In the successive editions of the "New Coronary Virus Pneumonia Diagnosis and Treatment Program" issued by the National Health and Health Commission, it was mentioned that "a-interferon aerosolized inhalation (5 million U or equivalent doses for adults each time, adding sterile water for injection) 2mL, aerosolized 2 times a day) ".

The alpha-interferon currently on the market in China has the characteristics of multiple varieties and multiple dosage forms. How to safely and reasonably perform α-interferon nebulization treatment is a problem that doctors and pharmacists should pay special attention to.

Interferon (IFN) is a virus or other factor that stimulates vertebrate tissue cells (in vitro or in vivo) to produce a special protein that can interfere with the proliferation of the virus. It is a broad-spectrum antiviral agent and does not directly kill or inhibit the virus.

Interferons are mainly divided into three categories based on their sources:

1. Alpha-interferon (IFNα)-derived from white blood cells.

2, β-interferon (IFNβ)-derived from fibroblasts.

3. γ-interferon (IFNγ)-derived from immune cells.

α-interferon can increase the expression level of major histocompatibility complex (MHC) I antigen, increase the presentation of viral antigens on the surface of infected cells, and promote the recognition of infected cells by the immune system of the body; it also acts on interferon Receptors activate target cells to express protein kinases and 2 ', 5' oligoadenylate synthase and other antiviral proteins, and inhibit viral replication. There are more than 20 subtypes of α-interferon. Currently, α-2a interferon and α-2b interferon are commonly used in clinical practice.

Dosage selection

Coronal virus SARS-CoV-2 infection issued by the Chinese Pharmaceutical Association: Expert Consensus on Guidance and Prevention and Control Strategies for Hospital Pharmaceutical Work (Second Edition), which lists a reference list of key therapeutic drugs for new coronavirus infection, covering China's clinical The commonly used dosage forms and specifications of α-interferon include recombinant human interferon α-2a injection, recombinant human interferon α-2a for injection, recombinant human interferon α-2b injection, and recombinant human interferon α-2b. Injection (pseudo-single cell), recombinant human interferon α-2b for injection, recombinant human interferon α-2b for injection (false single cell), and the like.

Some domestic alpha-interferon injections contain preservatives, such as methyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl alcohol, m-xylenol, etc., which can induce asthma attacks after inhalation, and should not be used in mist Chemical treatment.

Therefore, the use of alpha-interferon injection containing preservatives should be avoided when inhaling alpha-interferon to reduce the damage and inflammation of the respiratory mucosa.

Drug delivery device selection

At present, there are three kinds of atomization drug delivery devices commonly used in clinic: ultrasonic atomizers, air compression atomizers (jet atomizers), and vibrating screen atomizers. Alpha-interferon is a genetically recombinant protein, and most of the excipients of the dosage form contain albumin, which may be deformed when exposed to heat. The "Expert Consensus on the Rational Use of Nebulizing Inhalation Therapy (2019 Edition)" formulated by the relevant experts organized by the Chinese Medical Association's Clinical Pharmacy Branch pointed out that the ultrasonic nebulizer will affect the suspension release ratio of the suspension when it is working, which can make the liquid in the container Temperature rise affects the stability of protein or peptide compounds.

Air compression atomizer, also known as jet atomizer, its working mechanism is based on the Venturi spray principle, using compressed air to form a high-speed air flow through a small nozzle, generating negative pressure to drive liquid or other fluids to spray together to block On the object, it splashes around under high-speed impact, so that the liquid droplets become mist-like particles and are ejected from the outlet pipe.

Vibrating sieve atomizer is a device that generates medicine mist by passing high-frequency vibration of piezoelectric ceramics through small sieve holes, which can reduce the influence of ultrasonic vibration liquid heat generation on medicine. Both the air compression atomizer and the vibrating screen atomizer can meet the atomization requirements of protein drugs.

Therefore, for the administration of α-interferon atomization, it is recommended to choose an air compression atomizer and a vibrating screen atomizer. Ultrasonic atomization is not recommended.

