CN111281893A - Application of mycobacterium vaccae for injection in preparation of medicament for preventing and treating COVID-19 - Google Patents
Application of mycobacterium vaccae for injection in preparation of medicament for preventing and treating COVID-19 Download PDFInfo
- Publication number
- CN111281893A CN111281893A CN202010135842.3A CN202010135842A CN111281893A CN 111281893 A CN111281893 A CN 111281893A CN 202010135842 A CN202010135842 A CN 202010135842A CN 111281893 A CN111281893 A CN 111281893A
- Authority
- CN
- China
- Prior art keywords
- injection
- covid
- mycobacterium vaccae
- medicament
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- 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
-
- 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
-
- 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
Abstract
The invention belongs to the field of medicines, and particularly relates to application of mycobacterium vaccae for injection in preparation of a medicine for preventing and treating COVID-19 (diseases caused by novel coronavirus). The injection mycobacterium vaccae can rapidly promote the endogenous interferon level of respiratory tract-lung tissue to inhibit the replication of virus RNA, reduce cell damage or promote the repair of damaged cells to play a role in prevention and treatment, and simultaneously avoid or reduce the untoward effect which is difficult to avoid by an exogenous interferon preparation. The medicine prepared by the invention can be inhaled by atomization, and the medicine with special application can improve the compliance of patients, so that the patients can take medicine conveniently, the patient is relieved from turning into severe or critical state, the time of turning the nucleic acid into the negative is shortened by about 4 days, the treatment time is correspondingly shortened, and the medical cost is reduced. The new application of the mycobacterium vaccae for injection in preparing the medicament for preventing and treating COVID-19 disclosed by the invention provides a new scheme for clinically preventing and treating COVID-19 and preventing and treating respiratory virus infection.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of mycobacterium vaccae for injection in preparation of a medicine for preventing and treating COVID-19 (diseases caused by novel coronavirus).
Background
The country is faced with a serious epidemic of outbreak of severe COVID-19 (a disease caused by a novel coronavirus). Although the country is soon isolated and identified as the new type of coronavirus, the number of subsequently infected patients is increased sharply due to the lack of effective treatment means and the large migration of the people in spring due to the insufficient knowledge or dispute of the infection source, the transmission path, the susceptible host, the disease characteristics and the law of the new type of coronavirus, and the like, and the current epidemic situation prevention and control is still very severe. By the national data statistics of 2020-2-2424:00, the total confirmed new coronavirus infection is 77658 cases, the number of dead people is 2663 cases and the number of cured patients is 27323 cases, and 2824 cases of suspected cases and 9126 cases of severe cases are still remained. The method causes great damage to the health, life and property safety of residents in China, and simultaneously causes immeasurable attack on the economic and social development of China. 1 month 31 day Beijing time 3:30 in the morning, based on two facts that the number of Chinese infected persons is increased and epidemic situations occur in a plurality of countries, the world health organization calls a news release conference to conference results to inform the world: this new crown pneumonia epidemic in China constitutes an emergent Public Health event of international Concern (Public Health Emergency of International Concern, PHEIC).
At present, the infection epidemic situation of the novel coronavirus becomes a great and urgent international sanitary scientific problem. The WHO named the novel coronavirus 2019-nCoV at 12.1.2020, and named the disease caused by the novel coronavirus at 11.2.11.2.8 by the world health organization, and named the disease caused by the novel coronavirus as COVID-19. COVID-19 is a RNA virus with the largest genome known at present, and compared with the DNA used by human as genetic material, the RNA genome of the virus is relatively poor in fidelity during replication, more variation is easy to generate, the mutation is easy to generate, and the capacity of escaping memory B cells and long-acting anti-IgA neutralizing antibodies is obtained. Because the research and development cycle of the therapeutic drugs and vaccines is long, a series of animal experiments and clinical tests are required to verify after research and development, and the effectiveness and safety of the research and development of the vaccines cannot be guaranteed. Until now, no effective therapeutic drugs and vaccines have been developed. Since the research and development of classical therapeutic drugs and vaccines are both targeted at a certain virus specifically, a series of virus separation and identification, basic research, animal experiments, clinical test verification and the like are required, the immunity period is long, the vaccine which is researched reluctantly is in an embarrassing situation that the epidemic situation is ended, and the vaccines are ineffective to the next epidemic situation due to virus antigen variation (for example, the vaccine aiming at SARS is ineffective to the epidemic situation). Therefore, it has become an urgent and important social demand to find a new way to prevent and treat respiratory tract virus infection in a short time.
