Antiviral preparation and preparation method thereof

Abstract

The invention discloses an antiviral preparation and a preparation method thereof, and relates to the field of pharmaceutical preparations, the process is innovated, traditional Chinese medicinal materials with antiviral volatile oil as a main effective component are subjected to a supercritical CO2 extraction technology, high-purity antiviral volatile oil can be extracted at a low temperature, the problem that the antiviral volatile oil is unstable at a high temperature is avoided, and the antiviral volatile oil can be used for preparing the antiviral preparation. Meanwhile, specific steps of granulation, oil loading and closed braising are matched, an ethanol solvent is used as a medium, wetting is firstly carried out, soft material granulation is prepared, a hydrophilic particle skeleton is constructed, then dissolving is carried out, antiviral volatile oil is sprayed and attached to particles, and after closed braising, the anti-virus composition is obtained. The dispersion degree and the combination degree of the hydrophobic volatile oil in hydrophilic traditional Chinese medicine particles (soft materials) are remarkably improved, and the problems that the antiviral volatile oil is unstable in component and poor in uniformity in a preparation are fundamentally solved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparations, and in particular to an antiviral preparation and its preparation method. Background Technology

[0002] Viruses are a class of simple, non-cellular microorganisms measured in nanometers, exhibiting strict parasitism and reproducing through replication. Viruses can cause a wide range of diseases, from the common flu and chickenpox to serious illnesses such as AIDS, hepatitis B, and cancer, posing a significant threat to human health. Current antiviral drugs primarily work by inhibiting viral replication enzymes or blocking viral replication; however, some formulations suffer from problems such as unstable content and poor uniformity of active ingredients.

[0003] Forsythia, a traditional Chinese medicine commonly used for its antiviral effects, possesses properties such as clearing heat and detoxifying, anti-inflammatory and antibacterial effects, reducing swelling and dissipating nodules, and protecting the liver. It is an important component of antiviral preparations. However, traditional preparation processes directly pulverize or extract Forsythia with other medicinal materials (such as Isatis root, gypsum, and Rehmannia root) and then mix them. High temperatures can easily lead to substandard volatile oil content and uneven content between slices, and also require sophisticated mixing equipment, resulting in poor process stability. Therefore, it is necessary to develop a new method that can improve the utilization rate of antiviral volatile oil and the uniformity of the preparation. Summary of the Invention

[0004] The main objective of this invention is to propose a method for preparing antiviral agents. By innovating the process, this invention effectively solves the technical problems of insufficient content of antiviral volatile oils in the preparation and uneven content between tablets in antiviral agents prepared using traditional processes.

[0005] To achieve the above objectives, this invention proposes a method for preparing an antiviral agent, comprising the following steps: S1. Extraction of antiviral volatile oil: The main active ingredient of the Chinese herbal medicine, which is antiviral volatile oil, is taken separately in the prescription amount and pulverized. The antiviral volatile oil is extracted by supercritical CO2 extraction technology and stored for later use. This step aims to obtain high-purity heat-sensitive volatile oil efficiently and at low temperature.

[0006] S2. Preparation of antiviral mixed powder: Take other Chinese medicinal materials in the prescription according to the prescription amount, extract the effective components by water extraction process, concentrate, pulverize and sieve the extract to prepare antiviral mixed powder; S3. Granulation, oil loading, and simmering: S31. The antiviral mixed powder was mixed with excipients, ethanol was added to wet the mixture, a soft material was prepared, sieved and granulated, and dried; a hydrophilic particle skeleton was constructed. The introduction of ethanol pre-formed a microenvironment with good compatibility with volatile oil inside the particles, laying the skeleton foundation for the uniform adsorption of volatile oil in the subsequent process.

[0007] Suitable excipients include diluents, fillers, binders, etc., with starch being the preferred excipient. Specifically, the excipient accounts for 1 to 10% of the mass of the powder.

[0008] S32. Dissolve the reserved antiviral volatile oil in ethanol and spray it evenly into the dried antiviral particles. Since the particle skeleton is prepared by wetting with ethanol, it has a high affinity for the ethanol solution of volatile oil and can be absorbed quickly and evenly, effectively avoiding local enrichment of the oil phase.

