WO2021249501A1

WO2021249501A1 - Antiviral preparation

Info

Publication number: WO2021249501A1
Application number: PCT/CN2021/099481
Authority: WO
Inventors: 付军
Original assignee: 广东盛普生命科技有限公司
Priority date: 2020-06-11
Filing date: 2021-06-10
Publication date: 2021-12-16

Abstract

An antiviral composition, and a preparation method therefor and an application thereof. The antiviral composition comprises phyllanthus emblica or an extract thereof, preferably compounded with an antiviral metal salt and/or sialic acid. The composition can inhibit replication of viruses, has broad-spectrum antiviral activity, and particularly has an obvious inhibiting function against respiratory viruses. The composition can be prepared into dose forms such as oral liquid, a spray and an ophthalmic medicament.

Description

An antiviral preparation

Technical field

The invention belongs to the field of medical technology. More specifically, it relates to an antiviral preparation, which specifically includes an antiviral composition and a preparation method and application thereof.

Background technique

Viruses can invade, attack, and harm the human body in various ways; among them, respiratory viruses are an important pathogen that causes respiratory diseases. They can spread through the respiratory tract, spread into the air through a patient's sneeze, cough, etc., and become infected after healthy people inhale it. Respiratory tract viruses refer to a large class of viruses that can invade the respiratory tract and cause local respiratory tract disease; or only use the respiratory tract as the portal to invade, and mainly cause tissue and organ disease outside the respiratory tract. More than 90% of acute respiratory infections are caused by this type of virus. Acute upper respiratory tract infections caused by human infection with respiratory viruses mostly occur in winter. More than 90% of respiratory infections in children and adults are caused by viruses. The incidence is extremely high, spreads quickly, and has a wide range of epidemics. The annual incidence per capita is 5- 6 times; and the virus can spread to the lower respiratory tract, forming bronchitis and pneumonia, some can develop viremia, and can also invade other organs such as the intestines, seriously endangering human health.

Respiratory viruses are divided into two types: DNA viruses and RNA viruses. Common respiratory viruses include respiratory syncytial virus, influenza virus, parainfluenza virus, rubella virus, rhinovirus, coronavirus, and orthoreovirus belonging to RNA viruses, as well as those belonging to DNA viruses such as adenovirus, varicella-zoster virus and Boca virus; among them, 30%-35% of those that can cause a cold are rhinoviruses, and 20%-30% are coronaviruses. Coronaviruses belong to the order Nested virus, the Coronavirus family. Coronaviruses that can infect the human body include: severe acute respiratory syndrome coronavirus 2 (2019-nCoV or SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS- CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Human Coronavirus 229E (HCoV-229E), Human Coronavirus NL63 (HCoV-NL63), Human Coronavirus OC43 (HCoV-OC43) or Human Coronavirus HKU1 ( There are 7 kinds of HCoV-HKU1). Coronavirus is one of the main pathogens with high incidence of modern epidemics and often causes serious human respiratory infections; among them, 2019-nCoV is highly contagious, and pneumonia caused by new coronavirus infection is prevalent all over the world and has a global distribution. It has had a great impact on the global public health system.

At present, CN102836200A discloses the application of Phyllanthus emblica in the preparation of anti-H1N1 influenza virus drugs, specifically the flavonoid extract of Phyllanthus emblica has obvious inhibitory effect on H1N1 influenza virus-induced cytopathy; however, it is only for H1N1 influenza virus and is not applicable For other common respiratory viruses. And because the virus groups that cause respiratory infections have two characteristics: 1) diversity, the physical, chemical and biological activities of these viruses are different, and members of different virus families enter the upper respiratory epithelium to invade the upper respiratory tract epithelium. The receptors are also different; 2) mutations Sex, this group of viruses continue to mutate in nature, with many types, large mutations, and long-lasting immunity. Therefore, there is an urgent need to develop drugs with broad-spectrum antiviral activity to prevent or treat diseases caused by upper respiratory tract infections.

In addition, when the virus mutates or a new type of virus emerges and causes an infectious disease outbreak to occur again, the original specific drugs are difficult to exert effective prevention and control effects, which leads to the rapid spread of the virus, and even a catastrophic outbreak on a global scale. , Causing a huge impact on social politics and economy. Therefore, it is of great significance to screen for more effective and stable broad-spectrum antiviral drugs.

Summary of the invention

The technical problem to be solved by the present invention is to overcome the shortcomings and deficiencies of the above-mentioned prior art, and provide a new choice of new drugs with a relatively broad antiviral spectrum, especially developed into oral liquids, sprays, ophthalmic medicaments, etc. The dosage form has a good preventive and therapeutic effect on respiratory viruses.

The object of the present invention is to provide an antiviral composition.

Another object of the present invention is to provide the application of the composition in the preparation of antiviral drugs.

Another object of the present invention is to provide a series of antiviral preparations, including oral liquids, sprays, ophthalmic medicaments and the like.

The above objectives of the present invention are achieved through the following technical solutions:

The present invention provides an anti-viral composition, which includes Phyllanthus emblica.

Preferably, the Phyllanthus emblica is an extract of Phyllanthus emblica.

More preferably, the Phyllanthus emblica extract is a water extract of Phyllanthus emblica or an alcoholic extract of Phyllanthus emblica.

Among them, for the water extract of Phyllanthus emblica:

Preferably, the starting material-liquid ratio in the preparation method of the Phyllanthus emblica extract is 1:2-12 (g/ml) by mass.

More preferably, as an optional technical solution, the preparation method of the aqueous extract of Phyllanthus emblica is as follows: adding the powder of Phyllanthus emblica into deionized water, heating and refluxing for 2-6 hours according to the above-mentioned starting material-to-liquid ratio, and then filtering and concentrating. , That is, Phyllanthus emblica water extract.

Preferably, the Soxhlet extraction method can also be used to add amla emblica powder into deionized water for Soxhlet extraction for 3.5 to 4.5 hours, and after recovery and concentration, a water extract of amla emblica can be obtained.

Preferably, the alcohol extract of Phyllanthus emblica is an ethanol extract.

More preferably, as an optional technical solution, the preparation method of the emblica alcohol extract is as follows: the emblica powder is heated and refluxed with 80%-85% ethanol (preferably, the ethanol concentration is 85%) for 0.5-2h to extract 2 to 5 times (preferably 3 times), the solvent is recovered under reduced pressure to obtain an extract. The extract is dispersed in distilled water, and extracted with ethyl acetate for 4 to 6 times (preferably 5 times) to obtain an alcohol extract of emblica.

In addition, preferably, the above-mentioned antiviral composition further includes a metal salt.

Preferably, the mass ratio of the Phyllanthus emblica and the metal salt is 1: (0.01-10).

More preferably, the mass ratio of the Phyllanthus emblica extract and the metal salt is 1: (0.1-2.5).

More preferably, the metal salt is zinc salt, iron salt, calcium salt, magnesium salt, tungsten salt or rubidium salt.

More preferably, the zinc salt is zinc sulfate or zinc gluconate; the iron salt is ferrous gluconate; the calcium salt is calcium gluconate; the magnesium salt is magnesium oxide; the tungsten salt is tungsten Sodium; The rubidium salt is rubidium iodide.

Preferably, the aforementioned antiviral composition further includes sialic acid.

Preferably, the mass ratio of the Phyllanthus emblica extract and sialic acid is 1: (0.01-20).

More preferably, the mass ratio of the Phyllanthus emblica extract and sialic acid is 1:(0.01-10).

More preferably, the mass ratio of the Phyllanthus emblica extract and sialic acid is 1: (0.4-2.5).

The source of the sialic acid can be mammalian mandibular extract, bird's nest, breast milk, milk, eggs or cheese. Preferably, the mammal is a pig or a cow.

Furthermore, the above-mentioned antiviral composition can be appropriately compounded with suitable auxiliary materials to prepare different pharmaceutical dosage forms, such as oral liquid, spray, aerosol, ophthalmic medicament and so on.

Therefore, the application of the antiviral composition in the preparation of antiviral drugs should also fall within the protection scope of the present invention.

Specifically, preferably, the virus mentioned above in the present invention refers to a respiratory virus.

More preferably, the respiratory virus is a coronavirus or influenza virus.

More preferably, the coronavirus family viruses include 2019-nCoV, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1.

More preferably, the influenza virus is influenza A virus, influenza B virus or influenza C virus.

More preferably, the influenza A virus is a H1N1 influenza virus, a H3N2 influenza virus, a H5N1 influenza virus or a H7N9 influenza virus.

More preferably, the influenza B virus is Yamagata influenza B virus.

As a preferred implementation case, the present invention has also developed several antiviral preparations containing the above-mentioned composition, including oral liquids, sprays and ophthalmic agents, and the details are as follows:

An antiviral oral liquid containing the antiviral composition described above. Preferably, antioxidants and sweeteners are also included.

Specifically, preferably, in parts by weight, the anti-viral oral liquid comprises the following components: 10-22 parts of Phyllanthus emblica extract, 4-22 parts of metal salt, 5-53 parts of antioxidant, and 5-23 parts of sweetener .

More preferably, in parts by weight, the antiviral oral liquid further contains 10-22 parts of sialic acid.

Preferably, the antioxidant is vitamin C or rosemary.

Preferably, the sweetener is aspartame, stevia, sucrose, sorbitol mannitol, maltitol, glucose or AK sugar.

Specifically, preferably, in parts by weight, the anti-viral oral liquid comprises the following components: 10-22 parts of Phyllanthus emblica extract, 4-22 parts of metal salt, 5-53 parts of antioxidant, and 5-23 parts of sweetener , 10-22 parts of sialic acid.

Preferably, the preparation method of the antiviral oral liquid is as follows: according to the weight portion, the emblica extract, metal salt, antioxidant, sweetener, and sialic acid are fully dissolved in water to obtain it.

Preferably, the amount of water is adjusted through experiments according to the solubility and efficacy of the components.

Specifically, as a preferred solution, the anti-viral oral liquid may include the following components in weight percentage: Emblica extract 10-20%, metal salt 6-17%, antioxidant 5-30%, sweetener 5-18% %, sialic acid 12-22% and the balance water.

