Preparation method, product and application of antiviral oral liquid

Abstract

The invention provides a preparation method, a product and application of an antiviral oral liquid, and relates to the technical field of antiviral materials. The preparation method comprises the following steps: mixing the rhizoma phragmitis, the rhizoma anemarrhenae, the radix isatidis and the rhizoma acori graminei, performing pretreatment, and performing microwave-assisted water extraction to obtain an extract 1; the preparation method comprises the following steps: mixing radix curcumae and pogostemon cablin, performing supercritical CO2 extraction to obtain an extract A, and clathrating the extract A with a composite clathration agent to obtain an extract 2; performing multi-gradient alcohol extraction on fructus forsythiae and radix rehmanniae recen to obtain an extract 3; and mixing all the extracts with gypsum, adding a stabilizer, adjusting the pH value to 5.0-5.5, filtering, adding water to a constant volume, and sterilizing to obtain the antiviral oral liquid. The antiviral oral liquid prepared by the invention can remarkably prevent and treat viral influenza and improve the immunity of patients, and is high in stability and good in taste.

Description

Technical Field

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

[0002] Antibacterial oral liquid is a safe, effective, reasonably priced and easy-to-use medicine. It is a commonly used Chinese medicine in clinical practice with significant therapeutic effects, few side effects and ease of use. Patients in need can use it with confidence. Antiviral oral liquid is an antiviral drug and an over-the-counter medicine for internal medicine colds. It is mainly composed of isatis root, gypsum, reed root, raw rehmannia root, turmeric, anemarrhena, calamus, patchouli and forsythia. Gypsum is a mineral medicine and the rest are plant medicines. The auxiliary materials are a compound preparation composed of effective ingredients such as sucrose, honey, sodium cyclamate and orange essence. It can clear away heat and dampness, cool blood and detoxify. It contains a variety of antiviral ingredients, can effectively inhibit viruses, is quickly absorbed and takes effect quickly. It is the first choice for treating and preventing various viral infections such as colds, upper respiratory tract infections, mumps, hand, foot and mouth disease, etc.

[0003] The preparation method of the existing antiviral oral liquid generally comprises the following steps: decocting the above nine medicinal materials with water twice, the first time for 3 hours, collecting the volatile oil, and encapsulating it with hydroxypropyl beta-cyclodextrin, 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 filtrates, concentrating to an appropriate amount, adding 85% or more ethanol to adjust the alcohol content to 70%, standing, filtering, recovering the ethanol from 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 and sucrose; then cooling to below 30°C, adjusting the pH value with 10% sodium hydroxide solution, filtering; adding water to 1000 mL, mixing, filtering, encapsulating, and sterilizing to obtain the product.

[0004] The preparation method has drawbacks: First, traditional antiviral oral liquids have a poor taste because they contain concentrated liquids of herbs such as reed rhizome, raw rehmannia root, turmeric, and anemarrhena, resulting in a bitter taste. After taking the antiviral oral liquid, the bitter taste lingers in the mouth for a while. For example, Chinese patent application CN108159348A discloses a sugar-free antiviral oral liquid and its preparation method. To address the problem of poor efficacy due to outdated production processes and conventional concentration methods for existing antiviral oral liquids, a sugar-free antiviral oral liquid and its preparation method are provided. The liquid comprises the following main ingredients: isatis root, turmeric root, forsythia root, gypsum, anemarrhena root, reed rhizome, calamus, raw rehmannia root, and patchouli, and the following auxiliary ingredients: stevioside, sodium benzoate, and purified water. The oral liquid is extracted under vacuum conditions at a relatively low temperature and then diluted with purified water. This invention minimizes the loss of active ingredients in the decoction, significantly improving the efficacy of the finished product. However, the bitter taste makes it difficult for some patients to tolerate.

[0005] On the other hand, according to literature reports, pharmacodynamic experiments have demonstrated that patchouli alcohol (patchouli alcohol) in antiviral oral liquids has excellent antipyretic and antibacterial properties. However, because the volatile oil is poorly water-soluble and volatile, it is lost during the potting and sterilization processes when added to the filtrate. Furthermore, the volatile oil content in the finished product gradually depletes over time. Stability studies have shown that the finished product is poorly stable, potentially affecting its efficacy. Furthermore, the volatile oil has a strong, pungent flavor, which affects the taste and makes it difficult for children to accept. Chinese patent application CN118557685A discloses an antiviral oral liquid and its preparation method, comprising the following steps: boiling the raw medicinal materials with water, combining the filtrates, concentrating them, and adding excipients; adjusting the pH of the liquid while cooling it, filtering it to clarity, adding water to the fixed volume, filtering it, and sterilizing it to obtain the liquid; the specific steps of adjusting the pH of the liquid during cooling are: when the liquid is cooled to 50-60°C, adjusting the pH of the liquid to 4.0-5.0 using a 5.0-7.5 mol / L sodium hydroxide solution; when the liquid is further cooled to 20-50°C, adjusting the pH of the liquid to 5.5-6.0 using a 1.0-5.0 mol / L sodium hydroxide solution. Using this technical solution, the antiviral oral liquid can effectively maintain the clarity of the solution, the stability of the pH, and the stability of the forsythin content. While this improves stability, it does not address the issue of taste.

