CN115317470A - Application of alkanna tinctoria naphthoquinone in medicine for preventing and treating cytokine storm - Google Patents
Application of alkanna tinctoria naphthoquinone in medicine for preventing and treating cytokine storm Download PDFInfo
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- CN115317470A CN115317470A CN202210964010.1A CN202210964010A CN115317470A CN 115317470 A CN115317470 A CN 115317470A CN 202210964010 A CN202210964010 A CN 202210964010A CN 115317470 A CN115317470 A CN 115317470A
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Abstract
The invention relates to an application of alkanna tinctoria naphthoquinone in a medicine for preventing and treating a cytokine storm, relates to the field of the cytokine storm, and relates to an application of alkanna tinctoria naphthoquinone in a medicine for preventing or/and treating a cytokine storm syndrome and sequelae excited by broad-spectrum antigens. The lithospermum naphthoquinone can play a role in preventing, inhibiting and curing the diseases in each stage of the generation and development of the cytokine storm syndrome.
Description
Technical Field
The invention relates to the field of cytokine storm, in particular to application of alkanna tinctoria naphthoquinone in a medicine for preventing or/and treating cytokine storm syndrome and sequelae stimulated by broad-spectrum antigens.
Background
The cytokine storm syndrome refers to the phenomenon that a plurality of cytokines such as TNF-alpha, IL-1, IL-6, IL-12, IFN-alpha, IFN-beta, IFN-gamma, MCP-1, IL-8 and the like in body fluid are rapidly and massively produced after the organism is infected with microorganisms. The severe infection caused by the cytokine storm triggered by the microbial infection has high fatality rate.
At present, pathogens which can cause cytokine storm syndrome and sequelae thereof are too extensive and are not treatable by drugs. For example: a number of newly emerging or newly mutated virus strains; many pathogens that develop resistance to existing antibiotics; many deep-infected pathogens such as fungi and mycoplasma have inhibitory or even killing effects on such a broad spectrum of pathogenic microorganisms, and it is possible to avoid any exacerbation of infection and the initiation of a fatal cytokine storm.
Cytokine storm syndrome is a major cause of death from severe infections. The existing main treatment methods, support therapy for maintaining vital signs; suppression of hyperactive immune responses with hormones; oxygen inhalation and mechanical assisted respiration; or specifically inhibit a limited inflammatory factor. These methods have little effect on inhibiting cytokine storm induced by systemic immune factors, and even if cured, they often have severe sequelae. Cytokine storm causes vascular permeability and capillary damage, resulting in hemorrhage, blood stasis and edema in organ tissues, and often appears immunosuppression after cytokine storm, so severe secondary infection and multiple organ failure can occur, resulting in sepsis with extremely high mortality rate. In addition to sequelae caused by side effects of other drugs, the major sequelae of severe infections caused by cytokine storm are fibrosis leading to multiple tissue organ dysfunction and failure, which are hallmarks and common pathways leading to end-stage organ disease. There is currently no therapeutic available for reducing tissue organ fibrosis and maintaining organ function.
Therefore, the development and screening of a new drug with broad spectrum efficacy is urgently needed, i.e. the drug can treat severe infection, complicated infection, uremia or tissue organ fibrosis caused by any pathogen with unknown cause, so as to reduce the fatality rate and even eliminate the death risk.
The Shikonin compounds are generally called Shikonin, and can be classified as L-Shikonin, which is generally called Alkannin in Chinese, and D-Shikonin, which is generally called Shikonin in Chinese. At present, the lithospermum naphthoquinone compounds are reported in the aspects of diminishing inflammation, resisting infection and improving immunity.
The research results of shikonin anti-inflammatory pharmacological research progress, which is published in 03 journal of Shizhen national medicine 2020, are summarized in the text: shikonin has antiinflammatory effect on arthritis, asthma, psoriasis, mastitis, diabetic keratitis, inflammation causing heart failure, acute liver injury, lung injury, spinal cord injury, etc. Experimental study on in vitro antibacterial activity of alkannin published in S1 of 2017, study results, book of university of three gorges (Nature science edition): the alkannin shows antibacterial action on various common strains including gram-positive bacteria, gram-negative bacteria and fungi, and has remarkable inhibiting action on the growth of staphylococcus aureus, escherichia coli, candida albicans, bacillus cereus and salmonella. The antibacterial ability is equivalent to that of levofloxacin. Alkannin has good antibacterial effect, and can be used as lead compound of antibacterial agent.