More preferably, the anti-viral oral liquid comprises the following components in weight percentage: 16-18% emblica extract, 6-11% metal salt, 7-9% antioxidant, 5-8% sweetener, saliva Acid 16-18% and the balance water.

More preferably, the anti-viral oral liquid includes the following components in weight percentage: emblica extract 17.4%, metal salt 10.1%, vitamin C 8.4%, aspartame 5.8%, sialic acid 17.4% and the balance water.

The composition of the antiviral oral liquid provided by the present invention is reasonable, and the antioxidants therein can inhibit the oxidation of the composition, stabilize the performance of the composition, and at the same time can adjust the taste of the composition; it can produce a pleasant smell and cover up The smell of the composition matrix; sweeteners can impart sweetness to the composition and make it taste good; the synergistic compatibility of each component has played a significant synergistic effect, has a significant and relatively broad-spectrum antiviral effect, and is helpful for the respiratory tract The treatment and rehabilitation of virus-infected patients can improve the quality of life, and at the same time can be used as an effective method for normal people's daily protection and prevention of respiratory infections.

In the case of influenza virus, a specific and targeted priority solution: a special anti-influenza virus preparation, in parts by weight, said anti-influenza virus special preparation comprising the following components: 8-20 parts of Phyllanthus emblica extract, 8 sialic acid ～20 parts, 2～20 parts of metal salt, 2～50 parts of antioxidant, 2～18 parts of flavor, 2～20 parts of sweetener.

Preferably, the preparation method of the anti-influenza virus special preparation is: according to the weight portion, the amla extract, metal salt, antioxidant, flavor and sweetener are fully dissolved in purified water.

Specifically as a preferred solution, the anti-influenza virus special preparation may include the following components in weight percentage: Emblic extract 8-18%, sialic acid 10-20%, metal salt 2-15%, antioxidant 2-25% , Flavor 2-12%, sweetener 2-15% and the balance water.

More preferably, the anti-influenza virus special preparation may include the following components in weight percentage: emblica extract 14-16%, sialic acid 14-16%, metal salt 4-9%, antioxidant 4-6%, The flavor is 2 to 4%, the sweetener is 2 to 5% and the balance is water.

More preferably, the anti-influenza virus special preparation may include the following components in weight percentage: Emblic extract 15.4%, sialic acid 15.4%, metal salt 8.1%, vitamin C 5.4%, flavor 2.8%, aspartame 3.8% and the balance water.

An antiviral spray containing the antiviral composition described above.

Specifically, preferably, in parts by weight, the antiviral spray comprises the following components: 8-20 parts of Phyllanthus emblica extract, 8-20 parts of sialic acid, 2-20 parts of metal salt, 2-10 parts of solvent, glycerin 8-15 servings, 1-16 servings of flavor.

Preferably, the preparation method of the anti-viral spray is as follows: according to the weight portion, the emblica extract, sialic acid, metal salt, solvent, glycerin and flavor are fully dissolved in deionized water.

Specifically as a preferred solution, the antiviral spray may include the following components in weight percentage: Emblica extract 10-20%, sialic acid 10-20%, metal salt 2-18%, solvent 2-8%, 10-15% glycerin, 1-12% flavor and the balance water.

More preferably, the specific anti-viral spray may include the following components in weight percentage: Emblica extract 14-18%, sialic acid 14-18%, metal salt 4-15%, solvent 6-8%, glycerin 10 to 13%, flavor 2 to 10% and the balance water.

More preferably, the specific antiviral spray may include the following components: Phyllanthus emblica extract 18%, sialic acid 18%, metal salt 10.3%, solvent 6%, glycerol 11%, flavor 2% and the balance water.

Preferably, the solvent is a volatile solvent. The solvent can be selected according to its use conditions, and when used to prepare oral medicines, food-grade solvents are used.

More preferably, the solvent is ethanol.

An ophthalmic antiviral agent containing the antiviral composition described above.

Specifically, preferably, in parts by weight, each 1L of the ophthalmic antiviral agent contains: 8-20 parts of Phyllanthus emblica extract, 3-5 parts of osmotic pressure regulator, 0.1-5 parts of antioxidants, and 0.5-0.5 parts of solubilizers. 10 parts, 0.1-0.5 parts of bacteriostatic agent, 0.1-5 parts of thickener, 0.1-0.5 parts of borneol, 2-20 parts of metal salt, and the balance is water for injection.

Specifically as a preferred solution, each 1L of the ophthalmic antiviral agent may include the following components by weight percentage: Emblic extract 10-20%, osmotic pressure regulator 3-5%, antioxidant 0.1-4%, increasing Solvent 1-8%, bacteriostatic agent 0.1-0.4%, thickener 1-5%, borneol 0.1-0.3%, metal salt 4-20% and the balance water for injection.

More preferably, each 1L of the ophthalmic antiviral agent may include the following components in weight percentage: 10-18% of Phyllanthus emblica extract, 4-5% of osmotic pressure regulator, 0.5-3% of antioxidant, and solubilizer 2～6%, antibacterial agent 0.1～0.3%, viscosity increasing agent 1～3%, borneol 0.2～0.3%, metal salt 4～15% and the balance water for injection.

More preferably, each 1L of the ophthalmic antiviral agent may include the following components in weight percentage: 18% emblica extract, 4% osmotic pressure regulator, 2% antioxidant, 3% solubilizer, bacteriostatic agent 0.2%, thickener 2%, borneol 0.3%, metal salt 8% and the remainder water for injection.

Preferably, the osmotic pressure regulator includes but is not limited to sodium chloride or boric acid; the antioxidant includes but is not limited to one or more of sodium bisulfite, sodium sulfite, sodium thiosulfate, sodium metabisulfite and vitamin C. Species; the solubilizer includes but not limited to Tween-80 or Tween-20; the bacteriostatic agent includes, but is not limited to benzalkonium chloride or benzalkonium bromide; the thickener includes but is not limited to hyaluronic acid One or more of sodium, hypromellose, methyl cellulose, povidone and polyvinyl alcohol.

The preparation method of the ophthalmic antiviral agent is as follows: dissolve the Phyllanthus emblica extract, adjust the pH to 6.0-8.0 with a pH regulator, and filter; dissolve the borneol with ethanol, add it to the filtrate, and then add the osmotic pressure regulator and the antiviral agent. Oxidant, solubilizer, thickener, bacteriostatic agent, fully stir, adjust the pH value to 6.0-8.0 with a pH regulator, and finally add water for injection to adjust the volume to 1L, filter, separate the filtrate, and sterilize it.

Preferably, the pH adjusting agent includes, but is not limited to, one or more of phosphate buffer, Gieffer's buffer, and Pasteur's buffer.

More preferably, the pH value is adjusted to 6.0-7.4 with a pH adjusting agent.

In addition, it should be noted that when preparing the anti-coronavirus or influenza virus drugs of the antiviral composition of the present invention, including but not limited to, the effective amount of the composition of the present invention is administered to the patient to prepare for prevention or The use of medicines for treating diseases caused by coronavirus or influenza virus, reducing disease symptoms caused by coronavirus or influenza virus, or delaying the development or onset of diseases caused by coronavirus or influenza virus.

In addition to being beneficial to human treatment, the composition claimed in the present invention can also be applied to veterinary treatment of pets, introduced species of animals and farm animals, including mammals, rodents, and the like. Other examples of animals include horses, dogs, and cats.

The present invention has the following beneficial effects:

The present invention provides an anti-viral composition, the compatibility of each component in the formula is reasonable and optimized, can significantly inhibit virus replication, has broad-spectrum antiviral activity, especially respiratory viruses, and has a significant therapeutic effect; the combination Phyllanthus emblica in the formula is a traditional Chinese medicine, which has the advantages of naturalness, safety, and mild efficacy; in the development of antiviral drugs, especially for respiratory viruses such as coronavirus, it has good application value.

Based on the above composition, the present invention also provides an antiviral oral liquid, spray and ophthalmic antiviral agent. The antiviral oral liquid and spray are targeted at respiratory tract infection viruses, and can effectively inhibit the invasion of respiratory viruses and harm the human body. At the same time, the spray is used in the form of spray for disinfection of ambient air. It can effectively kill all kinds of viruses in a short period of time. It can also freshen the air and is non-toxic and harmless to the human body. The method of use is unique and easy to carry; With antiviral agents, Phyllanthus emblica extract as the active substance, it has a significant inhibitory effect on a variety of viruses that enter the eye, especially for coronavirus and influenza viruses, and has the advantages of naturalness, safety, and mild efficacy. In addition, sulfuric acid is added Zinc, calcium gluconate, zinc gluconate and other metal salts will work synergistically with the extract of Phyllanthus emblica to further inhibit the virus, thereby enhancing the antiviral effect.

The preparation method of the antiviral oral liquid, spray and ophthalmic antiviral agent is simple and low in cost, which is helpful for the treatment and rehabilitation of virus-infected patients, and improves the quality of life. At the same time, it can be used as daily protection for normal people and prevent respiratory infections. Effective methods of disease have great significance for the prevention and control of the spread and harm of diseases caused by viruses infecting the human body.

detailed description

Hereinafter, the present invention will be further described with reference to the drawings and specific embodiments of the specification, but the embodiments do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the technical field.

Unless otherwise specified, the reagents and materials used in the following examples are all commercially available.

The antiviral activity experiment in the embodiment of the present invention was commissioned by the Guangdong Provincial Center for Disease Control and Prevention.

Example 1 Preparation of Phyllanthus emblica aqueous extract 1

The preparation method of the aqueous extract of Phyllanthus emblica includes the following steps:

The fresh emblica fruit is dried and crushed to make emblica powder, weigh 100g of emblica powder, add 1100ml deionized water, heat and reflux for 2h, filter, and extract the residue again under the same conditions, filter, concentrate, and dry , That's it.

Example 2 Preparation of Phyllanthus emblica aqueous extract 2

The fresh emblica fruit is dried and crushed to make emblica powder, weigh 100g of emblica powder, add 1000ml deionized water, heat and reflux for 2h, filter, and extract the residue twice under the same conditions, filter, concentrate, and dry , That's it.

