100-23-2 ceramic membrane filter with a flow rate of 2000 kg / h). Concentrate the filtrate through a reverse osmosis organic membrane (a JSMST-RO-8040-12 reverse osmosis membrane concentrator with a flow rate of 2000 kg / h) to a thick paste with a relative density of 1.30 - 1.35 (at 80 °C). Dry the thick paste in vacuum at 75 - 85 °C to obtain the Callicarpa nudiflora dry extract. Crush the Callicarpa nudiflora dry extract into fine powder and sieve it through a 60-mesh sieve.

[0067] Take 266.7 g of the fine powder of Callicarpa nudiflora dry extract, add appropriate amounts of dextrin and stevioside, mix well, make granules with 60% ethanol, dry and size the granules to obtain 1000 g of Callicarpa nudiflora granules.

[0068] The produced Callicarpa nudiflora granules can be further mixed for 30 minutes, packed in aluminum-plastic composite film, and externally packaged according to the packaging specifications to obtain the packaged Callicarpa nudiflora granule product.

[0069] Comparative Example 5

[0070] A production process of Callicarpa nudiflora granules. Compared with Example 1, ceramic membrane filtration is omitted, and the rest are the same.

[0071] Take Callicarpa nudiflora, decoct it twice with water. The first decoction lasts for 2 hours and the second for 1 hour. Combine the decoction liquids. Filter using a 100-mesh sieve (a double-filter with a 100-mesh sieve of Φ230×750 DN50). After the filtrate is concentrated to 10% of the original volume through a reverse osmosis organic membrane (a JSMST-RO-8040-12 reverse osmosis membrane concentrator with a capacity of 2000 kg / h), continue to concentrate it under reduced pressure (an EJZN-2500 double-effect energy-saving concentrator with a capacity of 2500 kg / h) to a thick paste with a relative density of 1.30 - 1.35 (at 80 °C). Vacuum-dry the thick paste at 75 - 85 °C to obtain the dry extract of Callicarpa nudiflora. Crush the dry extract of Callicarpa nudiflora into fine powder and sieve it through a 60-mesh sieve.

[0072] Take 266.7 g of the fine powder of the dry extract of Callicarpa nudiflora, add appropriate amounts of dextrin and stevioside, mix well, make granules with 60% ethanol, dry and size the granules to obtain 1000 g of Callicarpa nudiflora granules.

[0073] The produced Callicarpa nudiflora granules can be further mixed for 30 minutes, packed in an aluminum-plastic composite film, and externally packed according to the packaging specifications to obtain the Callicarpa nudiflora granule product in a packaged form.

[0074] Comparative Example 6

[0075] A production process for Callicarpa nudiflora granules. Compared with Example 1, sieve filtration is omitted, and the rest are the same.

[0076] Take Callicarpa nudiflora, decoct it twice with water. The first decoction lasts for 2 hours and the second for 1 hour. Combine the decoction liquids. Filter using a 100-nm ceramic membrane (a JSMST-MF100-23-2 ceramic membrane filter with a capacity of 2000 kg / h). After the filtrate is concentrated to 10% of the original volume through a reverse osmosis organic membrane (a JSMST-RO-8040-12 reverse osmosis membrane concentrator with a capacity of 2000 kg / h), continue to concentrate it under reduced pressure (an EJZN-2500 double-effect energy-saving concentrator with a capacity of 2500 kg / h) to a thick paste with a relative density of 1.30 - 1.35 (at 80 °C). Vacuum-dry the thick paste at 75 - 85 °C to obtain the dry extract of Callicarpa nudiflora. Crush the dry extract of Callicarpa nudiflora into fine powder and sieve it through a 60-mesh sieve.

[0077] Take 266.7 g of the fine powder of the dry extract of Callicarpa nudiflora, add appropriate amounts of dextrin and stevioside, mix well, make granules with 60% ethanol, dry and size the granules to obtain 1000 g of Callicarpa nudiflora granules.

