Preparation method, product and application of antiviral oral liquid

Abstract

The application provides a preparation method, product and application of an antiviral oral liquid, and relates to the technical field of antiviral materials. The preparation method is as follows: after rhizoma phragmitis, rhizoma anemarrhenae, isatis root and rhizoma alocasia are mixed and pretreated, microwave-assisted water extraction is carried out to obtain extract 1; after radix curcumae and pachouli are mixed, supercritical CO2 extraction is carried out to obtain extract A, the extract A is wrapped with a composite wrapping agent to obtain extract 2; radix forsythiae and radix rehmanniae are subjected to multi-gradient alcohol extraction to obtain extract 3; all the extracts and gypsum are mixed, a stabilizer is added, the pH is adjusted to 5.0-5.5, filtration is carried out, water is added to constant volume, sterilization is carried out, and the antiviral oral liquid is obtained. The antiviral oral liquid prepared by the application can significantly prevent and treat viral cold and improve the immunity of patients, has high stability and good taste.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of antiviral materials, in particular to a preparation method, product and application of an antiviral oral liquid. BACKGROUND

[0002] The antiviral oral liquid is a safe and effective, reasonably priced, and convenient to use medicine, is a commonly used traditional Chinese medicine in clinical practice, and has a significant treatment effect, small side effects, and is convenient to use, so that patients in need can use it with confidence. The antiviral oral liquid is an antiviral drug, which is a non-prescription drug for internal medicine colds, mainly composed of radix isatidis, gypsium, rhizoma phrgmitis, radix rehmanniae, radix curcumae, radix anemarrhenae, rhizoma acori graminei, pachysandra terminalis, forsythia, gypsium, and the rest are plant medicines; the auxiliary materials are sucrose, honey, sodium cyclamate, orange essence, and other effective components of a composite preparation, which has the effects of clearing heat, removing dampness, cooling blood, and detoxifying, contains a variety of antiviral components, can effectively inhibit viruses, is quickly absorbed, and has a rapid effect, and is the first choice for treating and preventing colds, upper respiratory tract infections, mumps, hand-foot-mouth disease, and other viral infections.

[0003] The existing antiviral oral liquid is generally prepared by decocting the above nine medicinal materials with water twice, the first time for 3 hours, collecting the volatile oil, and using hydroxypropyl betacyclodextrin to enclose, or the first time for 1.5 hours (collecting the volatile oil and volatile oil emulsion at the same time); the second time for 1 hour and 20 minutes, filtering, combining the filtrate, concentrating to an appropriate amount, adding 85% or more ethanol to make the alcohol content 70%, standing, filtering, recovering the ethanol of the filtrate and concentrating to an appropriate amount, adding the volatile oil inclusion compound and an appropriate amount of honey, sucrose, orange essence, sodium cyclamate, or adding the volatile oil, volatile oil emulsion, and an appropriate amount of honey, sucrose; then cooling to below 30℃, adjusting the pH value with 10% sodium hydroxide solution, filtering; adding water to 1000mL, mixing, filtering, filling and sealing, sterilizing, and obtaining.

[0004] The preparation method has disadvantages: on the one hand, the taste of traditional antiviral oral liquid is poor, because the antiviral oral liquid contains concentrated liquid of medicines such as radix pellitae, radix rehmanniae, radix curcumae, and rhizoma anemarrhenae, so that the antiviral oral liquid tastes bitter, and the bitterness will exist in the mouth for a period of time after the user takes the antiviral oral liquid. For example, Chinese patent application CN108159348A discloses a sugar-free antiviral oral liquid and a preparation method thereof, in order to solve the problems of outdated antiviral oral liquid process, poor antiviral oral liquid efficacy caused by conventional concentration method, an sugar-free antiviral oral liquid and a preparation method thereof are provided, which comprises main materials: radix isatidis, radix curcumae, radix forsythiae, gypseum, rhizoma anemarrhenae, radix pellitae, rhizoma acori, radix rehmanniae, and ageratum houstoni, and auxiliary materials are stevioside, sodium benzoate, and purified water, the oral liquid is extracted under vacuum condition and at a lower temperature, then purified water is added to complete the preparation, the effective components of the total decoction pieces are lost very little, and the efficacy of the finished product is greatly improved. However, the taste is very bitter, and some patients cannot accept it.

[0005] On the other hand, according to literature reports, pharmacodynamic experiments prove that broadleaf chrysanthemum alcohol (baqiu li alcohol) in the antiviral oral liquid has good antipyretic and antibacterial effects, but because the volatile oil has small water solubility and is easy to volatilize, when the volatile oil is added to the filtrate, the volatile oil will be lost during the process of filling and sterilization, and with the extension of storage time, the volatile oil component in the finished product will also be gradually lost. Through stability investigation, the stability of the finished product is poor, which may affect the original efficacy of the product; and the volatile oil has a strong irritating taste, which affects the taste and is difficult for children to accept. Chinese patent application CN118557685A discloses an antiviral oral liquid and a preparation method thereof, which comprises the following steps in sequence: decocting raw medicinal materials with water, combining the filtrates, concentrating, and adding auxiliary materials; then adjusting the pH value during the cooling process of the medicinal liquid, filtering to be clear, adding water to constant volume, sterilizing, and obtaining the product; the specific steps of adjusting the pH value during the cooling process of the medicinal liquid are as follows: when the medicinal liquid is cooled to 50-60℃, the pH value of the medicinal liquid is adjusted to 4.0-5.0 by using 5.0-7.5 mol / L sodium hydroxide solution; when the medicinal liquid is continuously cooled to 20-50℃, the pH value of the medicinal liquid is adjusted to 5.5-6.0 by using 1.0-5.0 mol / L sodium hydroxide solution. By using the above technical scheme, the antiviral oral liquid prepared can effectively maintain the stability of solution clarity, pH value, and forsythoside content. Although the stability is improved, the taste problem is not considered.