Example 3 Preparation of Emblic Extract 1

Fresh emblica fruits are dried and crushed to make emblica powder. Weigh 100g of emblica powder, add 500ml of 85vol% ethanol solution, heat and reflux for 0.5h, filter, and extract the residue twice under the same conditions. Filter, concentrate, disperse the extract in distilled water, extract 5 times with ethyl acetate, and dry to obtain.

Example 4 Preparation of Emblic Extract 2

Fresh emblica fruits are dried and crushed to make emblica powder. Weigh 100g of emblica powder, add 1000ml of 80vol% ethanol solution, heat and reflux for 1 hour, filter, and extract the residue 4 times under the same conditions. Filter , Concentrate, disperse the extract in distilled water, extract 6 times with ethyl acetate, and dry to obtain.

Experimental example 1 Antiviral experiment of Phyllanthus emblica extract composition

Measurement materials: Phyllanthus emblica water extract, Phyllanthus emblica alcohol extract, Phyllanthus emblica water/alcohol extract+metal salt, Phyllanthus emblica water/alcohol extract+sialic acid, Phyllanthus emblica water/alcohol extract+metal salt+sialic acid .

Measurement objects: Coronavirus SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1; Influenza virus: A H1N1 influenza virus, B influenza virus, C Influenza virus

Other experimental materials: cell line: human embryonic kidney cell 293 (HEK293 cells); DMEM medium; 96-well culture plate.

Experimental procedure: Take cell culture fluid to dilute the above-mentioned test materials to a series of mass concentrations; then take 50TCID50 virus fluid and neutralize the above-mentioned drug solution in equal volumes; after incubating at 37°C for 1h, inoculate it in HEK293 cells, 100μL/well, each 4 replicate wells at a mass concentration, and set up normal cell control group, virus control group and drug-added group at the same time, cultured at 37°C, 5% CO2, and observed the cell morphology; after 48h, the OD490 value was measured by MTT method and microplate reader. Calculate cell survival rate and Jinzheng mean q value at the same time (q<0.85 is antagonistic effect, 0.85≤q<1.15 is additive effect, and q≥1.15 is synergistic effect).

The experimental results are shown in Tables 1-10. From the table, it can be seen that the Phyllanthus emblica extract, metal salt, and sialic acid have a significant synergistic antiviral effect.

Table 1 Anti-SARS CoV-2 coronavirus effects of Phyllanthus emblica extract, metal salt and sialic acid

Table 2 Anti-SARS-CoV coronavirus effect of Phyllanthus emblica extract, metal salt and sialic acid

Table 3 Anti-MERS-CoV coronavirus effects of Phyllanthus emblica extract, metal salt and sialic acid

Table 4 Anti-HCoV-229E coronavirus effect of Phyllanthus emblica extract, metal salt and sialic acid

Table 5 Anti-HCoV-NL63 coronavirus effect of Phyllanthus emblica extract, metal salt and sialic acid

Table 6 Anti-HCoV-OC43 coronavirus effect of Phyllanthus emblica extract, metal salt and sialic acid

Table 7 Anti-HCoV-HKU1 coronavirus effect of Phyllanthus emblica extract, metal salt and sialic acid

Table 8 Anti-A H1N1 influenza virus effect of Phyllanthus emblica extract, metal salt and sialic acid

Table 9 Anti-influenza B virus effect of Phyllanthus emblica extract, metal salt and sialic acid

Table 10 Anti-influenza C virus effect of Phyllanthus emblica extract, metal salt and sialic acid

Example 5 Preparation of antiviral oral liquid 1

Antiviral oral liquid 1, in parts by weight, includes the following components: 17.4 parts of Phyllanthus emblica aqueous extract, 17.4 parts of sialic acid, 10.1 parts of zinc sulfate, 8.4 parts of vitamin C, and 5.8 parts of aspartame.

The preparation method of anti-viral oral liquid 1 is as follows: dry and crush fresh emblica fruit to prepare emblica powder, weigh 100g of emblica powder, wrap it with filter paper, put it in a Soxhlet extractor, and add to it. Ionized water (the mass ratio of Phyllanthus emblica powder and deionized water is 1:11) Soxhlet extraction for 4 hours, the water extract is recovered, concentrated on a water bath and the volume is constant to obtain the Phyllanthus emblica water extract;

According to the above-mentioned parts by weight, the water extract of Phyllanthus emblica, sialic acid, zinc sulfate, vitamin C and aspartame are fully dissolved in distilled water, diluted with distilled water to the full amount, and divided to obtain antiviral oral liquid 1.

Example 6 Preparation of antiviral oral liquid 2

Antiviral oral liquid 2, in parts by weight, includes the following components: 16 parts of Phyllanthus emblica aqueous extract, 16 parts of sialic acid, 11 parts of calcium gluconate, 9 parts of rosemary, and 8 parts of stevioside.

The preparation method of the anti-viral oral liquid 2 is based on the above weight parts, except that the mass ratio of emblica powder and deionized water is 1:9, and the Soxhlet extraction time is 4.5 hours, and the other methods are the same as those of the anti-viral oral liquid 1. The method is the same.

Example 7 Preparation of antiviral oral liquid 3

Antiviral oral liquid 3, in parts by weight, includes the following components: 17.4 parts of Phyllanthus emblica aqueous extract, 10.1 parts of zinc sulfate, 8.4 parts of vitamin C, and 5.8 parts of aspartame.

The preparation method of anti-viral oral liquid 3 is based on the above weight parts, except that the mass ratio of Phyllanthus emblica powder to deionized water is 1:12, and the Soxhlet extraction time is 4.5 hours, and the other methods are the same as the preparation of anti-viral oral liquid 1. The method is the same.

Example 8 Preparation of antiviral oral liquid 4

Anti-viral oral liquid 4, in parts by weight, includes the following components: 18 parts of amylose alcohol extract, 18 parts of sialic acid, 6 parts of zinc gluconate, 7 parts of vitamin C, and 5 parts of sucrose.

The preparation method of anti-viral oral liquid 4 is based on the above weight parts, except that the mass ratio of emblica powder to deionized water is 1:12, and the Soxhlet extraction time is 3.5 hours, and the other methods are the same as the preparation of anti-viral oral liquid 1. The method is the same.

Example 9 Preparation of antiviral oral liquid 5

The anti-viral oral liquid 5, in parts by weight, includes the following components: 10 parts of amlic acid alcohol extract, 10 parts of sialic acid, 4 parts of ferrous gluconate, 53 parts of rosemary, and 23 parts of sorbose mannitol.

The preparation method of anti-viral oral liquid 5 is based on the above weight parts, except that the mass ratio of emblica powder to deionized water is 1:6, and the Soxhlet extraction time is 3.5 hours, and the other methods are the same as those of anti-viral oral liquid 1. The method is the same.

Example 10 Preparation of antiviral oral liquid 6

Antiviral oral liquid 6, in parts by weight, includes the following components: 22 parts of amlic acid alcohol extract, 22 parts of sialic acid, 22 parts of magnesium oxide, 5 parts of vitamin C, and 5 parts of maltitol.

The preparation method of antiviral oral liquid 6 is: after crushing Phyllanthus emblica, heating and refluxing extraction with 85% ethanol for 3 times, recovering the solvent under reduced pressure to obtain the extract, dispersing the extract in distilled water, and extracting it with ethyl acetate for 5 times. Obtain the ethanol extract of Phyllanthus emblica;

According to the above-mentioned weight portions, the ethanol extract of emblica, sialic acid, magnesium oxide, vitamin C and maltitol are fully dissolved in purified water, diluted with distilled water to the full amount, and divided to obtain an antiviral oral liquid 6.

Example 11 Preparation of antiviral oral liquid 7

Antiviral oral liquid 7, in parts by weight, includes the following components: 16 parts of amlic acid alcohol extract, 16 parts of sialic acid, 13 parts of sodium tungstate, 29 parts of rosemary, and 14 parts of glucose.

The preparation method of anti-viral oral liquid 7 is the same as the preparation method of anti-viral oral liquid 6 except that the concentration of ethanol is 80%, the number of reflux extraction is 5 times, and the number of extractions is 6 times. same.

Example 12 Preparation of antiviral oral liquid 8

The anti-viral oral liquid 8 includes the following components by weight percentage: Example 1 Emblica water extract 17.4%, sialic acid 17.4%, zinc sulfate 10.1%, vitamin C 8.4%, aspartame 5.8% and the balance water.

For the preparation method, refer to the anti-viral oral liquid 1.

Example 13 Preparation of antiviral oral liquid 9

The anti-viral oral liquid 9 includes the following components by weight percentage: Example 2 Emblica vulgare water extract 18%, sialic acid 16%, calcium gluconate 12%, rosemary 5%, stevioside 7% and the balance water.

For the preparation method, refer to the anti-viral oral liquid 1.

Example 14 Preparation of antiviral oral liquid 10

The antiviral oral liquid 10 includes the following components in weight percentage: Example 3 Ethanol extract of emblic 16%, sialic acid 18%, sodium tungstate 8%, rosemary 5%, sucrose 6% and the balance water.

For the preparation method, refer to the anti-viral oral liquid 1.

Example 15 Preparation of antiviral oral liquid 11

The anti-viral oral liquid 11 includes the following components in weight percentage: Example 4 Emblic extract 20%, sialic acid 8%, rubidium iodide 10%, vitamin C 12%, maltose 10% and the balance water.

For the preparation method, refer to the anti-viral oral liquid 1.

Example 16 Preparation of anti-influenza virus oral liquid 1

Anti-influenza virus oral liquid 1, in parts by weight, includes the following components: 15.4 parts of Phyllanthus emblica water extract, 15.4 parts of sialic acid, 8.1 parts of zinc sulfate, 5.4 parts of vitamin C, 2.8 parts of flavor, and 3.8 parts of aspartame share.

