CN112043688A - A composition for preventing and/or treating coronavirus infection - Google Patents

A composition for preventing and/or treating coronavirus infection Download PDF

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CN112043688A
CN112043688A CN202010735337.2A CN202010735337A CN112043688A CN 112043688 A CN112043688 A CN 112043688A CN 202010735337 A CN202010735337 A CN 202010735337A CN 112043688 A CN112043688 A CN 112043688A
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composition
caryophyllene
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coronavirus
sars
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聂棱
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • A61P11/00—Drugs for disorders of the respiratory system
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
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    • A—HUMAN NECESSITIES
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    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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Abstract

The invention provides a composition for preventing and/or treating coronavirus infection, which comprises beta-caryophyllene, derivatives of the beta-caryophyllene and/or pharmaceutically acceptable salts of the beta-caryophyllene; preferably, the coronavirus is SARS-CoV or SARS-CoV-2. The invention discovers that the beta-caryophyllene can effectively inhibit SARS-CoV-2 from entering ACE2 high expression cells, thereby effectively inhibiting the replication of novel coronavirus, therefore, the composition provided by the invention can effectively prevent and/or treat diseases caused by coronavirus infection, and can be applied as an anti-pneumonia medicament.

Description

A composition for preventing and/or treating coronavirus infection
Technical Field
The invention belongs to the technical field of pharmacy and lung diseases, and relates to a composition for preventing and/or treating coronavirus infection.
Background
Coronaviruses belong to the order capsulaviridae, the family coronaviridae, the genus coronaviruses, are viruses with a capsule membrane and a linear single-stranded positive-strand RNA as a genome, and are a large group of viruses widely existing in nature, and cause disease patients with different clinical symptoms from common cold to severe lung infection, such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS).
The novel coronavirus 2019-nCoV (WHO nomenclature) is a novel coronavirus that has not been previously found in humans. The international committee for viral taxonomy identified the formal taxonomic name of the new coronavirus (2019-nCoV) as severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (lung acute respiratory syndrome coronavirus 2), acronym of english, in 2020, 2 months. SARS-CoV-2 and SARS-CoV belong to the coronavirus beta family and have similar pathogenic mechanisms. The novel coronavirus pneumonia, called new coronavirus pneumonia for short (Corona Virus Disease 2019, COVID-19) is an acute respiratory infectious Disease caused by the infection of the novel coronavirus; it is highly contagious and finds itself rapidly abusive. Therefore, before the vaccine aiming at the COVID-19 is not successfully developed and widely applied to clinic, the active prevention and treatment of the COVID-19, the prevention of the disease attack and the truncation of the change from light to heavy are of great significance.
At present, western medicine treatment mainly aims at strengthening support treatment, ensuring sufficient heat, paying attention to water and electrolyte balance, and performing oxygen therapy, antiviral treatment and antibacterial treatment if necessary, but the Reidesvir commonly used in western medicine is proved to have limited effect, and chloroquine medicines are adopted, so that larger side effects can exist.
The traditional Chinese medicine treatment has obvious advantages in the aspects of preventing the onset of diseases, improving clinical symptoms, preventing the mild change to the severe state and the severe change to the critical state, and has better treatment effect on the treatment of the novel coronavirus pneumonia, but contains forbidden medicinal materials such as ephedra gypsum and the like, so the application of the traditional Chinese medicine is also limited.
Beta-caryophyllene is a bicyclic sesquiterpene compound, which is present in many plant essential oils, such as vanilla oil, zingiber oil, pepper oil or cinnamon oil, and the like, and is defined by the FDA in the united states as a gras (general recognited as safe) type food compound because of its low toxicity, and is approved for use in cosmetics and food additives; at present, there is not much concern about the medical application of beta-caryophyllene.
Disclosure of Invention
The invention aims to provide a composition for preventing and/or treating coronavirus infection. The invention discovers that the beta-caryophyllene can effectively inhibit SARS-CoV-2 from entering ACE2 high expression cells, thereby effectively inhibiting the replication of novel coronavirus, therefore, the composition provided by the invention can effectively prevent and/or treat diseases caused by coronavirus infection, and can be applied as an anti-pneumonia medicament.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides the use of β -caryophyllene, a derivative thereof, a pharmaceutically acceptable salt thereof or a composition containing β -caryophyllene for the manufacture of a medicament or food for the prevention and/or treatment of a disease caused by a coronavirus infection.
