CN111588744A - Antiviral composition and oral liquid as well as preparation method and application thereof - Google Patents
Antiviral composition and oral liquid as well as preparation method and application thereof Download PDFInfo
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- CN111588744A CN111588744A CN202010530948.3A CN202010530948A CN111588744A CN 111588744 A CN111588744 A CN 111588744A CN 202010530948 A CN202010530948 A CN 202010530948A CN 111588744 A CN111588744 A CN 111588744A
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- antiviral
- oral liquid
- parts
- composition
- extract
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/47—Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an antiviral composition, an antiviral oral liquid, and a preparation method and application thereof. The present invention provides, in a first aspect, an antiviral composition comprising emblic leafflower fruit or an extract thereof. The antiviral oral liquid preparation containing the composition is developed, the components in the formula are reasonably compatible, the combination is optimized, the antiviral oral liquid preparation has broad-spectrum antiviral activity, and can effectively inhibit virus invasion, harm human bodies and inhibit virus replication, so that the antiviral oral liquid preparation has prevention and treatment effects and has a remarkable antiviral effect. In addition, the preparation method of the antiviral oral liquid is simple, the cost is low, and the traditional Chinese medicine phyllanthus emblica has the advantages of being natural, safe, mild in drug effect and the like; therefore, the oral liquid is beneficial to the treatment and rehabilitation of virus infected patients, improves the life quality, can be used as an effective method for daily protection and prevention of respiratory system infectious diseases of normal people, has the potential of preparing broad-spectrum antiviral drugs, and has good prevention and control significance for the spread of diseases caused by virus infection of human bodies.
Description
Technical Field
The invention belongs to the technical field of medicines. More particularly, relates to an antiviral composition, an oral liquid, a preparation method and an application thereof.
Background
Viruses can invade, attack and harm the human body in various ways; among them, respiratory viruses are important pathogens causing respiratory diseases, can be transmitted through respiratory tracts, can be dispersed into the air through sneezing, coughing and the like of patients, and can cause infection after being inhaled by healthy people. Respiratory viruses refer to a large group of respiratory viruses which can invade respiratory tracts to cause local lesions of respiratory tracts; or only using respiratory tract as an invasion portal, mainly causing the virus of the external tissue organ lesion of the respiratory tract, and more than 90 percent of acute respiratory tract infection is caused by the virus.
Respiratory viruses are classified into two types, DNA viruses and RNA viruses, and common respiratory viruses include respiratory syncytial viruses, influenza viruses, parainfluenza viruses, rubella viruses, rhinoviruses, coronaviruses and orthoreoviruses belonging to RNA viruses, and adenoviruses, varicella-zoster viruses and bocaviruses belonging to DNA viruses; wherein, 30 to 35 percent of the medicine capable of causing cold is rhinovirus, and 20 to 30 percent of the medicine is coronavirus. Coronaviruses belong to the order nidoviridae, family coronaviridae, and examples of coronaviruses capable of infecting a human body include: severe acute respiratory syndrome coronavirus 2(2019-nCoV), 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(HCoV-HKU 1). Coronavirus is one of the main pathogens of modern epidemic situations, and often causes serious respiratory system infection of human beings; among them, 2019-nCoV has high infectivity, and pneumonia infected by novel coronavirus is prevalent all over the world and is distributed globally, thus causing great impact on the global public health system.
Acute upper respiratory tract infection caused by human body infected with respiratory tract virus mostly occurs in winter, more than 90% of respiratory tract infection in children and adults is caused by virus, the incidence rate is extremely high, the spread is fast, the epidemic range is wide, and the human body has 5-6 times of annual incidence; the virus can be expanded to lower respiratory tract to form bronchitis and pneumonia, some of which can cause viremia and invade other organs such as intestinal tract. At present, CN102836200A discloses the application of emblic leafflower fruit in preparing anti-H1N 1 influenza virus drugs, in particular to an application of an emblic leafflower fruit flavone extract in obviously inhibiting H1N1 influenza virus cytopathic effect; however, it is only against the H1N1 influenza virus and is not suitable for other common respiratory viruses. The virus group causing respiratory tract infection has two characteristics: 1) diversity, the physicochemical and biological activities of these viruses are different, and the receptors for the members of different virus families to invade the epithelium of the upper respiratory tract are also different; 2) the group of viruses has continuous variation in nature, multiple types, large variation and weak and lasting immunity. Therefore, there is a high necessity to develop a drug having a broad spectrum antiviral activity for preventing or treating diseases caused by upper respiratory infection.