[0006] Therefore, it is the research focus of researchers in the field to develop a preparation method of antiviral oral liquid, improve its stability, taste, and effect. SUMMARY

[0007] The present application aims at the above-mentioned problems, and provides a preparation method of an antiviral oral liquid, which has high stability and good taste, can prevent and treat viral cold, and can improve the immunity of patients by optimizing the auxiliary materials and the preparation method.

[0008] To achieve the above-mentioned purposes, the technical solutions adopted by the present application are as follows:

[0009] In a first aspect, the present application provides a preparation method of an antiviral oral liquid, comprising the following steps:

[0010] S1: mixing rhizoma phragmitis, rhizoma anemarrhenae, radix isatidis and rhizoma alocasia, pre-treating, and then microwave-assisted water extraction to obtain an extract 1;

[0011] S2: mixing radix anemarrhenae and agastache rugosa, and then supercritical CO2 extraction to obtain an extract A, and then using a composite inclusion agent to include the extract A to obtain an extract 2;

[0012] S3: multi-gradient alcohol extraction of forsythia suspense and radix rehmanniae to obtain an extract 3;

[0013] S4: mixing the extract 1, the extract 2, the extract 3 and gypsum, adding a stabilizer, and drying to obtain a composition;

[0014] S5: adjusting the pH of the composition to 5.0-5.5, filtering, adding water to constant volume, and sterilizing to obtain the antiviral oral liquid;

[0015] The raw materials of the antiviral oral liquid are composed of the following components in parts by weight: radix isatidis 105-115 parts, gypsum 41-49 parts, rhizoma phragmitis 66-75 parts, radix rehmanniae 37-44 parts, radix anemarrhenae 31-44 parts, radix isatidis 35-44 parts, rhizoma alocasia 31-34 parts, agastache rugosa 33-38 parts, forsythia suspense 53-59 parts, a composite inclusion agent 5-25 parts, and a stabilizer 40-60 parts.

[0016] Preferably, in step S1, the rhizoma phragmitis, the rhizoma anemarrhenae, the radix isatidis and the rhizoma alocasia need to be crushed and passed through a 40-50 mesh sieve;

[0017] Preferably, in step S1, the pre-treatment step is: mixing the rhizoma phragmitis, the rhizoma anemarrhenae, the radix isatidis and the rhizoma alocasia with water, adjusting the pH to 4.0-6.0, adding a composite enzyme, mixing at 30-45°C for 0.5-1h, and inactivating;

[0018] Preferably, the ratio of the total mass of the rhizoma phragmitis, the rhizoma anemarrhenae, the radix isatidis and the rhizoma alocasia to water is 1g:5-8L; further preferably, the ratio of the total mass of the rhizoma phragmitis, the rhizoma anemarrhenae, the radix isatidis and the rhizoma alocasia to water is 1g:6L.

[0019] Preferably, the composite enzyme is a mixture of cellulase, pectinase and protease.

[0020] Preferably, the mass ratio of the cellulase, pectinase and protease is 1-4:1-2:1-3; further preferably, the mass ratio of the cellulase, pectinase and protease is 3:1:2.

[0021] Preferably, the mass of the complex enzyme is 0.1%-1.5% of the mass of the raw material. Further preferably, the mass of the complex enzyme is 0.5% of the mass of the raw material.

[0022] Preferably, the enzyme activity of the cellulase is 50000-100000 U / g; the enzyme activity of the pectinase is 80000-100000 U / g; and the enzyme activity of the protease is 80000-100000 U / g.

[0023] Preferably, the protease is trypsin.

[0024] Preferably, in step S1, the temperature of the microwave-assisted water extraction is 40-60℃, the microwave power is 300-600W, the time is 5-25min, and the number of times is 1-3.

[0025] Further preferably, in step S1, the temperature of the microwave-assisted water extraction is 45℃, the microwave power is 450W, the time is 15min, and the number of times is 3.

[0026] Preferably, in step S2, the Yujin and Guanghuoxiang need to be crushed and passed through a 20-40 mesh sieve.

[0027] Preferably, in step S2, the parameters of the supercritical CO2 extraction are: the extraction pressure is 40-50MPa, the extraction temperature is 40-50℃, the CO2 flow rate is 22-28L / h, and the separation pressure is 5-10MPa.

[0028] Further preferably, in step S2, the parameters of the supercritical CO2 extraction are: the extraction pressure is 45MPa, the extraction temperature is 40℃, the CO2 flow rate is 25L / h, and the separation pressure is 8MPa.

[0029] Preferably, in step S2, the complex inclusion agent comprises trehalose and silicon dioxide.

