Product description

The name of the medicine is Pinen Hydronoplacton Ribonucleic acid 160 (abbreviated as PHR 160), which is designed and produced as a metered-dose inhaler (MDI).

Indication

PHR metered-dose inhaler 160 is indicated for the improvement of serious lung disease caused by COVID-19.

The recommended dose

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is:

- Adults and children 12 years and over,

1) Mild symptoms, five doses per day, one dose every two hours during a continuous period of time.

2) Severe symptoms, ten doses per day, one dose every hour during a continuous period of time.

- Children 5 to 11 years, five doses per day, one dose every two hours during a continuous period of time.

- Children under the age of 5 years, use and dosage of the medicine should be done only with a doctor's opinion.

An adult should always supervise children when they use PHR inhaler spray. Children may need help to use their inhaler. Parents can help by spraying the aerosol when the child begins to breathe in.

The time of re-use of the medicine is based on theoretical calculations which these calculations are related to formation rate of respiratory mucous glycoproteins and during the patient's waking hours, about one hour is provided to reach the maximum dose.

Pharmacokinetics and clearance

The medicine is absorbed slowly to bronchial smooth muscle by inhalation and a small fraction which is swallowed enters the gastrointestinal tract. The systemic levels of medicine are low after inhalation of recommended doses and the drug is undetectable in the blood and acts topically on bronchial smooth muscle.

The efficacy of the medicine begins after 5 to 15 minutes and reaches a maximum efficacy about 30 minutes after a deep inhalation. The duration of efficacy of the drug is one hour.

Route of elimination

The drug is metabolized in the liver and is ultimately excreted in the urine or feces.

Mechanism of action

CFTR (cystic fibrosis transmembrane conductance regulator), placed on the apical side of the non-ciliated epithelial cells, plays an important role in the transport of chloride ions. In addition to ion transport, it is also responsible for regulating the expression and activity of other membrane transporters, including ENaC (epithelial sodium channel), affecting ATP transport and acting on mucus secretion. CFTR protein processing defect is complicated and affects the activity of all cells in the respiratory tract. CFTR plays a regulatory function in epithelium in the mechanism of nucleotide signaling, especially changes in siRNA quality and quantity. CFTR is permeable to Cl^- and HCO₃^- ions.

In normal airway epithelia, CFTR-mediated Cl^- secretion and ENaC mediated Na⁺ absorption are coordinated to maintain ASL (airway surface layer) at a depth that allows cilia to beat effectively and move the mucus blanket across the surface of the epithelium. The absence of CFTR protein and/or function in CF airway epithelium produces two defects in this process. First, the reduced permeability of CF epithelia to Cl^- results in reduced Cl^- secretion and hence less mass of salt on the apical surface. The result is a reduced driving force for water to enter the lumen. Secondly in the absence of CFTR, ENaC activity is unchecked, resulting in an unregulated and inappropriate absorption of salt from ASL. The overlying mucus blanket, consequently, becomes dehydrated and compresses the cilia, resulting in the arrest of MCC (mucociliary clearance).

In fatal cases of COVID-19, similar to pulmonary fibrosis is generally present at autopsy. In these fatal cases, appear to have occurred a failure in CFTR functions or mucociliary clearance system.

PHR 160 inhaler spray supports and improves to CFTR functions and mucociliary clearance system in patients and increases the patient's sputum and peripheral capillary oxygen saturation (SPO₂).

Adverse effects

Currently, the based on reports, have not been observed side effects before and after use the medicine. If patients get any side effects, should stop taking medication and consult with a physician as soon as possible. However, studies and discussions still continue.

Drug interactions

According to available data and studies that have been done, drug interactions about PHR 160 inhaler spray not reported. Of course, research is ongoing.

Toxicity

The concentration of active pharmaceutical ingredients in medicine is low. In any dose about 300 mcg reaches to the patient, which is very low. This amount is less than LD₅₀ considered for each of the APIs and excipients. However, in children under the age of 5 years and pregnant women should be used with caution and the doctor's opinion. Of course, studies and discussions are ongoing.

Clinical studies

In this section we are considering a clinical assessment of the effect of PHR 160 inhaler spray in pulmonary problems of the patients with COVID-19.

Clinical trials design

This method is cluster randomization. First, two inpatient wards are selected with similar conditions. Secondly, two clusters are randomly assigned to the intervention group and the control group. This study has no concealment and patients in the intervention group will receive the intervention medicine, in addition to the routine treatment, but in the control group, they will only receive the routine treatment.

Intervention group uses the PHR 160 inhaler spray medicine, in addition to the routine standard treatment for COVID-19.

Control group only uses routine standard treatment for COVID-19.

Standard treatment is according to the IRAN's health ministry protocol for COVID-19.

Evaluation of peripheral capillary oxygen saturation (SPO₂) in patients

Using pulse oximeter, SPO₂ in patients was measured. The results of the initial (zero day) up to fourth days in both groups have been shown in the tables and diagram as follows;

 

 

As is clear, after using the PHR 160 inhaler spray in the intervention group during the specified period about 5.14 units SPO₂ have increased in patients (p<0.001) and a raise of 0.59 units every day.

Comparison of chest computed tomography (CT) scan in patients

CT scans help determine how much the lungs are affected by COVID-19.

In patients of intervention group which used the PHR 160 inhaler spray were detected an improvement of lung complications during the specified period.

Hospitalization time after use of PHR 160 inhaler spray

The mean length of time the patients were hospitalized after the diagnosis of COVID-19 in intervention group less than control group were observed.

 

 

Comparison the cough and shortness of breath

Shortness of breath measured by Visual analog scale (VAS) dyspnea score. The minimum score is zero means shortness of breath and the highest score is 10 means the maximum intensity of shortness of breath.

Checkup of patients during the specified period showed that the mean score of shortness of breath and cough in the intervention group was less than the control group.

Assessment of body temperature, blood pressure, heartbeat, blood platelets, White blood cell (WBC), Erythrocyte sedimentation rate (ESR) and C-reactive protein (CPR)

Comparison of seven parameters specified in both groups of patients was made and results showed that there is no significant difference between the mean results of each parameter in two groups.

Clinical conclusion

Clinical trials of inpatients of positive diagnosis the COVID-19 were performed. The results of intervention and control groups were compared. Increased of SPO₂ and decreased of the cough and shortness of breath in the intervention group was observed. The clinical results have established that PHR 160 inhaler spray will be useful for patients with COVID-19.