In addition, when the virus is mutated or a new virus is generated to cause epidemic outbreak of the infectious disease for another time, the original special-effect medicine is difficult to exert effective prevention and control effects, so that the virus is rapidly diffused, even disastrous outbreak in the global range causes huge impact on the politics and economy of the society. Therefore, it is of great significance to screen broad-spectrum antiviral drugs with more effective and stable effects.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the defects and shortcomings of the prior art, provide a new drug selection with a broad-spectrum antiviral spectrum, and particularly develop the new drug selection into an oral liquid preparation which has good prevention and treatment effects on respiratory viruses.
The invention aims to provide an antiviral composition.
The invention also aims to provide the application of the composition in preparing antiviral drugs.
The invention also aims to provide antiviral oral liquid.
The invention further aims to provide a preparation method of the oral liquid.
The above purpose of the invention is realized by the following technical scheme:
the invention provides an antiviral composition, which comprises emblic leafflower fruit.
Preferably, the emblic leafflower fruit is an emblic leafflower fruit extract.
More preferably, the emblic extract is an aqueous extract of emblic, or an alcoholic extract of emblic.
Preferably, the weight ratio of the starting materials to the liquid in the preparation method of the aqueous extract of phyllanthus emblica is 1: 6-12.
More preferably, the weight ratio of the starting materials to the liquid in the preparation method of the aqueous extract of emblic leafflower fruit is 1: 9-12.
More preferably, the emblic leafflower fruit water extract is obtained by adding emblic leafflower fruit powder into deionized water for Soxhlet extraction for 3.5-4.5 h by a Soxhlet extraction method, and recycling and concentrating.
Still more preferably, the mass ratio of the emblic leafflower fruit powder to the deionized water is 1: 11.
More preferably, the soxhlet extraction time is 4 h.
Preferably, the alcoholic extract of emblic leafflower fruit is an ethanol extract.
More preferably, the preparation method of the phyllanthus emblica alcohol extract comprises the following steps: heating and refluxing the emblic leafflower fruit powder by 80-85% ethanol for 2-5 times, recovering the solvent under reduced pressure to obtain an extract, dispersing the extract in distilled water, and extracting by ethyl acetate for 4-6 times to obtain the emblic leafflower fruit ethanol extract.
More preferably, the concentration of ethanol is 85%.
More preferably, the number of reflux extractions is 3.
More preferably, the number of extractions is 5.
In addition, preferably, the antiviral composition further comprises a metal salt.
More preferably, the metal salt is a zinc salt, an iron salt, a calcium salt, a magnesium salt, a tungsten salt, a rubidium salt, or the like.
Even more preferably, the zinc salt is zinc sulfate or zinc gluconate; the ferric salt is ferrous gluconate; the calcium salt is calcium gluconate; the magnesium salt is magnesium oxide; the tungsten salt is sodium tungstate; the rubidium salt is rubidium iodide.
Preferably, the antiviral composition further comprises sialic acid.
Preferably, the mass ratio of the emblic leafflower fruit extract to the sialic acid is 1 (0.01-20).
More preferably, the mass ratio of the emblic leafflower fruit extract to the sialic acid is 1 (0.01-10).
More preferably, the source of sialic acid may be mammalian mandibular extract, cubilose, breast milk, cow milk, egg or cheese.
Still more preferably, the mammal is a pig or a cow.
Based on the above results, the antiviral composition can be properly compounded with appropriate excipients to prepare different pharmaceutical dosage forms.
Therefore, the use of said composition in the preparation of an antiviral drug is also within the scope of the present invention.
If the composition is developed into oral liquid, the auxiliary materials can comprise antioxidants and sweeteners.
Preferably, the antioxidant is vitamin C or rosemary.
Preferably, the sweetener is aspartame, stevioside, sucrose, sorbitol mannitol, maltitol, glucose or AK sugar.
Particularly preferably, the oral liquid comprises the following components in parts by weight: 10-22 parts of emblic leafflower fruit extract, 4-22 parts of metal salt, 5-53 parts of antioxidant and 5-23 parts of sweetener.
More preferably, the oral liquid comprises the following components in parts by weight: also contains 10-22 parts of sialic acid.