In addition, the shikonins can activate and strengthen NK cells. NK cells are natural killer cells, and not only can specifically recognize and kill a certain pathogen, but also can recognize and kill all pathogens different from normal cells of a human body and infected diseased cells thereof. A paper on the journal 03 of 1990, china immunology journal, "enhancing effect of shikonin extract on mouse NK cell activity", shows that the shikonin naphthoquinone monomer extract has a regulating effect on mouse NK cell cytotoxic activity through experiments from the anticancer perspective. Proves that the NK cell toxicity of the spleen cells of the mice is improved by about 20 percent (p is less than 0.001) by intraperitoneal injection of 6mg of certain alkanna tinctoria naphthoquinone monomer compound per kilogram of body weight for 5 days continuously every day.
It was indicated above that gromwell naphthoquinones can activate NK cells. The article in "research progress on negative regulation adaptive immune response of NK cells" published in 2016 of China immunology journal in 2016 at stage 06 indicates that: the quantitative ratio between NK cells and target DCs (dendritic cells) is correlated, and when at high ratio, NK cells kill DCs, thereby suppressing subsequent T cell responses; while at low rates, NK cells tend to promote DC maturation, which is beneficial for enhancing T cell responses. Although most of the researches carried out in human or mice find that NK cells can promote CD 4T cells to be differentiated into Th1 cells by directly secreting IFN-gamma, thereby promoting the antiviral and anti-infection effects of the body. However, NK cells may also exert a negative regulatory function by releasing inhibitory cytokines, competing with T cells for cytokines, or killing T cells directly. Studies have shown that activated NK cells can promote B cell responses. Human NK cells can then kill B cells according to their activation state, and NK cells can also indirectly suppress the humoral immune response by killing DCs.
However, no reports have been made on the application of the shikonin naphthoquinone compound in the medicine for preventing or/and treating the cytokine storm syndrome and sequelae stimulated by broad-spectrum antigens. In view of the above, the present application provides an application of shikonin in the preparation of a medicament for preventing or/and treating cytokine storm syndrome and sequelae elicited by broad-spectrum antigens.
Disclosure of Invention
The invention aims to solve the technical problem of providing the application of the alkanna tinctoria naphthoquinone in the medicine for preventing and treating the cytokine storm. Aims at preventing and/or treating the cytokine storm syndrome and sequelae stimulated by broad-spectrum antigens.
The technical scheme for solving the technical problems is as follows: the lithospermum naphthoquinone is applied to the medicines for preventing or/and treating the cytokine storm syndrome and sequelae stimulated by broad-spectrum antigens, and is levo lithospermum naphthoquinone.
The invention has the beneficial effects that: the laevorotatory lithospermum naphthoquinone can play a role in preventing, stopping and curing the occurrence and development stages of the cytokine storm syndrome; the shikonins compound has a broad-spectrum antimicrobial infection function, is mutually cooperated with a bidirectional immunoregulation function, and inhibits systemic overstimulation immune response of the whole body, namely cytokine storm, so that severe and critical diseases and complicated infectious diseases are effectively treated; the shikonins have the treatment effects of relieving and improving the sequelae of the cytokine storm and prolonging the service life of patients by aiming at the critical infection in the immunosuppression stage after the cytokine storm and having the remarkable effects of preventing internal hemorrhage and inhibiting secondary infection in a broad spectrum manner, preventing and effectively relieving sepsis with extremely high lethality rate and aiming at the sequelae which are left or are light or heavy by the patients caused by the cytokine storm.
On the basis of the technical scheme, the invention can be further improved as follows.
Further, the laevorotation alkannin is acetyl acannin or beta, beta-dimethyl acryloyl acannin.
The technical scheme adopted by the invention has the beneficial effects that: the invention discovers that the L-alkannin and other D-alkannin compounds have higher activity and lower toxicity.
Furthermore, the medicament dosage form is oral dosage form, buccal dosage form, atomization inhalation dosage form, oral and nasal spray dosage form, injection dosage form or transdermal dosage form.
The technical scheme adopted by the invention has the beneficial effects that: the oral, buccal, aerosol inhalation, oral and nasal spray, injection or transdermal preparations can effectively prevent or/and treat the cytokine storm syndrome and sequelae stimulated by broad-spectrum antigens.
Further, the antigen includes a virus, a bacterium, a fungus, a mycoplasma, a chlamydia, or a variant of a virus, a bacterium, a fungus, a mycoplasma, a chlamydia.