The preparation method of the anti-influenza virus oral liquid 1 is: drying and crushing fresh emblica fruit to prepare emblica powder, weigh 100g of emblica powder, wrap it with filter paper, and put it in a Soxhlet extractor. Add deionized water (the mass ratio of Phyllanthus emblica powder and deionized water is 1:11) Soxhlet extraction for 4 hours, recover the water extract, concentrate on the water bath and constant volume, to obtain the Phyllanthus emblica water extract;

According to the above-mentioned weight parts, the water extract of Phyllanthus emblica, sialic acid, zinc sulfate, vitamin C, flavor and aspartame are fully dissolved in purified water, diluted with distilled water to the full amount, and then packed to obtain an anti-influenza virus oral liquid 1 .

Example 17 Preparation of oral liquid 2 against influenza virus

Anti-influenza virus oral liquid 2, in parts by weight, includes the following components: 15.4 parts of Phyllanthus emblica water extract, 15.4 parts of sialic acid, 8.4 parts of calcium gluconate, 4.9 parts of rosemary, 2.8 parts of flavor, and 3.8 parts of stevioside share.

The preparation method of the anti-influenza virus oral liquid 2 is based on the above weight parts, except that the mass ratio of emblica powder and deionized water is 1:6, and the Soxhlet extraction time is 3.5h. The preparation method of solution 1 is the same.

Example 18 Preparation of anti-influenza virus oral liquid 3

Anti-influenza virus oral liquid 3, in parts by weight, includes the following components: 15.4 parts of Phyllanthus emblica aqueous extract, 15.4 parts of sialic acid, 4.5 parts of zinc gluconate, 5.4 parts of vitamin C, 2.8 parts of essence, and 3.8 parts of sucrose.

The preparation method of the anti-influenza virus oral liquid 2 is based on the above weight parts, except that the mass ratio of emblica powder to deionized water is 1:9, and the Soxhlet extraction time is 4.5h, and the other methods are the same as those for anti-influenza virus oral The preparation method of solution 1 is the same.

Example 19 Preparation of anti-influenza virus oral liquid 4

Anti-influenza virus oral liquid 4, in parts by weight, includes the following components: 8 parts of emblica extract, 8 parts of sialic acid, 20 parts of ferrous gluconate, 50 parts of vitamin C, 2 parts of flavor, sorbitan mannose 20 parts of sugar alcohol.

The preparation method of the anti-influenza virus oral liquid 4 is based on the above weight parts, except that the mass ratio of emblica powder and deionized water is 1:12, and the Soxhlet extraction time is 3.5h. The preparation method of solution 1 is the same.

Example 20 Preparation of anti-influenza virus oral liquid 5

Anti-influenza virus oral liquid 5, in parts by weight, includes the following components: 20 parts of amlic acid alcohol extract, 20 parts of sialic acid, 2 parts of magnesium oxide, 2 parts of rosemary, 18 parts of flavor, and 2 parts of maltitol .

The preparation method of anti-influenza virus oral liquid 5 is: after crushing Phyllanthus emblica, heating and refluxing extraction with 85% ethanol for 3 times, recovering the solvent under reduced pressure to obtain the extract, dispersing the extract in distilled water, and extracting it with ethyl acetate. Then, the alcohol extract of Phyllanthus emblica was obtained;

According to the above-mentioned weight portions, the ethanol extract of emblica, sialic acid, magnesium oxide, flavor and maltitol are fully dissolved in purified water, diluted with distilled water to the full amount, and divided to obtain oral liquid 5 for anti-influenza virus.

Example 20 Preparation of anti-influenza virus oral liquid 6

The anti-influenza virus oral liquid 6, in parts by weight, includes the following components: 14 parts of amlic acid alcohol extract, 14 parts of sialic acid, 9 parts of sodium tungstate, 6 parts of vitamin C, 2 parts of flavor, and 5 parts of glucose.

The preparation method of anti-influenza virus oral liquid 6 is based on the above weight parts, except that the concentration of ethanol is 80%, the number of reflux extraction times is 5 times, and the number of extraction times is 6 times, the other methods are the same as those of anti-influenza virus oral liquid The preparation method of 5 is the same.

Example 21 Preparation of anti-influenza virus oral liquid 7

Anti-influenza virus oral liquid 7, in parts by weight, includes the following components: 16 parts of amlic acid alcohol extract, 16 parts of sialic acid, 4 parts of rubidium iodide, 4 parts of rosemary, 4 parts of flavor, and AK sugar 2 share.

The preparation method of anti-influenza virus oral liquid 7 is based on the above weight parts, except that the concentration of ethanol is 83%, the number of reflux extraction times is 2 times, and the number of extraction times is 4 times, the other methods are the same as those of the anti-influenza virus oral liquid The preparation method of 5 is the same.

Example 22 Preparation of anti-influenza virus oral liquid 8

Anti-influenza virus oral liquid 8, including the following components by weight percentage: Example 1 Emblica water extract 15.4%, sialic acid 15.4%, zinc sulfate 8.1%, vitamin C 5.4%, flavor 2.8%, aspartame 3.8 % And the balance water.

The preparation method refers to the oral liquid against influenza virus.

Example 23 Preparation of anti-influenza virus oral liquid 9

Anti-influenza virus oral liquid 9 includes the following components by weight percentage: Example 2 Emblica water extract 16%, sialic acid 15%, calcium gluconate 10%, rosemary 6%, flavor 3.5%, sorbose mannose Sugar alcohol 4% and the balance water.

The preparation method refers to the oral liquid against influenza virus.

Example 24 Preparation of anti-influenza virus oral liquid 10

The anti-influenza virus oral liquid 10 includes the following components by weight percentage: Example 3 Ethanol extract 20%, sialic acid 10%, zinc gluconate 5%, vitamin C 5%, flavor 5%, sucrose 5% and The remaining amount of water.

The preparation method refers to the oral liquid against influenza virus.

Example 25 Preparation of anti-influenza virus oral liquid 11

Anti-influenza virus oral liquid 11 includes the following components in weight percentage: Example 4 Ethanol extract of emblic 18%, sialic acid 12%, zinc sulfate 8%, rosemary 6%, flavor 4%, stevia 6% And the balance of water.

The preparation method refers to the oral liquid against influenza virus.

Example 26 Preparation of an antiviral spray 1

Antiviral spray 1, in parts by weight, includes the following components: 18 parts of Phyllanthus emblica water extract, 18 parts of sialic acid, 10.3 parts of zinc sulfate, 6 parts of ethanol, 11 parts of glycerol, and 2 parts of flavor.

The preparation method of antiviral spray 1 includes the following steps:

S1. Sun-dried and crushed fresh emblica fruit to prepare emblica powder;

S2. Weigh 100g of emblica powder, wrap it with filter paper, put it in a Soxhlet extractor, add deionized water (the mass ratio of emblica powder to deionized water is 1:11), and extract 4 hours after Soxhlet extraction. The water extract is concentrated on a water bath and the volume is fixed to obtain the water extract of Phyllanthus emblica;

S3. According to the above parts by weight, the amla extract, sialic acid, zinc sulfate, ethanol, glycerin and flavor obtained in step S2 are fully dissolved in deionized water, and then divided into 50mL aerosol bottles according to each bottle to obtain the anti Virus spray 1.

Example 27 Preparation of an antiviral spray 2

Antiviral spray 2, in parts by weight, includes the following components: 18 parts of Phyllanthus emblica aqueous extract, 18 parts of sialic acid, 10.9 parts of calcium gluconate, 6 parts of ethanol, 11 parts of glycerol, and 2 parts of flavor.

The preparation method of antiviral spray 2 is based on the above parts by weight, except that the mass ratio of amla powder to deionized water in step S2 is 1:9, and the Soxhlet extraction time is 4.5h, and the other methods are all the same as the antiviral spray The preparation method of 1 is the same.

Example 28 Preparation of an antiviral spray 3

Antiviral spray 3, in parts by weight, includes the following components: 18 parts of Phyllanthus emblica aqueous extract, 6.4 parts of zinc gluconate, 6 parts of ethanol, 11 parts of glycerin, and 2 parts of flavor.

The preparation method of anti-viral spray 2 is based on the above parts by weight, except that the mass ratio of amla powder to deionized water in step S2 is 1:6, and the Soxhlet extraction time is 3.5 hours, and the other methods are all the same as the anti-viral spray The preparation method of 1 is the same.

Example 29 Preparation of an antiviral spray 4

Antiviral spray 4, in parts by weight, includes the following components: 8 parts of Phyllanthus emblica aqueous extract, 8 parts of sialic acid, 20 parts of ferrous gluconate, 2 parts of ethanol, 8 parts of glycerol, and 16 parts of flavor.

The preparation method of anti-viral spray 4 is based on the above parts by weight, except that the mass ratio of amla powder to deionized water in step S2 is 1:12, and the Soxhlet extraction time is 3.5 hours, and the other methods are all the same as the anti-viral spray The preparation method of 1 is the same.

Example 30 Preparation of an antiviral spray 5

Anti-viral spray 5, in parts by weight, includes the following components: 20 parts of emblica alcohol extract, 20 parts of sialic acid, 2 parts of magnesium oxide, 10 parts of ethanol, 15 parts of glycerol, and 1 part of flavor.

The preparation method of antiviral spray 5 includes the following steps:

S1. Sun-dried and crushed fresh emblica fruit to prepare emblica powder;

S2. Weigh 100g of emblica powder, heat and reflux with 85% ethanol for 3 times, recover the solvent under reduced pressure to obtain an extract, disperse the extract in distilled water, and extract 5 times with ethyl acetate to obtain an alcohol extract of amlic;

S3. According to the above weight, fully dissolve the ethanol extract of Phyllanthus emblica, sialic acid, magnesium oxide, ethanol, glycerin and flavor obtained in step S2 in deionized water, and then divide them into aerosol bottles according to 50mL each to obtain Anti-viral spray 5.

Example 31 Preparation of an antiviral spray 6

Antiviral spray 6, in parts by weight, includes the following components: 18 parts of emblica alcohol extract, 18 parts of sialic acid, 4 parts of sodium tungstate, 8 parts of ethanol, 13 parts of glycerol, and 2 parts of flavor.

