A tripterygium regelii extract, tripterygium regelii anhydrous swallowing granules, a preparation method and applications thereof

Abstract

The application provides a Radix Ternatae extract, a Radix Ternatae anhydrous swallowing granule, a preparation method and an application, and belongs to the technical field of traditional Chinese medicine preparations. The Radix Ternatae is first soaked in a solvent to form a saturated solution, and then the saturated solution is slowly discharged from the lower liquid outlet and fresh solvent is added from the upper part in the percolation extraction process, so that a concentration difference is formed on the inside and outside of the plant cell wall, which is beneficial to the dissolution of effective components (such as saponins and flavones). The dynamic percolation extraction method can extract the effective components completely due to the concentration difference, and the impurities (such as starch and polysaccharides) which are not dissolved in the solvent are basically not extracted. The Radix Ternatae rhizome contains a large amount of starch, polysaccharides and other components, and the percolation extraction method of the application can effectively reduce the starch, polysaccharides and other impurities in the extract. The paste yield of the Radix Ternatae extract obtained by the percolation extraction method of the application is lower than that of the conventional reflux extraction, but the content of the effective components such as saponins and flavones is higher than that of the conventional reflux extraction.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a Tetrastigma hemsleyanum Diels et Gilg extract, a Tetrastigma hemsleyanum Diels et Gilg anhydrous swallowing granule, and a preparation method and application thereof. BACKGROUND

[0002] Tetrastigma hemsleyanum Diels et Gilg, also known as snake-attached, stone-holding son, stone monkey, stone mouse, and gold-line hanging gourd, is a perennial vine plant of the grape family and is a rare Chinese traditional Chinese medicine plant. Tetrastigma hemsleyanum Diels et Gilg is mainly distributed in Zhejiang, Hunan, Jiangxi, Fujian, Guangdong, Guangxi, and Sichuan.

[0003] Tetrastigma hemsleyanum Diels et Gilg is a Chinese unique plant with important medicinal value and has a long history of use as a heat-clearing and detoxifying drug. Pharmacological studies have shown that Tetrastigma hemsleyanum Diels et Gilg has various pharmacological effects, such as anti-tumor, anti-inflammatory, heat-clearing, analgesic, and anti-oxidation effects. In addition, Tetrastigma hemsleyanum Diels et Gilg also has the effects of reducing blood sugar and blood lipid.

[0004] The chemical composition of Tetrastigma hemsleyanum Diels et Gilg extract is very complex. The chemical components that have been identified include flavones, flavone glycosides, starch, reducing sugars, steroidal compounds, and amino acids. At present, the effective components in Tetrastigma hemsleyanum Diels et Gilg are generally extracted by a reflux extraction method. However, the content of effective components such as saponins and flavones in the Tetrastigma hemsleyanum Diels et Gilg extract obtained by the reflux extraction method needs to be improved. SUMMARY

[0005] The purpose of the present application is to provide a Tetrastigma hemsleyanum Diels et Gilg extract, a Tetrastigma hemsleyanum Diels et Gilg anhydrous swallowing granule, a preparation method, and an application. The content of effective components such as saponins and flavones in the Tetrastigma hemsleyanum Diels et Gilg extract of the present application is significantly higher than that of a conventional reflux extraction method.

[0006] The present application provides an extraction method of Tetrastigma hemsleyanum Diels et Gilg, which comprises the following steps:

[0007] The root and stem coarse powder of Tetrastigma hemsleyanum Diels et Gilg is sequentially soaked and percolated with solvents to obtain a Tetrastigma hemsleyanum Diels et Gilg extract.

[0008] Preferably, the solvent is an ethanol aqueous solution; and the volume content of ethanol in the ethanol aqueous solution is 50% to 80%.

[0009] Preferably, in the soaking process, the dosage of the solvent is 2 to 4 mL per 1 g of the root and stem coarse powder of Tetrastigma hemsleyanum Diels et Gilg; the temperature of the soaking is 40 to 60℃; and the time of the soaking is 5 to 24 hours.

[0010] Preferably, in the process of the percolation extraction, the solvent is used in an amount of 6-10 mL per 1 g of the rootstock coarse powder of Reineckea liukiuensis; the percolation extraction is performed at a speed of 1-1.8 times the volume per hour at the lower end of the outlet; the percolation extraction is performed for 4 hours or more; and the percolation extraction is performed at a temperature of 40-60 DEG C.

[0011] Preferably, after the percolation extraction, the percolation liquid obtained in the percolation extraction is filtered, and the filtered filtrate is sequentially concentrated and dried.

[0012] The application further provides a Reineckea liukiuensis extract obtained by the extraction method.

[0013] The application further provides application of the Reineckea liukiuensis extract in preparation of Reineckea liukiuensis anhydrous swallowing granules.

[0014] The application further provides a Reineckea liukiuensis anhydrous swallowing granule, which comprises the following components in parts by mass:

[0015] The Reineckea liukiuensis extract obtained by the extraction method, potato starch, microcrystalline cellulose, glyceryl behenate, anhydrous silicic acid, erythritol, steviol glycoside, menthol, essence and atomized ethanol are mixed and granulated to obtain flavored wet granules.

[0016] The application further provides a preparation method of the Reineckea liukiuensis anhydrous swallowing granule, which comprises the following steps:

[0017] The Reineckea liukiuensis extract, part of the microcrystalline cellulose and glyceryl behenate are mixed and granulated to obtain a drug core wet granule;

[0018] Potato starch, the remaining microcrystalline cellulose, anhydrous silicic acid, erythritol, steviol glycoside, menthol, essence and atomized ethanol are mixed and granulated to obtain flavored wet granules;

[0019] The drug core wet granule and the flavored wet granule are dried respectively to obtain a drug core granule and a flavored granule respectively;

[0020] The drug core granule and the flavored granule are mixed to obtain the Reineckea liukiuensis anhydrous swallowing granule.