IFN is the most important non-specific antiviral component in vivo and can be the only natural non-specific antiviral natural component, IFN is the most important non-specific antiviral component in vivo discovered and recognized at present, and is divided into I type (IFN- β and IFN- α), II type (IFN-gamma) and III type (IFN-lambda 1, IFN-lambda 2, IFN-lambda 3) IFN, after IFN is produced, by activating intracellular JAK-STAT pathway of infected site, regulating several hundred related effect antiviral gene (ISG) transcription, further inhibiting virus proliferation, promoting apoptosis of infected cells, and making uninfected cells enter into antiviral state, IFN can also promote development and maturation of various natural immune cells, adaptive immune cells and effector cells, promoting adaptive immune response to exert antiviral action, I type and III type IFN have antiviral action, especially type III IFN is important in respiratory antiviral defense, after respiratory virus infection, IFN receptor is acted on JAK infected cells, then through activating intracellular immune cell pathway of MRS-STAT 2, ISG15, and other types of IFN-CD 15, especially type III type IFN is important in respiratory virus defense, after respiratory virus infection, IFN is treated by human lung virus infection, it is treated by oral administration of HIV infection, lung virus infection is treated by oral administration, lung virus infection is treated by human lung virus infection, lung virus infection is treated by oral administration, lung virus infection is treated by oral administration, lung virus infection is treated by oral administration.
Mycobacterial preparations (such as bacillus calmette guerin, inactivated mycobacterium phlei, mycobacterium vaccae for injection and the like) are multifunctional immunomodulators, can be used for preventing and treating infection, mainly regulate the immune function of organisms by influencing immune response reaction, enhance the activity of Th cells, stimulate B cells to enter the proliferation and differentiation stages and finally promote the formation of specific antibodies. Studies such as Yangjing and the like show that the inactivated mycobacterium phlei can obviously improve the function of Th (including Th1 and Th2) cells in Peripheral Blood Mononuclear Cells (PBMC) of asthmatic patients, promote the PBMC to generate IFN-gamma and IL-4, particularly improve the Th1 type cell factor IFN-gamma, promote the maturation of Th1 and Th2 cells, simultaneously up-regulate the function of Th1 of asthmatic children, partially correct the Th2 dominant state of the asthmatic children, further improve the Th1/Th2 unbalanced state of the asthmatic children, and play an important role in asthma prevention and treatment.
Disclosure of Invention
The invention aims to provide application of mycobacterium vaccae for injection in preparing a medicament for preventing and treating COVID-19, and provides a new scheme for preventing and treating COVID-19. Can relieve the severe or critical condition of patients, shorten the time of nucleic acid to turn negative by about 4 days, and correspondingly shorten the treatment time.
In order to achieve the purpose, the invention provides the following technical scheme:
application of Mycobacterium vaccae for injection in preparing medicine for preventing and treating COVID-19 is provided.
The application of the mycobacterium vaccae for injection in preparing the medicament for preventing and treating COVID-19 comprises an active ingredient of the mycobacterium vaccae for injection and a pharmaceutically acceptable carrier.
The mycobacterium vaccae for injection can be used as a single preparation or can be compatible with other medicines, and is added with a proper amount of pharmaceutically acceptable auxiliary materials to prepare a medicinal preparation by adopting the prior art.
The Mycobacterium vaccae for injection is applied to the preparation of the medicament for preventing and treating COVID-19, and the dosage forms of the medicament for preventing and treating COVID-19 comprise aerosol, aqua and powder.
When the mycobacterium bovis for injection is used, the mycobacterium bovis for injection is prepared into a physiological saline injection of 2.25-6.75 mu g/ml, and the injection is atomized by jet flow into a patient for inhalation at an oxygen flow rate of 5L/min.
The Mycobacterium vaccae for injection can rapidly increase the endogenous interferon level of respiratory tract-lung tissue to inhibit the replication of virus RNA, reduce cell damage or promote the repair of damaged cells to play a role in prevention and treatment, and simultaneously avoid or reduce the untoward effect which is difficult to avoid by an exogenous interferon preparation because the endogenous interferon level is increased.