The components of the antiviral composition and the oral liquid provided by the invention are reasonably compatible, and the antioxidant can inhibit the oxidation of the composition, stabilize the performance of the composition and play a role in adjusting the taste of the composition; the composition can generate pleasant odor and mask the odor of the composition matrix; sweeteners are capable of imparting sweetness to the composition, making it taste-pleasing; the synergistic effect of the components is achieved, the antiviral effect is remarkable and broad-spectrum, the treatment and the rehabilitation of patients infected by coronavirus are facilitated, the life quality is improved, and the synergistic composition can be used as an effective method for daily protection and prevention of respiratory system infectious diseases of normal people.
More preferably, the oral liquid comprises the following components in parts by weight: 16-18 parts of emblic leafflower fruit extract, 16-18 parts of sialic acid, 6-11 parts of metal salt, 7-9 parts of antioxidant and 5-8 parts of sweetener.
Still more preferably, the oral liquid comprises the following components in parts by weight: 17.4 parts of emblic extract, 17.4 parts of sialic acid, 10.1 parts of metal salt, 8.4 parts of vitamin C and 5.8 parts of aspartame.
Preferably, the preparation method of the antiviral oral liquid comprises the following steps: fully dissolving the emblic leafflower fruit extract, the metal salt, the antioxidant or the sweetener in the purified water according to the weight parts.
In addition, preferably, the virus of the present invention as described above refers to a respiratory virus.
More preferably, the virus is a virus of the family coronaviridae.
More preferably, the coronavirus is 2019-nCoV, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, HCoV-OC43 or HCoV-HKU 1.
The use of the claimed compositions in the manufacture of a medicament for the treatment of a coronavirus, including, but not limited to, the use of an effective amount of the composition of the invention for the manufacture of a medicament for the prevention or treatment of a coronavirus-induced disease, for the alleviation of symptoms of a coronavirus-induced disease, or for the delay of progression or onset of a coronavirus-induced disease, to a patient.
In addition to being beneficial for human treatment, the presently claimed compositions find application in veterinary treatment of pets, animals of the species of import and farm animals, including mammals, rodents, and the like. Examples of other animals include horses, dogs, cats, and the like.
The invention has the following beneficial effects:
the invention provides an antiviral composition, which has reasonable compatibility of all components in the formula, optimized combination, can effectively inhibit virus invasion and harm human bodies, remarkably inhibits the replication of viruses, has broad-spectrum antiviral activity and remarkable treatment effect; the emblic leafflower fruit in the formula of the composition belongs to traditional Chinese medicines, and has the advantages of nature, safety, mild drug effect and the like; has good application value in the development of antiviral drugs, in particular to drugs aiming at respiratory viruses such as coronavirus and the like.
The invention also provides an antiviral oral liquid based on the composition, which has the advantages of simple preparation method and low cost, is beneficial to the treatment and rehabilitation of patients infected by viruses, improves the living quality, can be used as an effective method for protecting and preventing respiratory system infection diseases of normal people daily, and has good prevention and control significance for the transmission and harm of diseases caused by the virus infection of human bodies.
Detailed Description
The present invention is further illustrated by the following examples, which are not intended to limit the invention in any way. The reagents, methods and apparatus employed in the present invention are conventional in the art, unless otherwise specified.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
The antiviral activity test in the embodiment of the invention is carried out by committing the Guangdong disease prevention and control center.
EXAMPLE 1 preparation of antiviral oral liquid 1
The antiviral oral liquid 1 comprises the following components in parts by weight: 17.4 parts of emblic leafflower fruit 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 the antiviral oral liquid 1 comprises the following steps: drying and crushing fresh emblic leafflower fruits to prepare emblic leafflower fruit powder, weighing 100g of emblic leafflower fruit powder, wrapping the powder with filter paper, putting the wrapped powder into a Soxhlet extractor, adding deionized water (the mass ratio of the emblic leafflower fruit powder to the deionized water is 1:11) to carry out Soxhlet extraction for 4 hours, recovering an aqueous extract, concentrating the aqueous extract on a water bath pot and fixing the volume to obtain an aqueous extract of the emblic leafflower fruit;
fully dissolving the emblic leafflower fruit aqueous extract, the sialic acid, the zinc sulfate, the vitamin C and the aspartame into purified water according to the weight parts, adding distilled water to dilute to full dose, and subpackaging to obtain the antiviral oral liquid 1.