[0030] Preferably, in step S2, the mass ratio of the complex inclusion agent to the extract A is 1:4-8. Further preferably, in step S2, the mass ratio of the complex inclusion agent to the extract A is 1:5.

[0031] Preferably, the mass ratio of the trehalose to the silicon dioxide is 5-10:1. Further preferably, the mass ratio of the trehalose to the silicon dioxide is 6:1.

[0032] Preferably, the operation of the inclusion is: dissolving trehalose in water, the mass fraction of trehalose is 20%-30%, adding the extract obtained in step S2 homogenously emulsified, the rate is 8000-12000 rpm, the time is 5-10 min, then adding silicon dioxide, drying.

[0033] Further preferably, the operation of the inclusion is: dissolving trehalose in water, the mass fraction of trehalose is 25%, adding the extract obtained in step S2 homogenously emulsified, the rate is 10000 rpm, the time is 5 min, then adding silicon dioxide, drying.

[0034] Preferably, in step S3, the operation of the multi-gradient alcohol extraction is:

[0035] After the forsythia and rehmannia glutinosa are crushed, 30wt%-45wt% ethanol solution is added, and extraction is carried out at 30-50℃ for 0.5-1h;

[0036] The concentration of the ethanol solution is adjusted to 50wt%-65wt%, and extraction is carried out at 30-50℃ for 0.5-1h;

[0037] The concentration of the ethanol solution is adjusted to 70wt%-85wt%, and extraction is carried out at 70-75℃ for 0.5-1h;

[0038] The extract is combined.

[0039] Further preferably, in step S3, the operation of the multi-gradient alcohol extraction is:

[0040] After the forsythia and rehmannia glutinosa are crushed, 35wt% ethanol solution is added, and extraction is carried out at 45℃ for 1h;

[0041] The concentration of the ethanol solution is adjusted to 60wt%, and extraction is carried out at 50℃ for 1h;

[0042] The concentration of the ethanol solution is adjusted to 80wt%, and extraction is carried out at 70℃ for 1h;

[0043] The extract is combined.

[0044] Preferably, in step S4, the gypsum needs to be crushed and passed through a 20-40 mesh sieve.

[0045] Preferably, in step S4, the stabilizer is a mixture of astragalus polysaccharide, green apple extract and vitamin E.

[0046] Preferably, the mass ratio of the astragalus polysaccharide, green apple extract and vitamin E is 0.1-1:5-10:2-4; further preferably, the mass ratio of the astragalus polysaccharide, green apple extract and vitamin E is 1:8:2.

[0047] In a second aspect, the present application provides an antiviral oral liquid prepared by the preparation method.

[0048] In a third aspect, the present application provides an application of the antiviral oral liquid prepared by the preparation method in the preparation of a medicine for preventing or treating viral cold.

[0049] Compared with the prior art, the present application has the following beneficial effects:

[0050] 1. The present application optimizes the preparation method of the antiviral oral liquid, extracts radix rhizomatis, rhizoma anemarrhenae, radix isatidis and rhizoma alpiniae officinarum by a microwave-assisted water extraction method, extracts radix paeoniae and radix rehmanniae by a multi-gradient alcohol extraction method, and encapsulates the extracts of radix bupleuri and herba agastachis by a low-temperature supercritical CO2 extraction method.

[0051] 2. The present application optimizes the encapsulation components to trehalose and silicon dioxide, and adds stabilizers, i.e., astragalus polysaccharide, apple extract and vitamin E, so that the stability of the prepared antiviral oral liquid is significantly improved.

[0052] 3. The present application adds apple extract and trehalose, which significantly improves the stability of the prepared antiviral oral liquid and significantly improves the taste of the prepared antiviral oral liquid, so that people with higher requirements for the taste can accept it.

[0053] 4. The antiviral oral liquid prepared by the present application can significantly prevent and treat viral cold and improve the immunity of patients. DETAILED DESCRIPTION

[0054] In order to make the technical means, creative features, purposes and effects of the present application easy to understand, the present application is further illustrated by combining specific embodiments. However, the following embodiments are only preferred embodiments of the present application, not all. Based on the embodiments in the embodiments, other embodiments obtained by those skilled in the art without creative labor are within the protection scope of the present application. It is worth noting that the raw materials used in the present application are ordinary commercially available products, and their sources are not specifically limited. The technologies and scientific terms used in the embodiments have the meanings commonly understood by those skilled in the art to which the present application belongs.

[0055] The enzyme activity of the cellulase is 50000-100000 U / g;

[0056] The enzyme activity of the pectinase is 80000-100000 U / g;

[0057] The enzyme activity of the trypsin is 80000-100000 U / g;

[0058] The green apple extract is purchased from Baoji Liupan Yun Biological Science and Technology Co., Ltd.