The prepared medicament can safely and effectively prevent and treat the COVID-19 and can also nonspecifically prevent and treat other respiratory virus infection.
The performance and clinical application effect of the mycobacterium vaccae for injection are as follows:
mycobacterium vaccae for injection (microca), english name: mycobacterium vaccae for Injection; [ types of drugs ] biological products, [ major components ] Mycobacterium vaccae mycoprotein, [ properties ] white loose powder, [ specifications ] 22.5 μ g/bottle, [ pharmacological effects ] Mycobacterium vaccae for injection has bidirectional immunoregulation function, can improve the level of hydrogen peroxide and nitric oxide generated by normal mouse abdominal cavity macrophages and promote the proliferation reaction of T lymphocytes, can obviously inhibit the reaction of tubercle bacillus infected guinea pigs, and has obvious enhancement effect on lymphocyte transformation and macrophage phagocytic function of mice with low immune function; [ ADAPTIVE PROBLEMS ] the product is a bidirectional immunoregulation preparation, can be used as a combined medicine for adjuvant therapy of tuberculosis chemotherapy, and [ safety before clinic ] the product is injected into mice by muscle route in 3 different doses, wherein the doses are 5000 times, 2500 times and 1250 times of the human dose respectively, and the abnormal symptoms and death of the mice are not caused. The administration of the drug is 78 times and 1560 times of the dosage of a rat and 4 times and 100 times of the dosage of a clinical human of a test dog, and the experimental result shows that under the dosage, the test dog and the rat have no toxic reaction in the aspects of indexes such as general behaviors, hematology, biochemistry, pathology and the like; adverse reactions very individual patients may develop local rashes, induration or fever. [ contraindication ] patients with allergic or allergic constitution are disclosed. (2) Patients with severe heart disease, myocardial damage, significant vascular sclerosis, endocarditis. (3) Women in gestation period. (4) Extreme asthenia and severe anemia.
When the mycobacterium bovis for injection is used, the mycobacterium bovis for injection is prepared into a physiological saline injection of 2.25-6.75 mu g/ml, and the injection is atomized by jet flow into a patient for inhalation at an oxygen flow rate of 5L/min. The specific steps of using the medicament to prevent and treat COVID-19 are as follows: 22.5 microgrammes of x (1-3) of mycobacterium vaccae for injection and 10ml of normal saline are prepared into normal saline injection, a SW-II type jet atomizer is adopted to carry out jet atomization inhalation under the oxygen flow of 5L/min, and Qd is carried out for 10 days per treatment course (an example of jet atomization inhalation treatment is shown in figure 1); before atomization, salbutamol sulfate aerosol, namely Wantuo Lin 3 is sprayed firstly to relax bronchus and prevent induction of airway spasm; when atomizing, the patient is ordered to make a deep and slow breath, holds the breath slightly after inhaling the breath, and exhales the breath from the nostril; the conventional preparation of first-aid medicines such as Wantulin and the like, such as symptoms of tightness of breath, asthma or obvious cough, throat itching, skin itch, rash and the like, during atomization, immediately stops the atomization, and then sprays Wantulin 3 to stop the asthma attack.
The injection mycobacterium vaccae is applied to the preparation of the medicament for preventing and treating COVID-19, the prepared medicament dosage forms comprise aerosol, aqueous solution, powder and the like, and can adopt an atomization inhalation treatment mode, and the atomization inhalation treatment mode has the advantages that the medicament directly enters an airway and takes effect quickly; the particles are uniform and easy to deposit in an airway, and the atomized and inhaled medicine directly acts on a diseased bronchus-bronchiole-lung tissue, so that the treatment effect of the medicine can be improved, and the side effect of the whole body is less; the atomization time is short, and the tolerance of a patient is good; simple operation and easy matching (suitable for both the old and the young). The medicine with the special application provided for the patient can improve the compliance of the patient through short-term atomization inhalation, so that the patient can take the medicine conveniently, the medical cost is reduced, and the market prospect is good.
The invention has the beneficial effects that:
1. the mycobacterium vaccae for injection can rapidly increase the endogenous interferon level of respiratory tract-lung tissue to inhibit the replication of virus RNA, reduce cell damage or promote the repair of damaged cells to play a role in prevention and treatment, and simultaneously avoid or reduce the adverse reaction which is difficult to avoid by an exogenous interferon preparation because the endogenous interferon level is increased.