EXAMPLE 2 preparation of antiviral oral liquid 2
The antiviral oral liquid 2 comprises the following components in parts by weight: 16 parts of emblic leafflower fruit 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 antiviral oral liquid 2 is the same as the preparation method of the antiviral oral liquid 1 in the example 1 except that the weight ratio of the emblic leafflower fruit powder to the deionized water is 1:9, the Soxhlet extraction time is 4.5h, and the other methods are the same according to the parts by weight.
EXAMPLE 3 preparation of antiviral oral liquid 3
The antiviral oral liquid 3 comprises the following components in parts by weight: 17.4 parts of emblic leafflower fruit aqueous extract, 10.1 parts of zinc sulfate, 8.4 parts of vitamin C and 5.8 parts of aspartame.
The preparation method of the antiviral oral liquid 3 is the same as the preparation method of the antiviral oral liquid 1 in the example 1 except that the weight ratio of the emblic leafflower fruit powder to the deionized water is 1:12, the Soxhlet extraction time is 4.5h, and the other methods are the same according to the parts by weight.
EXAMPLE 4 preparation of antiviral oral liquid 4
The antiviral oral liquid 4 comprises the following components in parts by weight: 18 parts of emblic leafflower fruit extract, 18 parts of sialic acid, 6 parts of zinc gluconate, 7 parts of vitamin C and 5 parts of cane sugar.
The preparation method of the antiviral oral liquid 4 is the same as the preparation method of the antiviral oral liquid 1 in the example 1 except that the weight ratio of the emblic leafflower fruit powder to the deionized water is 1:12, the Soxhlet extraction time is 3.5h, and the other methods are the same according to the parts by weight.
EXAMPLE 5 preparation of antiviral oral liquid 5
The antiviral oral liquid 5 comprises the following components in parts by weight: 10 parts of emblic extract, 10 parts of sialic acid, 4 parts of ferrous gluconate, 53 parts of rosemary and 23 parts of sorbitol and mannitol.
The preparation method of the antiviral oral liquid 5 is the same as the preparation method of the antiviral oral liquid 1 in the example 1 except that the weight ratio of the emblic leafflower fruit powder to the deionized water is 1:6, the Soxhlet extraction time is 3.5h, and the other methods are the same according to the parts by weight.
EXAMPLE 6 preparation of antiviral oral liquid 6
The antiviral oral liquid 6 comprises the following components in parts by weight: 22 parts of emblic leafflower fruit ethanol 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 the antiviral oral liquid 6 comprises the following steps: pulverizing fructus Phyllanthi, extracting with 85% ethanol under reflux for 3 times, recovering solvent under reduced pressure to obtain extract, dispersing the extract in distilled water, and extracting with ethyl acetate for5 times to obtain fructus Phyllanthi ethanol extract;
fully dissolving the emblic leafflower fruit ethanol extract, the sialic acid, the magnesium oxide, the vitamin C and the maltitol into purified water according to the weight parts, adding distilled water to dilute to full dose, and subpackaging to obtain the antiviral oral liquid 6.
EXAMPLE 7 preparation of antiviral oral liquid 7
The antiviral oral liquid 7 comprises the following components in parts by weight: 16 parts of emblic leafflower fruit ethanol extract, 16 parts of sialic acid, 13 parts of sodium tungstate, 29 parts of rosemary and 14 parts of glucose.
The preparation method of the antiviral oral liquid 7 is the same as the preparation method of the antiviral oral liquid 6 in example 6 except that the concentration of ethanol is 80%, the reflux extraction times are 5 times and the extraction times are 6 times in parts by weight.
Comparative example 1
An oral liquid A was prepared in the same manner as in the antiviral oral liquid 1 of example 1, except that the aqueous extract of Phyllanthus emblica was not included.
Comparative example 2
An oral liquid B was prepared in the same manner as in the antiviral oral liquid 1 of example 1, except that aqueous extract of Phyllanthus emblica and zinc sulfate were not included.
Comparative example 3
An oral liquid C was prepared in the same manner as in antiviral oral liquid 5 of example 5, except that it did not include an alcohol extract of emblic leafflower fruit, magnesium oxide and sialic acid.
Comparative example 4
An oral liquid D, except that the weight portion of the water extract of the emblic leafflower fruit is 2 portions (the content is too low), the other components and the preparation method are the same as the antiviral oral liquid 1 of the embodiment 1.