The technical scheme adopted by the invention has the beneficial effects that: the levo-alkannin is a broad-spectrum anti-infective drug, and can directly inhibit the infection of antigens and variants thereof such as viruses, bacteria, fungi, mycoplasma, chlamydia and the like, thereby preventing the occurrence of cytokine storm.
Further, the antigen includes SARS virus, avian influenza virus, ebola virus or neocoronavirus.
The cytokine storm syndrome comprises liver failure, uremia, diabetic ketoacidosis, acute pancreatitis, eclampsia, pulmonary lymphangioma, goodpasture-nephritis syndrome, systemic lupus erythematosus and the like.
The laevorotation alkannin adopted by the invention can systematically and comprehensively inhibit the over-excitation reaction of various inflammatory factors, thereby relieving the occurred cell factor storm and stopping the injury and failure of multiple tissues and organs such as heart, lung, liver, kidney and the like. The L-alkannin inhibits various inflammatory factors by inhibiting the activity of NF-kB in the early stage of antigen infection, blocks the NF-kB channel, and can systematically avoid TNF-alpha, IL-1 beta, IL-2, IL-6, IL-8, IL-12, iNOS, COX2, chemotactic factors, adhesion molecules and colony stimulating factors, and finally inhibit various inflammatory cytokines excited by any pathogen, thereby avoiding cell storm syndrome caused by severe infection and concurrent infection; for the critical infection in the immunosuppression stage after the cytokine storm, the cytokine storm can cause blood vessel permeability, hemorrhage, blood coagulation and the like to cause tissue organ damage, and the cytokine storm can be reversed from immunity overstimulation to immunity suppression after the cytokine storm, so that secondary severe infection is generated and converted into sepsis with extremely high death rate, and the levorotatory shikonin achieves the anti-inflammatory effect by inhibiting the expansion of capillary vessels and reducing the permeability to reduce the exudation and the swelling, finally prevents the internal hemorrhage and has the remarkable effect of broad-spectrum inhibition on the secondary infection, and prevents and effectively relieves the sepsis with extremely high death rate.
Furthermore, the technical scheme adopted by the invention has the beneficial effects that: the L-alkannin of the invention has the functions of reducing and improving the tissue fibrosis of the cytokine storm sequelae and effectively treating the sequelae of the cytokine storm syndrome. The tissue fibrosis includes pulmonary fibrosis, liver fibrosis or kidney fibrosis. The L-lithospermum naphthoquinone inhibits the expression of NOX4 by activating AMPK, so that the deposition of extracellular matrix and the activation of fibroblasts are inhibited, and the pulmonary interstitial fibrosis is relieved; the L-alkannin can inhibit rat hepatic fibrosis by down-regulating the expression of TGF-beta 1 in carbon tetrachloride-induced hepatic fibrosis rat liver tissues, and can protect mouse immune liver injury caused by ConA by reducing transaminase level, reducing the release of inflammatory factors and the like under the condition of no cytotoxicity; levoradix Arnebiae naphthoquinone is effective in relieving renal fibrosis by regulating Smad3/Erbb4-IR axis.
Detailed Description
Example 1: clinical trials of Acetanin
Severe Acute Respiratory Syndrome (SARS), which occurred in 2003, is an Acute viral infectious disease with high infectivity and high mortality. During the SARS epidemic, acetoacannin is used to treat SARS cases, the clinical trial scenario follows.
1. Case selection
20 SARS patients with confirmed diagnosis in hospital were selected.
2. Grouping and treatment method
2.1 case grouping
By adopting a random parallel group control design, 20 diagnosed SARS patients are randomly divided into an experimental group and a control group 2, and each group comprises 10 patients.
2.2 methods of treatment
The test group hospital is treated with Acetabonine (capsule 1 time 2 capsules, 1 day 3 times, taken after meal, course of treatment 10 days) and the control group hospital is treated with conventional treatment.
2.3 the curative effect of the disease and the curative effect of the imaging are evaluated in 4 grades of clinical recovery, obvious effect, effective effect and ineffective effect.
3. Results
The curative effect of the disease is as follows: during the 10-day treatment period, the test group showed 90% effect and 10% effect, and the control group showed 10% effect, 80% effect and 10% no effect. See table 1 for details.
The imaging curative effect is as follows: the clinical cure rate of the test group is 30 percent, the effect is 70 percent, and the control group has 30 percent, 60 percent and 10 percent of effect. The difference P of the two groups is less than 0.001. See table 2 for details.