2. The application of the mycobacterium vaccae for injection in preparing the medicament for preventing and treating COVID-19 can prepare the medicament dosage form into aerosol, and the atomized medicament contains the active ingredients of the mycobacterium vaccae for injection, and the active ingredients have the following effects: (1) physical action: the atomized and inhaled normal saline can play the roles of cleaning and diluting pharyngeal virus so as to make the nucleic acid detection negative; the sputum of the respiratory tract is diluted, the sputum excretion is promoted, and the airway is unobstructed. (2) By using the immune characteristic of the respiratory tract mucosa, the expression of respiratory tract-lung tissues I and III-IFN is improved within a few days, the virus replication is inhibited, and the virus killing and cell repair of immune cells are promoted. The airway mucus is diluted and destroyed by atomization inhalation to enable the airway to be unobstructed, according to autopsy reports, a patient infected with COVID-19 has the symptoms that mucus in the airway of the lung is increased and is very thick to obstruct the airway from being unobstructed, oxygen can not enter the alveoli, so that the patient can suffer from obstructed breathing, finally the blood oxygen concentration is reduced, the respiratory failure is caused, the insufficient oxygen supply of brain cells and organs is caused, the brain cells and organs are difficult to cure, the patient becomes serious and dies, after the medicine is atomized and inhaled into the airway (the atomization of mycobacterium vaccae and salbutamol sulfate and physiological saline is also used for moistening the airway and air bubble), the surface tension of the airway mucus is destroyed, the viscosity is reduced, the cough is easy to be produced, the airway is unobstructed, the high-concentration oxygen immediately improves ventilation, the blood oxygen concentration is improved, and the symptom of difficult breathing of the patient is quickly improved, thereby avoiding the serious illness or quickly relieving the illness state of the serious patient and greatly shortening the treatment time.
3. The pharmaceutical composition for preventing and treating COVID-19 can be prepared into aerosol, or can be prepared into active ingredient medicines by compounding the mycobacterium vaccae for injection and salbutamol sulfate in atomized medicines. Clinical tests prove that the mycobacterium vaccae for aerosol inhalation injection (microcard) has better clinical effect on treating COVID-19, common patients are not easy to be converted into severe cases/critical cases, the cure rate is high, no death cases occur, the common patients are not easy to be converted into severe cases or critical cases through clinical tests in the fourth people hospital (infectious disease special hospital) in Guangxi Nanning City through more than ten days of domestic and domestic special hospitals, the cure rate is high, more than 30 cases of patients infected with new coronavirus do not die, the average treatment time is shortened by 4 days, the current COVID-19 prevention and control are facilitated, and the mycobacterium vaccae for injection is worthy of further clinical popularization and application, and is expected to become a vaccine with prevention and treatment effects on COVID-15 and even other respiratory virus infections.
4. The new application of the mycobacterium vaccae for injection in preparing the medicament for preventing and treating COVID-19 disclosed by the invention provides a new way and scheme for clinically preventing and treating COVID-19 and preventing and treating respiratory virus infection.
Drawings
FIG. 1 is an exemplary diagram of a jet nebulization inhalation therapy for M.bovis for injection using a jet nebulizer;
FIG. 2 is a Kaplan-Meier graph obtained by analyzing the negative conversion time in clinical trials by the Kaplan-Meier method;
FIG. 3 is a CT image of the breast before treatment of a patient of the patient's chenchenchen (common type) in a clinical trial, wherein the left lung of the patient is seen with a large thin and light image;
FIG. 4 is a CT image of the breast after treatment of the patient's chenchenchencheng (common type) in clinical trials, showing that the lesion is significantly absorbed after the treatment of the patient than before the treatment.
Detailed Description
Example 1 (general type patient):
application of Mycobacterium vaccae for injection in preparing medicine for preventing and treating COVID-19 is provided.
Preparing injection normal saline injection from 22.5 micrograms of Mycobacterium vaccae (microcard) per bottle multiplied by 2+ normal saline 10ml, and carrying out jet atomization inhalation at an oxygen flow rate of 5L/min by adopting an SW-II type jet atomizer until all the liquid medicine is completely inhaled (about 20 minutes), Qd, 10 days per treatment course; before atomization, salbutamol sulfate aerosol, namely 'Wantuo Lin' 3 is sprayed and absorbed.
