CN113288938A

CN113288938A - Antiviral traditional Chinese medicine composition

Info

Publication number: CN113288938A
Application number: CN202110801638.5A
Authority: CN
Inventors: 张靖华; 王翠敏
Original assignee: Anhui Xinquankang Pharmaceutical Co ltd
Current assignee: Anhui Xinquankang Pharmaceutical Co ltd
Priority date: 2021-07-15
Filing date: 2021-07-15
Publication date: 2021-08-24

Abstract

The invention discloses an antiviral traditional Chinese medicine composition, which belongs to the technical field of antiviral traditional Chinese medicines and comprises the following components in percentage by mass: 2.5: 0.1: 0.2 of traditional Chinese medicine extract, cross-linking components, a lubricant and a disintegrating agent, wherein the traditional Chinese medicine extract is extracted from honeysuckle, wild chrysanthemum flower, isatis root, scutellaria baicalensis, liquorice, white paeony root, astragalus mongholicus and fructus forsythiae, and the cross-linking components are starch, microcrystalline cellulose and cross-linked sodium carboxymethyl cellulose in a mass ratio of 1: 1: 0.1, the lubricant is magnesium stearate, the disintegrating agent is modified carboxymethyl starch, the finally prepared composition is a tablet, wherein the protocatechuic acid and the resveratrol which are active substances are introduced in the preparation process, and the prepared intermediate 3 is combined with the carboxymethyl starch in an esterification way, so that the decomposition speed of the compound in the body is reduced, the retention time of the medicine is increased, and the effect of the medicine is improved.

Description

Antiviral traditional Chinese medicine composition

Technical Field

The invention relates to the technical field of antiviral traditional Chinese medicines, and in particular relates to an antiviral traditional Chinese medicine composition.

Background

The virus is the smallest of the pathogenic microorganisms, propagates inside the cell, is core ribonucleic acid or deoxyribonucleic acid, and has a coat of protein and no cellular structure. Viruses parasitize in host cells, depend on the metabolic system of the host cells for multiplication and replication, are released from the cells in various ways to infect other cells, viral nucleic acids are sometimes integrated in cell DNA molecules and are not easy to eliminate, and the infection of the viruses can cause various diseases, including various colds, excessive internal heat and the like, or complications of the diseases. Most of the substances such as antibiotics and the like of the medicaments provided for resisting viruses at the present stage can cause adverse effects on organisms after long-term administration, and the traditional Chinese medicine has mild effects and few side effects, can effectively improve the physical quality and the life quality of patients while defending the viruses, and is paid great attention, so that the preparation of the traditional Chinese medicine composition for resisting the viruses is very necessary.

Disclosure of Invention

The invention aims to provide an antiviral traditional Chinese medicine composition for solving the problems in the background technology.

The purpose of the invention can be realized by the following technical scheme:

an antiviral traditional Chinese medicine composition comprises the following components in percentage by mass: 2.5: 0.1: 0.2 of traditional Chinese medicine extract, a crosslinking component, a lubricant and a disintegrating agent;

wherein the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 5-8 parts of honeysuckle, 3-5 parts of wild chrysanthemum flower, 3-5 parts of isatis root, 2-4 parts of scutellaria baicalensis, 2-4 parts of liquorice, 1-3 parts of white paeony root, 1-3 parts of astragalus mongholicus and 1-3 parts of fructus forsythiae;

the traditional Chinese medicine extract is prepared by the following steps: cleaning and draining weighed honeysuckle, wild chrysanthemum flower, isatis root, scutellaria baicalensis, liquorice, white paeony root, astragalus and weeping forsythia, respectively placing the weighed honeysuckle, wild chrysanthemum flower, isatis root, scutellaria baicalensis, liquorice, radix paeoniae alba, astragalus and weeping forsythia into different crushers for crushing, then adding the crushed honeysuckle, wild chrysanthemum flower and weeping forsythia into a boiling pot, adding distilled water for decocting for 3-5h, adding water every 1h during the decoction, adding 3 times of water for totally, filtering out decoction after the decoction is finished, squeezing the residual Chinese medicine with eight layers of gauze to obtain juice, combining the juice with the decoction, and concentrating to obtain a Chinese medicine extract;

furthermore, in the preparation process of the Chinese medicinal extract, the amount of water added for the first time is 6-8 times of the total weight of the Chinese medicinal materials, and the amount of water added for the second time and the third time is 5-7 times of the total weight of the Chinese medicinal materials.