The preparation method of anti-viral spray 6 is based on the above parts by weight, except that the concentration of ethanol in step S2 is 80%, the number of reflux extraction is 5 times, and the number of extractions is 6 times, the other methods are the same as those of anti-viral spray 5. The preparation method is the same.

Example 32 Preparation of an antiviral spray 7

Antiviral spray 7, in parts by weight, includes the following components: 14 parts of amlic acid alcohol extract, 14 parts of sialic acid, 9 parts of rubidium iodide, 6 parts of ethanol, 10 parts of glycerin, and 10 parts of flavor.

The preparation method of anti-viral spray 7 is based on the above parts by weight, except that the concentration of ethanol in step S2 is 83%, the number of reflux extraction is 2 times, and the number of extractions is 4 times, the other methods are the same as those of anti-viral spray 5. The preparation method is the same.

Example 33 Preparation of an antiviral spray 8

Anti-viral spray 8, in parts by weight, includes the following components: Example 1 15 parts of Phyllanthus emblica water extract, 15 parts of sialic acid, 5 parts of rubidium iodide, 8 parts of ethanol, 8 parts of glycerol, and 7 parts of flavor.

The preparation method of the antiviral spray 8 is the same as the preparation method of the antiviral spray 5.

Example 34 Preparation of an antiviral spray 9

Antiviral spray 9, in parts by weight, includes the following components: Example 2 18 parts of Phyllanthus emblica water extract, 5 parts of sialic acid, 15 parts of zinc gluconate, 10 parts of ethanol, 8 parts of glycerol, and 5 parts of essence.

The preparation method of antiviral spray 9 is the same as that of antiviral spray 5.

Example 35 Preparation of an antiviral spray 10

Antiviral spray 10, in parts by weight, includes the following components: Example 3 8 parts of emblic acid alcohol extract, 20 parts of sialic acid, 5 parts of sodium tungstate, 7 parts of ethanol, 12 parts of glycerol, and 8 parts of flavor.

The preparation method of the antiviral spray 10 is the same as the preparation method of the antiviral spray 5.

Example 36 Preparation of an ophthalmic antiviral agent 1

The ophthalmic medicament specifically includes the following raw materials: 18g of Phyllanthus emblica aqueous extract, 8g of zinc sulfate, 0.3g of borneol, 1.0ml of ethanol, 4g of osmotic pressure regulator sodium chloride, 2g of antioxidant sodium bisulfite, and 3ml of solubilizer Tween , Tackifier sodium hyaluronate 2g, bacteriostatic agent benzalkonium chloride 0.2g, balance water, pH value adjusted to 6.5.

Dissolve the aqueous extract of Phyllanthus emblica with water for injection, adjust the pH to 6.5, and filter; dissolve zinc sulfate, dissolve borneol with ethanol, add to the above-mentioned filtrate, and then sequentially add osmotic pressure regulator, antioxidant, solubilizer, and thickener Stir thoroughly, adjust the pH value to 6.5, finally add water for injection to adjust the volume to 1L, filter, separate the filtrate, and sterilize it.

Among them, the preparation method of the water extract of Phyllanthus emblica is sun-dried and crushed fresh Phyllanthus emblica fruit to prepare a powder. Weigh 100g of amla powder, wrap it with filter paper, put it in a Soxhlet extractor, add 1000g of neutral deionized water to Soxhlet extraction for 4 hours, recover the water extract, concentrate on a water bath and set the volume to obtain Phyllanthus emblica water extract. Example 37 Preparation of an ophthalmic antiviral agent 2

The ophthalmic medicament specifically includes the following raw materials: 10g of Phyllanthus emblica water extract, 4g of ferrous sulfate, 0.1g of borneol, 1.0ml of ethanol, 3g of osmotic pressure regulator sodium chloride, 0.5g of antioxidant sodium sulfite, 6ml of solubilizer Tween, The thickener hypromellose 1g, the bacteriostatic agent benzalkonium chloride 0.3g, the balance of water, the pH value is adjusted to 7.4.

Among them, in the preparation method of the aqueous extract of Phyllanthus emblica, the addition amount of neutral deionized water is 200g, the extraction time is 2h, and the rest of the preparation method refers to ophthalmic antiviral agent 1.

Example 38 Preparation of an ophthalmic antiviral agent 3

The ophthalmic medicament specifically includes the following raw materials: emblica extract 20g, calcium gluconate 15g, borneol 0.5g, ethanol 1.0ml, osmotic pressure regulator sodium chloride 5g, antioxidant sodium bisulfite 3g, solubilizer Tween 2ml , Thickener sodium hyaluronate 5g, bacteriostatic agent benzalkonium chloride 0.1g, balance water, pH value adjusted to 5.0.

For the preparation method, refer to ophthalmic antiviral agent 1.

Example 39 Preparation of an ophthalmic antiviral agent 4

The ophthalmic medicament specifically includes the following raw materials in weight ratio: Emblic extract 8g, magnesium oxide 2g, borneol 0.3g, ethanol 1.0ml, osmotic pressure regulator boric acid 4g, antioxidant sodium bisulfite 5g, solubilizer Tween 10ml, The thickener sodium hyaluronate 0.1g, the bacteriostatic agent benzalkonium chloride 0.5g, the balance water, the pH value is adjusted to 8.0.

For the preparation method, refer to ophthalmic antiviral agent 1.

Example 40 Preparation of an ophthalmic antiviral agent 5

The ophthalmic agent specifically includes the following raw materials in weight ratio: Emblic extract 8g, sodium tungstate 2g, borneol 0.2g, ethanol 1.0ml, osmotic pressure regulator boric acid 4g, antioxidant sodium bisulfite 5g, solubilizer Tween 10ml , 0.1g of thickener sodium hyaluronate, 0.5g of bacteriostatic agent benzalkonium chloride, balance water, pH value adjusted to 7.0.

For the preparation method, refer to ophthalmic antiviral agent 1.

Example 41 Preparation of an ophthalmic antiviral agent 6

The ophthalmic medicament specifically includes the following raw materials in weight ratio: Emblic extract 8g, rubidium iodide 2g, borneol 0.3g, ethanol 1.0ml, osmotic pressure regulator boric acid 4g, antioxidant sodium bisulfite 5g, solubilizer Tween 10ml , 0.1g of thickener sodium hyaluronate, 0.5g of bacteriostatic agent benzalkonium chloride, balance water, pH value adjusted to 6.0.

For the preparation method, refer to ophthalmic antiviral agent 1.

Example 42 Preparation of an ophthalmic antiviral agent 7

The ophthalmic medicament specifically includes the following raw materials: Example 1 18 g of Phyllanthus emblica aqueous extract, 8 g of zinc sulfate, 0.3 g of borneol, 1.0 ml of ethanol, 4 g of osmotic pressure regulator sodium chloride, 2 g of antioxidant sodium bisulfite, and solubilizer Tween 3ml, thickener sodium hyaluronate 2g, bacteriostatic agent benzalkonium chloride 0.2g, balance water, pH value adjusted to 6.5.

For the preparation method, refer to ophthalmic antiviral agent 1.

Example 43 Preparation of an ophthalmic antiviral agent 8

The ophthalmic medicament specifically includes the following raw materials: Example 2 12g of amlic officinalis water extract, 5g of ferrous sulfate, 0.2g of borneol, 1.0ml of ethanol, 4g of osmotic pressure regulator sodium chloride, 1g of antioxidant sodium sulfite, and solubilizer Tween 5ml, thickener hypromellose 1g, bacteriostatic agent benzalkonium chloride 0.3g, balance water, pH value adjusted to 7.2.

For the preparation method, refer to ophthalmic antiviral agent 1.

Example 44 Preparation of an ophthalmic antiviral agent 9

The ophthalmic medicament specifically includes the following raw materials: Example 3 15g of emblica extract, 15g of calcium gluconate, 0.4g of borneol, 1.0ml of ethanol, 5g of osmotic pressure regulator, sodium bisulfite 2g, antioxidant Solvent Tween 3ml, thickener sodium hyaluronate 4g, bacteriostatic agent benzalkonium chloride 0.2g, balance water, pH value adjusted to 6.0.

For the preparation method, refer to ophthalmic antiviral agent 1.

Example 45 Preparation of an ophthalmic antiviral agent 10

The ophthalmic medicament specifically includes the following raw materials in weight ratio: Example 4 15g of emblica extract, 2g of magnesium oxide, 0.3g of borneol, 1.0ml of ethanol, 4g of osmotic pressure regulator, sodium bisulfite 5g, and solubilizer Tween 10ml, thickener sodium hyaluronate 0.1g, bacteriostatic agent benzalkonium chloride 0.5g, balance water, pH value adjusted to 8.0.

For the preparation method, refer to ophthalmic antiviral agent 1.

Comparative example 1

An oral liquid A, except that the water extract of Phyllanthus emblica is not included, the rest of the components and the preparation method are the same as those of the antiviral oral liquid 1.

Comparative example 2

An oral liquid B, except that it does not include the water extract of Phyllanthus emblica and zinc sulfate, the rest of the components and the preparation method are the same as those of the antiviral oral liquid 1.

Comparative example 3

An oral liquid C, except that it does not include the alcohol extract of Phyllanthus emblica, magnesium oxide and sialic acid, the rest of the components and the preparation method are the same as the antiviral oral liquid 5.

Comparative example 4

An oral liquid D, except that Phyllanthus emblica extract is 2 parts by weight (the content is too low), and the remaining components and preparation methods are the same as the antiviral oral liquid 1.

Comparative example 5

A kind of oral liquid E, except that the weight part extracted from emblidine is 2 parts (the content is too low) and the weight part of sialic acid is 2 parts (the content is too low), the other components and preparation methods are the same as those of the anti-viral oral liquid 5. same.

Comparative example 6

An oral liquid a, except that it does not include the water extract of Phyllanthus emblica and zinc sulfate, the remaining components and preparation method are the same as those of the oral liquid 1 for anti-influenza virus.

