CN111632053A

CN111632053A - Application of pitavastatin calcium in preparing medicine for treating new coronary pneumonia

Info

Publication number: CN111632053A
Application number: CN202010648715.3A
Authority: CN
Inventors: 李成
Original assignee: Individual
Current assignee: Individual
Priority date: 2020-07-07
Filing date: 2020-07-07
Publication date: 2020-09-08

Abstract

The application of pitavastatin calcium in preparing the medicine for treating the new coronary pneumonia, the mechanism of pitavastatin calcium for relieving the new coronary pneumonia is to weaken the capability of COVID-19 virus invading human cells through ACE2, thereby inhibiting the replication of the COVID-19 virus.

Description

Application of pitavastatin calcium in preparing medicine for treating new coronary pneumonia

Technical Field

The invention belongs to the field of pharmacy, and relates to application of pitavastatin calcium in preparing a medicine for treating new coronary pneumonia.

Background

New coronary pneumonia has not been completely eliminated. In autumn and winter after several months, the temperature is reduced, the immune system of the human body is weakened, and the human body is susceptible to influenza and common pneumonia as well as new coronary pneumonia. If we refer to 1918 spring flu, the number of deaths caused by flu in the second wave and autumn far exceeds that in the first wave. Therefore, the epidemic prevention and control pressure in autumn and winter in this year is very high. Our vaccine is in good progress, but there is a third phase clinical trial to do, and it is difficult to tell whether time is available in view of productivity. The efficacy and duration of immunity of vaccines are also not completely clear. Therefore, a specific drug against new coronary pneumonia is urgently needed as a supplement of vaccine.

To date, researchers have explored the power of drugs for treating new coronary pneumonia, and have focused more on finding ways to kill new coronavirus drugs. Such drug finding methods may find effective drugs, but find specific drugs difficult.

The pitavastatin calcium for treating the new coronary pneumonia disclosed by the invention is effective to the new coronary pneumonia from the current data. In terms of the action mechanism, the virus is blocked from replicating, so that the virus has the potential to become a specific medicine. However, more data still needs to be determined by more clinical trials.

Disclosure of Invention

The application of pitavastatin calcium in preparing the medicine for treating the new coronary pneumonia; pitavastatin calcium is chemically named as (+) -bis { (3R,5S,6E) -7- [ 2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl ] -3, 5-dihydroxy-6-heptanoic acid } calcium salt, and has a molecular formula: C50H46CaF2N2O8, molecular weight: 880.98, respectively; the new coronary pneumonia refers to related diseases caused by the COVID-19 virus. Pitavastatin calcium is used for treating a patient with new coronary pneumonia, wherein the serum cholesterol of the patient is not increased due to the new coronary pneumonia, generally speaking, the cholesterol of the patient is reduced due to the new coronary pneumonia, the high serum cholesterol generally has two conditions, namely, the serum cholesterol of the patient is increased to a normal range before the patient suffers from the new coronary pneumonia, and the serum cholesterol of the patient is not reduced to a normal level after the patient is infected with the new coronary pneumonia, and the two conditions can effectively inhibit the COVID-19 virus replication and relieve the disease condition by using the pitavastatin calcium. The medicament is prepared from pitavastatin calcium and pharmaceutically acceptable auxiliary materials, and the medicament dosage form is gel, soft capsule, oral preparation, injection, freeze-dried powder injection or large infusion.

The mechanism by which pitavastatin calcium can relieve new coronary pneumonia in patients is to impair the ability of the covi-19 virus to invade human cells, thereby inhibiting the replication of the covi-19 virus.

The COVID-19 virus invades through human ACE2, which is a cell that has been shown experimentally to require cholesterol assistance or to be more accessible to the COVID-19 virus for cell invasion in patients with high concentrations of cholesterol. The patient uses pitavastatin calcium to reduce cholesterol, so that the progress of new coronary pneumonia is relieved, and the death probability is reduced. Has the potential of further developing into a new coronavirus entry inhibitor.