Example 2 (critically ill patient):
preparing 10ml of physiological saline sterile mixed solution by 25 micrograms of injection cow mycobacterium (microcard) per bottle multiplied by 2 bottles and salbutamol according to the weight ratio of 1:50-200, and carrying out jet atomization inhalation by adopting an SW-II type jet atomizer at the oxygen flow of 5L/min until all the liquid medicine is completely inhaled (about 20 minutes), Qd, 10 days per treatment course.
And (3) clinical trials:
1. materials and methods
1.1 materials and equipment: mycobacterium vaccae for injection (trade name: microcard, component is Mycobacterium vaccae mycoprotein, Chinese medicine standard S200110003) is available from Biopharmaceutical Co., Ltd, Naja Najordan Temminck, Japan; SW-II jet atomizer (Gui Jie Zhu Yuan 20182540033, Gui food and drug Surveillance Ji Huo No. 20110001).
1.2 methods
1.2.1 study subjects and inclusion criteria: the patient was admitted to the fourth hospital (fixed-point hospital) in Nanning from 2/5 of 2020, and confirmed 32 general patients according to the diagnosis and treatment protocol of novel coronavirus pneumonia (trial fifth edition) of Wei Jian Commission in China.
1.2.2 study grouping: the setting is carried out according to a random, blind method and a comparison group. The general data of the two groups are comparable with that of the conventional treatment control group and the conventional treatment intervention group, namely 18 cases and 14 cases.
1.2.3 treatment dispensing and infusion:
1) assigning patients using a computer-generated randomization scheme
2) One patient was assigned for dispensing (10 ml of normal saline was inhaled by nebulization in the control group, and 10ml of normal saline was inhaled by nebulization in the intervention group using 2 microcard. )
3) Clinical teams, researchers, and patients were blinded to the therapeutic drug composition (blinding).
4) The conventional treatment control group is treated according to the strict guideline scheme and is atomized and inhaled with normal saline, and the intervention group is treated with the conventional treatment control group and is atomized and inhaled with the microcard. The medicine liquid is sprayed and absorbed by the metoclopramide 3 in the first two groups after the atomization treatment once a day and each time until the medicine liquid is absorbed (about 20 minutes).
1.2.4 Observation indexes:
1) the primary results of the test are viral nucleic acids from respiratory specimens and blood specimens.
2) Secondary results were chest CT, blood routine, CRP, liver and kidney function, cardiac myozyme, arterial blood gas analysis. Finger pulse oxygen saturation was recorded every hour before and after the aerosol inhalation treatment.
3) Severe morbidity, mortality, length of hospitalization and complications during treatment.
1.2.5 statistical analysis
Negative conversion time analysis was performed between groups by the Kaplan-Meier method, statistical analysis was performed using SPSS 22.0 software, two-sided test, test level α =0.05, P <0.05 was considered statistically significant for the differences.
1.3 part of the results
1.3.1 comparison of the negative conversion time of two groups of throat swab nucleic acids (see Table 1, Table 2, Table 3 and FIG. 2 below)
Compared with the conventional control group, the P of the intervention group is less than 0.05
Compared with the conventional treatment control group (9.143 +/-1.678), the P of the intervention group (5.333 +/-0.800) is less than 0.05, which indicates that the negative turning time of the intervention group is obviously shortened compared with that of the conventional treatment group.
1.3.2 comparison of the negative conversion rate, the severe conversion rate and the death rate of the two groups
All intervention groups turn negative, and 1 case of conventional treatment groups still do not turn negative (turn negative for 1 month); the intervention group did not become severe, whereas 1 of the conventional treatment groups turned severe and neither group had any death cases.
