[公告] : 有關民眾對臺灣清冠一號（NRICM101）的疑問說明(FAQs on NRICM101)

有關民眾對臺灣清冠一號（NRICM101）的疑問說明： (FAQs on NRICM101)

一、什麼是《新型冠狀病毒病(COVID-19)中醫臨床分期治療指引》

說明：

  1. 《新型冠狀病毒病中醫臨床分期治療指引》(簡稱《臨床指引》)是由衛生福利部國家中醫藥研究所蘇奕彰所長於2020年1月31日研擬完成分期治療草案，並於2020年3月31日定稿供三軍總醫院中醫部、台中榮總傳統醫學科及其他教學醫院進行「中醫會診治療COVID-19患者」之依據。
  2. 本指引乃針對西醫隔離病房收治 COVID-19患者，採用「中西合作照護、中醫會診」模式。臨床實務上，醫師穿戴隔離衣及手套無法操作脈診，重症患者進行插管亦無法操作舌診。因此，為控管感染及防疫醫療物資消耗，並加速診療效率，中醫臨床上不對患者進行接觸診察，只要確定西醫臨床分期資訊及臨床醫護紀錄資料，並透過視訊進行確認後即可開立治療處方。此外針對具高風險因子患者（心腦血管疾病、肺病、糖尿病、肥胖等），臨床上為截斷病勢，醫師得超前用藥（使用更嚴重分期用方）。
  3. 由於兩個醫學中心依照《臨床指引》治療COVID-19危重症、重症、輕症患者臨床成效顯著，為了預防疫情擴散的需要，衛生福利部中醫藥司於2020年5月6日召開專家會議通過該《臨床指引》做為教學醫院中醫會診治療COVID-19患者之臨床依據；6月1日國家中醫藥所上網公告，以提供全球中醫治療COVID-19患者之參考。

1、What are the Traditional Chinese Medicine Treatment Guidelines for COVID-19 in Traditional Chinese Medicine?

  1. The Traditional Chinese Medicine Treatment Guidelines for COVID-19 (TCMTG) were developed based on research by the National Research Institute of Chinese Medicine (NRICM) led by Director Yi-Chang Su on January 31, 2020 and finalized on March 31, 2020. These guidelines serve as the basis for Chinese medicine treatment for COVID-19 at the Tri-Service General Hospital, Taichung Veterans General Hospital, and other teaching hospitals in Taiwan.
  2. These guidelines are designed for patients in isolation wards, using both Western and traditional Chinese medicine (TCM) approaches. In clinical practice, because physicians wear protective clothing and gloves, they have difficulty performing pulse diagnoses and tongue diagnoses for patients undergoing fluids transfusions or tracheal intubation. TCM physicians are not required to have direct physical contact in order to prevent infection, limit the consumption of medical supplies, and accelerate treatment. After a western medicine physician confirms clinical staging information, a TCM physician can prescribe treatment after assessing the condition through video communications and clinical data. In addition, for patients with high risk factors (cardiovascular diseases, pulmonary diseases, diabetes, obesity, etc.), the TCM physician may prescribe advanced medication (using the prescriptions for the next stage) in order to halt the progression of disease.
  3. Given the significant clinical outcomes seen in COVID-19 patients treated with TCMTG at the two medical centers, the Tri-Service General Hospital and Taichung Veterans General Hospital, the Department of Chinese Medicine and Pharmacy, Ministry of Health and Welfare adopted these guidelines on May 6, 2020 to serve as the basis for Chinese medicine treatment for COVID-19 in medical centers. On June 1, 2020, the NRICM released “Traditional Chinese Medicine Treatment Guidelines for COVID-19” online for global TCM physicians to follow.