The time from the onset of the disease to the start of the administration of the acetoacannin in the patients in the test group is positively correlated with the course of the disease (r =0.94, P < 0.01), and no adverse reaction or obvious side effect is observed.
The effects of administration of Acetaonine on the course of the disease, body temperature, changes in X-ray chest film lesions, and the glucocorticoid therapy required are shown in Table 3. The data of the correlation analysis of the antiviral action of aceacannin are shown in Table 4.
TABLE 1 results of disease efficacy determination in test group and control group
Note: comparison with control group, exact probability method, P <0.001
TABLE 2 determination of the effectiveness of the test and control groups in imaging
Note: comparing with control group, exact probability method, P <0.001
TABLE 3 results of the changes in the main conditions of the test and control groups
TABLE 4 relationship between morning and evening and course of disease in test groups patients taking acetoacannin
Note: the taking period X is the interval days from the onset to the taking of the antitoxic capsule, the course Y is the mean value of the administration course/the mean value of the course of the control group (42 days) within 1 week of the interval days from the onset to the discharge, is 0.57, the mean value of the administration course/the mean value of the course of the control group within 10 days of the onset is 0.64, and the mean value of the administration course/the mean value of the course of the control group after 10 days of the onset is 0.94.
The results of the curative effect are that after two adjacent items (healing and significant, effective and ineffective) in the table 1 and the table 2 are combined, the calculated P values are both less than 0.001, namely the two groups have very significant difference, and the exact curative effect of the acetyl acannin on SARS is shown.
In clinical trials, the use of acetyl acannin does not cancel the unified recommended treatment scheme, and more patients are treated by glucocorticoid (hereinafter referred to as hormone) due to severe fever symptoms, so that the observation effect on body temperature is larger. Table 3 shows: the time required for the body temperature of the test group to return to normal is longer than that of the control group, and is considered to be related to hormone treatment which is less than that of the control group (P < 0.01); however, the disease course of the test group is 9 days shorter than that of the control group, the disease course is shortened by 21 percent, and the curative effect of the acetoacannin is further determined; in addition, the pathological changes in the X-ray chest radiography of the test group are obviously rebounded less than that of the control group (P is less than 0.01), but the reason is that the control group generally uses hormone, so that the immunologic function is reduced, the infection chance of other microorganisms is increased, and the conditions of rise of blood images, slow absorption of lung shadows or rebounding are frequent; the acetoacannin used in the test group has certain antiviral, mycoplasma-resisting and antifungal effects, so that the chance of secondary infection is reduced, and the anti-inflammatory effect of the acetoacannin reduces the cases of hormone therapy. Therefore, it is believed that acetyl acannin reduces rebound in lung lesions.
In addition, research institutions have shown that: the viral load of SARS patients peaked on day 10 and dropped to acceptable levels on day 15, i.e. the period of high viral replication was within 10 days after onset. Therefore, the earlier the replication-suspended phase, the less viral infection and the shorter the course of disease, and antiviral treatment after day 11 is of no significance. The results in Table 4 match, and show that the course of the drug administration is shortened by 43% within 1 week of onset, 36% within 10 days of onset, and the course of the drug administration is not shortened significantly after 10 days of onset. Assuming that the course of the disease is shortened by halting the high-rate replication of the virus after administration of the acealcaine: linear correlation coefficient r =0.940 (P < 0.01), regression equation is Y =20.2+1.28X (2 ≦ X ≦ 17); the nonlinear correlation coefficient r =0.966 (P < 0.01), and the regression equation is Y = 18.5X 1.07X (0. Ltoreq. X.ltoreq.10), Y =39 (X. Ltoreq.11). Proves that the morning and evening of the administration of the medicine are closely related to the length of the disease course, and shows the pharmacodynamic action of the acetyl acannin in stopping virus replication.
The biochemical examination of using acetyl acannin shows that ALT is slightly increased, the difference is not obvious, and the method can also be related to SARS diseases or medicaments such as ribavirin and the like.
Therefore, the acetoacannin has definite curative effect on SARS, good safety and obvious curative effect when being taken at early stage. In addition, acetoacannin reduces rebound of lung lesions.
Example 2: clinical experiments on beta, beta' -dimethylacryloyl alkannin (alkannin B) for treating suspected SARS patients
During SARS epidemic situation in 2003, alkanin B was used in clinical treatment of SARS suspected patients in the designated hospital for SARS suspected patients.