[0021] The application further provides application of the Reineckea liukiuensis extract or the Reineckea liukiuensis anhydrous swallowing granule or the Reineckea liukiuensis anhydrous swallowing granule prepared by the preparation method in preparation of an antiviral drug.

[0022] The application provides a method for extracting Radix Ternatae. The method comprises the following steps: firstly, soaking the Radix Ternatae in a solvent to form a saturated solution; and then, slowly discharging the saturated solution from the lower outlet and adding fresh solvent from the upper part in the percolation extraction process, so that the concentration difference is formed on the inside and outside of the plant cell wall, which is beneficial to the dissolution of effective components (such as saponins and flavonoids). The dynamic percolation extraction method can extract the effective components completely due to the concentration difference, and the impurities (such as starch and polysaccharides) which are not dissolved in the solvent are basically not extracted. The Radix Ternatae contains a large amount of starch, polysaccharides and other components. The percolation extraction method of the application can effectively reduce the starch, polysaccharides and other impurities in the extract. The extract obtained by the percolation extraction method has a lower extract yield (about 1 / 3 or 1 / 4) than the reflux extraction, but the content of effective components such as saponins and flavonoids is higher than that of the conventional reflux extraction (the effective components of the percolation extraction are usually more than twice of the conventional reflux extraction). DETAILED DESCRIPTION

[0023] The application provides a method for extracting Radix Ternatae, which comprises the following steps:

[0024] The Radix Ternatae is soaked and extracted by percolation with a solvent to obtain the Radix Ternatae extract.

[0025] In the application, the Radix Ternatae coarse powder is preferably obtained by crushing the Radix Ternatae; and the particle size of the Radix Ternatae coarse powder is preferably 24-65 mesh. The application does not have special requirements for the source and origin of the Radix Ternatae.

[0026] In the application, the solvent is preferably an ethanol aqueous solution; and the volume content of ethanol in the ethanol aqueous solution is preferably 50%-80%, more preferably 60%-70%.

[0027] In the soaking process, the amount of the solvent is preferably 2-4 mL, more preferably 2-3 mL, based on 1 g of the Radix Ternatae coarse powder, and the liquid surface of the Radix Ternatae coarse powder is immersed in the solvent by 1-2 cm; the soaking temperature is preferably 40-60°C, more preferably 50°C; and the soaking time is preferably 5-24 h, more preferably 10-20 h.

[0028] In the process of the present application, the amount of solvent is preferably 6-10 mL, based on 1 g of the rootstock powder of Radix et Rhizoma Gromwell; the present application uses less solvent (1 / 2 or 1 / 3 of the amount used in conventional reflux extraction); the dripping speed of the lower outlet of the percolation extractor is preferably 1-1.8 times the volume per hour, more preferably 1.5 times the volume per hour; the present application controls the dripping speed of the lower outlet to regulate the speed of the whole percolation extraction; the percolation extraction time is preferably ≥4 h, more preferably 4-5 h; and the percolation extraction temperature is preferably 40-60°C, more preferably 50°C.

[0029] In the present application, the soaking and percolation extraction temperatures are both 40-60°C, which is much lower than the reflux extraction temperature (above 100°C), so that the heat-sensitive effective components are not destroyed and the activity of the effective components can be maintained.

[0030] After the percolation extraction, the present application preferably further comprises filtering the percolation liquid obtained by the percolation extraction, and sequentially concentrating and drying the filtered filtrate.

[0031] In the present application, the filter cloth aperture used in the filtering is preferably 300 mesh; the concentration is preferably reduced-pressure concentration, more preferably reduced-pressure concentration to a relative density of 1.05-1.1 g / ml at 60°C; the vacuum degree of the reduced-pressure concentration is preferably ≤-0.08 MPa; the reduced-pressure concentration temperature is preferably 70-80°C; after the reduced-pressure concentration and before the drying, the present application preferably further comprises re-filtering the concentrated liquid obtained by the reduced-pressure concentration to ensure the solubility of the particles; the filter screen aperture used in the re-filtering is preferably 100 mesh. In the present application, the drying preferably comprises spray drying; the inlet air temperature of the spray drying is preferably 160-180°C; and the outlet air temperature of the spray drying is preferably 70-120°C.

[0032] The extraction method of the present application has an extract yield of 11%-15%.

[0033] The present application also provides the Radix et Rhizoma Gromwell extract obtained by the extraction method described in the above scheme. The Radix et Rhizoma Gromwell extract of the present application contains the following components at the following concentrations: total saponins 2.6%, total flavones 3.5%, and total alkaloids 0.02%.

[0034] The present application also provides the use of the Radix et Rhizoma Gromwell extract described in the above scheme in the preparation of Radix et Rhizoma Gromwell anhydrous swallowing granules.

[0035] The extract rate of the extract of the three-leafed wild raspberry obtained by the extraction method is lower than the extract rate of the extract obtained by the reflux extraction (about 1 / 3 or 1 / 4), but the content of the effective components such as saponins and flavones is significantly higher than that of the extract obtained by the conventional reflux extraction (the effective components of the extract obtained by the percolation extraction are usually more than twice of the extract obtained by the conventional reflux extraction). The daily or per-time dosage of the three-leafed wild raspberry medicinal material is small (only 6-12 g), and the extract obtained by the percolation extraction process has low extract rate and high content of effective components, so that a sufficient amount of auxiliary materials can be conveniently added to prepare the anhydrous swallowing preparation. However, other heat-clearing and detoxifying drugs have large daily or per-time dosage (about 30-80 g), and the extract rate is greatly reduced by the conventional reflux extraction process, so that the anhydrous swallowing preparation cannot be prepared.