二、什麼是「臺灣清冠一號；NRICM101」？

說明：

  1. 2020年4月3日三軍總醫院中醫部與感染科合作建立「COVID-19患者中西醫共治模式」，開始為加護病房危重症、重症病患進行診治，因治療成效顯著，隨即擴及輕症患者，隨後台中榮民總醫院、高雄長庚紀念醫院陸續加入中醫會診治療。患者在中藥標準方介入後，發燒症狀緩解，心跳、血壓及生理徵象明顯穩定，平均中位數9天即能獲得三採陰性檢驗結果，且無任何副作用或中西藥交互作用。
  2. 因為醫學中心中藥局調製之中藥水煎劑無法因應大量病患，為了能迅速、大量提供品質穩定之標準化治療藥物，國家中醫藥研究所於2020年4月20日選擇《臨床指引》中以「抗病毒」與「免疫調節」藥物組成為主的「輕症方」作為治療患者之核心標準方劑（國家中醫藥研究所命名為「臺灣清冠一號；NRICM101」），並著手探討這個中藥標準複方水煎劑的作用機轉及處方組成化合物，以便作為製劑品質控制之基礎。
  3. 經過一系列生物分子及細胞層次的研究，以及P3實驗室直接針對 SARS-CoV-2的細胞感染研究，證實複方臺灣清冠一號具有多靶點的作用機轉，包括：
    1. 抑制新冠病毒棘蛋白(Spike Protein)與宿主細胞膜上ACE2的結合，阻止病毒入侵細胞。
    2. 抑制3CL蛋白酶的活性，阻斷病毒在細胞內的複製。
    3. 抑制肺泡巨噬細胞分泌的細胞激素TNF-α、IL-6，來調控所產生的發炎風暴，減少肺部的破壞及降低肺纖維化的發展。
  4. 為了能夠對臺灣社會及國際疫情有所幫助，國家中醫藥研究所已為「臺灣清冠一號」申請相關商標及專利，並採用「非專屬授權」來擴大組成「中醫藥國家隊」，目前已有八家GMP中藥廠取得授權(順天堂藥廠、莊松榮製藥廠、勸奉堂製藥、立康生物、天一藥廠、漢聖製藥、勝昌製藥及華陀扶元堂)，其中四間藥廠製劑產品已經通過衛生福利部外銷專用藥品許可證審查，並進行量產與出口來協助疫情嚴峻之國家（包括歐、美、亞、非洲及澳洲）。

2、What is NRICM101?

  1. The Tri-Service General Hospital’s TCM and Infectious Disease departments collaborated to develop the "Chinese and Western Medicine Co-Treatment Model for COVID-19 Patients" on April 3, 2020, which was initially used to treat critically ill patients in the intensive care unit (ICU). Its use was immediately extended to less severely ill patients due to the treatment’s success. Soon after, the Taichung Veterans General Hospital and Kaohsiung Chang-Geng Memorial Hospital, also adopted the model. COVID-19 patients who were treated with standardized traditional Chinese medicine prescriptions experienced alleviated fever symptoms and stabilized heartbeat, blood pressure, and physiological symptoms. Patients were able to achieve 3 consecutive negative test results within a median of 9 days while experiencing no side effects or drug-drug interactions between Chinese and Western medications.
  2. Typically, medical centers’ TCM pharmacies do not prepare decoctions for patients at a large scale. To provide high quality, standardized therapeutics rapidly, the National Research Institute of Chinese Medicine (NRICM) began a study on April 20, 2020 and coined NRICM101, the standardized TCM decoction for mild cases from TCMTG using antiviral and immunomodulatory herbs. The study evaluated NRICM101’s mechanism of action and composition to serve as a basis for quality control.
  3. After a series of molecular and cellular level studies, as well as investigation of SARS-CoV-2’s direct cellular infection in a P3 laboratory, the compound has been shown to have a multi-targeted mechanism of action, including:

a. Inhibiting the binding between SARS-COV-2’s spike proteins and ACE2 of host cell membranes, preventing the virus from invading cells. This works as a "vaccine-like effect".

b. Inhibiting the activity of 3CL protease, blocking viral replication in cells.

c. Inhibiting the cytokines TNF-α and IL-6 to regulate inflammatory cytokine storms in order to reduce lung damage and the risk of developing pulmonary fibrosis.

  1. To help combat the pandemic both in Taiwan and globally, the NRICM has submitted patent and trademark applications for NRICM101 and adopted a non-exclusive license to expand the medication’s supply chain. Thus far, 8 GMP-certified pharmaceutical companies have obtained the manufacturing license, and 4 of these companies have obtained the Ministry of Health and Welfare’s authorization to export to other countries in Europe, America, Africa and Asia Pacific severely affected by the pandemic.