1. Case selection and grouping
The medicine is applied to 10 suspected SARS patients, wherein the 10 patients are patients who are just transferred from fever clinic to hospital, 2 patients are transferred to SARS treatment hospital for continuous treatment, and the connective tissue disease is confirmed after one patient; one example is SARS tuberculosis complicated infection in convalescent period; 7 cases are all cured and discharged from hospital for viral pneumonia; another 1 suspected SARS was discharged from hospital after clinical treatment. Because SARS suspected patient is very limited in late epidemic situation, 10 similar SARS suspected patients treated by fever clinic are selected as control group. As can be seen from table 5, the treatment groups were at most 71 years old, at least 20 years old, and the mean age was 41.2 years old; the age of the control group is 60 years at maximum, 14 years at minimum, and the average age is 36.8 years; because the subjects were randomly selected, the proportion of men and women was not well balanced.
TABLE 5 Subjects' enrollment and demographic data for each group
2. Method of treatment
2.1 methods of treatment
The treatment group and the control group all adopt the treatment method published by the Ministry of health, the intravenous Rifampicin, the erythromycin, the ribavirin and the like are not treated by hormones, and the acannin B capsule is added for 3 times per day and 2 capsules are taken each time while the treatment group adopts the method.
2.2 the curative effect of the disease and the curative effect of the imaging are evaluated in 4 grades of clinical recovery, obvious effect, effective effect and ineffective effect.
3. Results
In the treatment group, 1 suspected SARS patient (see 0072) was discharged after 12 days, although the chest film was clearly absorbed in 6 days and the physical symptoms were completely normal, because the chest film was blurred in the form of spot. 1 suspected SARS patient (View 0063) had no fever and no absorption by chest X-ray, and was diagnosed as tuberculosis after treating SARS in designated Hospital by treating according to connective tissue inflammation to Beijing. Another 1 (View 0066) was diagnosed as SARS in Beijing hospital, and was discharged after recovery, and the exudative lesion inflammation of both lungs was again hospitalized in the suspected disease treatment hospital, and after taking alkannin B, the patient was transferred to the designated SARS hospital, and was diagnosed as SARS recovery period, and the chest card showed inflammation of both lungs, and after 2 weeks, the patient was discharged after recovery.
From table 6, the number of healing people in the treatment group reaches 9 from the main index statistics, the healing rate reaches 90%, the secondary index statistics reaches 8, and the healing rate reaches 80%; the number of the significant persons in the treatment group is 1 from the secondary index statistics, and the significant efficiency is 10 percent; the number of the ineffective people in the treatment group is 1 from the main index and 10% of ineffective rate, and the number of the secondary indexes is 1 from the main index and 10% of ineffective rate. The number of healing people in the control group reaches 8 from the statistics of main indexes, the healing rate reaches 80 percent, the statistics of secondary indexes reaches 9, and the healing rate reaches 90 percent; the number of effective people in the control group is 2 from the main index, the effective rate is 20%, the secondary index is 1 statistically, and the effective rate is 10%. To further illustrate the efficacy of acannin B, the duration of antipyretic action, chest absorption and disease course are further detailed below.
TABLE 6 statistics of the efficacy of the treatment and control groups
TABLE 7 statistical table of treatment results of SARS suspected patient treatment groups
TABLE 8 statistical table of SARS suspected patient control group treatment results
3.1 duration of defervescence
As can be seen from tables 7 and 8, treatment groups: 4 cases of 1 day defervescence, 4 cases of 2 days defervescence, 1 case of 3 days defervescence and 1 case of no effect. Control group: 3 cases of 1 day defervescence, 2 cases of 3 days defervescence, 2 cases of 4 days defervescence, 2 cases of 6 days defervescence and 1 case of 7 days defervescence; therefore, after the acannin B is taken in the treatment group, the defervescence time is obviously accelerated compared with that of the control group, the average defervescence time of the treatment group is 1.6 days, and the average defervescence time of the control group is 3.3 days.
3.2 chest film absorption time
As can be seen from tables 7 and 8, treatment groups: 6 cases were taken in 3 days, 2 cases were taken in 4-6 days, 1 case was ineffective (connective tissue disease), and 1 case was taken in (SARS recovery period) for 6 days. Control group: 2 cases were absorbed within 3 days, 6 cases were absorbed within 4-6 days, and 1 case was absorbed within 7 days. Therefore, after the acannin B is taken in the treatment group, the chest tablets show that the lung absorption speed is accelerated, the absorption time is reduced, the average absorption time of the treatment group is 3.7 days, and the average absorption time of the control group is 4.9 days.
