CN111249454A - Use of inactivated BCG for preventing or treating a new coronavirus related condition - Google Patents
Use of inactivated BCG for preventing or treating a new coronavirus related condition Download PDFInfo
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- CN111249454A CN111249454A CN202010222070.7A CN202010222070A CN111249454A CN 111249454 A CN111249454 A CN 111249454A CN 202010222070 A CN202010222070 A CN 202010222070A CN 111249454 A CN111249454 A CN 111249454A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/04—Mycobacterium, e.g. Mycobacterium tuberculosis
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- 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
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- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/521—Bacterial cells; Fungal cells; Protozoal cells inactivated (killed)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/542—Mucosal route oral/gastrointestinal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/543—Mucosal route intranasal
Abstract
The present invention discloses the use of inactivated BCG in the prevention or treatment of new coronavirus related conditions. The research of the invention shows that the BCG vaccine is a safe immunopotentiator besides preventing the infection of the tubercle bacillus, has wide protection effect on respiratory tract infection caused by new coronavirus, and can protect the organism from the infection of the respiratory tract virus. The research and development of new application of the old vaccine not only greatly shortens the research and development period and the cost, but also is safe and effective, and has important significance for the severe situation of preventing and treating the new coronavirus at present.
Description
Technical Field
The present invention relates to a novel use of bcg, in particular to the use of inactivated bcg for the prevention or treatment of a novel coronavirus related condition.
Background
The new coronavirus (new coronavirus, or SARS-CoV-2) has become a major threat to human health and economic development. Currently, the best means to prevent the spread of the virus is forced segregation, with no other means of prevention. Vaccines are the most likely effective prophylactic means, but successful vaccine development may take at least half a year or even more than 2 years to a three or four clinical trial. Coping with this dangerous epidemic may require a multi-tiered approach, and even a short-term unconventional approach to intervening 2019-nCoV epidemics is necessary.
BCG (BCG) is an inactivated vaccine against mycobacterium bovis, which has been used to treat recurrent respiratory virus infections and lung cancer in children as early as the 70 s and has achieved clinically significant efficacy. The current mouse model research shows that the BCG vaccine has obvious protective effect on preventing the infection of various respiratory viruses by inducing nonspecific (or xenogenic) immunity. However, there is no study and report on whether BCG is effective in preventing and treating the infection caused by the new coronavirus which is currently prevalent.
Disclosure of Invention
The inventor's earlier research shows that the use of heterologous immunity can prevent SARS virus, and the attenuated Japanese encephalitis virus immunity has protective effect on Zika virus infection, which also indicates that the innate immune response may have protective effect on heterologous virus infection. Based on this finding, the inventors screened potential drugs effective against the infection with the new coronavirus using a large number of known vaccines, and found that inactivated bcg had a good preventive effect against the current infection with the new coronavirus. Based on this, the inventors further propose a regimen for enhancing the prophylactic effect by local administration to the respiratory tract. Specifically, the present invention includes the following.
In one aspect of the invention there is provided the use of an inactivated bcg in the manufacture of a medicament for local administration to the respiratory tract for the prevention or treatment of a new coronavirus related condition.
According to the use of the present invention, preferably, the medicament is an immunopotentiator comprising 0.2 to 2 parts by weight of inactivated bcg, 0 to 100 parts by weight of a bioadhesive and 0 to 10 parts by weight of a flavoring agent. The amount of inactivated BCG is preferably 0.5-1.5 parts by weight, more preferably 1.0-1.5 parts by weight. The amount of the bioadhesive is preferably 0.5 to 8 parts by weight, more preferably 1 to 5 parts by weight. The amount of the flavoring agent is preferably 1 to 8 parts by weight, more preferably 2 to 5 parts by weight.
According to the use of the present invention, preferably, the medicament is a suspension comprising 0.2-2g/L of inactivated BCG, 0-100g/L of bioadhesive, 0-100g and 0-10g/L of flavoring agent. The concentration of inactivated BCG is preferably 0.5-1.5g/L, more preferably 1.0-1.4 g/L. The amount of bioadhesive is preferably from 0 to 50 g/L, more preferably from 0 to 20 g/L. The amount of flavoring agent is preferably 0 to 5g/L, more preferably 1 to 3 g/L.
According to the use of the present invention, preferably, the medicament is a suspension prepared by adding 0.2-2g of inactivated BCG, 0-100g of bioadhesive, 0-100g of flavoring agent per liter of physiological saline and mixing them well.
According to the use of the present invention, preferably, the respiratory topical administration is a spray administration.
According to the use of the present invention, preferably, the administration site of the drug is oral and/or nasal mucosa.