[0036] The present application also provides an anhydrous swallowing granule of three-leafed wild raspberry, which comprises the following components in mass parts:

[0037] The extract of the three-leafed wild raspberry obtained by the extraction method described in the above scheme, potato starch 2-10 parts by mass, microcrystalline cellulose 2-20 parts by mass, glyceryl behenate 5-20 parts by mass, anhydrous silicic acid 0.5-5 parts by mass, erythritol 5-20 parts by mass, steviol glycoside 0.005-0.1 parts by mass, menthol 0.2-2 parts by mass, and essence 0.5-5 parts by mass.

[0038] In the present application, the anhydrous swallowing granule of three-leafed wild raspberry is composed of the following components in mass parts: the extract of the three-leafed wild raspberry obtained by the extraction method described in the above scheme 5-20 parts, potato starch 2-10 parts, microcrystalline cellulose 2-20 parts, glyceryl behenate 5-20 parts, anhydrous silicic acid 0.5-5 parts, erythritol 5-20 parts, steviol glycoside 0.005-0.1 parts, menthol 0.2-2 parts, and essence 0.5-5 parts.

[0039] In the present application, the anhydrous swallowing granule of three-leafed wild raspberry comprises the extract of the three-leafed wild raspberry obtained by the extraction method described in the above scheme 5-20 parts by mass, preferably 10 parts by mass.

[0040] In the present application, the anhydrous swallowing granule of three-leafed wild raspberry comprises potato starch 2-10 parts by mass, preferably 7 parts by mass.

[0041] In the present application, the anhydrous swallowing granule of three-leafed wild raspberry comprises microcrystalline cellulose 2-20 parts by mass, preferably 10 parts by mass.

[0042] In the present application, the anhydrous swallowing granule of three-leafed wild raspberry comprises glyceryl behenate 5-20 parts by mass, preferably 10 parts by mass.

[0043] In the present application, the anhydrous swallowing granule of three-leafed wild raspberry comprises anhydrous silicic acid 0.5-5 parts by mass, preferably 2 parts by mass.

[0044] In the present application, the three-leaf Qian waterless swallowing granules include erythritol 5-20 parts by mass, preferably 13 parts.

[0045] In the present application, the three-leaf Qian waterless swallowing granules include steviol glycoside 0.005-0.1 parts by mass, preferably 0.02 parts.

[0046] In the present application, the three-leaf Qian waterless swallowing granules include menthol 0.2-2 parts by mass, preferably 0.5 parts.

[0047] In the present application, the three-leaf Qian waterless swallowing granules include essence 0.5-5 parts by mass, preferably 1.4 parts.

[0048] In an embodiment of the present application, the three-leaf Qian waterless swallowing granules are composed of the following components by mass: three-leaf Qian extract obtained by the extraction method described in the above scheme 10 parts, potato starch 7 parts, microcrystalline cellulose 10 parts, glyceryl behenate 10 parts, anhydrous silicic acid 2 parts, erythritol 13 parts, steviol glycoside 0.02 parts, menthol 0.5 parts, and essence 1.4 parts.

[0049] The waterless swallowing granules of the present application have good taste and melt in the mouth, and are particularly convenient for children with lower swallowing ability and patients with swallowing inconvenience to take.

[0050] In the present application, the microcrystalline cellulose, erythritol, and anhydrous silicic acid are preferably respectively treated by crushing through an 80-mesh screen.

[0051] In the present application, the three-leaf Qian extract obtained by the extraction method described in the above scheme is preferably the undersize component of a 100-mesh screen.

[0052] In the present application, the potato starch, glyceryl behenate, steviol glycoside, menthol, and essence are preferably undersize components of an 80-mesh screen.

[0053] The present application also provides a preparation method of the three-leaf Qian waterless swallowing granules described in the above scheme, comprising the following steps:

[0054] Mixing the three-leaf Qian extract, part of the microcrystalline cellulose, and glyceryl behenate, granulating to obtain a drug core wet granule;

[0055] Mixing potato starch, the remaining microcrystalline cellulose, anhydrous silicic acid, erythritol, steviol glycoside, menthol, essence, and atomized ethanol, granulating to obtain a flavored wet granule;

[0056] Drying the drug core wet granule and the flavored wet granule respectively to obtain a drug core granule and a flavored granule respectively;

[0057] Mixing the drug core granule and the flavored granule to obtain three-leaf Qian waterless swallowing granules.

[0058] The invention mixes the Gortynia japonica extract, part of the microcrystalline cellulose and glyceryl behenate, granulates to obtain the wet granules of medicine core. In the invention, the Gortynia japonica extract, part of the microcrystalline cellulose and glyceryl behenate are preferably mixed in a high-efficiency mixing granulator, the stirring paddle and the cutting paddle are opened, the rotating speed is 1000r / min and 2000r / min respectively, glyceryl behenate is melted by heating, the stirring is continued for 5 minutes, the rotating speed of the stirring paddle and the cutting paddle is adjusted to 500r / min and 1000r / min respectively, the granulation is completed by cooling to below 40℃, the granules are obtained by sizing.

[0059] The invention mixes the potato starch, the rest of the microcrystalline cellulose, anhydrous silicic acid, erythritol, stevioside, menthol, essence and atomized ethanol, granulates to obtain the flavored wet granules; preferably, the invention puts the potato starch, the rest of the microcrystalline cellulose, anhydrous silicic acid, erythritol, stevioside, menthol and essence in a high-efficiency mixing granulator, opens the stirring paddle and the cutting paddle, the rotating speed is 500r / min and 2500r / min respectively, ethanol is added in the form of atomization, granulates, sizes the granules to obtain the flavored wet granules; the amount of ethanol is preferably 10% to 18% of the mass percentage of the flavored wet granules; the granulation time is preferably 5 to 15 minutes; the sizing is preferably through a 14-mesh sieve.

[0060] After obtaining the wet granules of medicine core and the flavored wet granules, the invention dries the wet granules of medicine core and the flavored wet granules respectively to obtain the medicine core granules and the flavored granules respectively.