1.3.3 examples and CT Change photographs thereof
Name: the term "dry cough 1 day" refers to the term "chenchenchen X", 60 years old, and 11 months old, 2020. It is used for more than 10 years. The recent history of close contact with patients with the novel coronavirus pneumonia diagnosed by Wuhan; physical examination: t36.5 ℃, P90 times/min, R20 times/min, B171/90 mmHg. Shenqing, no yellow stain on skin and sclera, coarse respiratory sound of both lungs, and no smell or dry and wet rale of both lungs; arrhythmia, soft abdomen, tenderness, rebound pain, and edema in both lower limbs. Auxiliary inspection: the CDC result in Nanning is positive for the detection of novel coronavirus nucleic acid. 2020-02-11 flat scan (conventional) chest CT, shown in FIG. 3: (1) inflammation of both lungs, which is consistent with the new type of coronavirus pneumonia. (2) Aortic and coronary arteriosclerosis. And (3) diagnosis: (1) novel coronavirus pneumonia; (2) type 2 diabetes. After admission, they were randomized to intervention groups and given conventional therapy plus injected mycobacterium vaccae aerosol inhalation to modulate immunity. In the detection of the novel coronavirus nucleic acids at 02-14 and 02-17: it was not detected. After the symptoms are improved, 2020-02-23 chest CT indicates that the focus is obviously absorbed and improved and is discharged from hospital, and the CT picture is shown in figure 4.
1.4 discussion
The mycobacterial agent (such as Bacillus Calmette-Guerin, inactivated Mycobacterium phlei, and injectable Mycobacterium vaccae) can increase interferon level. The mycobacterial preparation is a multifunctional immunomodulator, can be used for preventing and treating infection, mainly regulates the immune function of an organism by influencing immune response reaction, enhances the activity of Th cells, stimulates B cells to enter the proliferation and differentiation stages, and finally promotes the formation of specific antibodies. The previous series of researches also prove that the aerosol inhalation inactivated mycobacterium can regulate the balance of Th1/Th2, obviously reduce the airway reactivity of patients with mild and moderate bronchial asthma and relieve asthma symptoms, and the main mechanism is to quickly up-regulate the level of respiratory mucosa-lung tissue interferon and correct the imbalance of Th1/Th 2. Meanwhile, the immunoreactivity of respiratory tract inhalation immunity and intradermal and subcutaneous injection immunity is found to have obvious difference, particularly the characteristics of quick and strong immunoreaction in the aspects of timeliness and local immunoreaction intensity, and obvious adverse reaction is not found in more than 500 cases of clinical application. (the series of research results successively obtain the second-class prize and the first-class prize of Guangxi scientific and technological progress). Based on these previous series of studies, combined with the similarities between viral infection and asthma immunity (both Th2 dominant responses) and the clinical manifestations of asthma induced by respiratory viral infection, we speculate that: (1) the aerosol inhalation inactivated mycobacterium can be used for non-specifically preventing and treating respiratory virus infection. (2) The aerosol inhalation inactivated mycobacteria can increase the expression of I-type IFN and III-type IFN by regulating DC innate immunity and can non-specifically prevent and treat respiratory virus infection. (3) The Mycobacterium vaccae for aerosol inhalation injection can prevent and treat COVID-19.
Therefore, relevant preliminary experiments including in vitro cell experiments and animal experiments are carried out in the previous period, the results show that the respiratory tract inflammation is obviously reduced, the airway responsiveness is not different from that of a normal control group, the lung RSV infiltration of mice (before RSV infection) is obviously reduced, the RSV mRNA expression is also obviously reduced, and the airway inflammation is obviously reduced in a short period of 5 days by preventive aerosol inhalation injection of Mycobacterium vaccae (trade name: microca), and simultaneously after the aerosol inhalation of inactivated Mycobacterium vaccum is predicted, the lung IFN- α - β expression of the mice (before RSV infection) is obviously increased compared with that of the normal group.
Preliminary results show that all patients in the intervention group turn negative completely within a few days (1 patient in the conventional treatment group still turns negative in 1 month), the time for turning negative is obviously shortened compared with that in the conventional treatment group, and no patient in the conventional treatment group turns to severe cases or dies, the recent discharge cases of the hospital are obviously increased, the cure discharge rate is over 60 percent quickly (see dynamic epidemic report in Guangxi in 25 days), and no adverse reaction related to the medicine is found; in addition, the scheme has the characteristics of simple equipment, materials and technology, low cost, easy popularization and suitability for primary epidemic prevention and control, and can be developed in any medical institution. As mentioned above, the inhalation of microcard mainly through rapid (3-5 days) increase respiratory tract-lung tissue endogenous interferon level to inhibit virus RNA replication, reduce cell damage or promote damaged cell repair and play a role in prevention, treatment, in addition, the atomization inhalation of physiological saline itself may play a role in cleaning, diluting pharyngeal virus, diluting respiratory tract sputum to promote sputum excretion and promote nucleic acid detection negative. Meanwhile, because the level of endogenous interferon is improved, adverse reactions which are difficult to avoid by an exogenous interferon preparation are avoided or reduced. Unfortunately, due to the tight control of patient specimen collection, transport, storage and related experiments, no corresponding basic study has been developed. In addition, since the clinical test is performed in a small amount in an independent hospital, the amount of samples needs to be increased and the clinical evidence-based test in multiple centers needs to be performed.