[0078] The produced Callicarpa nudiflora granules can be further mixed for 30 minutes, packed in an aluminum-plastic composite film, and externally packed according to the packaging specifications to obtain the Callicarpa nudiflora granule product in a packaged form.

[0079] In Examples 1-7 and Comparative Examples 1-6, the material of the ceramic membrane filter used is alumina, and the material of the organic membrane concentrator used is polyamide.

[0080] Comparative Example 7

[0081] A production process of Callicarpa nudiflora Hook. var. hancei (Benth.) Maxim. granules. Compared with Example 1, the ceramic membrane (alumina) was changed to a ceramic membrane made of silicon carbide, and the rest were the same.

[0082] Comparative Example 8

[0083] A production process of Callicarpa nudiflora Hook. var. hancei (Benth.) Maxim. granules. Compared with Example 1, the organic membrane (polyamide) was changed to an organic membrane made of polyvinylidene fluoride, and the rest were the same.

[0084] Effect Example 1

[0085] Energy consumption cost accounting.

[0086] Using the technical solutions of Examples 1-7 and Comparative Examples 1-8 to produce the same amount (10 kg) of Callicarpa nudiflora Hook. var. hancei (Benth.) Maxim. granules, the energy consumption costs and ratios are shown in Table 1.

[0087] Table 1

[0088]

[0089] It is particularly noteworthy that in Comparative Example 5, concentration was carried out by organic membrane concentration plus or minus pressure concentration, but ceramic membrane filtration was not used. Since organic membrane concentration requires the turbidity of the liquid to be concentrated to be low within a certain range, and the turbidity of the liquid to be concentrated cannot reach the requirements of organic membrane concentration when ceramic membrane filtration is not used, the process of organic membrane concentration cannot proceed normally, and the process cannot be carried out continuously.

[0090] Effect Example 2

[0091] Characterization method of Callicarpa nudiflora Hook. var. hancei (Benth.) Maxim. granules

[0092] 1. Qualitative characterization of product components.

[0093] 1.1. Qualitatively analyze the chemical components in Callicarpa nudiflora Hook. var. hancei (Benth.) Maxim. granules quickly and efficiently by liquid chromatography-mass spectrometry technology.

[0094] Instruments and reagents

[0095] Waters Acquity UPLC tandem G2-XS QTOF; Callicarpa nudiflora Hook. var. hancei (Benth.) Maxim. granules (provided by Jiangxi Puzheng Pharmaceutical Co., Ltd.).

[0096] Reference substances: forsythoside B (1), acteoside (2), verbascoside (3), 2'-acetylforsythoside B (4), 2'-acetylverbascoside (5), Alyssonoside (6), 2'-acetylacteoside (7), tubuloside E (8), caffeic acid (9), ferulic acid (10), acacetin-7-glucurono(1→2)-glucuronide (11),

[0097] chrysoeriol-7-glucurono-(1→2)-glucuronide (12), maluside (13), luteolin-7-O-[β-glucuronosyl(1→2)-[β-glucuronide] (14) were all isolated in this experiment with a content > 98%; ursolic acid (15), esculetin (16), luteoloside (17), luteolin (18), apigenin (19) were purchased from Nanjing Kangweisheng Biotechnology Co., Ltd. with a content ≥ 98%; protocatechuic acid (20), protocatechualdehyde (21), rutin (22), quercetin (23), isorhamnetin (24), catalpol (25), oleanolic acid (26) were purchased from the National Institute for the Control of Pharmaceutical and Biological Products.

[0098] Chromatographic conditions

[0099] The mass spectrometry detection conditions are shown in Table 2 (ESI-, resolution detection mode):

[0100] Table 2

[0101]

[0102] Chromatographic column: 1.8μm Ultimate XB-C18 column (100×2.1mm i.d.).

[0103] Column temperature: 30°C.

[0104] Mobile phase: A: H2O; B: CH3CN.

[0105] Flow rate: 0.25 mL / min.

[0106] Injection volume: 5 μL.