[0061] In the invention, the drying is preferably boiling drying; the initial air inlet temperature of the boiling drying is preferably 83 to 87℃, the setting of the material is preferably 50℃; when the temperature of the material rises to 43 to 47℃, the air inlet temperature is adjusted to 60℃, the drying time at 60℃ is preferably 30 minutes; the 60-mesh sieve passing rate of the medicine core granules and the flavored granules is preferably ≤40%; the moisture content of the medicine core granules and the flavored granules is preferably ≤3%; after the drying, the granules are preferably sized through a 14-mesh sieve.

[0062] After obtaining the medicine core granules and the flavored granules, the invention mixes the medicine core granules and the flavored granules to obtain the Gortynia japonica waterless swallowing granules. In the invention, the mixing time is preferably 20 to 40 minutes, more preferably 30 minutes.

[0063] The application further provides application of the three-leaf hollyhock extract, the three-leaf hollyhock anhydrous swallowing granule or the three-leaf hollyhock anhydrous swallowing granule prepared by the preparation method in the preparation of an antiviral drug.

[0064] In the application, the virus is preferably an influenza virus; and the influenza virus is preferably an influenza virus H1N1. The influenza virus belongs to the Orthomyxoviridae family, and can be divided into several subtypes (H1-H16, N1-N9) according to the antigenicity of the outer membrane hemagglutinin (H) and neuraminidase (N) proteins. H1N1 is the most common type A influenza virus that infects humans and is the most common influenza virus strain that causes upper respiratory tract infection in clinic. The clinical manifestations include sudden high fever, cough, sore throat, runny nose or nasal congestion, headache, muscle and joint pain, and general malaise.

[0065] In order to further illustrate the application, the three-leaf hollyhock extract, the three-leaf hollyhock anhydrous swallowing granule, the preparation method and the application provided by the application are described in detail below in conjunction with examples, but they should not be understood as limiting the protection scope of the application.

[0066] Example 1

[0067] Sample pretreatment: the three-leaf hollyhock medicinal material - rhizome is crushed into coarse powder for standby; solvent preparation: prepare 70% (volume concentration) ethanol aqueous solution, and the solvent amount is 8 times (V / W) of the three-leaf hollyhock medicinal material;

[0068] Soak and keep warm: the three-leaf hollyhock coarse powder is added into the 70% (volume concentration) ethanol aqueous solution, and the amount of the ethanol aqueous solution is 2 times (V / W) of the amount of the solvent for submerging the medicinal material by 1-2 cm (about 2 times (V / W) of the amount of the solvent) of liquid surface, and the soak and keep warm is performed at 50℃ for 10 hours.

[0069] Permeation and leaching extraction: the remaining about 6 times (V / W) of the solvent is slowly added at the flow rate of the lower end of the liquid outlet to maintain the original soak liquid level, and the permeation and leaching extraction is performed at the flow rate of 1.5 times (V / W) per hour, and the permeation and leaching extraction time is about 4-5 hours or more; the medicinal material and the solvent are kept at 50℃ during the permeation and leaching extraction.

[0070] Filtering and drying: the permeation and leaching liquid is combined and filtered by 300-mesh filter cloth, the filtrate is concentrated under reduced pressure to the relative density of 1.05-1.10 g / ml (60℃), the vacuum degree of the concentration is ≤-0.08 MPa, the temperature is controlled at 70-80℃, and the concentrated liquid is filtered through a 100-mesh screen. The concentrated liquid is dried by a spray drying method, the inlet air temperature is controlled at 160-180℃, and the outlet air temperature is controlled at 70-120℃, to obtain the three-leaf hollyhock extract for standby.

[0071] The three-leaf hollyhock permeation and leaching extract contains total saponins 2.64%, total flavonoids 3.58%, and total alkaloids 0.02%, and the extract yield is 13.53%.

[0072] Example 2

[0073] Sample pretreatment: The rootstock of Radix et Rhizoma Tripterygii was crushed into coarse powder for use; solvent preparation: 70% (V / V) ethanol aqueous solution was prepared, and the solvent amount was 8 times (V / W) of the rootstock of Radix et Rhizoma Tripterygii;

[0074] Soaking and keeping warm: the coarse powder of Radix et Rhizoma Tripterygii was added into 70% (V / V) ethanol aqueous solution, and the amount of the ethanol aqueous solution was 2 times (V / W) of the amount of the solvent, so that the liquid surface was 1-2 cm higher than the rootstock, and the soaking was carried out at 60°C for 12 h;

[0075] Percolation extraction: the remaining about 6 times (V / W) of the solvent was slowly added at the flow rate of the lower liquid outlet, so as to keep the original soaking liquid level, the percolation speed of the lower liquid outlet was 1.2 times of the volume per hour, and the percolation time was about 4-5 h or more; during the percolation, the rootstock and the solvent were kept at 60°C.

[0076] Filtration and drying: the percolation liquid was combined and filtered with 300-mesh filter cloth, the filtrate was concentrated under reduced pressure to the relative density of 1.05-1.10 g / ml (60°C), the vacuum degree of the concentration was ≤-0.08 MPa, the temperature was controlled at 70-80°C, and the concentrated liquid was filtered through a 100-mesh screen. The above concentrated liquid was dried by a spray drying method, the inlet air temperature was controlled at 160-180°C, and the outlet air temperature was controlled at 70-120°C, to obtain Radix et Rhizoma Tripterygii extract for use.

[0077] The percolation extract of Radix et Rhizoma Tripterygii contained total saponins 2.23%, total flavonoids 3.98%, and total alkaloids 0.03%, and the extract yield was 14.86%.