According to the use of the present invention, preferably, the novel coronavirus related condition comprises:
(1) replication, propagation or spread of the new coronavirus infection in vivo;
(2) cough, fever, inflammation, dyspnea and loss of appetite caused by the new coronavirus.
According to the use of the present invention, preferably, the prevention or treatment comprises:
(1') an increase or enhancement of immunity to said novel coronaviruses in vivo;
(2') the activity of the novel coronavirus in vivo is reduced or disappeared;
(3') the symptoms of cough, fever, inflammation, dyspnea and decreased appetite caused by the new coronavirus are reduced, alleviated or eliminated.
In another aspect of the present invention, there is provided a method for inhibiting the activity of a novel coronavirus in a cell, comprising the step of contacting a drug containing an inactivated BCG with a cell containing a novel coronavirus, or introducing the same into the interior of the cell.
According to the method of the invention, preferably, the cell is an in vitro cell.
The invention provides a new application of an old vaccine in prevention and treatment of new coronary pneumonia. Research shows that the BCG vaccine is a safe immunopotentiator besides preventing tubercle bacillus infection, has a wide protection effect on respiratory tract infection caused by new coronavirus, and can protect organisms from being infected by the respiratory tract virus. The research and development of new application of the old vaccine are particularly suitable for the severe situation of the prevention and the treatment of the new coronavirus at present. First, traditional vaccine development requires at least half a year to about 3 years, and whether it is safe, effective, and sufficient in yield is an unknown problem. The inactivated BCG vaccine is a commonly used vaccine and can be used in a large amount in clinical in second or even third or fourth stage in time. And secondly, the BCG production technology is mature, the yield is high, the use dosage of the BCG can be further reduced to one of 1/10 of the original inoculation dosage by utilizing a respiratory administration mode, namely, the yield can sufficiently meet the global requirement, and is greatly superior to the yield of the existing vaccine. In addition, the spraying method of the inactivated BCG vaccine is safe, and the local immunity of the respiratory tract can be improved through a direct administration way of the respiratory tract, so that the local antiviral effectiveness of the respiratory tract can be greatly improved.
The inactivated BCG vaccine spray can also be used for preventing various respiratory virus infections including coronavirus, influenza virus and the like, reducing fever outpatient service caused by the viruses, and reducing the national cost for screening patients, diagnosis and treatment and suspected coronavirus infection, thereby reducing the economic burden on the country and individuals and having great social and economic benefits.
The immunity increasing spray directly acts the inactivated BCG vaccine on the immune system of oral and nasal mucosa in a spray form, and has the effects of prevention and treatment. The medicine can be administered by infected people and risk exposure people without doctors, and is convenient to carry and use.
Drawings
FIG. 1 protective effect of BCG vaccination on coronavirus infection of genus Micro.
FIG. 2 is a graph of tumor growth following direct intratumoral injection of BCG into tumor-bearing mice.
FIG. 3 shows the disease severity changes of children with BCG vaccination and new coronavirus infection.
FIG. 4 shows the recovery time of children with BCG vaccine inoculated with the novel coronavirus infection.
Detailed Description
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that the upper and lower limits of the range, and each intervening value therebetween, is specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in a stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control. Unless otherwise indicated, "%" is percent by weight.
Examples
Firstly, mouse experiment:
survival of mice infected with coronavirus was analyzed by inoculating bcg to the mice, and the results are shown in fig. 1. As can be seen from FIG. 1, the survival rate of mice administered BCG was greatly improved.
In addition, experiments of BCG on tumor growth in mice were also performed. The results are shown in FIG. 2. As shown in FIG. 2, the direct intratumoral injection of BCG into tumor-bearing mice can enhance the anti-tumor immunity of the mice and inhibit the growth of tumors.
Second, analysis of clinical data
BCG vaccine is inoculated to people of different ages infected with the novel coronavirus, and the symptom condition of each individual is statistically analyzed. The results are shown in FIG. 3. As can be seen in FIG. 3, the disease symptoms of BCG-inoculated children with new coronary pneumonia were significantly lower than those of adult patients.
In addition, the recovery time of the infant suffering from the recent coronavirus infection and the infant not recently inoculated with the BCG vaccine is counted, and the recovery time of the former is obviously faster than that of the latter.
While the present invention has been described with reference to exemplary embodiments, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. Many modifications and variations may be made to the exemplary embodiments of the present description without departing from the scope or spirit of the present invention. The scope of the claims is to be accorded the broadest interpretation so as to encompass all modifications and equivalent structures and functions.
Claims (10)
1. Use of an inactivated bcg in the manufacture of a medicament for local administration to the respiratory tract for the prevention or treatment of a new coronavirus related condition.