Comparative example 5
An oral liquid E was prepared in the same manner as in antiviral oral liquid 5 of example 5, except that 2 parts by weight (too low content) of the alcohol extract of emblic leafflower fruit and 2 parts by weight (too low content) of sialic acid were used.
The following experiments were conducted to test the antiviral activity of the oral liquids 1, 2 and 3 prepared in examples 1 to 3 and A, B, C, D and E prepared in comparative examples 1 to 5, and the specific experimental methods and results were as follows:
application example 1 cytotoxicity test of oral liquid
1. Experimental methods
In the application example, an MTT method is used for testing the toxicity of the antiviral oral liquids 1, 2 and 3 prepared by the embodiment of the invention on cells, and the specific experimental steps are as follows:
(1) according to 1 × 105Concentration per well, human embryonic kidney cells 293(HEK293 cells) were seeded into 96-well plates and 100. mu.L DMEM medium was added thereto at 37 ℃ with 5% CO2Culturing until a monolayer of cells is formed;
(2) discarding the culture solution, washing with PBS for 2 times, diluting antiviral oral liquids 1, 2 and 3 prepared in the embodiment of the invention with DMEM in gradient, inoculating on cells, 100 μ L/well, each concentration is more than 4 multiple wells, setting the same concentration control group, and setting 5% CO at 37 deg.C2Culturing for 48 h;
(3) mu.L of MTT solution (2.5mg/mL) was added to each well at 37 ℃ with 5% CO2Incubating for 4 h; discarding the supernatant, adding 120 mu LDMSO/well, and oscillating for 20 min;
(4) the absorbance (OD) at 490nm of each well was measured on a multifunctional reader and the 50% toxic concentration was calculated by the Reed-Muench method as the half-value of the drugToxic Concentration (TC) of 50% of the treatment50)。
2. Results of the experiment
Determination of TC of antiviral 1, 2 and 3 pairs of HEK293 cells prepared by the embodiment of the invention by using MTT method50Values were 130.27, 132.32, and 140.46 μ g/mL, respectively; the oral liquid prepared by the invention has no cytotoxicity (the toxicity is low and can be ignored).
Application example 2 in vitro antiviral Performance test of oral liquid
1. Experimental methods
The application example tests in vitro anti-virus (2019-nCoV and MERS-CoV) experiments of the anti-virus oral liquids 1, 2 and 3 prepared in the embodiment of the invention, and the specific experimental steps are as follows:
(1) HEK293 cells were plated at 4.5 × 104The individual cells/well concentration were added to a 96 well plate in DMEM with 1% fetal bovine serum at 37 ℃ with 5% CO2Culturing for 24 h;
(2) discard the supernatant and add 100TCID to each well separately502019-nCoV and MERS-CoV 2 virus liquid, 5% CO at 37 DEG C2Adsorbing for 2 h;
(3) discarding the supernatant and washing the cells with PBS, the aqueous extract of Emblica officinalis prepared in example 1 of the present invention, the ethanol extract of Emblica officinalis prepared in example 6, and the antiviral oral solutions 1, 2 and 3 prepared in examples 1, 2 and 3 of the present invention were diluted with DMEM in a gradient manner, and added to each well to prepare an experimental group, and a blank control group was added with the same amount of DMEM at 37 ℃ with 5% CO2Incubating for 72h, and collecting virus supernatant;
(4) HEK293 cells were treated as 2 × 106One cell/well, seeded in 12-well plates, 5% CO at 37 ℃2Culturing for 24 h;
(5) diluting the virus supernatant collected in step (3) by 10 times gradient, inoculating to HEK293 cells, and culturing at 37 deg.C with 5% CO2Adsorbing for 2 h;
(6) the supernatant was discarded and the cells were washed with PBS, 2mL of 1% (w/v) methylcellulose-DMEM overlay was added, 5% CO at 37 deg.C2Culturing for 72 h;
(7) removing the methylcellulose-DMEM covering, washing the cells 2 times with PBS, and fixing the cells with 10% formaldehyde at room temperature for 30 min;
(8) discarding the supernatant, washing the cells with PBS for 2 times, adding 0.5% crystal violet, staining for 5min at room temperature, washing with deionized water for 2 times, drying, counting plaques, and calculating the half Inhibitory Concentration (IC) of 50% virus-inhibited drug by Reed-Muench method50)。
2. Results of the experiment
The in vitro inhibitory activity results of the antiviral oral liquid 1 prepared in example 1 of the invention on 2019-nCoV and MERS-CoV are shown in Table 1, and it can be seen that when the concentration of the oral liquid 1 is 6.25 mug/mL, the antiviral oral liquid can inhibit the replication of 2019-nCoV and MERS-CoV on HEK293 cells, and respectively reduce the average virus titer of 4.01lg PFU/mL and 5.99lg PFU/mL; when the concentration of the oral liquid 1 reaches 50 mu g/mL, the average virus titer can be respectively reduced by 6.28lgPFU/mL and 7.43lgPFU/mL, and the therapeutic indexes are respectively 9.19 and 7.64.