Preferably, the coronavirus is SARS-CoV or SARS-CoV-2.
The invention discovers that the beta-caryophyllene can effectively inhibit SARS-CoV-2 from entering ACE2 high expression cells, thereby effectively inhibiting the replication of novel coronavirus; moreover, the beta-caryophyllene is directly administrated in the trachea with high content, so that no toxic damage is caused to the lung tissue of the animal, and meanwhile, the skin irritation and allergy phenomena are not caused under the condition of high content; therefore, the beta-caryophyllene, the derivative thereof, the pharmaceutically acceptable salt thereof or the composition containing the beta-caryophyllene can be used for preventing and/or treating diseases caused by coronavirus infection.
Preferably, the disease is pneumonia, severe acute respiratory infection, intestinal disease or severe acute respiratory syndrome caused by coronavirus infection.
In a second aspect, the present invention provides the use of β -caryophyllene, a derivative thereof, a pharmaceutically acceptable salt thereof or a composition comprising β -caryophyllene for the prevention and/or treatment of a disease caused by a coronavirus infection.
Preferably, the coronavirus is SARS-CoV or SARS-CoV-2.
Preferably, the disease is pneumonia, severe acute respiratory infection, intestinal disease or severe acute respiratory syndrome caused by coronavirus infection.
In a third aspect, the present invention provides a composition for preventing and/or treating coronavirus infection, which comprises beta-caryophyllene, a derivative of beta-caryophyllene and/or a pharmaceutically acceptable salt of beta-caryophyllene.
Preferably, the coronavirus is SARS-CoV or SARS-CoV-2.
In the invention, the beta-caryophyllene, the derivative of the beta-caryophyllene and/or the pharmaceutically acceptable salt of the beta-caryophyllene contained in the composition exist in the form of a compound, a shortleaf kyllingia herb extract or shortleaf kyllingia herb.
Beta-caryophyllene can be separated from the ciliate desert-grass, the medicine composition can be a traditional Chinese medicine composition, and when the medicine composition is a traditional Chinese medicine composition, the ciliate desert-grass can be used as one of the components.
The shortleaf kyllinga herb of the invention refers to shortleaf kyllinga herb (Cyperaceae plants).
Preferably, the composition also comprises other components with the function of preventing and/or treating coronavirus infection.
Preferably, an immunopotentiator is also included in the composition.
In the invention, the beta-caryophyllene can inhibit the replication of coronavirus, meanwhile, other components for preventing and/or treating novel coronavirus are introduced to further inhibit coronavirus, and the introduced immunity enhancing agent can enhance the immunity of human body, thereby enhancing the inhibition and removal capacity of human body to virus, and achieving the purpose of thorough cure.
Preferably, the composition is a pharmaceutical composition, which further comprises a pharmaceutically acceptable adjuvant and/or carrier.
Preferably, the pharmaceutical composition is in a form of gastrointestinal administration, injection administration or respiratory administration.
Preferably, the pharmaceutical composition is in a dosage form selected from the group consisting of powder, tablet, granule, capsule, solution, emulsion, suspension, injection, spray, aerosol, and powder spray.
Preferably, the composition is a food composition, which further comprises a dietetically acceptable adjuvant and/or carrier.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention discovers that the beta-caryophyllene can effectively inhibit COVID-19 from entering ACE2 high-expression cells, thereby effectively inhibiting the replication of novel coronavirus; moreover, the beta-caryophyllene is directly administrated in the trachea with high content, so that no toxic damage is caused to the lung tissue of the animal, and meanwhile, the skin irritation and allergy phenomena are not caused under the condition of high content; therefore, the beta-caryophyllene, the derivative thereof, the pharmaceutically acceptable salt thereof or the composition containing the beta-caryophyllene can be used for preventing and/or treating diseases caused by coronavirus infection;
(2) the composition provided by the invention can effectively prevent and/or treat diseases (including pneumonia and the like) caused by coronavirus infection, and can be applied as an anti-pneumonia medicament;
(3) the beta-caryophyllene contained in the invention can inhibit the replication of the novel coronavirus, and other components for preventing and/or treating the novel coronavirus are introduced to further inhibit the novel coronavirus, and the introduced immunity enhancing agent can increase the immunity of a human body, so that the inhibition and removal capacity of the human body to the virus is enhanced, and the aim of thorough cure is achieved.
(4) Beta-caryophyllene can be separated from the shortleaf kyllinga herb, the pharmaceutical composition can be a traditional Chinese medicine composition, and when the pharmaceutical composition is a traditional Chinese medicine composition, the shortleaf kyllinga herb can be used as one of the components.
Drawings
FIG. 1 is a diagram showing the state of cells after 24 hours of culture in the drug-only group (sample of example 1).