[0009] S33. The antiviral particles, which are uniformly sprayed with an antiviral volatile oil ethanol solution, are sealed and left to steep. Through sealing and steeping, the volatile oil is ensured to fully penetrate and fix in the particles, so as to achieve uniform oil loading.

[0010] S4. Preparation of antiviral formulations: Add other excipients to the antiviral granules after they have been sealed and simmered, and mix them to prepare the corresponding antiviral formulation.

[0011] Specifically, in step S4, the excipients are known excipients that match the corresponding dosage form. Preferably, the excipients in step S4 are lubricants and / or fillers, wherein the lubricant is at least one of magnesium stearate, talc, and micronized silica gel, and the filler is at least one of microcrystalline cellulose and starch.

[0012] This invention innovates the overall process by employing supercritical CO2 extraction technology to extract high-purity antiviral volatile oils from traditional Chinese medicines whose main active ingredient is antiviral volatile oil. This avoids the instability of antiviral volatile oils at high temperatures. Simultaneously, specific granulation, oil loading, and curing steps are incorporated. Using ethanol as a solvent, the mixture is first wetted and granulated into a soft mass, constructing a hydrophilic particle skeleton. The antiviral volatile oil is then dissolved and sprayed onto the particles. After a sealed curing process, the dispersion and binding of the hydrophobic volatile oil within the hydrophilic Chinese medicine particles (soft mass) are significantly improved. This fundamentally solves the problems of unstable antiviral volatile oil composition and poor uniformity in formulations. Due to the reliability and reproducibility of the process, batch-to-batch stability is greatly enhanced, ensuring the consistency and effectiveness of the final formulation. This represents a significant improvement over traditional Chinese medicine solid dosage form processes.

[0013] Generally speaking, after adding ethanol to prepare a soft material and drying it, technicians would assume that the ethanol in the soft material particles has evaporated and would hardly think that it could synergistically interact with other steps. This invention utilizes ethanol to wet the soft material during granulation, so that a microenvironment with good compatibility with the subsequent volatile oil ethanol solution is formed inside the particles, laying the particle skeleton foundation for the uniform adsorption of the volatile oil.

[0014] Preferably, the Chinese medicinal herb whose main active ingredient is antiviral volatile oil is Forsythia suspensa. More preferably, the ethanol concentration in step S32 is 50-70%. Preparations made with ethanol at specific concentrations exhibit better uniformity of Forsythia suspensa volatile oil content. All ethanol concentration percentages mentioned in this invention refer to corresponding volume fractions of aqueous ethanol solutions.

[0015] A preferred embodiment is provided, comprising a method for preparing an antiviral agent, including the following steps: S1. Extraction of Forsythia suspensa volatile oil: Take the prescribed amount of Forsythia suspensa medicinal material, pulverize it, and use supercritical CO2 extraction technology. The extraction temperature is 30-50℃ and the extraction pressure is 25-30MPa to extract Forsythia suspensa volatile oil, which is then stored for later use. S2. Preparation of antiviral mixed powder: Take the following eight medicinal materials according to the prescription: Isatis root, gypsum, Rehmannia root, Patchouli, Phragmites rhizome, Curcuma root, Acorus tatarinowii and Anemarrhena rhizome. Extract and filter them by water decoction to obtain an aqueous extract. Concentrate the aqueous extract under reduced pressure at 60℃±5℃ to a clear extract with a relative density of 1.2 to 1.3. Then, vacuum dry it at 80℃±5℃, pulverize and sieve it to obtain antiviral mixed powder. S3. Granulation, oil loading and curing: S31. Mix the antiviral powder with excipients, add ethanol to wet, prepare soft material, sieve and granulate, and dry; S32. Dissolve the reserved fortified forsythia volatile oil in 50-70% ethanol, and spray it evenly into the dried antiviral granules; S33. Seal and cure the antiviral granules with the forsythia volatile oil ethanol solution for 2-3 hours. S4. Preparation of antiviral formulations: Add other excipients to the antiviral granules after they have been sealed and simmered, and mix them to prepare the corresponding antiviral formulation.

[0016] The prescription consists of the following Chinese herbal ingredients by weight: 30 parts forsythia, 360 parts for isatis root, 160 parts for gypsum, 90 parts for rehmannia root, 80 parts for patchouli, 170 parts for reed rhizome, 70 parts for turmeric, 70 parts for acorus tatarinowii, and 70 parts for anemarrhena rhizome.