Dosage

The "Diagnosis and Treatment of New Coronavirus Pneumonia (Trial Version 7)" stipulates the usage and dosage of α-interferon: "5 million U or equivalent per adult, add 2 mL of sterilized water for injection, and inhale 2 times a day" .

At present, the treatment of adult radon-interferon nebulization has not been reported in the literature and needs to be determined by evaluating the clinical efficacy. In terms of medication for children, the "Guidelines for the Diagnosis and Treatment of Coronavirus Disease (COVID-19) 2019 (Second Edition) for Children Coronavirus (COVID-19)" issued by the National Children's Health and Disease Clinical Medicine Research Center, National Children's Regional Medical Center, and Children's Hospital Affiliated to Zhejiang University Children are recommended to try ɑ-interferon nebulized inhalation, such as nebulized inhaled interferon α-2b injection: ordinary type 100,000 ~ 200,000 IU / kg each time, heavy type 200,000 ~ 400,000 IU / kg each time, 2 daily Second, the course of treatment is 5-7 days.

Influenza-like syndrome: clinical manifestations include fever, chills, headache, muscle soreness, and fatigue, with occasional nausea and vomiting and other digestive symptoms.

Myelosuppression: It usually occurs after 2 weeks to 2 months of medication, and it displays peripheral blood leukocytes (neutrophils) and thrombocytopenia, and hemoglobin decreases.

Mental abnormalities: Rarely, manifested as mental symptoms such as depression, paranoia, and severe anxiety.

Other adverse reactions: kidney damage, arrhythmia, retinopathy, etc.

Patients who are allergic to interferon and excipients, those who are pregnant or have a pregnancy plan in the short term, have a history of mental illness, uncontrolled epilepsy, decompensated liver cirrhosis, severe renal failure, uncontrolled autoimmune disease, severe infection , Retinal disease, heart failure, chronic obstructive pulmonary disease and other patients are disabled.

Patients with a history of allergies should closely monitor allergic reactions when first using alpha-interferon. Care should be taken to avoid contact with the eyes during atomization.

During storage and transportation, it should be stored at 2-8 ° C in the dark, and it should not be frozen.

The multiple editions of the "New Coronary Virus Pneumonia Diagnosis and Treatment Program" issued by the National Health and Health Commission all mention that alpha-interferon (IFNα) atomization inhalation can be tried. In fact, IFNα does not directly kill the virus. Under natural circumstances, IFNα is a very important immunoprotective cytokine for humans to respond to viral infections. It can induce the same type of cells to produce antiviral proteins, form an antiviral state, and limit further virus replication and spread. Mechanistically, interferon can strengthen different links of the innate and adaptive immune systems, thereby playing a role in actively removing pathogenic bacteria. However, the clinical efficacy of IFNα depends on the dosage, route of administration, and course of prevention. There are still many details to be clarified.

Nebulized IFNα drugs are mainly distributed in the respiratory tract. Some research results show that the biological activity retention rate of inhaled IFNα-1b and IFNα-2b is about 96%. After 2 hours (h), the distribution of IFN in the lung tissue will gradually increase, and the content in the lung tissue will gradually increase and maintain. At a higher concentration of about 12 hours, IFNα is basically catabolized in the lungs. Therefore, aerosolized inhaled IFNα can reach the lungs and exert biological effects. Compared with other modes of administration, nebulized IFNα is safer and the incidence of adverse reactions is lower.

Since there is no aerosolized IFNα preparation for inhalation in China, the injection form is used as a nebulized preparation in clinical practice, which belongs to a drug beyond the instruction manual, and there is a certain safety hazard. In the absence of other alternative medicines, the use of IFNα should follow the rules and procedures for medication beyond the instructions, and priority is given to the use of preservative-free injections for atomized inhalation.

Note: Eye drops, nasal drops, aerosols, sprays and long-acting IFN for injection cannot be inhaled.

Jointly released by Science and Technology Development Center of Chinese Pharmaceutical Association and Science Division of Guangming.com