SP-303 SMALL-PARTICLE AEROSOL TREATMENT OF INFLUENZA-A VIRUS-INFECTION IN MICE AND RESPIRATORY SYNCYTIAL VIRUS-INFECTION IN COTTON RATS

A natural plant product, SP-303, was administered by small-particle aerosol to influenza A/HK virus-infected mice and RSV-infected cotton rats. Aqueous SP-303 at 2 mg/ml in the Collison nebulizer reservoir generated an aerosol with an output of 26 mug/l and a particle size distribution of 1.4 mum +/- 4.6 (MMAD +/- GSD). SP-303 at a dosage of 0.5-9.4 mg/kg per day administered for 3-4 days significantly increased both the rate and duration of survival of mice lethally infected with influenza A/HK virus. SP-303 was toxic to mice at 16 mg/kg per day as indicated by weight loss and a decrease in the duration of survival compared to control animals. From these data, a maximum therapeutic index (T.I.) of 12 was calculated. SP-303 given 3-4 days at dosages of 1.3 9.8 mg/kg per day was effective in reducing the pulmonary titer of RSV in infected cotton rats. However, at the 18.7 mg/kg per day dose a significant weight loss compared to control animals was observed; a T.I. of less-than-or-equal-to 14 was estimated. These experiments demonstrate that aerosol administration of SP-303 was effective in the treatment of influenza A-infected mice and of RSV-infected cotton rats.