FIG. 2 is a diagram showing the state of cells after culturing for 72 hours in the drug-only group (sample of example 1).
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
Example 1
The substance provided by the embodiment is beta-caryophyllene.
Example 2
This example provides a composition comprising beta-caryophyllene and an adjuvant.
Example 3
The embodiment provides a composition, which consists of beta-caryophyllene, auxiliary materials and an immunopotentiator.
Example 4
The present example provides a composition comprising beta-caryophyllene, excipients, and other components that function to prevent and/or treat coronavirus infection.
Example 5
This example provides a derivative of β -caryophyllene.
Example 6
This example provides a pharmaceutically acceptable salt of β -caryophyllene.
Example 7
This example provides an ethyl acetate extract of Grateloupia filicina.
Comparative example 1
The difference from example 1 is that in this comparative example, β -caryophyllene was replaced by α -caryophyllene.
Comparative example 2
The difference from example 1 is that in this comparative example, β -caryophyllene was replaced with γ -caryophyllene.
Performance testing
The pharmaceutical compositions provided in examples 1-7 and comparative examples 1-2 were subjected to performance tests to determine whether the samples had a neutralizing effect on the new coronaviruses and whether they had an effect on the growth of cells, using the following test methods:
a. dilution of
Diluting a sample (5 mu L/mL) aqueous solution according to 0 time, 2 times, 4 times, 8 times, 16 times, 32 times, 64 times and 128 times;
b. experiment of
Adding the medicine and the pseudovirus at the same time:
after the drug is diluted, 50 mu L of the drug and new corona pseudovirus (Beijing Yiqiao Shenzhou science and technology Co., Ltd.) are respectively taken and mixed in equal volume, incubated for 1h at 37 ℃, added to 293T-ACE2 cells which are plated in advance, and each gradient has 2 multiple holes; respectively culturing for 24h, 48h and 72h, observing the cell state and photographing, and detecting the luminescence value of Luciferase by using a chemiluminescence apparatus on a sample in a 96-well plate after culturing for 72 h;
② only adding a false virus group:
adding 50 mu L of the new coronavirus to 293T-ACE2 cells plated in advance for 2 multiple wells; respectively culturing for 24h, 48h and 72h, observing the cell state and photographing, and detecting the luminescence value of Luciferase by using a chemiluminescence apparatus on a sample in a 96-well plate after culturing for 72 h;
③ addition of drug (sample) group only:
adding 50 mu L of the diluted medicine into 293T-ACE2 cells plated in advance, and repeating the steps for 2 times; after culturing for 24h, 48h and 72h, the cell state was observed and photographed.
Wherein the inhibition ratio (%) is 1- (sample RLU average-negative control PLU average)/(positive control RLU average-negative control RLU value).
Wherein FIG. 1 is a diagram showing the state of cells after 24 hours of culture in the drug-only group (sample of example 1), and FIG. 2 is a diagram showing the state of cells after 72 hours of culture in the drug-only group (sample of example 1); as can be seen from a comparison of FIG. 1 and FIG. 2, the pharmaceutical composition provided by the present invention does not inhibit cell growth.
Table 1 shows the test results for the pharmaceutical compositions provided in example 1:
TABLE 1
Figure BDA0002604814340000051
Figure BDA0002604814340000061
Table 2 shows the test results for the pharmaceutical compositions (undiluted) provided in examples 1, 7 and comparative examples 1-2:
TABLE 2
Sample (I) RLU1 RLU2 AVE Inhibition rate/%)
Example 1 3971 12903 8.44E+03 98.89
Example 7 90116 92323 9.12E+04 87.71
Comparative example 1 6.27E+05 6.67E+05 6.47E+05 12.68
Comparative example 2 7.73E+07 6.02E+05 6.88E+05 7.15
It should be noted that, since the inhibition rate is the relative value of the comparison between the sample and the positive and negative control, and the sensitivity of the chemiluminescence method is high, when the sample has no neutralization effect or has a small neutralization effect on the pseudovirus, the reading of the sample well is higher than that of the positive control well, and the calculated inhibition rate is a negative value; when the inhibition rate is less than 50%, it indicates that the sample has substantially no neutralization inhibition.
As can be seen from the examples and performance tests, the pharmaceutical composition provided by the invention has a good inhibitory effect on the novel coronavirus, and can be used for preventing and/or treating the novel coronavirus.
As is clear from the comparison between example 1 and examples 3 to 4, the composition further contains other components having the function of preventing and/or treating coronavirus infection or an immunopotentiator, and has a superior inhibitory effect on the novel coronaviruses.
As can be seen from the comparison between example 1 and comparative examples 1-2, the composition provided by the invention needs to specifically select beta-caryophyllene so as to have a good inhibitory effect on the new coronavirus.
The applicant states that the present invention is illustrated by the above examples of the composition for preventing and/or treating coronavirus infection, but the present invention is not limited to the above detailed methods, i.e. it does not mean that the present invention must be implemented by the above detailed methods. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.