Comparative example 7

An oral liquid b, except that it does not include the alcohol extract of emblica, magnesium oxide and sialic acid, and the remaining components and preparation methods are the same as those of the anti-influenza virus oral liquid 5.

Comparative example 8

An oral liquid c, except that Phyllanthus emblica extract is 2 parts by weight (the content is too low), and the remaining components and preparation method are the same as the anti-influenza virus poison oral liquid 1.

Comparative example 9

An oral liquid d, except that the weight part extracted from emblymol is 2 parts (the content is too low), the weight part of sialic acid is 2 parts (too low), and the remaining components and preparation methods are the same as those of the anti-influenza virus oral liquid 5 same.

Comparative example 10

A spray a, except that it does not include the water extract of Phyllanthus emblica and the metal salt, the rest of the components and the preparation method are the same as the antiviral spray 1.

Comparative example 11

A spray b, except that it does not include the water extract of Phyllanthus emblica, metal salt and solvent, the rest of the components and the preparation method are the same as those of antiviral spray 1.

Comparative example 12

A spray c, except that it does not include the alcohol extract of Phyllanthus emblica, metal salt, solvent and sialic acid, the rest of the components and the preparation method are the same as the antiviral spray 5.

Comparative example 13

The main components and preparation method of ophthalmic medicament are the same as those of ophthalmic antiviral medicament 1. Compared with ophthalmic antiviral medicament 1, the difference lies in:

(1) Comparative group 1: No Phyllanthus emblica extract.

(2) Comparative group 2: No zinc sulfate.

Application Example 1 Cytotoxicity test of oral liquid

1. Experimental method

In this application example, the MTT method is used to test the toxicity test of the antiviral oral liquids 1, 2, 3, 8, 9 and 10 prepared in the embodiments of the present invention on cells. The specific experimental steps are as follows:

(1) At ^{a concentration of 1×10 5} cells/well, inoculate human embryonic kidney cells 293 (HEK293 cells) into a 96-well plate, add 100 μL of DMEM medium, and culture at 37°C and 5% CO ₂ to form a monolayer;

(2) Discard the culture medium, wash twice with PBS, and dilute the antiviral oral liquids 1, 2, 3, 8, 9 and 10 prepared in the examples of the present invention with DMEM and inoculate them on the cells, 100 μL/well, each 4 multiple wells with a concentration of more than 4, set the same concentration control group, 37 ℃ 5% CO ₂ culture for 48 hours;

(3) Add 20μL of MTT solution (2.5mg/mL) to each well, _{incubate at 37°C and 5% CO 2} for 4h; discard the supernatant, add 120μL of DMSO/well, and shake for 20min;

(4) Measure the optical density (OD) of each hole at 490nm wavelength on the multi-function reader, and use the Reed-Muench method to calculate the 50% toxic concentration of the drug (toxic concentration for 50% of the population, TC). ₅₀ ).

2. Experimental results

_{The TC 50} values of the antiviral oral liquids 1, 2, 3, 8, 9 and 10 prepared in the examples of the present invention on HEK293 cells measured by the MTT method were 130.27 μg/mL, 132.32 μg/mL and 140.46 μg/mL, respectively , 133.22μg/mL, 135.02μg/mL, 135.69μg/mL; indicating that the oral liquid prepared by the present invention has no cytotoxicity (the toxicity is very low and can be ignored).

Application Example 2 In vitro antiviral performance test of oral liquid

1. Experimental method

This application example tests the in vitro antiviral (2019-nCoV and MERS-CoV) experiments of the antiviral oral liquids 1, 2, 3, 8, 9 and 10 prepared in the examples of the present invention. The specific experimental steps are as follows:

(1) Add HEK293 cells ^{to a 96-well plate at a concentration of 4.5×10 4} cells/well, and culture in DMEM containing 1% fetal bovine serum at 37°C with 5% CO _{2 for} 24 hours;

(2) Discard the supernatant, add 100TCID ₅₀ 2019-nCoV and MERS-CoV to _{each well, and absorb at 37°C with 5% CO 2 for 2} hours;

(3) The supernatant was discarded and the cells were washed with PBS, and the aqueous extract of amla prepared in Example 1 of the present invention, the ethanol extract of amla prepared in Example 6 and those prepared in Examples 1, 2 and 3 of the present invention Anti-viral oral liquid 1, 2, 3, 8, 9 and 10 were diluted with DMEM and added to each well to set it as the experimental group. The blank control group was added with the same amount of DMEM and _{incubated at 37°C with 5% CO 2} for 72 hours. Collect the virus supernatant;

(4) ^{Inoculate HEK293 cells into a 12-well plate at 2×10 6} cells/well, and incubate at 37°C with 5% CO _{2 for} 24 hours;

(5) Perform 10-fold serial dilution of the virus supernatant collected in step (3), inoculate HEK293 cells, and _{absorb at 37°C with 5% CO 2 for 2} hours;

(6) Discard the supernatant and wash the cells with PBS, add 2 mL of 1% (w/v) methylcellulose-DMEM cover, and incubate at 37°C with 5% CO _{2 for} 72 hours;

(7) Remove the methylcellulose-DMEM covering, wash the cells twice with PBS, and fix the cells with 10% formaldehyde for 30 minutes at room temperature;

(8) Discard the supernatant, wash the cells twice with PBS, add 0.5% crystal violet to stain at room temperature for 5 minutes, wash twice with deionized water, count the plaques after drying, and use the Reed-Muench method to calculate the 50% virus inhibited drug concentration as The half maximal inhibitory concentration of the drug (half maximal inhibitory concentration, IC ₅₀ ).

2. Experimental results

The antiviral oral liquid 1, 2, 3, 8, 9, 10 prepared by the present invention has in vitro inhibitory activity results against 2019-nCoV and MERS-CoV as shown in Tables 11-16. It can be seen that when the concentration of the oral liquid is At 6.25μg/mL, it can inhibit the replication of 2019-nCoV and MERS-CoV in HEK293 cells; when the concentration of oral liquid reaches 50μg/mL, it can significantly reduce the average virus titer, and the therapeutic index is high.

In addition, it can be seen from Tables 11-16 that the aqueous extract of Phyllanthus emblica and the ethanol extract of Phyllanthus emblica prepared by the present invention have good in vitro inhibitory activities of 2019-nCoV and MERS-CoV, but both are lower than the antiviral oral liquid. The inhibitory effect of 1, 2, 3, 8, 9 and 10 on 2019-nCoV and MERS-CoV shows that the combination of Phyllanthus emblica extract and metal salt has a significant synergistic effect; and the antiviral oral liquid 3 has a significant synergistic effect. The inhibitory effect is lower than that of the antiviral oral liquids 1 and 2.

Table 11 In vitro inhibitory activity results of antiviral oral liquid 1 against 2019-nCoV and MERS-CoV

Table 12 Results of in vitro inhibitory activity of antiviral oral liquid 2 on 2019-nCoV and MERS-CoV

Table 13 In vitro inhibitory activity results of antiviral oral liquid 3 on 2019-nCoV and MERS-CoV

Table 14 Results of in vitro inhibitory activity of antiviral oral liquid 8 on 2019-nCoV and MERS-CoV

Table 15 Results of in vitro inhibitory activity of antiviral oral liquid 9 on 2019-nCoV and MERS-CoV

Table 16 Results of in vitro inhibitory activity of antiviral oral liquid 10 on 2019-nCoV and MERS-CoV

The above results indicate that the antiviral oral liquid prepared by the present invention has good in vitro antiviral (2019-nCoV and MERS-CoV) activity.

Application Example 3 In vivo antiviral performance test of oral liquid

1. Experimental method

This application example tests the in vivo antiviral (2019-nCoV and MERS-CoV) experiments of the antiviral oral liquids 1, 2, 3, 8, 9, and 10 prepared in the examples of the present invention. The specific experimental steps are as follows:

(1) ^{Transfect BALB/c mice intranasally with 2.5×10 8} PFU recombinant adenovirus vector expressing hCD26 (purchased from Guangdong Laboratory Animal Monitoring Institute);

(2) On the 4th day after transfection, mice expressing hCD26 were infected with 2019-nCoV and MERS-CoV intranasally, and the mice were randomly divided into blank control group and anti-viral oral liquid group 1 [90mg/(kg·d )], antiviral oral liquid 2 groups [90mg/(kg·d)], antiviral oral liquid 3 groups [90mg/(kg·d)], comparative oral liquid group A, comparative oral liquid group B, right Proportional oral liquid C group, comparative oral liquid D group and comparative oral liquid E group, each of 6 animals, all females, were administered by gavage, and the blank control group used the same amount of 0.1% DMSO solution;

(3) On the 3rd and 5th day after infection, 3 mice in each group were randomly selected and _{killed by CO 2} after anesthesia. The lungs of the mice were transferred into PBS, homogenized on ice using a manual homogenizer, and centrifuged at 4°C at 12000r/min for 5min. Collect the supernatant;

(14) Perform virus titer detection, and the detection method is the same as the in vitro antiviral experiment of Application Example 2 above.

2. Experimental results

The results of anti-viral oral liquid 1, 2, 3, 8, 9, 10 on the in vivo inhibition of new coronaviruses (2019-nCoV and MERS-CoV) are shown in Tables 17-20. It can be seen that compared with the blank control group Compared with oral liquid A, B, C, D and E groups, BALB/c mice were infected with 2019-nCoV and MERS-CoV on the 3rd day, antiviral oral liquid 1, 2 and 3, 8, 9 and 10 groups The inhibitory effect of viruses (2019-nCoV and MERS-CoV) in mice was significantly enhanced; on the 5th day after infection in BALB/c mice, the inhibitory effects of antiviral oral liquids 1, 2 and 3 on the virus were further significantly enhanced , And the inhibitory effect of anti-viral oral liquid 3 is lower than that of anti-viral oral liquid 1 and 2, while the inhibitory effect of oral liquid A, B, C, D and E groups on viruses (2019-nCoV and MERS-CoV) There is no significant difference from the blank control group.