3.3 course of disease
As can be seen from tables 7 and 8, treatment groups: 7 cases of viral pneumonia were discharged from hospital on an average of 4.5 days, 1 case of SARS convalescent patients was re-hospitalized after combined infection with tuberculosis, 14 days later, 1 case of SARS suspected patients was discharged from hospital on 12 days, and 1 other case of connective tissue disease was ineffective. Control group: 10 cases are all viral pneumonia, and the average course of disease is 5.8 days. Therefore, the disease course of the treatment group is 1.8 days shorter than that of the control group and is 31 percent earlier than that of the control group.
In conclusion, clinical trials show that the curative effect of the acannin B on the viral pneumonia which is not effective in antibiotic treatment is obvious. Is characterized in that: the fever is fast, except 1 patient of 10 patients who have finished treatment, the rest 9 patients have the average fever reduction of 1.6 days, and the body temperature returns to normal in 2 days; the lung focus is absorbed rapidly, 1 suspected confirmed SARS patient is transferred to SARS designated hospital 1 week later, and no development is seen according to the focus tracking.
Example 3: clinical data on the treatment of novel coronavirus pneumonia (COVID-19) with acetyl acannin and acannin B
Jeffrey Burns medical doctor, severe medical director and Shapiro director International health service executive director, anesthesia and pediatrics of Harvard medical institute, conducted related studies on sprays made of acetyl acannin or acannin B. Studies were conducted to test the ability of sprays (made of acetyl acannin or acannin B) to inhibit infection, which is used by many patients infected with the novel coronavirus pneumonia (COVID-19). The research group found that for individuals using sprays, the cell virus cultures began to be inhibited almost immediately, and that almost all of these infected individuals recovered significantly or completely within a short period of time after treatment with the spray. The research group also found that patients suffered from pulmonary fibrosis to a relatively lesser degree.
There are two main modes of action of spraying. First, it traps and coats the virus inside the nose, from where it can be removed by the usual route (blowing the nose or swallowing). Second, since the virus is encapsulated in a spray-viscous coating, it is prevented from being absorbed by the human body. This means that it will reduce the viral load in the body and that even if the viral particles are transmitted to another person by sneezing or coughing, the person is less likely to be infected by active viral particles.
In conclusion, the laevorotation lithospermum naphthoquinone has obvious effect in preventing or/and treating the cytokine storm syndrome and sequelae stimulated by broad-spectrum antigens.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.
Claims (5)
1. The application of the lithospermum naphthoquinone in the medicines for preventing or/and treating the cytokine storm syndrome and sequelae stimulated by broad-spectrum antigens is characterized in that the lithospermum naphthoquinone is levo-lithospermum naphthoquinone.
2. The use as claimed in claim 1, wherein the laevorotatory lithospermum naphthoquinone is acetoacannin or β, β -dimethylacrylalkannin.
3. The use according to claim 1 or 2, wherein the pharmaceutical dosage form is an oral dosage form, a buccal dosage form, an aerosol inhalation dosage form, an oronasal spray dosage form, an injection dosage form or a transdermal dosage form.
4. The use of claim 1, wherein said antigen comprises a virus, bacterium, fungus, mycoplasma, chlamydia or variant thereof.
5. The use of claim 1, wherein the antigen comprises SARS virus, avian influenza virus, ebola virus, or neocoronavirus.
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| CN102198120A (en) * | 2010-03-26 | 2011-09-28 | 山东靶点药物研究有限公司 | Medicinal use of lithospermi naphthoquinone compounds |
| CN111166734A (en) * | 2020-02-27 | 2020-05-19 | 黄铭 | Use of naphthoquinones to treat pneumonia caused by pathogenic organisms |
| CN114159420A (en) * | 2021-12-08 | 2022-03-11 | 郑州大学 | Application of acetylshikonin in preparation of anti-lung inflammatory factor storm medicine |
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2022
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102198120A (en) * | 2010-03-26 | 2011-09-28 | 山东靶点药物研究有限公司 | Medicinal use of lithospermi naphthoquinone compounds |
| CN111166734A (en) * | 2020-02-27 | 2020-05-19 | 黄铭 | Use of naphthoquinones to treat pneumonia caused by pathogenic organisms |
| CN114159420A (en) * | 2021-12-08 | 2022-03-11 | 郑州大学 | Application of acetylshikonin in preparation of anti-lung inflammatory factor storm medicine |
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