The conclusion is that the clinical trial preliminarily verifies that the cow mycobacterium (microcard) for aerosol inhalation injection has better clinical effect on treating COVID-19, is beneficial to the prevention and control of the current COVID-19, and is worthy of further clinical popularization and application, and the cow mycobacterium (injected) is expected to become a vaccine with prevention and treatment effects on the COVID-15 and even other respiratory virus infections.
Claims (7)
1. Application of Mycobacterium vaccae for injection in preparing medicine for preventing and treating COVID-19 is provided.
2. Use of mycobacterium vaccae for injection according to claim 1, in the manufacture of a medicament for the prevention and treatment of COVID-19, wherein: the medicament for preventing and treating COVID-19 comprises an active ingredient of the mycobacterium vaccae for injection and a pharmaceutically acceptable carrier.
3. Use of mycobacterium vaccae for injection according to claim 1, in the manufacture of a medicament for the prevention and treatment of COVID-19, wherein: the mycobacterium vaccae for injection can be used as a single preparation, can also be compatible with other medicines, is added with a proper amount of pharmaceutically acceptable auxiliary materials, and is prepared into a pharmaceutically acceptable preparation by adopting the prior art.
4. Use of mycobacterium vaccae for injection according to claim 1, in the manufacture of a medicament for the prevention and treatment of COVID-19, wherein: the dosage forms of the medicament for preventing and treating COVID-19 comprise aerosol, aqua and powder.
5. Use of mycobacterium vaccae for injection according to claim 1, in the manufacture of a medicament for the prevention and treatment of COVID-19, wherein: when the injection mycobacterium bovis is used, the injection mycobacterium bovis is prepared into a normal saline injection of 2.25-6.75 mu g/ml, and the injection mycobacterium bovis is atomized to a patient for inhalation under the condition of oxygen flow of 5L/min.
6. Use of mycobacterium vaccae for injection according to claim 1, in the manufacture of a medicament for the prevention and treatment of COVID-19, wherein: the injection mycobacterium vaccae can rapidly promote the endogenous interferon level of respiratory tract-lung tissue to inhibit the replication of virus RNA, reduce cell damage or promote the repair of damaged cells to play a role in prevention and treatment, and simultaneously, because the endogenous interferon level is promoted, the adverse reaction which is difficult to avoid by an exogenous interferon preparation is avoided or reduced.
7. Use of mycobacterium vaccae for injection according to claim 1, in the manufacture of a medicament for the prevention and treatment of COVID-19, wherein: the prepared medicine can be used for non-specifically preventing and treating other respiratory virus infection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010135842.3A CN111281893B (en) | 2020-03-02 | 2020-03-02 | Application of mycobacterium vaccae for injection in preparation of medicament for preventing and treating COVID-19 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010135842.3A CN111281893B (en) | 2020-03-02 | 2020-03-02 | Application of mycobacterium vaccae for injection in preparation of medicament for preventing and treating COVID-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111281893A true CN111281893A (en) | 2020-06-16 |
| CN111281893B CN111281893B (en) | 2021-11-19 |
Family
ID=71018130
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010135842.3A Active CN111281893B (en) | 2020-03-02 | 2020-03-02 | Application of mycobacterium vaccae for injection in preparation of medicament for preventing and treating COVID-19 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111281893B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000048615A2 (en) * | 1999-02-16 | 2000-08-24 | Stanford Rook Limited | TREATMENT OF CHRONIC VIRAL INFECTIONS WITH $i(M. VACCAE) |
| US20020197265A1 (en) * | 1997-12-23 | 2002-12-26 | Watson James D. | Methods and compounds for the treatment of immunologically - mediated diseases of the respiratory system using mycobacterium vaccae |