[0059] Example 1

[0060] An antiviral oral liquid, the raw materials are composed of the following components by weight: 110 parts of radix isatidis, 46 parts of gypsum, 72 parts of rhizoma phragmitis, 40 parts of radix rehmanniae, 36 parts of radix curcumae, 42 parts of radix anemarrhenae, 32 parts of rhizoma alocasia, 36 parts of ageratum houstonianum, 56 parts of forsythia suspensa, 20 parts of composite inclusion agent, 50 parts of stabilizer;

[0061] The preparation method is as follows:

[0062] S1: Rhizoma phragmitis, radix anemarrhenae, radix isatidis and rhizoma alocasia need to be mixed and crushed, then passed through a 40-mesh sieve, then mixed with water at a solid-liquid ratio of 1 g:6 L, adjust the pH to 5.0, add 0.5% of the composite enzyme based on the total mass of rhizoma phragmitis, radix anemarrhenae, radix isatidis and rhizoma alocasia, mix at 40℃ for 0.5h, and inactivate; the composite enzyme is a mixture of cellulase, pectinase and trypsin, and the mass ratio of cellulase, pectinase and trypsin is 3:1:2; microwave-assisted water extraction at 45℃ for 15min, repeat 3 times, combine the extracts, and obtain extract 1;

[0063] S2: Mix radix curcumae and ageratum houstonianum, crush, pass through a 20-mesh sieve, and extract by supercritical CO2, parameters: extraction pressure 45MPa, extraction temperature 40℃, CO2 flow rate 25L / h, separation pressure 8MPa; obtain extract A;

[0064] The extract A is packaged with a composite inclusion agent, the specific operation is: dissolve trehalose in water, the mass fraction of trehalose is 25%, homogenize and emulsify the extract A obtained in step S2, the speed is 10000 rpm, the time is 5min, then add silicon dioxide, and dry.

[0065] The mass ratio of the composite inclusion agent to the mass of extract A is 1:5, and obtain extract 2;

[0066] The composite inclusion agent contains trehalose and silicon dioxide, and the mass ratio of trehalose to silicon dioxide is 6:1.

[0067] S3: Multi-gradient alcohol extraction of forsythia suspensa and radix rehmanniae, the specific operation is:

[0068] After forsythia suspensa and radix rehmanniae are crushed, 35wt% ethanol solution is added, and extracted at 45℃ for 1h;

[0069] Adjust the concentration of the ethanol solution to 60wt%, and extract at 50℃ for 1h;

[0070] Adjust the concentration of the ethanol solution to 80wt%, and extract at 70℃ for 1h;

[0071] The extraction liquid is combined to obtain extract 3;

[0072] S4: After the gypsum is crushed and passed through a 20-mesh sieve, the gypsum is mixed with extract 1, extract 2, and extract 3, a stabilizer is added, drying is performed, sieving is performed, and a composition is obtained;

[0073] S5: 20 g of the composition is mixed with water, the pH is adjusted to 5.0, filtration is performed, water is added to make up to 1000 mL, and sterilization is performed to obtain an antiviral oral liquid;

[0074] The stabilizer is a mixture of astragalus polysaccharides, green apple extract, and vitamin E, and the mass ratio of the astragalus polysaccharides, green apple extract, and vitamin E is 1:8:2.

[0075] Example 2

[0076] An antiviral oral liquid is prepared from the following components by weight: 105 parts of radix isatidis, 49 parts of gypsum, 66 parts of rhizoma phragmitis, 44 parts of radix rehmanniae, 31 parts of radix curcumae, 44 parts of radix anemarrhenae, 31 parts of rhizoma alocasia, 38 parts of ageratum houstonianum, 53 parts of forsythia suspensa, 5 parts of a composite inclusion agent, and 40 parts of a stabilizer.

[0077] The preparation method is as follows:

[0078] S1: Rhizoma phragmitis, radix anemarrhenae, radix isatidis, and rhizoma alocasia are mixed and crushed, passed through a 50-mesh sieve, mixed with water at a solid-liquid ratio of 1 g:5 L, the pH is adjusted to 4.0, 0.1% of a composite enzyme based on the total mass of rhizoma phragmitis, radix anemarrhenae, radix isatidis, and rhizoma alocasia is added, mixed at 30°C for 1 h, and inactivated; the composite enzyme is a mixture of cellulase, pectinase, and trypsin, and the mass ratio of the cellulase, pectinase, and trypsin is 1:2:3; microwave-assisted water extraction is performed at 40°C for 25 min at a power of 300 W, and the extraction is repeated once to obtain extract 1;

[0079] S2: Radix curcumae and ageratum houstonianum are mixed and crushed, passed through a 40-mesh sieve, and extracted by supercritical CO2, and the parameters are as follows: the extraction pressure is 40 MPa, the extraction temperature is 45°C, the CO2 flow rate is 22 L / h, and the separation pressure is 5 MPa; extract A is obtained;

[0080] The extract A is packaged with a composite inclusion agent, and the specific operation is as follows: trehalose is dissolved in water to obtain a mass fraction of 20%, the extract A obtained in step S2 is homogenized and emulsified at a speed of 8000 rpm for 10 min, and then silica is added and dried.

[0081] The mass ratio of the composite inclusion agent to the mass of extract A is 1:4 to obtain extract 2;

[0082] The composite inclusion agent comprises trehalose and silica, and the mass ratio of the trehalose to the silica is 5:1.