Further, the cross-linking component is starch, microcrystalline cellulose and cross-linked sodium carboxymethyl cellulose in a mass ratio of 1: 1: 0.1 mixing to obtain;

further, the lubricant is magnesium stearate;

further, the disintegrant is prepared by the following steps:

step S1: adding a mixed solution of corn starch, isopropanol and deionized water and sodium hydroxide into a flask, reacting for 1.5h at the temperature of 40 ℃, cooling to 30 ℃, dropwise adding an isopropanol solution of chloroacetic acid, adding sodium hydroxide, reacting for 30min under an ice bath condition, heating to 50 ℃ again, reacting for 3h, after the reaction is finished, adjusting the pH to 8 by using glacial acetic acid, performing suction filtration, washing by using a methanol water solution with the volume fraction of 80%, and drying a filter cake at the temperature of 100 ℃ to obtain an intermediate 1; wherein the dosage ratio of the mixed solution of corn starch, isopropanol and deionized water, the first-time added sodium hydroxide, the chloroacetic acid isopropanol solution and the second-time added sodium hydroxide is 4 g: 70mL of: 4 g: 15mL of: 4.8 g; mixing deionized water and isopropanol according to a volume ratio of 1: 3, mixing the mixture, wherein the isopropanol solution of the chloroacetic acid is chloroacetic acid and isopropanol according to the dosage ratio of 0.8 mol: 150mL of the mixture is obtained;

step S2: adding protocatechuic acid and deionized water into a flask, then dropwise adding a catalyst and thionyl chloride, and heating to reflux for reaction for 3 hours to obtain an intermediate 2; wherein the dosage ratio of protocatechuic acid, deionized water, catalyst and thionyl chloride is 0.1 mol: 25mL of: 0.05 mL: 0.12mol, and the catalyst is DMF;

step S3: mixing the intermediate 2 with dichloromethane, then dropwise adding a mixed solution of the intermediate 2 and dichloromethane into a flask containing resveratrol and triethylamine by using a dropping funnel under the conditions of ice bath and stirring, reacting for 5 hours at room temperature, filtering under reduced pressure after the reaction is finished, and evaporating to remove a solvent to obtain an intermediate 3; the dosage ratio of the intermediate 2 to the dichloromethane is 0.1 mol: 20 mL; the dosage ratio of the intermediate 2, the resveratrol and the triethylamine is 0.1 mol: 0.1 mol: 0.12 mol;

step S4: adding the intermediate 1 into a flask filled with a dimethyl sulfoxide aqueous solution with a volume fraction of 50%, then adding an activating agent and the dimethyl sulfoxide solution of the intermediate 3, stirring, adding 4-dimethylpiperidine, maintaining the pH at 7.5, reacting at 35 ℃ in a dark place for 24 hours, adding into absolute ethyl alcohol after the reaction is finished, standing for 30min, washing with methanol, and drying to obtain a disintegrating agent; wherein the dosage ratio of the intermediate 1, the dimethyl sulfoxide aqueous solution, the activating agent, the dimethyl sulfoxide solution of the intermediate 3 and the 4-dimethylpiperidine is 2 g: 50mL of: 0.05 mol: 5mL of: 1.2 g; the dimethyl sulfoxide solution of the intermediate 3 is prepared by mixing the intermediate 3 with a dimethyl sulfoxide aqueous solution with a volume fraction of 50% according to a dosage ratio of 0.1 mol: 20mL of the mixture is mixed, and the activating agent is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride.