Experimentally, it was observed that the new coronaviruses only enter cells by endocytosis when GM1 lipid rafts are enriched in the culture. Endocytosis of pseudoneocoronaviruses can be enhanced by cholesterol-loaded cells from serum using the cholesterol transport protein apoE. Super-resolution imaging showed that virus entry increased significantly in the cholesterol-loaded (forming GM1 lipid rafts) state and decreased significantly in the unloaded state. The inhibition of viral entry into cells following cholesterol unloading is repeatedly shown following the addition of the cholesterol-removing chemical of methyl- β -cyclodextrin (M β CD) to the cells. Compared with the cholesterol dependence of the new coronavirus infection, the infection rate of the high cholesterol (apoE + serum) virus is higher by more than 3 times; depletion of cellular cholesterol with M β CD blocks nearly all viral entry, and viral entry is blocked, associated with a lack of cholesterol, not due to lack of ACE2 receptor, which is normally expressed at high levels in the presence of apoE and M β CD. At the same time, cholesterol may also help the ACE2 receptor move to the lipid raft site. In addition, the cholesterol-dependent model shows that as infection progresses, serum cholesterol levels fall rapidly, while the cholesterol in peripheral tissues is heavily loaded. The molecular basis for cholesterol-dependent cellular entry of the novel coronavirus, GM1 lipid raft, ACE2 receptor. The assembly of viral entry factors in GM1 lipid rafts, compared to TMPRSS2, Furin protein has a higher correlation with cholesterol in promoting viral entry into cells. It follows that there are at least three cholesterol-dependent mechanisms of infection by the novel coronavirus and that it can be used as an explanation for the different infectivity of elderly with underlying disease and chronic inflammation. The size and number of viral entry sites is cholesterol dependent. The ACE2 receptor is cholesterol dependent, determining the lipid docking capacity of the virus. If the virus is not properly positioned on the membrane, it is likely that it will not enter the cell efficiently. Proteases that activate viral membrane insertion are also cholesterol dependent and dependent on the membrane translocation mechanism. Based on these findings, cholesterol is likely to be a prerequisite for new coronavirus infections. This cholesterol-dependent viral infection may be responsible for the greater fatality of new combs in the elderly.

Recall that some patients with COVID-19 (a novel coronavirus) infection were treated at the indicated hospital and tested positive for viral nucleic acid by PCR, and at the early stage of infection, by lipid testing: the patients had very low levels of total cholesterol, high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL). However, towards the end of the course of the disease, these cholesterol levels began to rise gradually, and were restored as early as 14 days after discharge.

Reviewing the hospitalized patient with the new coronary pneumonia, the statin drug can reduce invasive mechanical ventilation, enter an intensive care unit and the incidence rate of acute respiratory distress syndrome, reduce the blood inflammatory factor level of the patient, prevent the mild new coronary pneumonia from progressing to the severe state, and reduce the mortality rate from 9.4% to 5.2%. Statins are currently the most effective lipid-lowering drugs in common use, and in addition to lowering cholesterol, can reduce inflammation, reduce thrombosis, and prevent endothelial cell injury in blood vessels and other organs. The statins can improve the immune cell reaction of experimental animals, effectively reduce inflammation and relieve the lung injury of the experimental animals. A systematic retrospective study was performed on 13981 hospitalized patients with new coronary pneumonia, with 1219 patients using statins during hospitalization and on average 22 days in hospital; among patients with new coronary pneumonia complicated with hypertension, 319 patients used statin-combined pril or sartans, and 603 patients used statin-combined other antihypertensive drugs. comparative analyses of mortality and invasive mechanical ventilation, access to intensive care unit, acute respiratory distress syndrome, incidence of hepatic and renal injury, and incidence of cardiac injury in patients with and without statins. The study data showed that the 28-day all-cause mortality rate with statin group was 5.2%, which was lower than the 9.4% mortality rate with non-statin group. The use of statins also obviously reduces the invasive mechanical ventilation, the entrance into intensive care units and the incidence rate of acute respiratory distress syndrome of patients with new coronary pneumonia; the levels of inflammatory factors in the blood during hospital periods in patients with statins are also significantly lower than in non-users.

If there is a case where blood cholesterol is higher than the normal range or a case where the prognosis of the underlying disease for new coronary pneumonia is poor before the patient is not infected with the COVID-19 virus, the preventive cholesterol-lowering therapy using the pitavastatin calcium drug can be performed in advance, so that the prognosis is good when the patient is infected with the COVID-19 virus.

By retrospective study of hospitalized patients with new coronary pneumonia, patients with low blood cholesterol levels before infection with new coronary pneumonia had less symptoms of new coronary pneumonia than patients with higher cholesterol levels. Qualitative analysis concluded that patients with lower levels of cholesterol at the beginning of infection had better ability to fight new coronary pneumonia.

The pitavastatin calcium is used in a dosage of 1-2 mg once a day. If the cholesterol content in serum needs to be reduced rapidly, the dosage can be increased properly, and generally the dosage does not exceed 4 mg per day.

Detailed Description

The present invention will be further described with reference to examples.

Claims

1. The application of pitavastatin calcium in preparing the medicine for treating the new coronary pneumonia; pitavastatin calcium is chemically named as (+) -bis { (3R,5S,6E) -7- [ 2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl ] -3, 5-dihydroxy-6-heptanoic acid } calcium salt, and has a molecular formula: C50H46CaF2N2O8, molecular weight: 880.98.

2. the use as claimed in claim 1, for the treatment of patients with new coronary pneumonia having serum cholesterol levels above normal.

3. The application of claim 2, wherein the medicament is prepared from pitavastatin calcium and pharmaceutically acceptable auxiliary materials, and the medicament is in the form of gel, soft capsule, oral preparation, injection, freeze-dried powder injection or infusion solution.