The above results indicate that the antiviral oral liquid prepared by the present invention can effectively and significantly inhibit the replication of 2019-nCoV and MERS-CoV in mice, and its inhibitory effect is time-dependent.

Table 17 Inhibition results of antiviral oral liquid 1, 2 and 3 on 2019-nCoV in vivo (2019-nCoV titer (lg PFU/mL))

Table 18 Inhibition results of antiviral oral liquids 8, 9 and 10 on 2019-nCoV in vivo (2019-nCoV titer (lg PFU/mL))

Table 19 Inhibition results of antiviral oral liquid 1, 2 and 3 on MERS-CoV in vivo (MERS-CoV titer (lg PFU/mL))

Table 20 Inhibition results of antiviral oral liquid 8, 9 and 10 on MERS-CoV in vivo (MERS-CoV titer (lg PFU/mL))

Application Example 4 Cytotoxicity test of anti-influenza virus oral liquid

1. Experimental method

In this application example, the MTT method is used to test the toxicity test of the anti-influenza virus oral liquids 1, 2, and 3 prepared in the embodiment of the present invention on cells, and the specific experimental steps refer to application example 1.

2. Experimental results

_{The TC 50} values of the anti-influenza virus oral liquids 1, 2, and 3, 8, 9 and 10 prepared in the examples of the present invention measured by the MTT method on HEK293 cells were 141.77 μg/mL, 137.93 μg/mL and 149.57 μg, respectively /mL, 145.9μg/mL, 135.03μg/mL and 140.34μg/mL; indicating that the oral liquid prepared by the present invention has no cytotoxicity (the toxicity is very low and can be ignored).

Application Example 5 In vitro anti-influenza virus performance test of anti-influenza virus oral liquid

1. Experimental method

In this application example, the anti-influenza virus oral liquids 1, 2 and 3, 8, 9 and 10 prepared in this application example were tested against influenza virus in vitro. The virus was influenza A H1N1 virus. Refer to application example 2 for other experimental procedures.

2. Experimental results

The anti-influenza virus oral liquid 1, 2, 3, 8, 9, 10 prepared by the present invention has in vitro inhibitory activity against influenza A H1N1 virus. The results are shown in Tables 21 to 26. It can be seen that when the concentration of the oral liquid is At 6.25μg/mL, it can inhibit the replication of influenza A H1N1 virus in HEK293 cells; when the concentration of the oral liquid reaches 50μg/mL, it can significantly reduce the average virus titer, and the therapeutic index is high.

Table 21 Results of in vitro inhibitory activity of anti-influenza virus oral liquid 1 on influenza A H1N1 virus

Table 22 The results of in vitro inhibitory activity of anti-influenza virus oral liquid 2 on influenza A H1N1 virus

Table 23 Results of in vitro inhibitory activity of anti-influenza virus oral liquid 3 on influenza A H1N1 virus

Table 24 Results of in vitro inhibitory activity of anti-influenza virus oral liquid 8 on influenza A H1N1 virus

Table 25 The results of in vitro inhibitory activity of anti-influenza virus oral liquid 9 on influenza A H1N1 virus

Table 26 Results of in vitro inhibitory activity of anti-influenza virus oral liquid 10 against influenza A H1N1 virus

The above results indicate that the anti-influenza virus oral liquid prepared by the present invention has good in vitro anti-influenza virus activity.

Application Example 6 In vivo anti-influenza virus performance test of anti-influenza virus oral liquid

1. Experimental method

This application example tests the in vivo anti-influenza virus experiment of the anti-influenza virus oral liquids 1, 2, 3, 8, 9 and 10 prepared in the examples of the present invention. The virus is influenza A H1N1 virus. For other experimental steps, please refer to application example 3. .

2. Experimental results

The results of anti-influenza virus oral liquid 1, 2, 3, 8, 9 and 10 on the in vivo inhibition of influenza A H1N1 virus are shown in Tables 27 and 28. It can be seen that compared with the blank control group and oral liquid a, Compared with groups b, c and d, on the third day after BALB/c mice were infected with H1N1 influenza virus, anti-influenza virus oral liquids 1, 2, and 3 inhibited the replication of H1N1 influenza virus in mice Significantly enhanced; on the 5th day after the infection of BALB/c mice, the anti-influenza virus oral liquid 1, 2 and 3, 8, 9 and 10 further significantly enhanced the inhibitory effect of the H1N1 influenza virus, and the oral liquid 3 groups The inhibitory effect on influenza A H1N1 virus is lower than that of oral liquid 1 and 2 groups; while the inhibitory effect of oral liquid a, b, c and d groups on influenza A H1N1 virus is not significantly different from that of the blank control group, and they are all significantly lower The inhibitory effect of oral liquid 1, 2 and 3, 8, 9 and 10 against influenza virus.

Table 27 Anti-influenza virus oral liquid 1, 2 and 3 groups in vivo inhibition of influenza A H1N1 virus results (A H1N1 influenza virus titer (lg PFU/mL))

Table 28 The results of in vivo inhibition of influenza A H1N1 influenza virus in groups 8, 9 and 10 of oral liquids against influenza virus (A H1N1 influenza virus titer (lg PFU/mL))

The above results indicate that the anti-influenza virus oral liquid prepared by the present invention can effectively and significantly inhibit the replication of influenza A H1N1 virus in mice, and its inhibitory effect is time-dependent.

Application Example 7 Cytotoxicity test of antiviral spray

1. Experimental method

In this application example, the MTT method is used to test the toxicity test of the antiviral sprays 1, 2, 3, 8, 9, and 10 prepared in the examples of the present invention on cells. The specific experimental steps are as follows, refer to Application Example 1.

2. Experimental results

_{The TC 50} values of antiviral sprays 1, 2, 3, 8, 9, and 10 on HEK293 cells were 135.21μg/mL, 132.79μg/mL and 139.32μg/mL, 145.89μg/mL, 150.28μg/mL, 146.99, respectively μg/mL; indicating that the spray prepared by the present invention has no cytotoxicity (the toxicity is very low and can be ignored).

Application Example 8 In vitro antiviral performance test of antiviral spray

1. Experimental method

This application example tests the in vitro antiviral experiments of the antiviral sprays 1, 2, 3, 8, 9, and 10 prepared in the examples of the present invention. The viruses are TCID ₅₀ 2019-nCoV and influenza A H1N1. Refer to Application Example 2 for specific experimental procedures.

2. Experimental results

The results of in vitro inhibitory activity of antiviral sprays against 2019-nCoV and influenza A H1N1 viruses are shown in Tables 29 to 34. It can be seen that when the concentration of antiviral sprays is 6.25μg/mL, it can inhibit 2019-nCoV and The replication of H1N1 influenza virus in HEK293 cells; when the spray concentration reaches 50μg/mL, it can significantly reduce the average virus titer and increase the therapeutic index.

Table 29 In vitro inhibitory activity results of antiviral spray 1 against 2019-nCoV and influenza A H1N1 viruses

Table 30 Results of in vitro inhibitory activity of antiviral spray 2 on 2019-nCoV and influenza A H1N1 viruses

Table 31 Results of in vitro inhibitory activity of antiviral spray 3 against 2019-nCoV and influenza A H1N1 viruses

Table 32 In vitro inhibitory activity results of antiviral spray 8 against 2019-nCoV and influenza A H1N1 viruses

Table 33 Results of in vitro inhibitory activity of antiviral spray 9 against 2019-nCoV and influenza A H1N1 viruses

Table 34 Results of in vitro inhibitory activity of antiviral spray 10 against 2019-nCoV and influenza A H1N1 viruses

The above results indicate that the antiviral spray prepared by the present invention has good in vitro antiviral (2019-nCoV and influenza A H1N1 virus) activity.

Application Example 9 In vivo antiviral performance test of spray

1. Experimental method

This application example tests the in vivo antiviral (2019-nCoV and influenza A H1N1 influenza virus) experiments of the antiviral sprays 1, 2, 3, 8, 9, and 10 prepared in the examples of the present invention. Refer to Application Example 3 for specific experimental steps .

2. Experimental results

The results of in vivo inhibition of antiviral sprays 1, 2, 3, 8, 9, 10 on 2019-nCoV and influenza A H1N1 viruses are shown in Table 13. It can be seen that compared with the blank control group and sprays a, b Compared with group c, on the 5th day after BALB/c mice were infected with 2019-nCoV and A H1N1 influenza virus, antiviral sprays 1, 2, 3, 8, 9, 10 inhibited the virus (2019-nCoV and A H1N1 H1N1 influenza virus) has a significantly enhanced replication effect in mice, and the inhibitory effects of antiviral sprays 1 and 2 on 2019-nCoV and H1N1 influenza virus are higher than those of antiviral spray 3; while sprays a and b The inhibitory effect of group c on viruses (2019-nCoV and influenza A H1N1 virus) was not significantly different from that of the blank control group.

The above results indicate that the antiviral spray prepared by the present invention can effectively and significantly inhibit the replication of 2019-nCoV and influenza A H1N1 viruses in mice.

Table 35 Results of in vivo inhibition of antiviral sprays 1, 2 and 3 on 2019-nCoV and influenza A H1N1 viruses

Table 36 Results of in vivo inhibition of antiviral sprays 8, 9 and 10 on 2019-nCoV and influenza A H1N1 viruses

Application Example 10 Performance test of ophthalmic antiviral agents

1. Stability test

Take ophthalmic agent 1 as an example.

Take an appropriate amount of ophthalmic drug 1 sample, and place it under high temperature (65°C), low temperature (3°C) and strong light (4500Lx) for 15 days. Take samples on 0, 8, and 15 days for testing to check the stability of the sample. Results See Table 37.

Table 37 Stability test of ophthalmic antiviral composition

time

Visible foreign body

pH value

0天0 days	符合规定Compliance	6.236.23
低温8天Low temperature 8 days	符合规定Compliance	6.206.20
高温8天High temperature 8 days	符合规定Compliance	6.226.22
光照8天Light for 8 days	符合规定Compliance	6.266.26
低温15天Low temperature for 15 days	符合规定Compliance	6.286.28
高温15天High temperature 15 days	符合规定Compliance	6.216.21
光照15天Light for 15 days	符合规定Compliance	6.236.23

From the results in Table 37, it can be known that the ophthalmic antiviral composition prepared by the present invention is placed under the conditions of high temperature, low temperature and light for 15 days, and the indicators still meet the standards. Therefore, the quality of the composition obtained in this application is stable and meets the requirements. .