Further, the antiviral traditional Chinese medicine composition is prepared by the following steps:

the method comprises the following steps: adding deionized water 3-5 times the mass of disintegrant and disintegrant into a stirring kettle, and stirring at 40 deg.C for 30min to obtain coagulation liquid;

step two: adding the traditional Chinese medicine extract and the crosslinking component into a stirring kettle, stirring and mixing, and obtaining a mixed material after mixing;

step three: adding the mixed material into the condensation liquid, adding into a high-speed mixing granulator for granulation to obtain wet granules, and freeze-drying at-50 ℃ to-40 ℃ to obtain primary granules;

step four: mixing the primary granules with a lubricant, and tabletting to obtain the antiviral Chinese medicinal composition.

The invention provides an antiviral traditional Chinese medicine composition. Compared with the prior art, the method has the following beneficial effects: the active substance sources of the antiviral traditional Chinese medicine composition of honeysuckle, wild chrysanthemum, isatis root, scutellaria, liquorice, white paeony root, astragalus and forsythia are used for extracting the active substances, and the traditional Chinese medicines have obvious and excellent effects of resisting viruses, clearing heat and expelling wind-damp and different antiviral effects, are combined together to enlarge the defense range of the antiviral effect, and have better effect of defending viruses;

the invention also prepares a disintegrating agent, the disintegrating agent uses corn starch as a matrix for modification, the corn starch is natural in source and can be dissolved and broken after entering a human body, so that the traditional Chinese medicine extract in the prepared composition tablet can be released for action, and the starch is modified, firstly, the starch is prepared into carboxymethyl starch, namely an intermediate 1, and then chlorinated protocatechuic acid, namely an intermediate 2, is reacted with the hydroxyl of resveratrol to prepare an intermediate 3, wherein the protocatechuic acid and the resveratrol are natural in source and non-toxic, and have good antioxidant activity of phenolic hydroxyl, the health care performance of the traditional Chinese medicine composition is further improved, the intermediate 3 is reacted with the carboxymethyl starch to prepare the disintegrating agent, the intermediate 3 is connected with the carboxymethyl starch through esterification reaction, and the esterified starch can generate a slow digestion effect in the body, the medicine is slowly released, and the time for the medicine components to act is not too short because the organism metabolizes too fast, so that the medicine effect is more effective.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

Preparing a disintegrant, the disintegrant being prepared by the steps of:

Example 2

Preparing a traditional Chinese medicine extract, wherein the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 5 parts of honeysuckle, 3 parts of wild chrysanthemum flower, 3 parts of isatis root, 2 parts of scutellaria baicalensis, 2 parts of liquorice, 1 part of white paeony root, 1 part of astragalus mongholicus and 1 part of fructus forsythiae;

the traditional Chinese medicine extract is prepared by the following steps: cleaning and draining weighed honeysuckle, wild chrysanthemum flower, isatis root, scutellaria baicalensis, liquorice, white paeony root, astragalus and weeping forsythia, respectively placing the materials into different crushers for crushing, adding the materials into a boiling pot, adding distilled water for decocting for 3 hours, adding water every 1 hour during the decoction, adding 3 times of water, filtering decoction after the decoction is finished, squeezing the residual Chinese medicine, namely eight layers of gauze to obtain juice, combining the juice with the decoction, and concentrating to obtain the Chinese medicine extract.

Example 3

Preparing a traditional Chinese medicine extract, wherein the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 6.5 parts of honeysuckle, 4 parts of wild chrysanthemum flower, 4 parts of isatis root, 3 parts of scutellaria baicalensis, 3 parts of liquorice, 2 parts of white paeony root, 2 parts of astragalus mongholicus and 2 parts of fructus forsythiae;

the traditional Chinese medicine extract is prepared by the following steps: cleaning and draining weighed honeysuckle, wild chrysanthemum flower, isatis root, scutellaria baicalensis, liquorice, white paeony root, astragalus and weeping forsythia, respectively placing the materials into different crushers for crushing, adding the materials into a boiling pot, adding distilled water for decocting for 4 hours, adding water every 1 hour during the decoction, adding 3 times of water, filtering decoction after the decoction is finished, squeezing the residual Chinese medicine, namely eight layers of gauze to obtain juice, combining the juice with the decoction, and concentrating to obtain the Chinese medicine extract.