[0006] Based on this, developing a preparation method for antiviral oral liquid and improving its stability, taste and effect are the research focuses of researchers in this field. Summary of the Invention

[0007] In response to the above problems, the present invention provides a method for preparing an antiviral oral liquid. By optimizing the auxiliary materials and the preparation method, the antiviral oral liquid prepared has high stability and good taste, has a preventive and good therapeutic effect on viral colds, and can improve the patient's immunity.

[0008] To achieve the above object, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides a method for preparing an antiviral oral liquid, comprising the following steps: S1: Phragmites australis, Anemarrhena asphodeloides, Isatis indigotica and Acorus tatarinowii were mixed and pretreated, and then microwave-assisted water extraction was performed to obtain extract 1; S2: Curcuma and Patchouli are mixed and extracted by supercritical CO2 to obtain Extract A, which is then encapsulated with a composite encapsulation agent to obtain Extract 2; S3: Multiple gradient alcohol extraction of Forsythia suspensa and Rehmannia root to obtain extract 3; S4: extract 1, extract 2, extract 3 and gypsum are mixed, a stabilizer is added, and the mixture is dried to obtain a composition; S5: adjusting the pH of the composition to 5.0-5.5, filtering, adding water to make up the volume, and sterilizing to obtain the antiviral oral solution; The raw materials of the antiviral oral liquid are composed of the following components in parts by weight: 105-115 parts of isatis root, 41-49 parts of gypsum, 66-75 parts of rehmannia root, 37-44 parts of raw rehmannia root, 31-44 parts of curcuma, 35-44 parts of anemarrhena, 31-34 parts of calamus, 33-38 parts of patchouli, 53-59 parts of forsythia, 5-25 parts of a composite inclusion agent and 40-60 parts of a stabilizer.

[0009] Preferably, in step S1, the Phragmites australis, Rhizoma Anemarrhenae, Radix Isatidis and Rhizoma Acorus tatarinowii are crushed and passed through a 40-50 mesh sieve; Preferably, in step S1, the pretreatment step is: mixing Phragmites australis, Rhizoma Anemarrhenae, Radix Isatidis and Acorus calamus with water, adjusting the pH to 4.0-6.0, adding complex enzyme, mixing at 30-45° C. for 0.5-1 h, and inactivating; Preferably, the solid-liquid ratio of the total mass of the reed rhizome, anemarrhena, isatis root and calamus to water is 1g:5-8L; further preferably, the solid-liquid ratio of the total mass of the reed rhizome, anemarrhena, isatis root and calamus to water is 1g:6L.

[0010] Preferably, the complex enzyme is a mixture of cellulase, pectinase and protease.

[0011] 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.

[0012] 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.

[0013] Preferably, the enzymatic activity of the cellulase is 50,000-100,000 U / g; the enzymatic activity of the pectinase is 80,000-100,000 U / g; and the enzymatic activity of the protease is 80,000-100,000 U / g.

[0014] Preferably, the protease is trypsin.

[0015] Preferably, in step S1, the temperature of the microwave-assisted water extraction is 40-60° C., the microwave power is 300-600 W, the time is 5-25 min, and the number of times is 1-3 times.

[0016] Further preferably, in step S1, the temperature of the microwave-assisted water extraction is 45° C., the microwave power is 450 W, the time is 15 min, and the number of times is 3 times.

[0017] Preferably, in step S2, the turmeric and patchouli are ground and passed through a 20-40 mesh sieve; Preferably, in step S2, the parameters of the supercritical CO2 extraction are: extraction pressure of 40-50 MPa, extraction temperature of 40-50°C, CO2 flow rate of 22-28 L / h, and separation pressure of 5-10 MPa.

[0018] Further preferably, in step S2, the parameters of the supercritical CO2 extraction are: extraction pressure of 45 MPa, extraction temperature of 40°C, CO2 flow rate of 25 L / h, and separation pressure of 8 MPa.

[0019] Preferably, in step S2, the composite inclusion agent comprises trehalose and silicon dioxide.

[0020] Preferably, in step S2, the mass ratio of the composite inclusion agent to the mass ratio of the extract A is 1:4-8. Further preferably, in step S2, the mass ratio of the composite inclusion agent to the mass ratio of the extract A is 1:5.