[0078] Example 3

[0079] Sample pretreatment: The rootstock of Radix et Rhizoma Tripterygii was crushed into coarse powder for use; solvent preparation: 70% (V / V) ethanol aqueous solution was prepared, and the solvent amount was 8 times (V / W) of the rootstock of Radix et Rhizoma Tripterygii;

[0080] Soaking and keeping warm: the coarse powder of Radix et Rhizoma Tripterygii was added into 70% (V / V) ethanol aqueous solution, and the amount of the ethanol aqueous solution was 2 times (V / W) of the amount of the solvent, so that the liquid surface was 1-2 cm higher than the rootstock, and the soaking was carried out at 60°C for 12 h;

[0081] Percolation extraction: the remaining about 6 times (V / W) of the solvent was slowly added at the flow rate of the lower liquid outlet, so as to keep the original soaking liquid level, the percolation speed of the lower liquid outlet was 1.2 times of the volume per hour, and the percolation time was about 4-5 h or more; during the percolation, the rootstock and the solvent were kept at 60°C.

[0082] Filtration and drying: the combined percolate was filtered with 300 mesh filter cloth, and the filtrate was concentrated under reduced pressure to a relative density of 1.05-1.10 g / ml (60°C), the vacuum degree of concentration was ≤-0.08 MPa, and the temperature was controlled at 70-80°C, and then filtered through a 100 mesh screen. The above concentrated solution was dried by spray drying, the inlet air temperature was controlled at 160-180°C, and the outlet air temperature was controlled at 70-120°C, to obtain a three-leaf extract, which was used as needed.

[0083] The three-leaf extract contained total saponins 1.74%, total flavonoids 3.26%, and total alkaloids 0.02%, and the extract yield was 12.35%.

[0084] Example 4

[0085] Screening and crushing: take three-leaf extract (three-leaf percolate extract in example 1), potato starch, microcrystalline cellulose, anhydrous silicic acid, erythritol, stevioside, menthol, strawberry flavor, wherein the microcrystalline cellulose, erythritol, and anhydrous silicic acid are respectively crushed to 80 mesh, the three-leaf extract is crushed to 100 mesh, and the other materials are crushed to 80 mesh, for standby;

[0086] Granulation

[0087] Granulation of the drug core part: 10 parts of three-leaf extract (three-leaf percolate extract extracted in example 1), 3 parts of microcrystalline cellulose, and 10 parts of glyceryl behenate were placed in a high-efficiency mixing granulator, the stirring paddle and cutting paddle were opened, the rotating speeds were 1000 and 2000 r / min respectively, heating to 80°C to melt the glyceryl behenate, continue stirring for 5 min, adjust the rotating speeds of the stirring paddle and cutting paddle to 500 and 1000 r / min respectively, open the cooling water to gradually cool to below 40°C, complete the granulation, pass through a 14 mesh screen to granulate, and obtain the drug core wet granules;

[0088] Granulation of the flavoring part: 8 parts of potato starch, 4 parts of microcrystalline cellulose, 2 parts of anhydrous silicic acid, 15 parts of erythritol, 0.02 parts of stevioside, 0.5 parts of menthol, and 1.4 parts of strawberry flavor were placed in a high-efficiency mixing granulator, the stirring paddle and cutting paddle were opened, the rotating speeds were 500 and 2500 r / min respectively, a proper amount of ethanol was added in the form of atomization, granulation was carried out for a certain time, 14 mesh screen was used for granulation, and the flavoring wet granules were obtained.

[0089] Drying: the drug core and flavoring wet granules were respectively put into a boiling drying equipment for drying, the initial inlet air temperature was set to 85±2°C, and the material temperature was set to 50°C. When the material temperature rose to 45±2°C, the inlet air temperature was set to 60°C, and the drying was carried out for 30 min to obtain dry granules, the control indexes of the granules were: 60 mesh passing rate ≤40%, and moisture content ≤3%; the dry granules were granulated through a swing granulator, the screen mesh was 14 mesh, and the drug core granules and flavoring granules were respectively obtained.

[0090] Mixing: the drug core granules and the flavored granules are mixed for 20-40 min to obtain the Smilax sieboldii no-water swallowing granules.

[0091] Taste: fast dissolution in the mouth, fast release of the active ingredients. No sticky teeth, no Smilax sieboldii extract taste, strawberry fragrance and sweetness, good taste, small dosage (daily dosage 5.4 g, 1.8 g / bag), convenient to carry, comprehensive score 10 (full score 10).

[0092] Example 5

[0093] Screening and crushing: Smilax sieboldii extract (Smilax sieboldii percolation extract extracted in Example 1), potato starch, microcrystalline cellulose, anhydrous silicic acid, erythritol, steviol glycoside, menthol, strawberry flavor are taken, the microcrystalline cellulose, erythritol, and anhydrous silicic acid are respectively crushed to pass through an 80-mesh screen, the Smilax sieboldii extract is crushed to pass through a 100-mesh screen, and the other materials are crushed to pass through an 80-mesh screen, for standby use;

[0094] Granulation

[0095] Drug core part granulation: 8 parts of Smilax sieboldii extract (Smilax sieboldii percolation extract extracted in Example 1), 5 parts of microcrystalline cellulose, and 6 parts of glyceryl behenate are placed in a high-efficiency mixing granulator, the stirring paddle and the cutting paddle are turned on, the rotating speeds are 1000 r / min and 2000 r / min respectively, heating to 80℃ to melt the glyceryl behenate, continuing to stir for 5 min, adjusting the rotating speeds of the stirring paddle and the cutting paddle to 500 r / min and 1000 r / min respectively, opening the cooling water to gradually cool to below 40℃, completing the granulation, sieving to pass through a 14-mesh screen to obtain the drug core wet granules;

[0096] Flavored part granulation: 10 parts of potato starch, 2 parts of microcrystalline cellulose, 1 part of anhydrous silicic acid, 13 parts of erythritol, 0.03 parts of steviol glycoside, 0.8 parts of menthol, and 2.2 parts of strawberry flavor are placed in a high-efficiency mixing granulator, the stirring paddle and the cutting paddle are turned on, the rotating speeds are 500 r / min and 2500 r / min respectively, a proper amount of ethanol is added in the form of atomization, granulation is carried out for a certain time, sieving is carried out with a 14-mesh screen to obtain the flavored wet granules.