三、依照《臨床指引》中「輕症方」組成，自行取得藥材煎煮服用與使用授權藥廠生產「臺灣清冠一號；NRICM101」製劑之差別？

說明：

  1. 《臨床指引》中提供分期治療處方，使用劑型包括傳統複方飲片以及濃縮中藥粉劑，並提供處方之藥材名稱及劑量，中醫師可依照臨床患者表現及各教學醫院中藥局備用之中藥品質進行劑量調整，由於處方後之調劑與製劑均由教學醫院中藥局具中藥專業藥師為之，並可依照患者服用結果與中醫師進行討論與修正劑量。
  2. 由於中藥材品質管理屬於高度專業內涵，各醫療院所、中藥房準備的藥材飲片粗細規格差異會影響製劑（煎煮）時有效成分萃取之濃度，進而影響臨床治療效果。因此為了能夠快速治療感染患者，達到控制疫情目標，該《臨床指引》設定為在「收治COVID-19患者，並設有中醫科部之教學醫院」之中醫師處方使用。至於在國外疫情嚴重國家，沒有專業中醫師協助下，民眾自行購買中藥材煎煮，雖然可能因為藥材品質問題而無法達到臨床預期的治療效益，卻也是不得已的應急方式。
  3. 為了使「臺灣清冠一號；NRICM101」能達到臨床治療COVID-19的足夠效價，國家中醫藥研究所研究人員以兩間醫學中心調劑之樣品為基礎，依照「抗病毒」與「免疫調節」試驗結果重新調整複方中藥物的劑量，最後得到了最佳的「抗病毒」與「免疫調節」作用之生物活性結果，以及複方HPLC（高效能液相層析儀）分析的「指紋圖譜」，以作為授權藥廠產品品質確認之標準。
  4. 每一家授權藥廠除了藥廠本身之製劑品管外，其製劑產品皆須通過國家中醫藥所對其產品進行HPLC分析的「指紋圖譜」，以及「抗病毒」與「免疫調節」作用之生物活性多重試驗，才會提供證明文件向衛生福利部送審外銷專用藥品許可證，以確保外銷國際之「臺灣清冠一號；NRICM101」具有穩定可靠之製劑品質，可以提供疫情嚴重國家大量與快速使用。
  5. 那麼有需要再調整《臨床指引》中「輕症方」之組成劑量嗎？本所認為不需要。原因在於《臨床指引》中所列各分期處方之組成劑量，乃根據中醫典籍中藥常用劑量，參考教學醫院採購臺灣市場中等品質中藥材為基準所提供之建議劑量，因為實務上各教學醫院中藥局不可能做到採用「相同品質」中藥材，所以還是相信專業能力，交由各醫院中醫師及藥師依照各院藥材品質自行調整劑量。

3、What is the difference between preparing a decoction using herbs from the local TCM pharmacy in accordance with the guidelines’ “mild case prescription” vs. NRICM101’s standardized decoction?

  1. The guidelines detail prescriptions based on different stages of disease. The prescriptions include both traditional decoctions and herbal powder along with the details of individual ingredients and dosage. TCM physicians can adjust the prescription or dosage based on an individual patient’s condition. Follow-up sessions with the TCM physician can inform further adjustments in the prescription based on patient progress.
  2. The quality of TCM ingredients from different sources and processing methods may not always be consistent, as different processing methods may yield differences in the extraction of active ingredients, thereby affecting clinical efficacy. In order to rapidly treat affected patients and achieve desired outcomes, the guidelines were designed to be used by TCM physicians at medical centers with specialized TCM departments which can ensure the quality of the prescriptions. Self-preparing decoctions without a TCM physician’s guidance may not achieve desired clinical efficacy, but it may serve as a last resort for those who are affected by COVID-19 and lack easy access to TCM physicians.
  3. To ensure high quality and potency for NRICM101’s standardized decoction, researchers from the NRICM analyzed samples of the decoction at two medical centers, adjusted the amount of each TCM ingredient in the prescription to achieve optimal antiviral and immunomodulatory bioactivities, and obtained the high-performance liquid chromatography (HPLC) fingerprint of the optimized decoction. 
  4. In addition to achieving consistency, licensed manufacturers were required by the NRICM to match the HPLC fingerprint and demonstrate the necessary antiviral and immunomodulatory bioactivities prior to obtaining the Ministry of Health and Welfare’s authorization. This ensures that NRICM101 marketed overseas are of high-quality and can be rapidly distributed to countries severely impacted by COVID-19.
  5. Is it necessary to adjust the “mild case prescription” from the Guidelines for different patients? We don’t think it’s necessary. The dosages outlined by the guidelines have been developed based on TCM classic works and on the average quality of TCM herbs available in Taiwan’s market. As TCM herbs acquired by different medical centers may not always be of the same quality, it should be left to the discretion of the TCM physicians and pharmacists to modify the prescription as needed.