[0021] Preferably, the mass ratio of trehalose to silicon dioxide is 5-10: 1. Further preferably, the mass ratio of trehalose to silicon dioxide is 6:1.

[0022] Preferably, the inclusion operation is as follows: dissolving trehalose in water with a mass fraction of trehalose of 20%-30%, adding the extract obtained in step S2 and homogenizing and emulsifying at a rate of 8000-12000 rpm for 5-10 min, then adding silicon dioxide and drying.

[0023] Further preferably, the inclusion operation is: dissolving trehalose in water with a mass fraction of trehalose of 25%, adding the extract obtained in step S2 and homogenizing and emulsifying at a rate of 10,000 rpm for 5 minutes, then adding silicon dioxide and drying.

[0024] Preferably, in step S3, the multi-gradient alcohol extraction operation is: After grinding Forsythia suspensa and Rehmannia root, add 30wt%-45wt% ethanol solution and extract at 30-50℃ for 0.5-1h; Adjust the concentration of the ethanol solution to 50wt%-65wt% and extract at 30-50°C for 0.5-1h; Adjust the concentration of the ethanol solution to 70wt%-85wt% and extract at 70-75°C for 0.5-1h; Combine the extracts.

[0025] Further preferably, in step S3, the multi-gradient alcohol extraction operation is: Forsythia suspensa and Rehmannia root were crushed and added with 35 wt% ethanol solution and extracted at 45 °C for 1 h; The concentration of the ethanol solution was adjusted to 60 wt % and the extraction was carried out at 50 °C for 1 h; The concentration of the ethanol solution was adjusted to 80 wt % and the extraction was carried out at 70 °C for 1 h; Combine the extracts.

[0026] Preferably, in step S4, the gypsum needs to be crushed and passed through a 20-40 mesh sieve.

[0027] Preferably, in step S4, the stabilizer is a mixture of astragalus polysaccharide, green apple extract and vitamin E.

[0028] 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.

[0029] In a second aspect, the present invention provides an antiviral oral liquid prepared by the above-mentioned preparation method.

[0030] In a third aspect, the present invention provides the use of the antiviral oral liquid prepared by the above-mentioned preparation method in the preparation of medicines for preventing or treating viral colds.

[0031] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention optimizes the preparation method of the antiviral oral liquid, extracts Phragmites australis, Anemarrhena asphodeloides, Isatis indigotica and Acorus tatarinowii by microwave-assisted water extraction; performs low-temperature supercritical CO2 extraction on Curcuma aromatica and Patchouli, and includes their extracts; performs multi-gradient alcohol extraction on Forsythia suspensa and Rehmannia glutinosa; and under the specific preparation method of the present invention, significantly improves the stability and efficacy of the prepared antiviral oral liquid.

[0032] 2. The present invention optimizes the inclusion components to trehalose and silicon dioxide, and adds stabilizers: astragalus polysaccharide, green apple extract and vitamin E. The components cooperate with each other, thereby significantly improving the stability of the prepared antiviral oral liquid.

[0033] 3. The present invention significantly improves the stability of the prepared antiviral oral liquid by adding green apple extract and trehalose, and significantly improves its taste, which is conducive to the acceptance of people who have higher requirements for taste.

[0034] 4. The antiviral oral liquid prepared by the present invention can significantly prevent and treat viral colds and improve the patient's immunity. DETAILED DESCRIPTION

[0035] In order to make the technical means, creative features, purpose and effect of the present invention easy to understand, the present invention is further illustrated below in conjunction with specific embodiment, but the following embodiment is only a preferred embodiment of the present invention, not all. Based on the embodiment in the embodiment, other embodiments obtained by those skilled in the art without making creative work all fall within the protection scope of the present invention. It is worth noting that the raw materials used in the present invention are all common commercial products, and their source is not specifically limited. The technology and scientific terms used in the embodiment have the meaning commonly understood by those of ordinary skill in the art to which the present invention belongs.

[0036] The enzymatic activity of cellulase is 50,000-100,000 U / g; The enzyme activity of pectinase is 80,000-100,000 U / g; The enzyme activity of trypsin is 80,000-100,000 U / g; Green apple extract was purchased from Baoji Liupanyun Biotechnology Co., Ltd.