[0083] S3: multi-gradient alcohol extraction of forsythia suspense and rehmannia glutinosa, the specific operation is as follows:

[0084] After forsythia suspense and rehmannia glutinosa are crushed, 30wt% ethanol solution is added, and extraction is carried out at 30℃ for 1h;

[0085] The concentration of the ethanol solution is adjusted to 50wt%, and extraction is carried out at 30℃ for 1h;

[0086] The concentration of the ethanol solution is adjusted to 70wt%, and extraction is carried out at 70℃ for 1h;

[0087] The extraction solutions are combined to obtain extract 3;

[0088] S4: gypsum is crushed and passed through a 30-mesh sieve, then mixed with extract 1, extract 2 and extract 3, a stabilizer is added, dried, sieved, and a composition is obtained;

[0089] S5: 20g of the composition is mixed with water, the pH is adjusted to 5.5, filtered, water is added to make up to 1000mL, and sterilized to obtain an antiviral oral solution;

[0090] The stabilizer is a mixture of astragalus polysaccharide, green apple extract and vitamin E, and the mass ratio of the astragalus polysaccharide, green apple extract and vitamin E is 0.1:5:2.

[0091] Example 3

[0092] An antiviral oral solution, the raw materials of which are composed of the following components in parts by weight: 115 parts of radix isatidis, 41 parts of gypsum, 75 parts of rhizome of phragmites communis, 37 parts of rehmannia glutinosa, 44 parts of curcuma zedoary, 35 parts of anemarrhena asphodeloides, 34 parts of acorus gramineus, 33 parts of pachystachys lutea, 59 parts of forsythia suspense, 25 parts of composite inclusion agent, and 60 parts of stabilizer;

[0093] The preparation method is as follows:

[0094] S1: rhizome of phragmites communis, anemarrhena asphodeloides, radix isatidis and acorus gramineus are mixed and crushed, then passed through a 40-mesh sieve, then mixed with water at a solid-liquid ratio of 1g:8L, the pH is adjusted to 6.0, 1.5% of a composite enzyme based on the total mass of rhizome of phragmites communis, anemarrhena asphodeloides, radix isatidis and acorus gramineus is added, mixed at 45℃ for 0.5h, and inactivated; the composite enzyme is a mixture of cellulase, pectinase and trypsin, and the mass ratio of the cellulase, pectinase and trypsin is 4:1:1; microwave-assisted water extraction is carried out at 600W for 5min at 60℃, and the extraction is repeated twice, and the extraction solutions are combined to obtain extract 1;

[0095] S2: curcuma zedoary and pachystachys lutea are mixed and crushed, then passed through a 30-mesh sieve, and then extracted by supercritical CO2, and the parameters are as follows: extraction pressure is 50MPa, extraction temperature is 50℃, CO2 flow rate is 28L / h, and separation pressure is 10MPa; extract A is obtained;

[0096] The extract A is complexly included with the complex inclusion agent, and the specific operation is as follows: trehalose is dissolved in water, the mass fraction of trehalose is 30%, the extract A obtained in step S2 is homogenized and emulsified at a speed of 12000 rpm for 8 min, then silica is added, and drying is performed.

[0097] The mass ratio of the complex inclusion agent to the extract A is 1:10, and the extract 2 is obtained.

[0098] The complex inclusion agent comprises trehalose and silica, and the mass ratio of the trehalose to the silica is 10:1.

[0099] S3: multi-gradient alcohol extraction of forsythia suspense and rehmannia glutinosa, and the specific operation is as follows:

[0100] After forsythia suspense and rehmannia glutinosa are crushed, 45wt% ethanol solution is added, and extraction is performed at 50℃ for 0.5h;

[0101] The concentration of the ethanol solution is adjusted to 65wt%, and extraction is performed at 30℃ for 0.5h;

[0102] The concentration of the ethanol solution is adjusted to 85wt%, and extraction is performed at 75℃ for 0.5h;

[0103] The extract liquids are combined, and the extract 3 is obtained.

[0104] S4: gypsum is crushed and passed through a 30-mesh sieve, then mixed with the extract 1, the extract 2 and the extract 3, a stabilizer is added, drying is performed, and sieving is performed, and the composition is obtained.

[0105] S5: 20g of the composition is mixed with water, the pH is adjusted to 5.0, filtration is performed, water is added to make up to 1000mL, and sterilization is performed, and an antiviral oral liquid is obtained.

[0106] The stabilizer is a mixture of astragalus polysaccharide, green apple extract and vitamin E, and the mass ratio of the astragalus polysaccharide, the green apple extract and the vitamin E is 1:10:4.

[0107] Comparative Example 1

[0108] An antiviral oral liquid is prepared according to the preparation method of Example 1 of Chinese Patent Application CN 118557685 A.

[0109] Comparative Example 2

[0110] An antiviral oral liquid, compared with Example 1, changes the preparation method.

[0111] The preparation method is as follows:

[0112] 1: The rehmannia, anemarrhena asphodeloides, isatis root and rhizoma alocasia are mixed, crushed, passed through a 40-mesh sieve, then mixed with water at a ratio of 1 g:6 L, microwave-assisted water extraction at 45℃ for 15 min, repeated 3 times, the extract was combined, and extract 1 was obtained;

[0113] S2: The curcuma zedoary and patchouli are mixed, crushed, passed through a 20-mesh sieve, and extracted by supercritical CO2, with parameters of extraction pressure of 45 MPa, extraction temperature of 40℃, CO2 flow rate of 25 L / h, and separation pressure of 8 MPa; extract 2 is obtained;

[0114] S3: The forsythia and rehmannia are alcohol extracted, with specific operations as follows:

[0115] The forsythia and rehmannia are crushed, then 80wt% ethanol solution is added, and extracted at 70℃ for 3h; extract 3 is obtained;

[0116] S4: The gypsum is crushed, passed through a 20-mesh sieve, then mixed with extract 1, extract 2, extract 3, and a stabilizer, dried, sieved, and a composition is obtained;

[0117] S5: 20g of the composition is mixed with water, the pH is adjusted to 5.0, filtered, water is added to a constant volume of 1000mL, and sterilized, and an antiviral oral solution is obtained;

[0118] The stabilizer is a mixture of astragalus polysaccharide, green apple extract and vitamin E, with a mass ratio of 1:8:2.