[0017] Specifically, an appropriate amount of magnesium stearate is added to S4 as a lubricant, and after mixing, it is compressed into tablets to obtain 1000 antiviral tablets. It can also be combined with appropriate known excipients and processes to obtain antiviral granules, pills, capsules (such as hard capsules), or buffered-release capsules.

[0018] The above-mentioned formulation, through the preparation process of the present invention, achieves a forsythia volatile oil content that meets the standard compared with traditional technology, while significantly improving the uniformity of forsythia volatile oil content in the formulation. Experiments have shown that 70% ethanol is the optimal wetting carrier for preparing soft materials.

[0019] The present invention provides an antiviral preparation, which is prepared by the method for preparing an antiviral preparation according to any of the foregoing schemes.

[0020] Specifically, the dosage form of antiviral agents is one of granules, tablets, pills, capsules, and sustained-release capsules.

[0021] Unlike existing technologies, this invention innovates the process by employing supercritical CO2 extraction technology to extract high-purity antiviral volatile oils from traditional Chinese medicines whose main active ingredient is antiviral volatile oil. This avoids the instability of antiviral volatile oils at high temperatures. Simultaneously, specific granulation, oil loading, and curing steps are incorporated. Using ethanol as a solvent, the mixture is first wetted and granulated into a soft mass, constructing a hydrophilic particle skeleton. The antiviral volatile oil is then dissolved and sprayed onto the particles. After a sealed curing process, the dispersion and binding of the hydrophobic volatile oil within the hydrophilic Chinese medicine particles (soft mass) are significantly improved. This fundamentally solves the problems of unstable antiviral volatile oil composition and poor uniformity in formulations. Due to the reliability and reproducibility of the process, batch-to-batch stability is greatly enhanced, ensuring the consistency and effectiveness of the final formulation. This represents a significant improvement over traditional Chinese medicine solid dosage form processes. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 The HPLC chromatogram shows the content of the reference standard, Forsythia suspensa. Figure 2 This is a representative HPLC chromatogram of the content of Forsythia suspensa in Example 1; Figure 3 This is a representative HPLC chromatogram of the content of Forsythia suspensa in Example 2; Figure 4 The HPLC chromatogram of the forsythia content in Example 3 is shown. Figure 5 The HPLC chromatogram of the forsythia content in Example 4 is shown. Figure 6 The HPLC chromatograms are representative of the content of Forsythia suspensa in Comparative Example 1-1. Figure 7 The HPLC chromatograms are representative of the content of Forsythia suspensa in Comparative Examples 1-2; Figure 8 The HPLC chromatogram shows the content of the reference standard, Forsythia suspensa. Figure 9 The HPLC chromatograms are representative of the content of Forsythia suspensa in Comparative Example 2-1. Figure 10 The HPLC chromatograms are representative of the content of Forsythia suspensa in Comparative Example 2-2. Figure 11 The HPLC chromatograms are representative of the content of Forsythia suspensa in comparative examples 2-3; Figure 12 The HPLC chromatograms are representative of the content of Forsythia suspensa in Comparative Example 3; The realization of the purpose, functional features and advantages of this application will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0024] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. In addition, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such combination of technical solutions does not exist and is not within the scope of protection claimed by the present invention.

[0025] This application discloses a method for preparing an antiviral agent, comprising the following steps: S1. Extraction of antiviral volatile oil: The main active ingredient of the Chinese herbal medicine, which is antiviral volatile oil, is taken separately in the prescription amount and pulverized. The antiviral volatile oil is extracted by supercritical CO2 extraction technology and stored for later use. This step aims to obtain high-purity heat-sensitive volatile oil efficiently and at low temperature.

[0026] S2. Preparation of antiviral mixed powder: Take other Chinese medicinal materials in the prescription according to the prescription amount, extract the effective components by water extraction process, concentrate, pulverize and sieve the extract to prepare antiviral mixed powder; S3. Granulation, oil loading, and simmering: S31. The antiviral mixed powder is mixed with excipients, moistened with ethanol, and a soft material is prepared. The mixture is then sieved, granulated, and dried. This constructs a hydrophilic particle framework. The introduction of ethanol pre-creates a microenvironment with good compatibility with volatile oils within the particles, laying the skeletal foundation for the subsequent uniform adsorption of volatile oils. In specific embodiments, suitable excipients include diluents, fillers, binders, etc. In a preferred embodiment, the excipient is starch.