[0037] Example 1 An antiviral oral liquid, comprising the following ingredients in parts by weight: 110 parts of isatis root, 46 parts of gypsum, 72 parts of rehmannia root, 40 parts of raw rehmannia root, 36 parts of turmeric, 42 parts of anemarrhena, 32 parts of calamus, 36 parts of patchouli, 56 parts of forsythia, 20 parts of a composite inclusion agent, and 50 parts of a stabilizer; The preparation method is as follows: S1: Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii were mixed and crushed, passed through a 40-mesh sieve, and then mixed with water at a solid-liquid ratio of 1 g:6 L. The pH was adjusted to 5.0, and a composite enzyme (0.5% of the total mass of the Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii) was added. The mixture was mixed at 40°C for 0.5 h and inactivated. The composite enzyme was a mixture of cellulase, pectinase, and trypsin, with a mass ratio of cellulase, pectinase, and trypsin of 3:1:2. Microwave-assisted water extraction was performed at 45°C with a power of 450 W for 15 min. The extraction was repeated three times, and the extracts were combined to obtain Extract 1. S2: Curcuma zedoaria and Patchouli were mixed and ground, passed through a 20-mesh sieve, and extracted with supercritical CO2 at the following parameters: extraction pressure of 45 MPa, extraction temperature of 40°C, CO2 flow rate of 25 L / h, and separation pressure of 8 MPa; extract A was obtained; Extract A was encapsulated with a composite encapsulation agent. The specific operation was as follows: trehalose was dissolved in water with a mass fraction of trehalose of 25%, and the extract A obtained in step S2 was added and homogenized and emulsified at a rate of 10,000 rpm for 5 minutes, and then silicon dioxide was added and dried.

[0038] The mass ratio of the composite inclusion agent to the extract A is 1:5, to obtain extract 2; The composite inclusion agent comprises trehalose and silicon dioxide, and the mass ratio of the trehalose to silicon dioxide is 6:1.

[0039] S3: Multi-gradient alcohol extraction of Forsythia suspensa and Rehmannia root. The specific operation is as follows: Forsythia suspensa and Rehmannia root were crushed and added with 35 wt% ethanol solution and extracted at 45 °C for 1 h; The concentration of the ethanol solution was adjusted to 60 wt % and the extraction was carried out at 50 °C for 1 h; The concentration of the ethanol solution was adjusted to 80 wt % and the extraction was carried out at 70 °C for 1 h; The extracts were combined to obtain extract 3; S4: Gypsum is crushed and passed through a 20-mesh sieve, then mixed with extract 1, extract 2, and extract 3, a stabilizer is added, dried, and sieved to obtain a composition; S5: Take 20 g of the composition and mix it with water, adjust the pH to 5.0, filter, add water to make up to 1000 mL, and sterilize to obtain the antiviral oral solution; 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 1:8:2.

[0040] Example 2 An antiviral oral liquid, comprising the following ingredients in parts by weight: 105 parts of isatis root, 49 parts of gypsum, 66 parts of rehmannia root, 44 parts of raw rehmannia root, 31 parts of turmeric, 44 parts of anemarrhena, 31 parts of calamus, 38 parts of patchouli, 53 parts of forsythia, 5 parts of a composite inclusion agent, and 40 parts of a stabilizer. The preparation method is as follows: S1: Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii were mixed and crushed, passed through a 50-mesh sieve, and then mixed with water at a solid-liquid ratio of 1 g:5 L. The pH was adjusted to 4.0, and a composite enzyme (0.1% of the total mass of the Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii) was added. The mixture was mixed at 30°C for 1 hour and inactivated. The composite enzyme was a mixture of cellulase, pectinase, and trypsin in a mass ratio of 1:2:3. Microwave-assisted water extraction was performed at 40°C at a power of 300 W for 25 minutes. The extraction was repeated once to obtain Extract 1. S2: Curcuma and Patchouli were mixed and ground, passed through a 40-mesh sieve, and extracted with supercritical CO2 at the following parameters: extraction pressure of 40 MPa, extraction temperature of 45°C, CO2 flow rate of 22 L / h, and separation pressure of 5 MPa; extract A was obtained; Extract A was encapsulated with a composite encapsulation agent. The specific operation was as follows: trehalose was dissolved in water with a mass fraction of trehalose of 20%, and the extract A obtained in step S2 was added and homogenized and emulsified at a rate of 8000 rpm for 10 minutes, and then silicon dioxide was added and dried.

[0041] The mass ratio of the composite inclusion agent to the extract A is 1:4, to obtain extract 2; The composite inclusion agent comprises trehalose and silicon dioxide, and the mass ratio of the trehalose to silicon dioxide is 5:1.

[0042] S3: Multi-gradient alcohol extraction of Forsythia suspensa and Rehmannia root. The specific operation is as follows: Forsythia suspensa and Rehmannia root were crushed and added with 30 wt% ethanol solution and extracted at 30 °C for 1 h; The concentration of the ethanol solution was adjusted to 50 wt % and the extraction was carried out at 30 °C for 1 h; The concentration of the ethanol solution was adjusted to 70 wt % and the extraction was carried out at 70 °C for 1 h; The extracts were combined to obtain extract 3; 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, and sieved to obtain a composition; S5: Take 20 g of the composition and mix it with water, adjust the pH to 5.5, filter, add water to make up to 1000 mL, and sterilize to obtain the antiviral oral solution; 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.