2. Rabbit eye irritation experiment

The ophthalmic agent 1 was used as the experimental sample, and the control drug was physiological saline.

Experimental animals: New Zealand rabbits 1.0-1.5Kg (purchased from Guangdong Laboratory Animal Monitoring Institute), half male and half male. Before the experiment, the animals were kept for 7 days, and the animal behavior, activity, diet, mental state and normal eye conditions were observed and recorded.

experimental method:

The rabbits were randomly divided into 2 groups, each with 5 rabbits, divided into a control group and an experimental group; the control group received 1.0 ml of saline infusion, and the experimental group received 11.0 ml of ophthalmic agent.

Eye drops 3 times a day (8:00, 13:00, 17:00), for 20 consecutive days, observe the changes of rabbit eye conjunctiva every day, observe the eye conjunctiva 4 hours after the last administration, and instill 1% after 10 hours Fluorescein sodium solution, 11 hours later, check the results with a slit lamp biological microscope, and record. After stopping the drug, observe the animal's stimulus response, conjunctival hyperemia, secretion and corneal staining on 1, 8, 15, and 20 days, and score records. The scoring criteria are shown in Table 38.

Table 38 Evaluation Criteria for Eye Irritation

刺激程度Stimulus	评分score
无刺激性Non-irritating	0-30-3
轻度刺激性Mild irritation	4-84-8
中度刺激性Moderately irritating	9-129-12
强度刺激性Intensity irritation	13-1613-16

In each experimental group in the rabbit eyes, after instilling the composition, observe the irritation response of the animals on 1, 8, 15, and 20 days respectively, and add the irritation response scores of each rabbit’s cornea, iris, and conjunctiva to get the result The total score of the irritation response of the test animal's conjunctiva, cornea, iris, etc., and then the total score of a group is divided by the number of animals to obtain the eye irritation score of the ophthalmic antiviral combination. The larger the score, the more irritation. powerful. The results are shown in Table 39. From the table, it can be seen that the cornea, iris, and conjunctiva are all normal. Therefore, it shows that the drug of the present invention has no irritating effect on the eyes.

Table 39 Rabbit eye irritation evaluation score

眼刺激反应情况Eye irritation	分值Points
角膜cornea	00
虹膜Iris	11
结膜conjunctiva	00

Application Example 11 Cytotoxicity test of ophthalmic agents

1. Experimental method

In this application example, the MTT method is used to test the toxicity test of the ophthalmic agents 1, 2, 3, 7, 8, and 9 prepared in Examples 22-24 of the present invention on cells. For specific experimental procedures, refer to Application Example 1.

2. Experimental results

_{The TC 50} values of the three ophthalmic agents in Examples 22-24 on HEK293 cells measured by MTT method were 137.43μg/mL, 139.52μg/mL and 143.39μg/mL, 135.45μg/mL, 141.25μg/mL, 139.52, respectively. μg/mL, indicating that the ophthalmic antiviral composition prepared by the present invention has very low cytotoxicity and little cytotoxicity.

Application Example 12 In vitro antiviral experiment of ophthalmic agents

1. Experimental method

In this example, in vitro antiviral experiments were carried out with the ophthalmic drugs prepared by ophthalmic drugs 1, 2, 3, 7, 8, 9 and comparative groups 1 to 2 of Comparative Example 13. The tested viruses were 2019-nCoV and type A For H1N1 influenza virus, refer to Application Example 2 for specific experimental procedures.

2. Experimental results

When the concentration of the ophthalmic antiviral agent prepared by the present invention is 6.25 μg/mL, it can inhibit the replication of 2019-nCoV and influenza A H1N1 virus in HEK293 cells; when the drug concentration reaches 50 μg/mL, the average virus titer can be reduced, See Tables 40-46 for specific results.

Table 40 The inhibitory effect of ophthalmic agent 1 on two viruses

Table 41 Inhibitory effect of ophthalmic agent 2 on two viruses

Table 42 The inhibitory effect of ophthalmic agent 3 on two viruses

Table 43 Inhibitory effect of ophthalmic agent 7 on two viruses

Table 44 The inhibitory effect of ophthalmic agent 8 on two viruses

Table 45 Inhibitory effect of ophthalmic agent 9 on two viruses

Table 46 Inhibitory effects of the comparison group 1 ophthalmic agents on the two viruses

Table 47 Inhibitory effects of contrast group 2 ophthalmic agents on two viruses

The above results show that the antiviral effect of the ophthalmic agent prepared by the formula described in this application is significantly better than that of the comparative group 1-2.

Application Example 13 In vitro antiviral experiment of ophthalmic agents

1. Experimental method

Take ophthalmic agent 1 as an example, and use the same experimental method in application example 12 to test the antiviral effects of ophthalmic agents against adenovirus (Adenovirus), varicella-zoster virus (VZV), and cytomegalovirus (Cytomegalovirus) effect. The results are shown in Table 48.

Table 48 Inhibitory effects of ophthalmic agent 1 on adenovirus, varicella-zoster virus, and cytomegalovirus

It can be seen from the results in Table 48 that the ophthalmic agent of the present invention has a significant inhibitory effect on adenovirus, varicella-zoster virus, and cytomegalovirus.

Take the ophthalmic agent 7 as an example, and use the same experimental method as the application example 12 to test the ophthalmic antiviral agent 7 against Adenovirus, varicella-zoster virus (VZV), and Cytomegalovirus. The antiviral effect. The results are shown in Table 49.

Table 49 Inhibitory effects of ophthalmic antiviral agents 7 on adenovirus, varicella-zoster virus, and cytomegalovirus

From the results in Table 49, it can be seen that the ophthalmic antiviral agent 7 of the present invention has a significant inhibitory effect on adenovirus, varicella-zoster virus, and cytomegalovirus.

Taking the ophthalmic antiviral agent 8 as an example, and the experimental method of application example 12, the ocular antiviral agent 8 was tested against Adenovirus, varicella-zoster virus (VZV), and cytomegalovirus ( Cytomegalovirus) antiviral effect. The results are shown in Table 50.

Table 50 Inhibitory effect of ophthalmic antiviral agent 8 on adenovirus, varicella-zoster virus and cytomegalovirus

From the results in Table 50, it can be seen that the ophthalmic antiviral agent 8 of the present invention has a significant inhibitory effect on adenovirus, varicella-zoster virus, and cytomegalovirus.

Taking the ophthalmic antiviral agent 9 as an example, and the experimental method of application example 12, the ocular antiviral agent 9 was tested against Adenovirus, varicella-zoster virus (VZV), and cytomegalovirus ( Cytomegalovirus) antiviral effect. The results are shown in Table 51.

Table 51 Inhibitory effects of ophthalmic antiviral agents 9 on adenovirus, varicella-zoster virus, and cytomegalovirus

It can be seen from the results in Table 51 that the ophthalmic antiviral agent 9 of the present invention has a significant inhibitory effect on adenovirus, varicella-zoster virus, and cytomegalovirus.

The above-mentioned embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above-mentioned embodiments, and any other changes, modifications, substitutions, combinations, etc. made without departing from the spirit and principle of the present invention Simplified, all should be equivalent replacement methods, and they are all included in the protection scope of the present invention.

Claims

An antiviral composition characterized by comprising Phyllanthus emblica.
The composition according to claim 1, wherein the Phyllanthus emblica is an extract of Phyllanthus emblica.
The composition according to claim 2, wherein the Phyllanthus emblica extract is a water extract of Phyllanthus emblica or an alcoholic extract of Phyllanthus emblica.
The composition according to any one of claims 1 to 3, characterized in that it further comprises a metal salt.
The composition according to claim 4, wherein the mass ratio of amla and the metal salt is 1: (0.01-10).
The composition according to any one of claims 1 to 3, characterized in that it further comprises sialic acid.
The composition according to claim 6, wherein the mass ratio of amla and sialic acid is 1:(0.01-20).
Use of the composition according to any one of claims 1 to 7 in the preparation of antiviral drugs.
The use according to claim 8, wherein the virus is a respiratory virus.
The application according to claim 9, wherein the respiratory virus is coronavirus or influenza virus.
An antiviral oral liquid, characterized in that it contains the composition according to any one of claims 1-7.
The anti-viral oral liquid according to claim 11, characterized in that it comprises the following components in parts by weight: 10-22 parts of Phyllanthus emblica, 4-22 parts of metal salt, 5-53 parts of antioxidant, and 5 parts of sweetener. ~23 copies.
The antiviral oral liquid according to claim 12, characterized in that it further contains 10-22 parts by weight of sialic acid.
A special preparation for anti-influenza virus, characterized in that, in parts by weight, it comprises the following components: 8-20 parts of Phyllanthus emblica extract, 8-20 parts of sialic acid, 2-20 parts of metal salt, 2-50 parts of antioxidant Servings, 2-18 servings of flavor and 2-20 servings of sweetener.
An antiviral spray, which is characterized by containing the composition according to any one of claims 1-7.
The antiviral spray according to claim 15, characterized in that it comprises the following components in parts by weight: 8-20 parts of emblica, 8-20 parts of sialic acid, 2-20 parts of metal salt, and 2-10 parts of solvent. Servings, 8-15 glycerin, 1-16 flavors.
An ophthalmic antiviral agent characterized by containing the composition according to any one of claims 1 to 5.
The ophthalmic antiviral agent according to claim 17, characterized in that, in parts by weight, each 1L of the composition contains the following components: 8-20 parts of Phyllanthus emblica, 3-5 parts of osmotic pressure regulator, 0.1% antioxidant ~5 parts, solubilizer 0.5-10 parts, bacteriostatic agent 0.1-5 parts, thickener 0.1-5 parts, borneol 0.1-0.5 parts, metal salt 2-20 parts, the balance is water for injection.