Example 4

Preparing a traditional Chinese medicine extract, wherein the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 8 parts of honeysuckle, 5 parts of wild chrysanthemum, 5 parts of isatis root, 4 parts of scutellaria baicalensis, 4 parts of liquorice, 3 parts of white paeony root, 3 parts of astragalus mongholicus and 3 parts of fructus forsythiae;

the traditional Chinese medicine extract is prepared by the following steps: cleaning and draining weighed honeysuckle, wild chrysanthemum flower, isatis root, scutellaria baicalensis, liquorice, white paeony root, astragalus and weeping forsythia, respectively placing the materials into different crushers for crushing, adding the materials into a boiling pot, adding distilled water for decocting for 5 hours, adding water every 1 hour during the process, adding 3 times of water, filtering decoction after the decoction is finished, squeezing the residual Chinese medicine, namely eight layers of gauze to obtain juice, combining the juice with the decoction, and concentrating to obtain the Chinese medicine extract.

Example 5

An antiviral traditional Chinese medicine composition comprises the following components in percentage by mass: 2.5: 0.1: 0.2 of the herbal extract prepared in example 3, the cross-linking component, magnesium stearate, the disintegrant prepared in example 1;

the cross-linking component is starch, microcrystalline cellulose and cross-linked sodium carboxymethyl cellulose in a mass ratio of 1: 1: 0.1 mixing to obtain;

the antiviral traditional Chinese medicine composition is prepared by the following steps:

the method comprises the following steps: adding deionized water with 3 times of the mass of the disintegrating agent and the disintegrating agent into a stirring kettle, and stirring for 30min at the temperature of 40 ℃ to obtain a condensation liquid;

step three: adding the mixed material into the condensation liquid, adding into a high-speed mixing granulator for granulation to obtain wet granules, and freeze-drying at-50 ℃ to obtain primary granules;

Example 6

the method comprises the following steps: adding deionized water 4 times the mass of the disintegrating agent and the disintegrating agent into a stirring kettle, and stirring for 30min at the temperature of 40 ℃ to obtain a condensation liquid;

step three: adding the mixed material into the condensation liquid, adding into a high-speed mixing granulator for granulation to obtain wet granules, and freeze-drying at-45 ℃ to obtain primary granules;

Example 7

the method comprises the following steps: adding the disintegrant and deionized water with the mass 5 times that of the disintegrant into a stirring kettle, and stirring for 30min at the temperature of 40 ℃ to obtain a condensation liquid;

step three: adding the mixed material into the condensation liquid, adding into a high-speed mixing granulator for granulation to obtain wet granules, and freeze-drying at-40 ℃ to obtain primary granules;

Comparative example 1: no disintegrant was used as in example 6;

comparative example 2: corn starch was used as disintegrant compared to example 6;

comparative example 3; compared with example 6, no herbal extract was added;

the examples 5 to 7 and comparative examples 1 to 3 were subjected to performance tests:

the disintegration time of the tablets was measured according to the method prescribed in the Chinese pharmacopoeia (2015 edition) to obtain the results shown in Table 1 below:

TABLE 1

Example 5

Example 6

Example 7

Comparative example 1

Comparative example 2

Comparative example 3

Disintegration time

25min

24min

25min

60min

15min

16min

As can be seen from Table 1 above, the tablets prepared in examples 5 to 7 have a prolonged disintegration time and a sustained release effect, while having a disintegrating effect.