[0119] The raw materials are composed of the following components by weight: isatis root 110 parts, gypsum 46 parts, rehmannia 72 parts, rehmannia 40 parts, curcuma zedoary 36 parts, anemarrhena asphodeloides 42 parts, rhizoma alocasia 32 parts, patchouli 36 parts, forsythia 56 parts, and stabilizer 50 parts.

[0120] Comparative example 3

[0121] An antiviral oral solution, compared with example 1, only replaces the green apple extract with pomegranate seed extract.

[0122] The raw materials are composed of the following components by weight: isatis root 110 parts, gypsum 46 parts, rehmannia 72 parts, rehmannia 40 parts, curcuma zedoary 36 parts, anemarrhena asphodeloides 42 parts, rhizoma alocasia 32 parts, patchouli 36 parts, forsythia 56 parts, and stabilizer 50 parts.

[0123] The preparation method is as follows:

[0124] S1: the rhizoma phragmitis, the anemarrhena asphodeloides, the isatis root and the rhizoma acori graminei are mixed, crushed, passed through a 40-mesh sieve, then mixed with water at a solid-liquid ratio of 1 g:6 L, the pH is adjusted to 5.0, 0.5% of a compound enzyme of the total mass of the rhizoma phragmitis, the anemarrhena asphodeloides, the isatis root and the rhizoma acori graminei is added, mixed at 40 DEG C for 0.5 h, and inactivated; the compound enzyme is a mixture of cellulase, pectinase and trypsin, and the mass ratio of the cellulase, the pectinase and the trypsin is 3:1:2; microwave-assisted water extraction is carried out at 45 DEG C for 15 min at a power of 450 W, repeated for 3 times, and the extracts are combined to obtain extract 1;

[0125] S2: the radix anemarrhena asphodeloides and the agastache rugosa are mixed, crushed, passed through a 20-mesh sieve, and extracted by supercritical CO2, and the parameters are as follows: the extraction pressure is 45 MPa, the extraction temperature is 40 DEG C, the CO2 flow rate is 25 L / h, and the separation pressure is 8 MPa; extract A is obtained;

[0126] The extract A is packaged with a compound inclusion agent, and the specific operation is as follows: trehalose is dissolved in water, the mass fraction of trehalose is 25%, the extract A obtained in step S2 is homogenized and emulsified, the speed is 10000 rpm, the time is 5 min, then silica is added, and dried.

[0127] The mass ratio of the compound inclusion agent to the extract A is 1:5, and extract 2 is obtained;

[0128] The compound inclusion agent comprises trehalose and silica, and the mass ratio of the trehalose to the silica is 6:1.

[0129] S3: multi-gradient alcohol extraction of forsythia suspense and rehmannia glutinosa, and the specific operation is as follows:

[0130] Forsythia suspense and rehmannia glutinosa are crushed, 35wt% ethanol solution is added, and extracted at 45 DEG C for 1 h;

[0131] The concentration of the ethanol solution is adjusted to 60wt%, and extracted at 50 DEG C for 1 h;

[0132] The concentration of the ethanol solution is adjusted to 80wt%, and extracted at 70 DEG C for 1 h;

[0133] The extract is combined to obtain extract 3;

[0134] S4: gypsum is crushed, passed through a 20-mesh sieve, then mixed with the extract 1, the extract 2 and the extract 3, a stabilizer is added, dried, and sieved to obtain a composition;

[0135] S5: 20g of the composition is mixed with water, the pH is adjusted to 5.0, filtered, diluted with water to 1000mL, and sterilized to obtain an antiviral oral solution;

[0136] The stabilizer is a mixture of astragalus polysaccharide, pomegranate seed extract and vitamin E, and the mass ratio of the astragalus polysaccharide, pomegranate seed extract and vitamin E is 1:8:2.

[0137] Comparative Example 4

[0138] An antiviral oral liquid, compared with Example 1, the stabilizer is a mixture of astragalus polysaccharide, green apple extract, vitamin E and xanthan gum.