[0107] The gradient elution conditions are shown in Table 3:

[0108] Table 3

[0109]

[0110]

[0111] Import the UPLC / QTof-MS / MS data acquisition into the chemical composition library of Callicarpa L. (self-made) and UNIFI automatic data processing. The detected compounds are given the matching order again according to the information of adducts, the intensity ratio of isotope peaks, and the mass deviation ratio of isotope peaks. For the finally obtained compounds, the possible secondary fragmentation pathways are confirmed by automated secondary fragmentation, and the confidence level of confirmation is determined. Multiple factors such as accurate molecular weight + fragment ions + isotope distribution are used to jointly confirm the MassFragment secondary fragment structure of the compound composition, and the online database is searched to automatically generate a compound identification report. Conduct component detection on the Callicarpa nudiflora particles produced in Examples 1-7. The results are shown in Table 4 (√ indicates detected, × indicates not detected):

[0112] Table 4

[0113]

[0114]

[0115]

[0116]

[0117] Conduct component detection on the Callicarpa nudiflora particles produced in Comparative Examples 1-8. The results are shown in Table 5 (√ indicates detected, × indicates not detected):

[0118] Table 5

[0119]

[0120]

[0121]

[0122]

[0123] 2. Determination of multi-component content

[0124] 2.1. Determination conditions and analysis methods

[0125] Chromatographic conditions and system suitability: Use octadecylsilane-bonded silica gel as the filler; use methanol as mobile phase A, acetonitrile as mobile phase B, and 0.1% phosphoric acid as mobile phase C, and perform gradient elution according to the regulations in Table 6; the detection wavelength is 332 nm; the flow rate is 1.5 mL / min, and the column temperature is 30 °C.

[0126] Table 6

[0127] Time (min) Mobile phase A (%) Mobile phase B (%) Mobile phase C (%) 0 3 7 90 35 6 14 80 49 10 26 64 52 3 7 90 55 3 7 90

[0128] Preparation of reference substance solution: Weigh an appropriate amount of reference substances of caffeic acid, forsythoside B, acteoside, and isoacteoside accurately, dissolve them in 50% methanol to prepare a mixed solution containing 50 μg of caffeic acid, 50 μg of forsythoside B, 50 μg of acteoside, and 50 μg of isoacteoside per 1 mL, and you will get it.

[0129] Preparation of test solution: Take an appropriate amount of this product, grind it finely, weigh about 0.7 g accurately, place it in a stoppered conical flask, accurately add 25 mL of 50% methanol, stopper it, weigh it, ultrasonically treat it (power 250 W, frequency 33 kHz) for 30 minutes, let it cool, weigh it again, make up the lost weight with 50% methanol, shake well, filter, and take the subsequent filtrate, and you will get it.

[0130] Determination method: Accurately pipette 10 μL of the reference substance solution and the test solution respectively, inject them into the liquid chromatograph for determination, and you will get it.

[0131] Using the above chromatographic quantitative method, detect the contents of caffeic acid, forsythoside B, acteoside, and isoacteoside in the Callicarpa nudiflora Hook. & Arn. granules provided in Examples 1 - 7 and Comparative Examples 1 - 8, measure 5 times repeatedly, and take the average value. The results are shown in Table 7:

[0132] Table 7

[0133]

[0134]