[0043] Example 3 An antiviral oral liquid, comprising the following ingredients in parts by weight: 115 parts of isatis root, 41 parts of gypsum, 75 parts of rehmannia root, 37 parts of raw rehmannia root, 44 parts of curcuma, 35 parts of anemarrhena, 34 parts of calamus, 33 parts of patchouli, 59 parts of forsythia, 25 parts of a composite inclusion agent, and 60 parts of a stabilizer. The preparation method is as follows: S1: Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii were mixed and crushed, passed through a 40-mesh sieve, and then mixed with water at a solid-liquid ratio of 1 g:8 L. The pH was adjusted to 6.0, and a composite enzyme (1.5% of the total mass of the Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii) was added. The mixture was mixed at 45°C for 0.5 h and inactivated. The composite enzyme was a mixture of cellulase, pectinase, and trypsin in a mass ratio of 4:1:1. Microwave-assisted water extraction was performed at 60°C with a power of 600 W for 5 min. The extraction was repeated twice, and the extracts were combined to obtain Extract 1. S2: Curcuma zedoaria and Patchouli were mixed and ground, passed through a 30-mesh sieve, and extracted with supercritical CO2 at the following parameters: extraction pressure of 50 MPa, extraction temperature of 50°C, CO2 flow rate of 28 L / h, and separation pressure of 10 MPa; extract A was obtained; Extract A was encapsulated with a composite encapsulation agent. The specific operation was as follows: trehalose was dissolved in water with a mass fraction of trehalose of 30%, and the extract A obtained in step S2 was added and homogenized and emulsified at a rate of 12,000 rpm for 8 minutes. Then, silicon dioxide was added and dried.

[0044] The mass ratio of the composite inclusion agent to the extract A is 1:10, to obtain extract 2; The composite inclusion agent comprises trehalose and silicon dioxide, and the mass ratio of the trehalose to the silicon dioxide is 10:1.

[0045] S3: Multi-gradient alcohol extraction of Forsythia suspensa and Rehmannia root. The specific operation is as follows: Forsythia suspensa and Rehmannia root were crushed and added with 45 wt% ethanol solution and extracted at 50 °C for 0.5 h; The concentration of the ethanol solution was adjusted to 65 wt % and the extraction was carried out at 30 °C for 0.5 h; The concentration of the ethanol solution was adjusted to 85 wt % and the extraction was carried out at 75 °C for 0.5 h; The extracts were combined to obtain extract 3; 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, and sieved to obtain a composition; S5: Take 20 g of the composition and mix it with water, adjust the pH to 5.0, filter, add water to make up to 1000 mL, and sterilize to obtain the antiviral oral solution; 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 1:10:4.

[0046] Comparative Example 1 An antiviral oral liquid is prepared according to the preparation method of Example 1 of Chinese patent application CN 118557685 A.

[0047] Comparative Example 2 An antiviral oral liquid, compared with Example 1, has a different preparation method.

[0048] The preparation method is as follows: 1: Phragmites australis, Anemarrhena asphodeloides, Isatis indigotica, and Acorus tatarinowii were mixed and ground, passed through a 40-mesh sieve, and then mixed with water at a solid-liquid ratio of 1 g:6 L. Microwave-assisted water extraction was performed at 45°C with a power of 450 W for 15 min. The extraction was repeated three times, and the extracts were combined to obtain Extract 1. S2: Curcuma zedoaria and Patchouli were mixed and ground, passed through a 20-mesh sieve, and extracted with supercritical CO2 at the following parameters: extraction pressure of 45 MPa, extraction temperature of 40°C, CO2 flow rate of 25 L / h, and separation pressure of 8 MPa; extract 2 was obtained; S3: Alcohol extraction of Forsythia suspensa and Rehmannia root, the specific operation is as follows: After the forsythia suspensa and Rehmannia root were crushed, 80 wt% ethanol solution was added and extracted at 70 °C for 3 h to obtain extract 3; S4: Gypsum is crushed and passed through a 20-mesh sieve, then mixed with extract 1, extract 2, and extract 3, a stabilizer is added, dried, and sieved to obtain a composition; S5: Take 20 g of the composition and mix it with water, adjust the pH to 5.0, filter, add water to make up to 1000 mL, and sterilize to obtain the antiviral oral solution; 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 1:8:2.