[0097] Drying: the drug core wet granules and the flavored wet granules are respectively put into a boiling drying equipment for drying, the initial air inlet temperature is set to 85±2℃, and the material temperature is set to 50℃. When the material temperature rises to 45℃±2℃, the air inlet temperature is set to 60℃, and the drying is carried out for 30 min to obtain the dry granules, the control indexes of the granules: 60-mesh passing rate ≤40%, moisture content ≤3%; the dry granules are sieved with a swinging granulator to pass through a 14-mesh screen to respectively obtain the drug core granules and the flavored granules;

[0098] Mixing: the drug core granules and the flavored granules are mixed for 20-40 min to obtain the Smilax sieboldii no-water swallowing granules.

[0099] Taste: fast dissolving in mouth, fast release of active ingredients. No sticky teeth, no taste of three-leaf clover extract, strawberry flavor and sweet taste, good taste, small amount of taking (daily intake 5.4g, 1.8g / bag), convenient to carry, comprehensive score 9 points (full score 10 points).

[0100] Comparative Example 1 reflux extraction

[0101] 1. Three-leaf clover medicinal materials were weighed, 8 times (V / W) of 70% ethanol aqueous solution was added, and reflux extraction was carried out (temperature reached 95℃ or above) for 2h. After the extraction was completed, the hot 300 mesh filter cloth was filtered, and the extract was collected;

[0102] 2. 6 times (V / W) of 70% ethanol aqueous solution was added to the residue, and reflux extraction was carried out for 1h. After the extraction was completed, the hot 300 mesh filter cloth was filtered, and the extract was collected;

[0103] 3. Filtration and drying: the extract was combined and filtered with 300 mesh filter cloth, the filtrate was concentrated to a relative density of 1.05-1.10g / ml (60℃), the vacuum degree of concentration was ≤-0.08MPa, and the temperature was controlled at 70-80℃, and filtered through a 100 mesh screen. The above concentrated liquid was dried by spray drying method, the inlet air temperature was controlled at 160-180℃, and the outlet air temperature was controlled at 70-120℃, to obtain three-leaf clover extract, which was ready for use.

[0104] The three-leaf clover reflux extract contains total saponins 0.46%, total flavonoids 0.85%, and total alkaloids not detected, with an extract yield of 24%-30%.

[0105] Comparative Example 2

[0106] Sample pretreatment: three-leaf clover medicinal materials were crushed into coarse powder, and prepared for use; solvent preparation: 70% ethanol aqueous solution was prepared, and the solvent amount was 8 times (V / W) of three-leaf clover medicinal materials;

[0107] Soaking with heat preservation: three-leaf clover coarse powder was added to 70% ethanol aqueous solution, and the amount of ethanol aqueous solution was 2 times the amount of solvent (V / W) to immerse the medicinal materials 1-2cm high, and soaked at room temperature for 15h;

[0108] Permeation extraction: the remaining about 6 times (V / W) of solvent was slowly added through the flow rate of the lower outlet, so as to maintain the original immersion liquid level. The percolation rate of the lower outlet was 1.5 times the volume / h, and the percolation time was about 4-5h or more;

[0109] Filtration and drying: the combined percolation liquid is filtered with 300 mesh filter cloth, and the filtrate is concentrated under reduced pressure to a relative density of 1.05-1.10 g / ml (60°C), the concentration vacuum degree is ≤-0.08 MPa, and the temperature is controlled at 70-80°C, and then filtered through a 100 mesh screen. The above concentrated liquid is dried by spray drying method, the inlet air temperature is controlled at 160-180°C, and the outlet air temperature is controlled at 70-120°C, to obtain a three-leafed clover extract for standby.

[0110] The percolation extract of three-leafed clover contains total saponins 0.67%, total flavonoids 1.2%, and no total alkaloids, and the extract yield is 9%.

[0111] Comparative Example 3

[0112] Sample pretreatment: the three-leafed clover medicinal material-root stem is crushed into coarse powder for standby; solvent preparation: a 70% (volume concentration) ethanol aqueous solution is prepared, and the solvent amount is 8 times of the three-leafed clover medicinal material;

[0113] Soaking and keeping warm: the three-leafed clover coarse powder is added into the 70% (volume concentration) ethanol aqueous solution, the amount of the ethanol aqueous solution is about 2 times of the amount of the solvent (V / W) to immerse the medicinal material by 1-2 cm high, and the soaking is performed at 50°C for 10 h;

[0114] Percolation extraction: about 6 times of the remaining amount of the solvent is slowly added at a flow rate of the lower end liquid outlet, so as to maintain the original immersion liquid level, the percolation speed of the lower end liquid outlet is 2.5 times of the volume per hour, and the percolation time is about 4-5 h or more; the medicinal material and the solvent are kept at 50°C during the percolation.

[0115] Filtration and drying: the combined percolation liquid is filtered with 300 mesh filter cloth, and the filtrate is concentrated under reduced pressure to a relative density of 1.05-1.10 g / ml (60°C), the concentration vacuum degree is ≤-0.08 MPa, and the temperature is controlled at 70-80°C, and then filtered through a 100 mesh screen. The above concentrated liquid is dried by spray drying method, the inlet air temperature is controlled at 160-180°C, and the outlet air temperature is controlled at 70-120°C, to obtain a three-leafed clover extract for standby.

[0116] The percolation extract of three-leafed clover contains total saponins 1.28%, total flavonoids 2.2%, and no total alkaloids, and the extract yield is 14%.