| CN1613456A (en) * | 2003-11-03 | 2005-05-11 | 安徽龙科马生物制药有限责任公司 | Freezing dried mycobatctericsis preparation and its preparing method and use |
-
2020
- 2020-03-02 CN CN202010135842.3A patent/CN111281893B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020197265A1 (en) * | 1997-12-23 | 2002-12-26 | Watson James D. | Methods and compounds for the treatment of immunologically - mediated diseases of the respiratory system using mycobacterium vaccae |
| WO2000048615A2 (en) * | 1999-02-16 | 2000-08-24 | Stanford Rook Limited | TREATMENT OF CHRONIC VIRAL INFECTIONS WITH $i(M. VACCAE) |
| CN1613456A (en) * | 2003-11-03 | 2005-05-11 | 安徽龙科马生物制药有限责任公司 | Freezing dried mycobatctericsis preparation and its preparing method and use |
Non-Patent Citations (2)
| Title |
|---|
| DURBAN IMMUNOTHERAPY TRIAL GROUP: "Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial", 《THE LANCET》 * |
| 临床试验公共管理平台: "雾化吸入灭活分枝杆菌疫苗治疗(COVID-19)新冠病毒感染性肺炎的基础与临床研究", 《临床试验公共管理平台》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111281893B (en) | 2021-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111265500B (en) | Pharmaceutical composition for preventing and treating COVID-19 and preparation method thereof | |
| Zhang et al. | A rare presentation of coronavirus disease 2019 (COVID-19) induced viral myositis with subsequent rhabdomyolysis | |
| Hanna et al. | Understanding COVID-19 pandemic: molecular mechanisms and potential therapeutic strategies. An evidence-based review | |
| Bernard et al. | Neuroparalytic illness and human diploid cell rabies vaccine | |
| US20110020279A1 (en) | Rabies cure | |
| Bag et al. | Treatment of COVID-19 patients: Justicia adhatoda leaves extract is a strong remedy for COVID-19–Case report analysis and docking based study | |
| CN112791097A (en) | Application of iodine in preparing medicament for preventing and treating respiratory infectious diseases and method for preparing low-particle-size iodine-containing aerosol | |
| WO2022199049A1 (en) | Use of ulinastatin in preparation of drug for treating novel coronavirus pneumonia | |
| CN111281893B (en) | Application of mycobacterium vaccae for injection in preparation of medicament for preventing and treating COVID-19 | |
| Sankar et al. | Nosodes and sarcodes | |
| CN101829154B (en) | Preparation method of medicine composition for preventing and treating asthma | |
| CN1165343C (en) | Indications for use as medicaments of multipotent parapox immunity inducers from attenuated, non-immunogenic pox viruses or parapox viruses | |
| CN111214495B (en) | Application of mycobacterium vaccae for injection in preparation of medicine for preventing and treating respiratory system RSV infection | |
| CN114668788A (en) | Application of blumea oil inclusion compound in preparation of medical spray for treating asthma | |
| WO2022063320A1 (en) | Composition for inhibiting respiratory virus and respiratory virus prevention and treatment method | |
| US20090169519A1 (en) | Medicinal formulation containing a combination of hiv type i and hiv type ii | |
| CN113384688A (en) | Application of chymotrypsin in resisting coronavirus | |
| RU2297846C2 (en) | Method for treatment of focal and infiltrative pulmonary tuberculosis | |
| CN116712480B (en) | Pharmaceutical composition for preventing influenza, preparation and application thereof | |
| US10071258B2 (en) | DNA oxidative damage repairing device and application method thereof | |
| CN112386682B (en) | Application of fibronectin in preparing medicine for treating novel coronavirus pneumonia | |
| Zhang et al. | Effects of Modified Sang ju-Yin Decoction Combined with IFNαlb Nebulization on IL-1β and HBD2 in Children with Asthmatic Bronchitis | |
| CN109394776B (en) | Traditional Chinese medicine component formula for treating diffuse interstitial pulmonary fibrosis and application thereof | |
| Bag et al. | Search for natural alkaloids as SARS-CoV-2 proteas and RdRp inhibitors: A docking-based study | |
| Ramos-Kuri et al. | Cov-2 Co-Adjuvant Treat-ment with Ethanol Nebulizations: Report of Three Cases with Good Outcomes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |