RESUMO
We report for the first time that ephedrine alkaloids-free Ephedra Herb extract (EFE) directly inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and that the addition of EFE to the culture medium before viral infection reduces virus titers in the culture supernatant of SARS-CoV-2, including those of variant strains, by more than 99%, 24 h after infection. The addition of Ephedra Herb macromolecule condensed-tannin, which is the main active ingredient responsible for the anticancer, pain suppression, and anti-influenza effects of EFE, similarly suppressed virus production in the culture supernatant by 99% before infection and by more than 90% after infection. Since EFE does not have the side effects caused by ephedrine alkaloids, such as hypertension, palpitations, and insomnia, our results showed the potential of EFE as a safe therapeutic agent against coronavirus disease 2019.
RESUMO
Coronavirus disease 2019 (COVID-19) spread to Japan in 2020, where the number of infected patients exceeded 250,000 and COVID-related deaths exceeded 3,500 in one year. Basic guidelines for infection control were implemented in Japan, and research and development of effective drugs and vaccines were promoted. This included considering Kampo medicine, which has a long history of treating recurring emerging viral infections. Considering the characteristics of the disease (inflammation of the upper and lower respiratory tract as well as potential neural damage and vasculitis), Kampo medicine could be considered as a treatment strategy due to its antiviral and anti-inflammatory effects induced by multiple active substances that could aid in disease prevention and recovery. In this study, case reports on the management of COVID-19 with Kampo medicine, which were published until March 31, 2021, were reviewed. The search strategy involved the use of Medline and hand-searching. Twenty two patients were treated using Kampo medicines with or without Western medicine, based on individual conditions. On the other hand, the effects of Kampo medicines as a potential preventive treatment (pre-infection), active treatment (especially in the acute and subacute stage), or treatment of sequelae to aid recovery (after infection) in the different stages of COVID-19 are being studied as research projects in the Japan Society for Oriental Medicine (JSOM). JSOM has also organized a pioneering project of clinical trials for COVID-19, some of which are now in progress.
RESUMO
Condition:
COVID-19Intervention:
Part1: 6 subjectsTake EFE twice a day, after waking up and before bed, with 150 mL of water for 14 days
Part2: 150 subjects
Take EFE or placebo twice a day, after waking up and before bed, with 150 mL of water for 14 days
Primary outcome:
Non-severity rate at Day 15 (Rate of subjects who completed the study without becoming moderate or higher)Part 2 will start, after comfirmation that "adverse events which is causally related to the investigational drug, with Grade 3 or higher based on CTCAE," would not find during the study period (until Day 21) .
Criteria:
Inclusion criteria: (1) Subjects who can obtain written consent, based on their free intention(2) Subjects whose age at the time of obtaining consent is 20 years or older and under 80 years
(3) Subjects who are SARS-CoV-2 positive by PCR or antigen test within 3 days before baseline-test
(4) Subjects whose COVID-19 symptoms (upper respiratory tract inflammation such as fever and cough) appiered within 7 days before baseline-test and mild (Resting SpO2 96% or more)
(5) Subjects who were judged no problem by the investigator to participate in this clinical trial based on medical examination, vital signs, laboratory test values, chest X-ray, etc.
Exclusion criteria: (1) Subjects who participated in other clinical studies and clinical trials within 12 weeks before the start of study drug administration. And subjects who are planning to participate in clinical studies and clinical trials of unapproved drugs during this study period.
(2) Subjects who administered therapeutic medication for COVID-19 within 7 days before the start of study drug administration.
(3) Subjects without symptoms due to COVID-19 (upper respiratory tract inflammation such as fever and cough)
(4) Subjects whose infection episode is recurrence or reinfection of SARS-CoV-2
(5)Subjects who cannot interrupt the administration of prohibited drugs specified in the clinical trial protocol during the study period
(6)Subjects with SpO2 less than 96% without oxygen therapy
(7) Subjects with serious or uncontrolled underlying disease, e.g. chronic obstructive pulmonary disease, chronic kidney disease, hepatic dysfunction, diabetes mellitus, hypertension, cardiovascular disease, malignant tumor, body mass index; BMI 30 or higher obesity (not excluded if the disease are mild and controlled)
(8) Subjects with impaired consciousness such as the disorientation
(9) Subjects with hypersensitivity to Ephedra Herb or Kampo medicines containing Ephedra Herb
(10)Pregnant women, subjects who are breastfeeding or may be pregnant
(11) In the case the subject is women who can pregnant, whose pregnancy test is positive For both men and women, subjects who do not agree to perform contraception during the clinical trial.
(12) Subjects with pacemakers
(13) Subjects who have cohabitant participating or have participated in this clinical trial.
(14) Subjects who judged by the investigators to be ineligible