It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims

1. An antiviral traditional Chinese medicine composition is characterized by comprising the following components in percentage by mass: 2.5: 0.1: 0.2 of traditional Chinese medicine extract, a crosslinking component, a lubricant and a disintegrating agent;

the disintegrating agent is prepared by the following steps:

step S2: adding protocatechuic acid and deionized water into a flask, then dropwise adding a catalyst and thionyl chloride, and heating to reflux for reaction for 3 hours to obtain an intermediate 2;

step S3: mixing the intermediate 2 with dichloromethane, then dropwise adding a mixed solution of the intermediate 2 and dichloromethane into a flask containing resveratrol and triethylamine by using a dropping funnel under the conditions of ice bath and stirring, reacting for 5 hours at room temperature, and obtaining an intermediate 3 after the reaction is finished;

step S4: adding the intermediate 1 into a flask filled with dimethyl sulfoxide aqueous solution with volume fraction of 50%, adding the dimethyl sulfoxide solution of an activating agent and the intermediate 3, stirring, adding 4-dimethylpiperidine, maintaining the pH at 7.5, and reacting at 35 ℃ in a dark place for 24h to obtain the disintegrant.

2. The antiviral traditional Chinese medicine composition according to claim 1, wherein the intermediate 1 is prepared by the following steps:

adding a mixed solution of corn starch, isopropanol and deionized water and sodium hydroxide into a flask, reacting for 1.5h at the temperature of 40 ℃, cooling to 30 ℃, dropwise adding an isopropanol solution of chloroacetic acid, adding sodium hydroxide, reacting for 30min under an ice bath condition, heating to 50 ℃ again, reacting for 3h, after the reaction is finished, adjusting the pH to 8 by using glacial acetic acid, performing suction filtration, washing by using a methanol water solution with the volume fraction of 80%, and drying a filter cake at the temperature of 100 ℃ to obtain an intermediate 1.

3. The antiviral traditional Chinese medicine composition according to claim 1, wherein the dosage ratio of protocatechuic acid, deionized water, catalyst and thionyl chloride in step S2 is 0.1 mol: 25mL of: 0.05 mL: 0.12mol, and the catalyst is DMF.

4. The antiviral traditional Chinese medicine composition according to claim 1, wherein in the step S3, the dosage ratio of the intermediate 2, resveratrol and triethylamine is 0.1 mol: 0.1 mol: 0.12 mol.

5. The antiviral traditional Chinese medicine composition according to claim 1, wherein in step S4, the ratio of the amount of intermediate 1, the aqueous solution of dimethyl sulfoxide, the activator, the solution of intermediate 3 in dimethyl sulfoxide, and the amount of 4-dimethylpiperidine is 2 g: 50mL of: 0.05 mol: 5mL of: 1.2 g; the dimethyl sulfoxide solution of the intermediate 3 is prepared by mixing the intermediate 3 with a dimethyl sulfoxide aqueous solution with a volume fraction of 50% according to a dosage ratio of 0.1 mol: 20mL of the mixture is mixed, and the activating agent is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride.

6. The antiviral traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 5-8 parts of honeysuckle, 3-5 parts of wild chrysanthemum flower, 3-5 parts of isatis root, 2-4 parts of scutellaria baicalensis, 2-4 parts of liquorice, 1-3 parts of white paeony root, 1-3 parts of astragalus mongholicus and 1-3 parts of fructus forsythiae.

7. The antiviral traditional Chinese medicine composition according to claim 6, wherein the traditional Chinese medicine extract is prepared by the following steps: cleaning and draining weighed honeysuckle, wild chrysanthemum flower, isatis root, scutellaria baicalensis, liquorice, white paeony root, astragalus and weeping forsythia, respectively placing the mixture into different crushers for crushing, adding the crushed mixture into a boiling pot, adding distilled water for decocting for 3-5h, adding water every 1h during the decoction for 3 times, filtering out the decoction after the decoction is finished, extruding the residual traditional Chinese medicine by using gauze to obtain juice, combining the juice with the decoction, and concentrating to obtain the traditional Chinese medicine extract.

8. The antiviral traditional Chinese medicine composition according to claim 1, wherein the cross-linking component is starch, microcrystalline cellulose, croscarmellose sodium in a mass ratio of 1: 1: 0.1 and mixing.

9. The antiviral traditional Chinese medicine composition of claim 1, wherein the lubricant is magnesium stearate.