[0027] S32. Dissolve the reserved antiviral volatile oil in ethanol and spray it evenly into the dried antiviral particles. Since the particle skeleton is prepared by wetting with ethanol, it has a high affinity for the ethanol solution of volatile oil and can be absorbed quickly and evenly, effectively avoiding local enrichment of the oil phase.

[0028] S33. The antiviral particles, which are uniformly sprayed with an antiviral volatile oil ethanol solution, are sealed and left to steep. Through sealing and steeping, the volatile oil is ensured to fully penetrate and fix in the particles, so as to achieve uniform oil loading.

[0029] S4. Preparation of antiviral formulations: Add other excipients to the antiviral granules after they have been sealed and simmered, and mix them to prepare the corresponding antiviral formulation.

[0030] In a specific embodiment, the excipient in step S4 is a known excipient that matches the corresponding dosage form. In a preferred embodiment, the excipient in step S4 is a lubricant and / or a filler, wherein the lubricant is at least one of magnesium stearate, talc, and micronized silica gel, and the filler is at least one of microcrystalline cellulose and starch.

[0031] In a preferred embodiment, the Chinese medicinal herb whose main active ingredient is antiviral volatile oil is Forsythia suspensa. When Forsythia suspensa is used as the Chinese medicinal herb with antiviral volatile oil as the main active ingredient, in a preferred embodiment, the ethanol concentration in step S3 is 50-70%. Preparations prepared using ethanol at a specific concentration exhibit high uniformity in the content of Forsythia suspensa volatile oil.

[0032] In a preferred embodiment, a method for preparing an antiviral agent includes the following steps: S1. Extraction of Forsythia suspensa volatile oil: Take the prescribed amount of Forsythia suspensa medicinal material, pulverize it, and use supercritical CO2 extraction technology. The extraction temperature is 30-50℃ and the extraction pressure is 25-30MPa to extract Forsythia suspensa volatile oil, which is then stored for later use. S2. Preparation of antiviral mixed powder: Take the following eight medicinal materials according to the prescription: Isatis root, gypsum, Rehmannia root, Patchouli, Phragmites rhizome, Curcuma root, Acorus tatarinowii and Anemarrhena rhizome. Extract and filter them by water decoction to obtain an aqueous extract. Concentrate the aqueous extract under reduced pressure at 60℃±5℃ to a clear extract with a relative density of 1.2 to 1.3. Then, vacuum dry it at 80℃±5℃, pulverize and sieve it to obtain antiviral mixed powder. S3. Granulation, oil loading and curing: S31. Mix the antiviral powder with excipients, add ethanol to wet, prepare soft material, sieve and granulate, and dry; S32. Dissolve the reserved fortified forsythia volatile oil in 50-70% ethanol, and spray it evenly into the dried antiviral granules; S33. Seal and cure the antiviral granules with the forsythia volatile oil ethanol solution for 2-3 hours. S4. Preparation of antiviral formulations: Add other excipients to the antiviral granules after they have been sealed and simmered, and mix them to prepare the corresponding antiviral formulation.

[0033] The prescription consists of the following Chinese herbal ingredients by weight: 30 parts forsythia, 360 parts for isatis root, 160 parts for gypsum, 90 parts for rehmannia root, 80 parts for patchouli, 170 parts for reed rhizome, 70 parts for turmeric, 70 parts for acorus tatarinowii, and 70 parts for anemarrhena rhizome.

[0034] In a specific embodiment, an appropriate amount of magnesium stearate is added to S4 as a lubricant, and after mixing, the mixture is compressed into tablets to obtain 1000 antiviral tablets. Antiviral granules, pills, capsules (such as hard capsules), or buffered-release capsules can also be obtained by combining with appropriate known excipients and processes.

[0035] The above-mentioned prescription, through the formulation process of the present invention, achieves a forsythia volatile oil content that meets the standard compared with traditional technology, while significantly improving the uniformity of forsythia volatile oil content in the formulation.

[0036] This application provides an antiviral preparation, which is prepared by the method for preparing an antiviral preparation according to any of the foregoing schemes.

[0037] In a specific embodiment, the dosage form of the antiviral preparation is one of granules, tablets, pills, capsules, and sustained-release capsules.