[0049] The raw materials are composed of the following components in parts by weight: 110 parts of isatis root, 46 parts of gypsum, 72 parts of rehmannia root, 40 parts of raw rehmannia root, 36 parts of turmeric, 42 parts of anemarrhena, 32 parts of calamus, 36 parts of patchouli, 56 parts of forsythia and 50 parts of stabilizer.

[0050] Comparative Example 3 An antiviral oral liquid, compared with Example 1, wherein only the green apple extract is replaced by the pomegranate seed extract.

[0051] The raw materials are composed of the following components in parts by weight: 110 parts of isatis root, 46 parts of gypsum, 72 parts of rehmannia root, 40 parts of raw rehmannia root, 36 parts of turmeric, 42 parts of anemarrhena, 32 parts of calamus, 36 parts of patchouli, 56 parts of forsythia, 20 parts of a composite inclusion agent, and 50 parts of a stabilizer; The preparation method is as follows: S1: Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii were mixed and crushed, passed through a 40-mesh sieve, and then mixed with water at a solid-liquid ratio of 1 g:6 L. The pH was adjusted to 5.0, and a composite enzyme (0.5% of the total mass of the Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii) was added. The mixture was mixed at 40°C for 0.5 h and inactivated. The composite enzyme was a mixture of cellulase, pectinase, and trypsin, with a mass ratio of cellulase, pectinase, and trypsin of 3:1:2. Microwave-assisted water extraction was performed at 45°C with a power of 450 W for 15 min. The extraction was repeated three times, and the extracts were combined to obtain Extract 1. S2: Curcuma zedoaria and Patchouli were mixed and ground, passed through a 20-mesh sieve, and extracted with supercritical CO2 at the following parameters: extraction pressure of 45 MPa, extraction temperature of 40°C, CO2 flow rate of 25 L / h, and separation pressure of 8 MPa; extract A was obtained; Extract A was encapsulated with a composite encapsulation agent. The specific operation was as follows: trehalose was dissolved in water with a mass fraction of trehalose of 25%, and the extract A obtained in step S2 was added and homogenized and emulsified at a rate of 10,000 rpm for 5 minutes, and then silicon dioxide was added and dried.

[0052] The mass ratio of the composite inclusion agent to the extract A is 1:5, to obtain extract 2; The composite inclusion agent comprises trehalose and silicon dioxide, and the mass ratio of the trehalose to silicon dioxide is 6:1.

[0053] S3: Multi-gradient alcohol extraction of Forsythia suspensa and Rehmannia root. The specific operation is as follows: Forsythia suspensa and Rehmannia root were crushed and added with 35 wt% ethanol solution and extracted at 45 °C for 1 h; The concentration of the ethanol solution was adjusted to 60 wt % and the extraction was carried out at 50 °C for 1 h; The concentration of the ethanol solution was adjusted to 80 wt % and the extraction was carried out at 70 °C for 1 h; The extracts were combined to obtain extract 3; S4: Gypsum is crushed and passed through a 20-mesh sieve, then mixed with extract 1, extract 2, and extract 3, a stabilizer is added, dried, and sieved to obtain a composition; S5: Take 20 g of the composition and mix it with water, adjust the pH to 5.0, filter, add water to make up to 1000 mL, and sterilize to obtain the antiviral oral solution; 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.

[0054] Comparative Example 4 An antiviral oral liquid, compared with Example 1, wherein the stabilizers are astragalus polysaccharide, green apple extract, vitamin E and xanthan gum.

[0055] The raw materials are composed of the following components in parts by weight: 110 parts of isatis root, 46 parts of gypsum, 72 parts of rehmannia root, 40 parts of raw rehmannia root, 36 parts of turmeric, 42 parts of anemarrhena, 32 parts of calamus, 36 parts of patchouli, 56 parts of forsythia, 20 parts of a composite inclusion agent, and 50 parts of a stabilizer; The preparation method is as follows: S1: Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii were mixed and crushed, passed through a 40-mesh sieve, and then mixed with water at a solid-liquid ratio of 1 g:6 L. The pH was adjusted to 5.0, and a composite enzyme (0.5% of the total mass of the Phragmites australis, Anemarrhena asphodeloides, Radix Isatidis, and Acorus tatarinowii) was added. The mixture was mixed at 40°C for 0.5 h and inactivated. The composite enzyme was a mixture of cellulase, pectinase, and trypsin, with a mass ratio of cellulase, pectinase, and trypsin of 3:1:2. Microwave-assisted water extraction was performed at 45°C with a power of 450 W for 15 min. The extraction was repeated three times, and the extracts were combined to obtain Extract 1. S2: Curcuma zedoaria and Patchouli were mixed and ground, passed through a 20-mesh sieve, and extracted with supercritical CO2 at the following parameters: extraction pressure of 45 MPa, extraction temperature of 40°C, CO2 flow rate of 25 L / h, and separation pressure of 8 MPa; extract A was obtained; Extract A was encapsulated with a composite encapsulation agent. The specific operation was as follows: trehalose was dissolved in water with a mass fraction of trehalose of 25%, and the extract A obtained in step S2 was added and homogenized and emulsified at a rate of 10,000 rpm for 5 minutes, and then silicon dioxide was added and dried.