2. The use according to claim 1, wherein the medicament is an immunopotentiator comprising 0.2-2 parts by weight of inactivated bcg, 0-100 parts by weight of a bioadhesive and 0-10 parts by weight of a flavoring agent.
3. The use according to claim 1, wherein the medicament is a suspension comprising 0.2-2g/L inactivated bcg, 0-100g/L bioadhesive, 0-100g/L and 0-10g/L flavouring agent.
4. The use according to claim 3, wherein the medicament is a suspension prepared by adding 0.2-2g of inactivated BCG, 0-100g of bioadhesive, 0-100g of flavoring agent per liter of physiological saline and mixing.
5. Use according to claim 1, wherein the topical administration to the respiratory tract is a spray administration.
6. Use according to claim 5, wherein the site of administration of the medicament is the oral and/or nasal mucosa.
7. The use according to claim 1, wherein the new coronavirus related condition comprises:
(1) replication, propagation or spread of the new coronavirus infection in vivo;
(2) cough, fever, inflammation, dyspnea and loss of appetite caused by the new coronavirus.
8. The use according to claim 1, wherein the prevention or treatment comprises:
(1') an increase or enhancement of immunity to said novel coronaviruses in vivo;
(2') the activity of the novel coronavirus in vivo is reduced or disappeared;
(3') the symptoms of cough, fever, inflammation, dyspnea and decreased appetite caused by the new coronavirus are reduced, alleviated or eliminated.
9. A method for inhibiting the activity of a neocoronavirus in a cell, comprising the step of contacting a drug comprising an inactivated bcg with a cell comprising a neocoronavirus, or introducing it into the interior of said cell.
10. The method of claim 9, wherein the cell is in vitro.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010222070.7A CN111249454A (en) | 2020-03-26 | 2020-03-26 | Use of inactivated BCG for preventing or treating a new coronavirus related condition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010222070.7A CN111249454A (en) | 2020-03-26 | 2020-03-26 | Use of inactivated BCG for preventing or treating a new coronavirus related condition |
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| CN111249454A true CN111249454A (en) | 2020-06-09 |
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| CN202010222070.7A Pending CN111249454A (en) | 2020-03-26 | 2020-03-26 | Use of inactivated BCG for preventing or treating a new coronavirus related condition |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634579A (en) * | 2003-12-30 | 2005-07-06 | 通用技术集团医药控股有限公司 | Inactivated BCG vaccine spray and method for preparing the same |
| CN101069743A (en) * | 2004-07-27 | 2007-11-14 | 张锦铭 | Use of inactive BCG vaccine in preparation of use for treatment of allergic action diseases |
| CN101451148A (en) * | 2007-11-29 | 2009-06-10 | 深圳市疾病预防控制中心 | Bacillus coli-mycobacteria shuttling expression plasmid vector and its application in preparation of pathogenic microorganism vaccine |
-
2020
- 2020-03-26 CN CN202010222070.7A patent/CN111249454A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634579A (en) * | 2003-12-30 | 2005-07-06 | 通用技术集团医药控股有限公司 | Inactivated BCG vaccine spray and method for preparing the same |
| CN101069743A (en) * | 2004-07-27 | 2007-11-14 | 张锦铭 | Use of inactive BCG vaccine in preparation of use for treatment of allergic action diseases |
| CN101451148A (en) * | 2007-11-29 | 2009-06-10 | 深圳市疾病预防控制中心 | Bacillus coli-mycobacteria shuttling expression plasmid vector and its application in preparation of pathogenic microorganism vaccine |
Non-Patent Citations (6)
| Title |
|---|
| ASHOK ASPATWAR ET AL.: "Tuberculosis vaccine BCG: the magical effect of the old vaccine in the fight against the COVID-19 pandemic", 《INT REV IMMUNOL》 * |
| MOORLAG SIMONE J C F M ET AL.: "Efficacy of Bacillus Calmette-Guérin vaccination against respiratory tract infections in the elderly during the Covid-19 pandemic", 《CLINICAL INFECTIOUS DISEASES》 * |
| 佘翠萍: "卡介苗雾化吸入对呼吸道动物过敏反应的免疫调节作用", 《中华耳鼻咽喉科杂志》 * |
| 侯松萍: "卡介苗多糖核酸或卡介苗吸入对呼吸道Toll样受体、β-防御素的mRNA表达的影响", 《中国优秀博硕士学位论文全文数据库（博士）医药卫生科技辑》 * |
| 段红梅;申昆玲;: "儿童SARS特点与免疫关系探讨" * |
| 王永清: "卡介苗素雾化吸入治疗小儿反复呼吸道感染疗效观察及护理", 《成都医药》 * |
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