[0038] The technical solution of the present invention will be further described in detail below with reference to specific embodiments or comparative examples. In the following embodiments and comparative examples, the raw materials and reagents, unless otherwise specified, are all obtained commercially available, and the same batch of raw materials or reagents are used in the embodiments and comparative examples. The preparation methods without special conditions are all prepared by conventional and well-known preparation methods.

[0039] Example 1 Preparation of antiviral tablets (1) Extraction of Forsythia volatile oil: Take 30g of Forsythia suspensa medicinal material, crush it, and use supercritical CO2 extraction technology to extract it for 3 hours at a temperature of 35℃ and a pressure of 25Mpa. High-purity Forsythia volatile oil is collected and used for later use.

[0040] (2) Preparation of the aqueous extract: Take 360g of Isatis root, 160g of gypsum, 90g of Rehmannia root, 80g of Pogostemon cablin, 170g of Phragmites communis rhizome, 70g of Curcuma longa, 70g of Acorus tatarinowii, and 70g of Anemarrhena asphodeloides. Extract and filter the extract using the conventional decoction method to obtain an aqueous extract. Concentrate the extract under reduced pressure at 60℃ to a clear extract with a relative density of 1.3, then vacuum dry at 80℃, and pulverize through an 80-mesh sieve to obtain the aqueous extract powder.

[0041] (3) Simultaneous ethanol granulation and oil loading: ① Constructing an affinity particle skeleton: Add 5% starch by mass of the above-mentioned water extract dry powder, wet with 70% ethanol to prepare a soft material, granulate through a 20-mesh sieve, and dry at 60℃ to obtain dry particles.

[0042] ②Uniform oil loading achieved by using ethanol as a medium: The forsythia volatile oil prepared in step (1) is fully dissolved in 80% ethanol and sprayed evenly into the dried particles. The antiviral particles with the forsythia volatile oil ethanol solution sprayed evenly are placed in a sealed stainless steel container and left to stand at 20±5℃ for 3 hours.

[0043] (4) Tableting: Add magnesium stearate at 0.6% of the particle mass as a lubricant, mix well and then compress to obtain 1000 antiviral tablets.

[0044] Example 2 Preparation of antiviral tablets (1) Extraction of Forsythia volatile oil: Take 30g of Forsythia suspensa medicinal material, crush it, and use supercritical CO2 extraction technology to extract it for 3 hours at a temperature of 35℃ and a pressure of 25Mpa. High-purity Forsythia volatile oil is collected and used for later use.

[0045] (2) Preparation of the aqueous extract: Take 360g of Isatis root, 160g of gypsum, 90g of Rehmannia root, 80g of Pogostemon cablin, 170g of Phragmites communis rhizome, 70g of Curcuma longa, 70g of Acorus tatarinowii, and 70g of Anemarrhena asphodeloides. Extract and filter the extract using the conventional decoction method to obtain an aqueous extract. Concentrate the extract under reduced pressure at 60℃ to a clear extract with a relative density of 1.3, then vacuum dry at 80℃, and pulverize through an 80-mesh sieve to obtain the aqueous extract powder.

[0046] (3) Simultaneous ethanol granulation and oil loading: ① Constructing an affinity particle skeleton: Add 5% starch by weight of the above-mentioned water extract dry powder, wet with 60% ethanol to prepare a soft material, granulate through a 20-mesh sieve, and dry at 60℃ to obtain dry particles.

[0047] ②Uniform oil loading achieved with ethanol as a medium: The forsythia volatile oil prepared in step (1) is fully dissolved in 80% ethanol and sprayed evenly into the dried particles. The antiviral particles with the forsythia volatile oil ethanol solution sprayed evenly are placed in a sealed stainless steel container and sealed and simmered at 20±5℃ for 3 hours; (4) Tableting: Add magnesium stearate at 0.6% of the particle mass as a lubricant, mix well and then compress to obtain 1000 antiviral tablets.

[0048] Example 3 Preparation of antiviral tablets (1) Extraction of Forsythia volatile oil: Take 30g of Forsythia suspensa medicinal material, crush it, and use supercritical CO2 extraction technology to extract it for 3 hours at a temperature of 35℃ and a pressure of 25Mpa. High-purity Forsythia volatile oil is collected and used for later use.