[0117] Comparative Example 4

[0118] Screening and crushing: the percolation extract of three-leafed clover extracted in Example 1, potato starch, microcrystalline cellulose, anhydrous silicic acid, erythritol, stevioside, menthol, and strawberry essence are taken, the microcrystalline cellulose, erythritol, and anhydrous silicic acid are respectively crushed through an 80 mesh screen, the three-leafed clover extract is crushed through a 100 mesh screen, and the other materials are crushed through an 80 mesh screen for standby;

[0119] Granulation

[0120] Drug core part granulation: 15 parts of Gromwell extract, 5 parts of microcrystalline cellulose and 20 parts of glyceryl behenate were placed in a high-efficiency mixing granulator, the stirring paddle and the cutting paddle were opened, the rotating speeds were 1000 r / min and 2000 r / min respectively, glyceryl behenate was melted by heating to 80°C, and the stirring was continued for 5 min, then the rotating speeds of the stirring paddle and the cutting paddle were adjusted to 500 r / min and 1000 r / min respectively, and the cooling water was opened to gradually cool to below 40°C to complete the granulation, and the granules were sieved through a 14-mesh sieve to obtain the drug core wet granules;

[0121] Flavoring part granulation: 15 parts of potato starch, 5 parts of microcrystalline cellulose, 0.2 parts of anhydrous silicic acid, 6 parts of erythritol, 0.1 part of steviol glycoside, 0.2 part of menthol and 1 part of strawberry flavor were placed in a high-efficiency mixing granulator, the stirring paddle and the cutting paddle were opened, the rotating speeds were 500 r / min and 2500 r / min respectively, and a proper amount of ethanol was added in the form of atomization, and the granulation was carried out for a certain time, then the granules were sieved through a 14-mesh sieve to obtain the flavored wet granules.

[0122] Drying: the drug core wet granules and the flavored wet granules were respectively placed in a boiling drying equipment for drying, the initial air inlet temperature was set to 85±2°C, and the material temperature was set to 50°C. When the material temperature rose to 45±2°C, the air inlet temperature was set to 60°C, and the drying was carried out for 30 min to obtain the dry granules, the control indexes of the granules were as follows: 60-mesh passing rate ≤40%, and moisture content ≤3%; the dry granules were sieved through a swinging granulator with a 14-mesh sieve to obtain the drug core granules and the flavored granules respectively.

[0123] Mixing: the drug core granules and the flavored granules were mixed for 20-40 min to obtain the Gromwell waterless swallowing granules.

[0124] Taste: the granules cannot be quickly dissolved in the mouth, and the active ingredients cannot be quickly released. The granules stick to the teeth after meeting saliva, and the taste is poor, the dosage is large, and the carrying is not convenient. The comprehensive score of taste is 6 points (full score 10 points).

[0125] Comparative Example 5: Granulation after taste inclusion with cyclodextrin

[0126] Gromwell extract inclusion: 20 parts of β-cyclodextrin were taken, 10 times the amount of water was added, and the mixture was stirred at 65°C until the β-cyclodextrin was completely dissolved, then 10 parts of Gromwell extract (Gromwell percolation extract extracted in Example 1) was added, and the stirring was continued for 20 min, and then the mixture was spray dried to obtain Gromwell cyclodextrin mixed powder.

[0127] Granulation: take the above three-leafed green ginseng dextrin mixed powder, 44 parts of microcrystalline cellulose, 20 parts of anhydrous silicic acid, 50 parts of erythritol, 0.06 parts of stevioside, 6 parts of menthol, 20 parts of strawberry flavor, and place them in a high-efficiency mixing granulator. Turn on the stirring paddle and cutting paddle at speeds of 500 and 2500 r / min, respectively. Add an appropriate amount of ethanol in the form of atomization, granulate for a certain period of time, and use a 14-mesh screen to granulate. The flavored wet granules are obtained.

[0128] Drying: dry the drug core and flavored wet granules separately in a boiling drying device. Set the initial air inlet temperature to 85±2℃ and the material temperature to 50℃. When the material temperature rises to 45±2℃, set the air inlet temperature to 60℃. Dry for 30 min to obtain dry granules. The control indicators are: 60-mesh passing rate ≤40%, moisture content ≤3%. Granulate the dry granules in a swing granulator using a 14-mesh screen to obtain drug core granules and flavored granules.

[0129] Mixing: mix the drug core granules and flavored granules for 20-40 min to obtain three-leafed green ginseng anhydrous swallowing granules.

[0130] Taste: cannot be quickly dissolved in the mouth, and the active ingredients cannot be quickly released. The granules are easily hygroscopic and sticky when encountering saliva. There is no three-leafed green ginseng extract flavor, only strawberry flavor and sweetness. The taste is good, the dosage is large, and it is not convenient to carry (daily dosage of 18g, 6g / bag). The comprehensive score is 7 points (out of 10 points).

[0131] Clinical Example 1

[0132] Ten children aged 3-12 years old with influenza were given three-leafed green ginseng anhydrous swallowing granules prepared according to Example 4. The patients had symptoms such as high fever, cough, and runny nose. They were given the granules twice a day, with a dosage of one-third of the adult dosage for children aged 3-6 years old or one-half of the adult dosage for children aged 6-12 years old. The granules could be directly dissolved in the oral cavity, and the taste was good, so the children did not resist taking the medicine. At the same time, the normal body temperature was restored within 2h, and most importantly, the therapeutic effect was stable and did not rebound.