[0056] The mass ratio of the composite inclusion agent to the extract A is 1:5, to obtain extract 2; The composite inclusion agent comprises trehalose and silicon dioxide, and the mass ratio of the trehalose to silicon dioxide is 6:1.

[0057] S3: Multi-gradient alcohol extraction of Forsythia suspensa and Rehmannia root. The specific operation is as follows: Forsythia suspensa and Rehmannia root were crushed and added with 35 wt% ethanol solution and extracted at 45 °C for 1 h; The concentration of the ethanol solution was adjusted to 60 wt % and the extraction was carried out at 50 °C for 1 h; The concentration of the ethanol solution was adjusted to 80 wt % and the extraction was carried out at 70 °C for 1 h; The extracts were combined to obtain extract 3; S4: Gypsum is crushed and passed through a 20-mesh sieve, then mixed with extract 1, extract 2, and extract 3, a stabilizer is added, dried, and sieved to obtain a composition; S5: Take 20 g of the composition and mix it with water, adjust the pH to 5.0, filter, add water to make up to 1000 mL, and sterilize to obtain the antiviral oral solution; The stabilizer is a mixture of astragalus polysaccharide, green apple extract, vitamin E and xanthan gum, and the mass ratio of the astragalus polysaccharide, green apple extract, vitamin E and xanthan gum is 1:8:2:2.

[0058] Test Example 1 Stability test: The antiviral oral liquid samples prepared according to Examples 1 to 3 and Comparative Examples 1 to 4 were taken for stability testing.

[0059] Stability assessment: Antiviral oral solution samples were placed simultaneously in a constant temperature and humidity chamber at 40±2°C and 75±5%. The pH and forsythin content of the antiviral oral solution were measured at 0, 3, and 6 months.

[0060] The specific method for detecting the content of forsythiaside is: referring to the forsythiaside quality detection standard in Part 1 of the 2020 edition of the "Chinese Pharmacopoeia", using the HPLC detection method, using octadecylsilane bonded silica gel as the filler; using acetonitrile-water solution with a volume ratio of 25:75 as the mobile phase; the detection wavelength is 277nm.

[0061] The results are shown in Table 1: Table 1. Stability test results

[0062] Test Example 2 Taste test: Test method: The products prepared from Examples 1 to 3 and Comparative Examples 1 to 4 were used as research objects, and the irritation, bitterness, and acceptability after the trial were scored respectively. In this trial, Examples 1 to 3 and Comparative Examples 1 to 4 were divided into 7 groups, and 5 people were selected from each group for testing. The trial subjects were healthy people aged 18-45 years old with no history of smoking or alcoholism. The scoring criteria are shown in Table 2. The scores are from 1 to 10 for irritation, with the higher the score, the stronger the irritation; from 1 to 10 for bitterness, with the higher the score, the stronger the bitterness; and from 1 to 10 for acceptability, with the higher the score, the stronger the acceptability. The average score was calculated, and the final trial statistical results are shown in Table 3: Table 2. Scoring criteria

[0063] Table 3. Taste test results (points)

[0064] Test Example 3 Immunity enhancement test: Experimental subjects: Kunming mice were provided by Shanghai Slake Laboratory Animal Co., Ltd. 32 healthy mice weighing 18-22 g were selected, half male and half female, and divided into 8 groups, with 2 females and 2 males in each group, and divided into blank group, Example 1 to Example 3 groups, and Comparative Example 1 to Comparative Example 4 groups; Blank group: 5 mL of normal saline was administered every morning and evening; Groups of Example 1-Example 3: The oral solution prepared in Example 1-Example 3 was fed every morning and evening, 3 mL each time, for 20 consecutive days; Comparative Example 1-Comparative Example 4 Groups: The oral solution prepared for Comparative Example 1-Comparative Example 4 Groups were fed every morning and evening, 3 mL each time, for 20 consecutive days.

[0065] Testing mice's weight-bearing swimming test, running test and immunity test: Weighted swimming test: The mice were placed in 25°C warm water and a stone was tied to the mouse's tail. The weight of the stone was 10% of the mouse's own weight. The time the mouse could endure was recorded.

[0066] Running experiment: Place the mice in a rotating cage and record the running time and rest times of the mice.

[0067] Immunity 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.