[0049] (2) Preparation of the aqueous extract: Take 360g of Isatis root, 160g of gypsum, 90g of Rehmannia root, 80g of Pogostemon cablin, 170g of Phragmites communis rhizome, 70g of Curcuma longa, 70g of Acorus tatarinowii, and 70g of Anemarrhena asphodeloides. Extract and filter the extract using the conventional decoction method to obtain an aqueous extract. Concentrate the extract under reduced pressure at 60℃ to a clear extract with a relative density of 1.3, then vacuum dry at 80℃, and pulverize through an 80-mesh sieve to obtain the aqueous extract powder.

[0050] (3) Simultaneous ethanol granulation and oil loading: ① Constructing an affinity particle skeleton: Add 5% starch by weight of the above-mentioned water extract dry powder, wet with 50% ethanol to prepare a soft material, granulate through a 20-mesh sieve, and dry at 60℃.

[0051] ②Uniform oil loading achieved by using ethanol as a medium: The forsythia volatile oil prepared in step (1) is fully dissolved in 80% ethanol and sprayed evenly into the dried particles. The antiviral particles with the forsythia volatile oil ethanol solution sprayed evenly are placed in a sealed stainless steel container and left to stand at 20±5℃ for 3 hours.

[0052] (4) Tableting: Add magnesium stearate at 0.6% of the particle mass as a lubricant, mix well and then compress to obtain 1000 antiviral tablets.

[0053] Example 4 Preparation of antiviral capsules (1) Extraction of Forsythia volatile oil: Take 30g of Forsythia suspensa medicinal material, crush it, and use supercritical CO2 extraction technology to extract it for 3 hours at a temperature of 35℃ and a pressure of 25Mpa. High-purity Forsythia volatile oil is collected and used for later use.

[0054] (2) Preparation of the aqueous extract: Take 360g of Isatis root, 160g of gypsum, 90g of Rehmannia root, 80g of Pogostemon cablin, 170g of Phragmites communis rhizome, 70g of Curcuma longa, 70g of Acorus tatarinowii, and 70g of Anemarrhena asphodeloides. Extract and filter the extract using the conventional decoction method to obtain an aqueous extract. Concentrate the extract under reduced pressure at 60℃ to a clear extract with a relative density of 1.3, then vacuum dry at 80℃, and pulverize through an 80-mesh sieve to obtain the aqueous extract powder.

[0055] (3) Simultaneous ethanol granulation and oil loading: ① Constructing an affinity particle skeleton: Add 5% starch by mass of the above-mentioned water extract dry powder, wet with 70% ethanol to prepare a soft material, granulate through a 20-mesh sieve, and dry at 60℃ to obtain dry particles.

[0056] ②Uniform oil loading achieved with ethanol as a medium: The forsythia volatile oil prepared in step (1) is fully dissolved in 80% ethanol and sprayed evenly into the dried particles. The antiviral particles with the forsythia volatile oil ethanol solution are placed in a sealed stainless steel container and sealed and left to stand at 20±5℃ for 3 hours; (4) Tableting: Add microcrystalline cellulose at 30% of the particle mass as a filler, mix well, and fill into capsules to obtain 1000 antiviral capsules.

[0057] Comparative Example 1 The preparation steps for antiviral tablets are basically the same as those in Example 1, except that: (3) Ethanol is used for simultaneous granulation and the solvent for wetting the soft material in the carrier oil.

[0058] Comparative Example 2 The preparation steps for antiviral tablets are basically the same as those in Example 1, except that: (3) simultaneous granulation of ethanol and oil loading steps.

[0059] Comparative Example 3 The preparation steps for antiviral tablets are basically the same as those in Example 1, except that: (1) the extraction steps of Forsythia suspensa volatile oil.

[0060] Comparison of content uniformity To verify the beneficial effects of the present invention, the formulations prepared in the above embodiments and comparative examples were subjected to quality testing.

[0061] 1. Determination of the uniformity of forsythoside content Content determination The content is calculated based on peak area using the external standard method. Each tablet of this product contains forsythoside C. 29 H 36 O 15 The total amount should not be less than 100µg.