[0133] Test Example 1 In vivo exploration test of three-leafed green ginseng percolation extract against H1N1 influenza virus

[0134] To investigate the anti-viral effect of Tripterygium wilfordii Hook. f. extract on influenza virus (H1N1) infected mice in vivo by the model of mice infected with virus by nose drop, and to provide basic data for its clinical application. According to the body weight, the animals were randomly and equally divided into 6 groups, namely, negative control group, model control group, oseltamivir phosphate capsule group, Lianhuaqingwen capsule group, low-dose Tripterygium wilfordii Hook. f. extract group (0.78 g crude drug / kg), and high-dose Tripterygium wilfordii Hook. f. extract group (1.56 g crude drug / kg). The equivalent of 1 and 2 times of the clinical dose was calculated according to the body surface area. There were 20 animals in each group, half of them were male and half of them were female. After grouping, the animals in each group were modeled, administered, and the death of animals was recorded according to the experimental design. The test results are discussed as follows:

[0135] The test results of animals in each group showed that after viral infection, the animals in the model control group began to show loose hair, weight loss, and death from D7 after infection. By D11, the mortality rate of the model control group was 70% (14 / 20), and the average survival time was 10 days. The mortality rate of the oseltamivir phosphate capsule group was 30% (6 / 20), the death protection rate was 40%, and the average survival time was significantly prolonged to 13 days. The mortality rate of the Lianhuaqingwen capsule group was 65% (13 / 20), the death protection rate was 5%, and the average survival time was 11 days. The mortality rate of the low-dose Tripterygium wilfordii Hook. f. extract group was 50% (10 / 20), the death protection rate was 20%, and the average survival time was 11 days. The mortality rate of the high-dose Tripterygium wilfordii Hook. f. extract group was 30% (6 / 20), the death protection rate was 40%, and the average survival time was significantly prolonged to 12 days, which showed obvious death protection effect on influenza infected mice (Table 1).

[0136] The results of gross observation of the lungs of animals showed that the mice in the model control group showed lung tissue congestion, edema, volume increase, and necrosis. Compared with the negative control group, the body weight of the animals in the model control group was significantly reduced, and the lung index was significantly increased, indicating that the influenza virus infected mouse model was successful. The lung index of the animals in the high-dose Tripterygium wilfordii Hook. f. extract group was significantly lower than that of the model control group, and the lung index inhibition rate was 27.20%, which showed good protection effect on viral pneumonia in infected mice. There was no significant difference in the lung index of the animals in the other groups compared with the model control group (Table 2).

[0137] Table 1 Protection effect of drugs on death of mice caused by influenza virus

[0138]

[0139]

[0140] Note: Compared with the negative control group, * indicates P<0.05, and ** indicates P<0.01; compared with the model control group, # indicates P<0.05, and ## indicates P<0.01.

[0141] Table 2 Inhibition of lung index of drug on influenza virus infected mice

[0142]

[0143] Note: Compared with the negative control group, * means P < 0.05, ** means P < 0.01; compared with the model control group, # means P < 0.05, ## means P < 0.01.

[0144] In summary, the extract of H. trifoliata prepared in Example 1 has a good protective effect on the death of influenza virus infected mice at a dose of 0.78g crude drug / kg (equivalent to 1 times of the clinical dose according to the body surface area conversion method). The extract of H. trifoliata has a significant protective effect on the death of influenza virus infected mice at a dose of 1.56g crude drug / kg (equivalent to 2 times of the dose according to the body surface area conversion method), and has a significant protective effect on the lung.

[0145] Although the above embodiment has made a detailed description of the present application, it is only a part of the embodiments of the present application, not all the embodiments, and other embodiments can be obtained according to the present embodiment without creativity, which all belong to the protection scope of the present application.

Claims

1. A Radix tetrastigme non-aqueous swallowable granule, characterized in that, Components comprising the following parts by mass: Threeleaf milkwort extract 5~20 parts, potato starch 2~10 parts, microcrystalline cellulose 2~20 parts, glyceryl behenate 5~20 parts, anhydrous silicic acid 0.5~5 parts, erythritol 5~20 parts, steviol glycoside 0.005~0.1 parts, menthol 0.2~2 parts and essence 0.5~5 parts; The preparation method of the threeleaf milkwort extract comprises the following steps: The rootstock coarse powder of threeleaf milkwort is sequentially soaked and percolated with solvents, the percolation liquid obtained by percolation is filtered, and the filtered filtrate is sequentially concentrated and dried to obtain the threeleaf milkwort extract. The solvent is an ethanol aqueous solution; the volume content of ethanol in the ethanol aqueous solution is 50%~80%.

2. The Radix tinosporae anhydrous swallowable granules according to claim 1, characterized in that, In the soaking process, the dosage of the solvent is 2~4 mL for 1 g of the threeleaf milkwort rootstock coarse powder; the soaking temperature is 40~60℃; and the soaking time is 5~24 h.

3. The Gynostemma pentaphyllum anhydrous swallow granule according to claim 1, characterized in that, In the percolation process, the dosage of the solvent is 6~10 mL for 1 g of the threeleaf milkwort rootstock coarse powder; the percolation speed of the lower liquid outlet is 1~1.8 times the volume per hour; the percolation time is ≥4 h; and the percolation temperature is 40~60℃.

4. The process for the preparation of the Gynostemma pentaphyllum anhydrous swallowable granules according to any one of claims 1 to 3, characterized by the fact that, The method comprises the following steps: The threeleaf milkwort extract, part of the microcrystalline cellulose and glyceryl behenate are mixed and granulated to obtain a drug core wet granule; Potato starch, the remaining microcrystalline cellulose, anhydrous silicic acid, erythritol, steviol glycoside, menthol, essence and atomized ethanol are mixed and granulated to obtain a flavored wet granule; The drug core wet granule and the flavored wet granule are dried respectively to obtain a drug core granule and a flavored granule respectively; The drug core granule and the flavored granule are mixed to obtain the threeleaf milkwort anhydrous swallowing granule.

5. Use of the threeleaf milkwort anhydrous swallowing granule of any one of claims 1~3 or the threeleaf milkwort anhydrous swallowing granule prepared by the preparation method of claim 4 in the preparation of an anti-H1N1 influenza virus drug.

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