[0139] The raw materials are composed of the following components by weight: 110 parts of radix isatidis, 46 parts of gypsum, 72 parts of rhizoma phragmitis, 40 parts of radix rehmanniae, 36 parts of radix curcumae, 42 parts of rhizoma anemarrhenae, 32 parts of rhizoma acori graminei, 36 parts of agastache rugosa, 56 parts of forsythia suspensa, 20 parts of a composite inclusion agent, and 50 parts of a stabilizer;

[0140] The preparation method is as follows:

[0141] S1: Rhizoma phragmitis, rhizoma anemarrhenae, radix isatidis and rhizoma acori graminei need to be mixed and crushed, then passed through a 40-mesh sieve, then mixed with water at a solid-liquid ratio of 1 g:6 L, adjusted to pH 5.0, and 0.5% of a composite enzyme based on the total mass of rhizoma phragmitis, rhizoma anemarrhenae, radix isatidis and rhizoma acori graminei was added, mixed at 40°C for 0.5 h, and inactivated; the composite enzyme is a mixture of cellulase, pectinase and trypsin, and the mass ratio of cellulase, pectinase and trypsin is 3:1:2; microwave-assisted water extraction was carried out at 45°C for 15 min at a power of 450W, and the extraction was repeated 3 times, the extracts were combined, and extract 1 was obtained;

[0142] S2: Radix curcumae and agastache rugosa were mixed and crushed, passed through a 20-mesh sieve, and extracted by supercritical CO2, with the following parameters: extraction pressure 45 MPa, extraction temperature 40°C, CO2 flow rate 25 L / h, and separation pressure 8 MPa; extract A was obtained;

[0143] The extract A was inlaid with a composite inclusion agent, and the specific operation was as follows: trehalose was dissolved in water, the mass fraction of trehalose was 25%, extract A obtained in step S2 was homogenized and emulsified at a speed of 10000 rpm for 5 min, then silicon dioxide was added, and dried.

[0144] The mass ratio of the composite inclusion agent to extract A was 1:5, and extract 2 was obtained;

[0145] The composite inclusion agent comprises trehalose and silicon dioxide, and the mass ratio of the trehalose to silicon dioxide is 6:1.

[0146] S3: Multi-gradient alcohol extraction of forsythia suspensa and radix rehmanniae, and the specific operation was as follows:

[0147] Forsythia suspensa and radix rehmanniae were crushed and added to 35wt% ethanol solution, and extracted at 45°C for 1h;

[0148] Adjust the concentration of the ethanol solution to 60wt%, extract at 50℃ for 1h;

[0149] Adjust the concentration of the ethanol solution to 80wt%, extract at 70℃ for 1h;

[0150] Combine the extracts to obtain extract 3;

[0151] S4: After the gypsum powder is crushed and passed through a 20-mesh sieve, it is mixed with extract 1, extract 2, and extract 3, a stabilizer is added, dried, and sieved to obtain a composition;

[0152] S5: 20g of the composition is mixed with water, the pH is adjusted to 5.0, filtered, water is added to a constant volume of 1000mL, and sterilized to obtain an antiviral oral solution;

[0153] The stabilizer is a mixture of astragalus polysaccharides, green apple extract, vitamin E, and xanthan gum, and the mass ratio of the astragalus polysaccharides, green apple extract, vitamin E, and xanthan gum is 1:8:2:2.

[0154] Test Example 1

[0155] Stability Test:

[0156] The antiviral oral solution samples prepared according to Examples 1-3 and Comparative Examples 1-4 were taken for stability test.

[0157] Stability Test Method: The antiviral oral solution samples were simultaneously placed in a constant temperature and humidity chamber, the temperature was controlled at 40±2℃, and the relative humidity was controlled at 75±5%. The pH and forsythia osmanthus glycoside content of the antiviral oral solution were detected at 0 months, 3 months, and 6 months, respectively.

[0158] The detection method of forsythia osmanthus glycoside content is as follows: referring to the forsythia osmanthus glycoside quality detection standard in the first part of the Chinese Pharmacopoeia 2020 edition, the HPLC detection method is used, octadecylsilane bonded silica gel is used as the filling agent, the volume ratio of acetonitrile-water solution is 25:75 as the mobile phase, and the detection wavelength is 277nm.

[0159] The results are shown in Table 1:

[0160] Table 1. Stability test results

[0161]

[0162] Test Example 2

[0163] Taste Test:

[0164] Test method: The products prepared in Example 1-Example 3 and Comparative Example 1-Comparative Example 4 were used as the research object, and the irritation, bitterness, and acceptability after the trial were scored respectively. In this trial, Example 1-Example 3 and Comparative Example 1-Comparative Example 4 were divided into 7 groups, and 5 people were selected from each group for testing. The trial subjects were 18-45 year-old healthy people without a history of smoking or alcohol abuse. The scoring criteria are shown in Table 2. The irritation score was from 1 to 10, with a higher score indicating stronger irritation. The bitterness score was from 1 to 10, with a higher score indicating stronger bitterness. The acceptability score was from 1 to 10, with a higher score indicating stronger acceptability. The average score was calculated, and the final trial statistical results are shown in Table 3:

[0165] Table 2. Scoring criteria

[0166]

[0167] Table 3. Taste test results (points)

[0168]

[0169] Test Example 3

[0170] Immunopotency test:

[0171] Experimental subjects: Kunming mice were provided by Shanghai Slek Experimental Animal Co., Ltd. 32 healthy mice weighing 18-22 g were selected, with half male and half female, divided into 8 groups, 2 males and 2 females in each group, divided into a blank group, Example 1-Example 3 groups, and Comparative Example 1-Comparative Example 4 groups.

[0172] Blank group: 5 mL of normal saline was fed to the mice twice a day;

[0173] Example 1-Example 3 groups: The oral solution prepared in Example 1-Example 3 was fed to the mice twice a day, 3 mL each time, for 20 consecutive days;

[0174] Comparative Example 1-Comparative Example 4 groups: The oral solution prepared in Comparative Example 1-Comparative Example 4 was fed to the mice twice a day, 3 mL each time, for 20 consecutive days.