[0062] Sample solution preparation: Take 10 tablets of this product, remove the coating, accurately weigh, grind finely, take 0.9g, accurately weigh, place in a stoppered conical flask, add methanol and sonicate (power 50W, frequency 50kHz) 3 times, 40ml each time, 10 minutes each time, remove, cool, filter, collect the filtrate, wash the residue and container with 10ml of methanol, combine the filtrate and washings, concentrate to about 15ml, add to a neutral alumina column (100-200 mesh, 6g, inner diameter 0.7cm, dry packing), elute with 50ml of 50% methanol, collect the eluent, evaporate to dryness, dissolve the residue in methanol, transfer to a 10ml volumetric flask, dilute to the mark with methanol, shake well, filter, and take the filtrate as the test solution.

[0063] Preparation of reference solution: Weigh 12.5 mg of forsythoside reference standard accurately, place it in a 50 ml volumetric flask, dissolve and dilute to the mark with methanol, shake well, then accurately measure 1 ml and place it in a 50 ml volumetric flask, dilute to the mark with methanol, shake well, filter, and take the filtrate as the reference solution.

[0064] Ten tablets were randomly selected from the formulations prepared in the examples and comparative examples, and the content of forsythoside in each tablet was determined. The average value and relative standard deviation (RSD) were calculated. The results are shown in the table below.

[0065] The experimental data for Examples 1-4 are shown in the table below: Table 1 Comparative Example 1 used different solvents as carriers to prepare soft materials. The experimental data are shown in the table below: Table 2 Comparative Examples 2 and 3 used different preparation processes, and the experimental data are shown in the table below: Table 3 Process Comparison and Effect Analysis Examples 1-4 of this invention (ethanol-carrier linked process) employ a linked granulation and oil loading method: 50-70% ethanol is used as a solvent to prepare a soft material. The volatile oil is dissolved in ethanol, sprayed onto the dried soft material particles, and then sealed and left to steep. The resulting formulation exhibits high uniformity of content. Similar experiments showed that at both lower concentrations (e.g., 30%) and higher concentrations (e.g., 90%), the RSD% of uniformity in the formulation content was below 2%, with 50-70% ethanol showing the best effect, and 70% ethanol exhibiting the best uniformity. Examples 1 and 4 demonstrate that Forsythia suspensa volatile oil, in ethanol solution form, is uniformly absorbed and distributed by particles with affinity, exhibits high batch-to-batch stability, and good process reproducibility. Furthermore, this demonstrates that the above formulation process is applicable not only to tablet preparation but also to capsule preparation, indicating that this invention demonstrates the same beneficial effects when applied to different dosage forms.

[0066] As can be seen from Comparative Examples 1-1 to 1-3, when using purified water as a carrier to prepare soft materials, the preparations after dissolving volatile oils in ethanol and adsorbing them by spraying resulted in poor uniformity of content, uneven distribution, and poor batch-to-batch stability. When using isopropanol as a carrier to prepare soft materials, the preparations after dissolving volatile oils in ethanol and adsorbing them by spraying them by spraying resulted in better uniformity of content. However, isopropanol is a Class II organic solvent and should be avoided in pharmaceutical preparations. When using acetone as a carrier to prepare soft materials, the soft materials prepared by acetone are brittle due to its volatile nature, proving that acetone is not suitable as a carrier.

[0067] Comparing Example 1, Comparative Examples 2-1 to 2-3, and Comparative Example 3, it can be seen that: Comparative Example 2-1 used the process conditions of Example 1, but did not perform closed curing; the content was close to the standard, but there were differences between tablets, and the uniformity was critical or unqualified; and there were problems with tablet sticking and cracking during the tableting process. Comparative Example 2-2 used the process conditions of Example 1, but performed open curing; the content was close to the standard, but there were differences between tablets, and the uniformity was critical or unqualified. Comparative Example 2-3 used the process conditions of Example 1, but the volatile oil was not dissolved in ethanol; the content was close to the standard, but there were large differences between tablets, and the uniformity was critical or unqualified. Comparative Example 3 used the process conditions of Example 1, but used the conventional water decoction method to extract the volatile oil of Forsythia suspensa; the content was close to the standard, but there were large differences between tablets, and the uniformity was critical or unqualified.

[0068] The above description is merely a preferred embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural transformations made using the contents of the present invention under the inventive concept of the present invention, or direct / indirect applications in other related technical fields, are included within the patent protection scope of the present invention.