[0068] The results are shown in Table 4: Table 4. Immunity test results

[0069] From the above results, it can be seen that under the action of the specific preparation method and stabilizer of the present invention, the stability of the antiviral oral liquid prepared by the present invention is significantly improved, the taste is better, and it can improve the immunity and physical strength of mice, and can prevent viral colds.

[0070] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing an antiviral oral liquid, characterized in that: The following steps are involved: S1: Phragmites australis, Anemarrhena asphodeloides, Isatis indigotica and Acorus tatarinowii were mixed and pretreated, and then microwave-assisted water extraction was performed to obtain extract 1; S2: Curcuma and Patchouli are mixed and extracted by supercritical CO2 to obtain Extract A, which is then encapsulated with a composite encapsulation agent to obtain Extract 2; S3: Extract 3 was obtained by multi-gradient alcohol extraction of Forsythia suspensa and Rehmannia root; S4: extract 1, extract 2, extract 3 and gypsum are mixed, a stabilizer is added, and the mixture is dried to obtain a composition; S5: adjusting the pH of the composition to 5.0-5.5, filtering, adding water to make up the volume, and sterilizing to obtain the antiviral oral solution; The raw materials of the antiviral oral liquid are composed of the following components in parts by weight: 105-115 parts of isatis root, 41-49 parts of gypsum, 66-75 parts of rehmannia root, 37-44 parts of raw rehmannia root, 31-44 parts of curcuma, 35-44 parts of anemarrhena, 31-34 parts of calamus, 33-38 parts of patchouli, 53-59 parts of forsythia, 5-25 parts of a composite inclusion agent and 40-60 parts of a stabilizer.

2. The preparation method according to claim 1, characterized in that In step S1, the pretreatment step is: after passing the rhizome of Phragmites australis, the root of Anemarrhena asphodeloides, the root of Isatis indigotica and the root of Acorus calamus through a 40-50 mesh sieve, the mixture is mixed with water, the pH is adjusted to 4.0-6.0, a complex enzyme is added, and the mixture is mixed at 30-45° C. for 0.5-1 hour to inactivate the mixture; the temperature of the microwave-assisted water extraction is 40-60° C., the microwave power is 300-600 W, the time is 5-25 minutes, and the number of times is 1-3.

3. The preparation method according to claim 2, characterized in that The complex enzyme is a mixture of cellulase, pectinase and protease; the mass ratio of the cellulase, pectinase and protease is 1-4:1-2:1-3; the mass of the complex enzyme is 0.1%-1.5% of the mass of the raw materials; the enzymatic activity of the cellulase is 50,000-100,000 U / g; the enzymatic activity of the pectinase is 80,000-100,000 U / g; and the enzymatic activity of the protease is 80,000-100,000 U / g.

4. The preparation method according to claim 1, characterized in that In step S2, the turmeric and patchouli need to be crushed and passed through a 20-40 mesh sieve; the parameters of the supercritical CO2 extraction are: extraction pressure of 40-50 MPa, extraction temperature of 40-50°C, CO2 flow rate of 22-28 L / h, and separation pressure of 5-10 MPa.

5. The preparation method according to claim 1, characterized in that In step S2, the composite inclusion agent comprises trehalose and silicon dioxide; the mass ratio of the composite inclusion agent to the mass ratio of extract A is 1:4-8; and the mass ratio of the trehalose to silicon dioxide is 5-10:

1.

6. The preparation method according to claim 1, wherein In step S2, the inclusion operation is as follows: dissolving trehalose in water with a mass fraction of trehalose of 20%-30%, adding the extract A obtained in step S2 and homogenizing and emulsifying at a rate of 8000-12000 rpm for 5-10 min, then adding silicon dioxide and drying.

7. The preparation method according to claim 1, characterized in that In step S3, the multi-gradient alcohol extraction operation is as follows: After grinding Forsythia suspensa and Rehmannia root, add 30wt%-45wt% ethanol solution and extract at 30-50℃ for 0.5-1h; Adjust the concentration of the ethanol solution to 50wt%-65wt% and extract at 30-50°C for 0.5-1h; Adjust the concentration of the ethanol solution to 70wt%-85wt% and extract at 70-75°C for 0.5-1h; Combine the extracts.

8. The preparation method according to claim 1, characterized in that In step S4, the gypsum needs to be crushed and passed through a 20-40 mesh sieve; the stabilizer is a mixture of astragalus polysaccharide, green apple extract and vitamin E; the mass ratio of the astragalus polysaccharide, green apple extract and vitamin E is 0.1-1:5-10:2-4.

9. An antiviral oral liquid, characterized in that: The invention is prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the antiviral oral liquid prepared according to the preparation method according to any one of claims 1 to 8 in preparing medicines for preventing or treating viral colds.

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