[0175] Detection of mouse weight-loaded swimming test, running experiment, and immunopotency test:

[0176] Weight-loaded swimming test: The mice were placed in warm water at 25°C, and a stone was tied to the mouse's tail, with the stone weighing 10% of the mouse's own weight. The time the mouse could withstand was recorded.

[0177] Running experiment: The mice were placed in a rotating cage, and the running time and resting frequency of the mice were recorded.

[0178] Immunopotency test: 0.1 mL of influenza virus was injected into the mice after the running test, and the performance of the four groups of mice was observed.

[0179] The results are shown in Table 4:

[0180] Table 4. Immunity test results

[0181]

[0182] From the above results, under the action of the specific preparation method and stabilizer of the present application, the stability of the prepared antiviral oral liquid is significantly improved, the taste is better, and the immunity and physical strength of mice can be improved, and the effect of preventing viral cold can be achieved.

[0183] Finally, it should be noted that the above content is only used to illustrate the technical solutions of the present application, and is not a limitation on the protection scope of the present application. Simple modifications or equivalent replacements of the technical solutions of the present application made by those skilled in the art do not deviate from the essence and scope of the technical solutions of the present application.

Claims

1. A method for preparing an antiviral oral solution, characterized by, The method comprises the following steps: S1: mixing radix pellitae, rhizoma anemarrhenae, radix isatidis and rhizoma alocasia, and then pre-treating and extracting by microwave-assisted water extraction to obtain extract 1; the pre-treatment step is as follows: after being sieved through a 40-50 mesh sieve, the radix pellitae, rhizoma anemarrhenae, radix isatidis and rhizoma alocasia are mixed with water, the pH is adjusted to 4.0-6.0, a composite enzyme is added, and then mixed at 30-45℃ for 0.5-1h, and then inactivated; the composite enzyme is a mixture of cellulase, pectinase and protease with a mass ratio of 1-4:1-2:1-3; the mass of the composite enzyme is 0.1%-1.5% of the mass of the raw materials; S2: mixing radix notopterygii and agastache rugosa, and then extracting by supercritical CO2 extraction to obtain extract A, and then using a composite inclusion agent to include the extract A to obtain extract 2; the composite inclusion agent is a mixture of trehalose and silicon dioxide with a mass ratio of 5-10:1; the mass ratio of the composite inclusion agent to the extract A is 1:4-8; the operation of inclusion is as follows: dissolving trehalose in water, the mass fraction of trehalose is 20%-30%, adding the extract A obtained in step S2 for homogenization and emulsification at a speed of 8000-12000 rpm for 5-10 min, and then adding silicon dioxide and drying; S3: multi-gradient alcohol extraction: powdering forsythia suspense and rehmannia glutinosa, and then adding 30wt%-45wt% ethanol solution, and then extracting at 30-50℃ for 0.5-1h; adjusting the concentration of the ethanol solution to 50wt%-65wt%, and then extracting at 30-50℃ for 0.5-1h; adjusting the concentration of the ethanol solution to 70wt%-85wt%, and then extracting at 70-75℃ for 0.5-1h; combining the extract solutions to obtain extract 3; S4: mixing the extract 1, the extract 2, the extract 3 and gypsum, the gypsum needs to be crushed and sieved through a 20-40 mesh sieve, adding a stabilizer, the stabilizer is a mixture of astragalus polysaccharide, green apple extract and vitamin E with a mass ratio of 0.1-1:5-10:2-4, and then drying to obtain a composition; S5: adjusting the pH of the composition to 5.0-5.5, filtering, adding water to constant volume, sterilizing, and then obtaining an antiviral oral solution; the raw materials of the antiviral oral solution are composed of the following components with the following weight parts: radix isatidis 105-115 parts, gypsum 41-49 parts, radix pellitae 66-75 parts, rehmannia glutinosa 37-44 parts, radix notopterygii 31-44 parts, rhizoma anemarrhenae 35-44 parts, rhizoma alocasia 31-34 parts, agastache rugosa 33-38 parts, forsythia suspense 53-59 parts, composite inclusion agent 5-25 parts and stabilizer 40-60 parts.

2. The production method according to claim 1, characterized by, in step S1, the temperature of the microwave-assisted water extraction is 40-60℃, the microwave power is 300-600W, the time is 5-25min, and the number of times is 1-3.

3. The preparation method according to claim 1, characterized in that, in step S1, the enzyme activity of the cellulase is 50000-100000U / g; the enzyme activity of the pectinase is 80000-100000U / g; and the enzyme activity of the protease is 80000-100000U / g.

4. The method of claim 1, wherein, In step S2, the Radix Notoginseng and Herba Pogostemi are crushed and passed through a 20-40 mesh sieve; the parameters for supercritical CO2 extraction are: extraction pressure of 40-50 MPa, extraction temperature of 40-50℃, CO2 flow rate of 22-28 L / h, and separation pressure of 5-10 MPa.

5. An antiviral oral solution, characterized in that, Prepared by the method of any one of claims 1-4.

6. Use of the antiviral oral liquid prepared by the method of any one of claims 1-4 in the preparation of a medicine for preventing or treating viral colds.

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