[0135] The callicarpa nudiflora particles produced by the production processes provided in Examples 1-7 have the contents of caffeic acid, forsythoside B, acteoside, and actein in the ranges of 0.21-0.23 mg / g, 1.34-1.42 mg / g, 10.29-10.41 mg / g, and 3.49-3.55 mg / g, respectively. It should be particularly noted that, compared with each example, Comparative Example 1 did not adopt ceramic membrane filtration and membrane concentration, and the contents of caffeic acid, forsythoside B, acteoside, and actein in the callicarpa nudiflora particles produced were 0.21 mg / g, 1.34 mg / g, 10.23 mg / g, and 3.48 mg / g, respectively. The content levels of caffeic acid and forsythoside B are comparable to those of each example, while the contents of acteoside and actein are lower than those of each example. Moreover, the production energy consumption cost of Comparative Example 1 is significantly higher than that of each example. Therefore, each example has obvious technological progress compared with Comparative Example 1. Comparative Example 2 prepared callicarpa nudiflora particles using the prior art. In the callicarpa nudiflora particles produced by the production process provided in Comparative Example 2, the contents of caffeic acid, forsythoside B, acteoside, and actein are 0.23 mg / g, 1.26 mg / g, 10.13 mg / g, and 3.55 mg / g, respectively, among which the contents of forsythoside B and acteoside are lower than those of each example, and the contents of caffeic acid and actein are comparable to those of each example. Moreover, the relative value of the energy consumption cost of Comparative Example 2 is 1.53, and the relative values of the energy consumption costs of Examples 1-7 are 0.57-0.77. It can be calculated that the energy consumption cost of Comparative Example 2 is 1.99-2.68 times that of Examples 1-7. It can be seen that each example has obvious technological progress compared with Comparative Example 2.

[0136] In summary, in combination with the energy consumption cost and the determination results of the contents of multiple components, the callicarpa nudiflora particles prepared by the preparation processes provided in each example of the present invention can, on the basis of maintaining the contents of caffeic acid, forsythoside B, acteoside, and actein within a certain range, significantly reduce the production energy consumption cost by improving the filtration and concentration process steps, and thus overall greatly reduce the process cost.

[0137] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the protection scope of the present invention. Any simple modification or equivalent replacement made by those of ordinary skill in the art to the technical solution of the present invention does not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A production process of Callicarpa nudiflora granules, characterized in that: The following steps are involved: S1. Decoction of Callicarpa nudiflora with water, filtering, concentrating the filtrate to obtain a thick paste, and drying the thick paste to obtain Callicarpa nudiflora dry extract; S2, mixing the dry extract of Callicarpa nudiflora obtained in step S1 with auxiliary materials, granulating, and drying to obtain Callicarpa nudiflora granules; Wherein, in step S1, the filtration includes screen filtration and ceramic membrane filtration, and the concentrated filtrate includes membrane concentration and reduced pressure concentration; in step S1, the ceramic membrane filtration uses a ceramic membrane filter with a pore size of 5-200nm, and the membrane concentration uses a reverse osmosis organic membrane concentrator or a nanofiltration organic membrane concentrator.

2. The production process according to claim 1, characterized in that: In step S1, the ceramic membrane filtration uses a ceramic membrane filter with a pore size of 100 nm, and the membrane concentration uses a reverse osmosis organic membrane concentrator.

3. The production process according to claim 1, characterized in that: In step S1, the concentrated filtrate comprises the following steps: the filtrate is concentrated to 5%-30% of the original volume through a membrane, and then concentrated under reduced pressure at 75-85°C to a relative density of 1.30-1.

35.

4. The production process according to claim 3, characterized in that: In step S1, the filtrate is concentrated to 5%-25% of the original volume through a membrane, and then concentrated under reduced pressure at 80°C to a relative density of 1.30-1.

35.

5. The production process according to claim 1, characterized in that: In step S2, the auxiliary material is selected from one or more of dextrin, starch, lactose, lactose monohydrate, sucrose, mannitol, microcrystalline cellulose, pregelatinized starch, glucose, stevioside, microcrystalline cellulose, povidone, mogroside and xylitol.

6. The production process according to claim 5, characterized in that: In step S2, the auxiliary material is a mixture of stevia and dextrin.

7. The production process according to claim 1, characterized in that: In step S2, the granulation is performed using an ethanol aqueous solution.

8. The production process according to claim 1, characterized in that: In step S2, the weight ratio of the Callicarpa nudiflora dry extract to the Callicarpa nudiflora granules is 4:

15.

9. A Callicarpa nudiflora granule, characterized in that: The product is produced by the production process described in any one of claims 1 to 8.

10. Application of the production process described in any one of claims 1 to 8 in the production of Callicarpa nudiflora granules.

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