Claims

1. A method for preparing an antiviral preparation, characterized by, Comprising the following steps: S1. Extraction of antiviral volatile oil: The prescription amount of Chinese herbal medicine with main effective component of antiviral volatile oil is crushed, and antiviral volatile oil is extracted by supercritical CO2 extraction technology, and is stored for standby; S2. Preparation of antiviral mixed powder: The prescription amount of other Chinese herbal medicines in the prescription is taken, and the effective components are extracted by water extraction process, and the extract is concentrated, crushed, and sieved to prepare the antiviral mixed powder; S3. Granulation, oil loading and standing: S31. The antiviral mixed powder and excipients are mixed, wetted with ethanol, prepared into soft material, sieved and granulated, and dried; S32. The antiviral volatile oil stored for standby is dissolved in ethanol, and is uniformly sprayed into the dried antiviral granules; S33. The antiviral granules uniformly sprayed with the antiviral volatile oil ethanol solution are sealed and stood in a stainless steel container; S4. Preparation of antiviral preparation: The antiviral granules after sealed standing are added with other excipients, and are uniformly mixed to prepare the corresponding antiviral dosage form.

2. The method of claim 1, wherein the antiviral formulation is prepared by mixing the antiviral agent and the carrier in a ratio of 1: 1 to 1:

10. In step S1, the Chinese herbal medicine with main effective component of antiviral volatile oil is forsythia suspense.

3. The method of claim 1, wherein the antiviral formulation is prepared by mixing the antiviral agent and the carrier in a ratio of 1: 1 to 1:

10. The ethanol concentration in step S32 is 50-70%.

4. The method of claim 3, wherein the antiviral formulation is prepared by mixing the antiviral agent and the carrier in a ratio of 1: 1 to 1:

10. Comprising the following steps: S1. Extraction of forsythia suspense volatile oil: The prescription amount of forsythia suspense Chinese herbal medicine is crushed, and forsythia suspense volatile oil is extracted by supercritical CO2 extraction technology at an extraction temperature of 30-50 ℃ and an extraction pressure of 25-30 MPa, and is stored for standby; S2. Preparation of antiviral mixed powder: The prescription amount of radix isatidis, gypsium, radix rehmanniae, pachystachys juttah, radix ofphorbia pectinata, curcuma zedoary and anemarrhena asphodeloides are taken, and are extracted by water decoction method, and the water extract is filtered to obtain water extract, and the water extract is concentrated to a clear extract with a relative density of 1.2-1.3 at 60 ℃±5 ℃ under reduced pressure, and is vacuum dried at 80 ℃±5 ℃, crushed and sieved to obtain the antiviral mixed powder; S3. Granulation, oil loading and standing: S31. The antiviral mixed powder is added with suitable excipients, wetted with ethanol, prepared into soft material, sieved and granulated, and dried; S32. The forsythia suspense volatile oil stored for standby is dissolved in 50-70% ethanol, and is uniformly sprayed into the dried antiviral granules; S33. The antiviral granules uniformly sprayed with the forsythia suspense volatile oil ethanol solution are sealed and stood in a stainless steel container at 20±5 ℃ for 2-3 hours; S4. Preparation of antiviral preparation: The antiviral granules after sealed standing are added with other excipients, and are uniformly mixed to prepare the corresponding antiviral dosage form.

5. The method of claim 4, wherein the antiviral formulation is prepared by mixing the antiviral agent and the carrier in a ratio of 1: 1 to 1:

10. According to weight parts, the prescription is composed of the following Chinese medicine components: forsythia suspense 30 parts, radix isatidis 360 parts, gypsium 160 parts, radix rehmanniae 90 parts, pachystachys juttah 80 parts, radix ofphorbia pectinata 170 parts, curcuma zedoary 70 parts and anemarrhena asphodeloides 70 parts.

6. The method of claim 1, wherein the antiviral formulation is prepared by mixing the antiviral agent and the carrier in a ratio of 1: 1 to 1:

10. The excipient in step S31 is starch, and the excipient in step S4 is lubricant and / or filler, the lubricant is at least one of magnesium stearate, talc and micronized silica gel, and the filler is at least one of microcrystalline cellulose and starch.

7. An antiviral preparation characterised in that, Prepared by the preparation method of the antiviral preparation in any one of claims 1-6.

8. The antiviral preparation of claim 7, wherein The dosage form of the antiviral preparation is one of granules, tablets, pills, capsules and controlled-release capsules.

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