Claims (10)

1. The application of beta-caryophyllene, derivatives thereof, pharmaceutically acceptable salts thereof or a composition containing the beta-caryophyllene in preparing medicines or foods for preventing and/or treating diseases caused by coronavirus infection;
preferably, the coronavirus is SARS-CoV or SARS-CoV-2.
2. The use according to claim 1, wherein the disease is pneumonia, severe acute respiratory infection, intestinal disease or severe acute respiratory syndrome caused by coronavirus infection.
3. The application of beta-caryophyllene, derivatives thereof, pharmaceutically acceptable salts thereof or a composition containing the beta-caryophyllene in preventing and/or treating diseases caused by coronavirus infection;
preferably, the coronavirus is SARS-CoV or SARS-CoV-2.
4. The use according to claim 3, wherein the disease is pneumonia, severe acute respiratory infection, intestinal disease or severe acute respiratory syndrome caused by coronavirus infection.
5. A composition for the prevention and/or treatment of coronavirus infection, comprising β -caryophyllene, a derivative of β -caryophyllene, and/or a pharmaceutically acceptable salt of β -caryophyllene;
preferably, the coronavirus is SARS-CoV or SARS-CoV-2.
6. The composition as claimed in claim 5, wherein the beta-caryophyllene, the derivative of beta-caryophyllene and/or the pharmaceutically acceptable salt of beta-caryophyllene contained in the composition is in the form of compound, extract of Grateloupia filicina or Grateloupia filicina.
7. The composition according to claim 5, wherein the composition further comprises other components having a function of preventing and/or treating coronavirus infection;
preferably, an immunopotentiator is also included in the composition.
8. The composition according to any one of claims 5 to 7, wherein the composition is a pharmaceutical composition, and further comprises a pharmaceutically acceptable adjuvant and/or carrier.
9. The composition of claim 8, wherein the pharmaceutical composition is in a form for gastrointestinal administration, injection administration or respiratory administration;
preferably, the pharmaceutical composition is in a dosage form selected from the group consisting of powder, tablet, granule, capsule, solution, emulsion, suspension, injection, spray, aerosol, and powder spray.
10. The composition according to any one of claims 5 to 7, wherein the composition is a food composition, further comprising a dietetically acceptable adjuvant and/or carrier.
CN202010735337.2A 2020-07-28 2020-07-28 A composition for preventing and/or treating coronavirus infection Pending CN112043688A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114452346A (en) * 2021-01-26 2022-05-10 聂棱 Application of ciliate desert-grass in preventing and treating virus infection
CN114557984A (en) * 2021-02-02 2022-05-31 深圳柏悦基因科技有限公司 Composition containing caryophyllene and application thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012104845A1 (en) * 2011-02-06 2012-08-09 Ben Gurion University Of The Negev Research And Development Authority Compositions comprising beta-caryophyllene and methods of utilizing the same
CN111265500B (en) * 2020-03-02 2022-02-01 广西医科大学第一附属医院 Pharmaceutical composition for preventing and treating COVID-19 and preparation method thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114452346A (en) * 2021-01-26 2022-05-10 聂棱 Application of ciliate desert-grass in preventing and treating virus infection
CN114557984A (en) * 2021-02-02 2022-05-31 深圳柏悦基因科技有限公司 Composition containing caryophyllene and application thereof

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