The in vitro inhibitory activity results of the antiviral oral liquid 2 prepared in example 2 of the invention on 2019-nCoV and MERS-CoV are shown in Table 2, and it can be seen that when the concentration of the oral liquid 2 is 6.25 mug/mL, the replication of 2019-nCoV and MERS-CoV on HEK293 cells can be inhibited, and the average virus titer of 3.46lg PFU/mL and 4.75lg PFU/mL are respectively reduced; when the concentration of the oral liquid 2 reaches 50 mu g/mL, the average virus titer can be respectively reduced by 5.72 g of PFU/mL and 6.52 g of PFU/mL, and the therapeutic indexes are respectively 6.87 and 5.96.
The in vitro inhibitory activity results of the antiviral oral liquid 3 prepared in example 3 of the invention on 2019-nCoV and MERS-CoV are shown in Table 3, and it can be seen that when the concentration of the oral liquid 3 is 6.25 mug/mL, the replication of 2019-nCoV and MERS-CoV in HEK293 cells can be inhibited, and the average virus titer of 3.73lg PFU/mL and 5.11lg PFU/mL are respectively reduced; when the concentration of the oral liquid 3 reaches 50 mu g/mL, the average virus titer can be respectively reduced by 4.73lgPFU/mL and 6.61lgPFU/mL, and the therapeutic indexes are respectively 7.60 and 6.28.
In addition, as can be seen from tables 1 to 3, the aqueous extract and the ethanol extract of emblic leafflower fruit, which are prepared by the method disclosed by the invention, have good in-vitro inhibitory activity of 2019-nCoV and MERS-CoV, but are lower than the inhibitory effect of antiviral oral liquids 1, 2 and 3 on 2019-nCoV and MERS-CoV, and the inhibitory effect of antiviral oral liquid 3 is lower than the inhibitory effect of antiviral oral liquids 1 and 2.
TABLE 1 results of in vitro inhibitory Activity of antiviral oral liquid 1 against 2019-nCoV and MERS-CoV
TABLE 2 results of in vitro inhibitory Activity of antiviral oral liquid 2 on 2019-nCoV and MERS-CoV
TABLE 3 results of in vitro inhibitory Activity of antiviral oral liquid 3 against 2019-nCoV and MERS-CoV
The above results illustrate that: the antiviral oral liquid prepared by the 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 methods
The application example tests in vivo anti-virus (2019-nCoV and MERS-CoV) experiments of the anti-virus oral liquids 1, 2 and 3 prepared in the embodiment of the invention, and the specific experimental steps are as follows:
(1) 2.5 × 108PFU hCD 26-expressing recombinant adenovirus vector was nasally transfected into BALB/c mice (purchased from Guangdong province laboratory animal monitoring institute);
(2) infecting mice expressing hCD26 with 2019-nCoV and MERS-CoV by dropping nose on day 4 after transfection, randomly grouping the mice into a blank control group, an antiviral oral liquid 1 group [90 mg/(kg. D) ], an antiviral oral liquid 2 group [90 mg/(kg. D) ], an antiviral oral liquid 3 group [90 mg/(kg. D) ], an oral liquid A group, an oral liquid B group, an oral liquid C group, an oral liquid D group and an oral liquid E group, wherein 6 mice in each group are female, and performing intragastric administration, and the blank control group uses an equivalent amount of 0.1% DMSO solution;
(3) 3 mice per group were randomly selected 3 mice post-anesthesia CO 3, 5 days post infection2Sacrifice, taking mouse lung, transferring into PBS, homogenizing on ice by using a manual homogenizer, centrifuging for 5min at 4 ℃ at 12000r/min, and collecting supernatant;
(14) and (3) carrying out virus titer detection by the same method as the in vitro antiviral experiment of the application example 2.
2. Results of the experiment
The results of in vivo inhibitory effect of antiviral oral liquids 1, 2 and 3 on novel coronaviruses (2019-nCoV and MERS-CoV) are shown in tables 4 and 5, respectively, and it can be seen that the replication effect of antiviral oral liquids 1, 2 and 3 (2019-nCoV and MERS-CoV) in mice is significantly enhanced on day 3 after BALB/c mice are infected with 2019-nCoV and MERS-CoV, as compared with the blank control group and oral liquids A, B, C, D and E group; on the 5 th day after BALB/c mouse infection, the inhibition effect of the antiviral oral liquids 1, 2 and 3 on viruses is further remarkably enhanced, and the inhibition effect of the antiviral oral liquid 3 is lower than that of the antiviral oral liquids 1 and 2; the inhibition effect of the oral liquid A, B, C, D and the group E on viruses (2019-nCoV and MERS-CoV) is not obviously different from that of a blank control group.
The above results illustrate that: the antiviral oral liquid prepared by the invention can effectively and obviously inhibit the replication of 2019-nCoV and MERS-CoV in mice, and the inhibition effect of the antiviral oral liquid is time-dependent.
TABLE 4 in vivo inhibitory Effect of antiviral oral liquids 1, 2 and 3 on 2019-nCoV results (2019-nCoV titer (lgPFU/mL))
TABLE 5 in vivo inhibitory Effect of antiviral oral solutions 1, 2 and 3 on MERS-CoV results (MERS-CoV titer (lgPFU/mL))
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, and simplifications are intended to be included in the scope of the present invention.
Claims (14)
1. An antiviral composition comprising emblic leafflower fruit.
2. The composition as claimed in claim 1, wherein the emblic leafflower fruit is an extract of emblic leafflower fruit.
3. The composition as claimed in claim 2, wherein the extract of emblic leafflower fruit is an aqueous extract of emblic leafflower fruit or an alcoholic extract of emblic leafflower fruit.
4. The composition according to claim 3, wherein the preparation method of the aqueous phyllanthus emblica extract is characterized in that the mass ratio of the starting materials to the liquid is 1: 6-12.
5. The composition as claimed in claim 3, wherein the alcoholic extract of emblica officinalis is an ethanol extract.
6. The composition of any one of claims 1 to 5, further comprising a metal salt.
7. The composition of any one of claims 1 to 6, further comprising sialic acid.
8. The composition of any one of claims 1 to 7, further comprising an antioxidant and a sweetener.
9. The composition according to claim 8, characterized by comprising the following components in parts by weight: 10-22 parts of emblic leafflower fruit extract, 4-22 parts of metal salt, 5-53 parts of antioxidant and 5-23 parts of sweetener.
10. The composition according to claim 9, further comprising 10 to 22 parts by weight of sialic acid.
11. Use of a composition as claimed in any one of claims 1 to 10 in the preparation of an antiviral medicament.
12. The use of claim 11, wherein the virus is a respiratory virus.
13. An antiviral oral liquid comprising the composition according to any one of claims 1 to 10.
14. The method for preparing an oral liquid according to claim 13, wherein the extract of emblic leafflower fruit, the metal salt, the antioxidant or the sweetener is sufficiently dissolved in the purified water in the weight part according to any one of claims 1 to 10.
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| CN112451576A (en) * | 2020-11-10 | 2021-03-09 | 贵州省金黔果生物科技有限责任公司 | Anti-coronavirus composition, preparation method and application thereof |
| WO2021249501A1 (en) * | 2020-06-11 | 2021-12-16 | 广东盛普生命科技有限公司 | Antiviral preparation |
| IT202100022865A1 (en) * | 2021-09-03 | 2023-03-03 | Phytoitalia Srl | COMPOSITIONS WITH ANTIVIRAL ACTION FOR NASAL OR OROPHARYNGEAL ADMINISTRATION BY SPRAY |
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| IT202100022865A1 (en) * | 2021-09-03 | 2023-03-03 | Phytoitalia Srl | COMPOSITIONS WITH ANTIVIRAL ACTION FOR NASAL OR OROPHARYNGEAL ADMINISTRATION BY SPRAY |
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