Formulations decreasing particle exhalation

Abstract

Formulations have been developed for pulmonary delivery to treat or reduce the infectivity of diseases such as viral infections, especially tuberculosis, SARS, influenza and respiratory synticial virus in humans and hoof and mouth disease in animals, or to reduce the symptoms of allergy or other pulmonary disease. Formulations for pulmonary administration include a material that significantly alters physical properties such as surface tension and surface elasticity of lung mucus lining fluid, which may be isotonic saline and, optionally, a carrier. The formulation may be administered as a liquid solution, suspension, aerosol, or powder where the particles consist basically of an osmotically active solute. Drugs, especially antivirals or antibiotics, may optionally be included with the formulation. These may be administered with or incorporated into the formulation.

1 . A biocompatible non-surfactant formulation that when administered to a human or other animal, dilutes endogenous surfactant fluid, to alter surface tension, surface elasticity, or bulk viscosity, thereby decreasing aerosol exhalation.  
     
     
         2 . The formulation of  claim 1  selected from the group consisting of aqueous solutions, dry powders, vapors, aqueous suspensions, non-toxic organic solutions or suspensions, and solid dosage form other than dry powder.  
     
     
         3 . The formulation of  claim 1  formulated for administration to a region selected from the group consisting of the respiratory tract, the gastrointestinal tract, and the oropharynx or nasal cavities.  
     
     
         4 . The formulation of  claim 1  comprising an effective amount of a compound selected from the group consisting of salts and sugars to decrease aerosol exhalation.  
     
     
         5 . The formulation of  claim 1  further comprising an agent selected from the group consisting of surfactants and phospholipids.  
     
     
         6 . The formulation of  claim 1  comprising an active agent selected from the group consisting of nucleic acids, proteins, carbohydrates, synthetic polymers, amino acids, inorganic substances, and organic substances.  
     
     
         7 . The formulation of  claim 6  wherein the concentration of the active agent ranges from about 0.01% to about 20% by weight.  
     
     
         8 . The formulation of  claim 7  wherein the concentration of active agent ranges from between 0.9% to about 10%.  
     
     
         9 . The formulation of  claim 1  in a form selected from the group consisting of particles dispersed or in an inert substrate, droplets dispersed on or in an inert substrate, vapor dispersed on or in an inert substrate, and mist dispersed on or in an inert substrate.  
     
     
         10 . The formulation of  claim 6  wherein the active agent is selected from the group consisting of antivirals, antibiotics, bronchodilators, antihistamines, cough suppressants, anti-inflammatories, expectorants, and vaccines.  
     
     
         11 . The formulation of  claim 1  in an effective amount to limit infectivity of an infectious agent.  
     
     
         12 . The formulation of  claim 1  wherein the formulation is saline.  
     
     
         13 . The formulation of  claim 1  wherein the formulation comprises an aqueous solution delivered as an aerosol with particles having a diameter between about 0.1 and about 30 microns, most preferably between about 1 and about 10 microns.  
     
     
         14 . The formulation of  claim 1  wherein the formulation is delivered in an effective duration to suppress exhaled bioaerosol formation between 0 and 20 minutes, most preferably between 0-3 minutes.  
     
     
         15 . The formulation of  claim 1  in a device selected from the group consisting of a metered dose inhaler including HFA propellant, a metered dose inhaler with non-HFA propellant, a nebulizer, a pressurized can, and a continuous sprayer.  
     
     
         16 . The formulation of  claim 1  wherein the formulation consists of a dry powder of mass median aerodynamic diameter of less than about 10 microns.  
     
     
         17 . The formulation of  claim 1  comprising a powder selected from the group consisting of isotonic dry powder, a hypertonic dry powder, a hyptonic dry powder, a dry powder including osmotically active excipient, a dry powder of an excipient that changes surface tension, a dry powder of an excipient that changes viscosity, a dry powder of an excipient that changes surface pressure, or a dry powder of an excipient that changes surface energy.  
     
     
         18 . The formulation of  claim 1  wherein the formulation is in a device selected from the group consisting of a single-dose dry powder inhaler and multi-dose dry powder inhaler.  
     
     
         19 . The formulation of  claim 1  wherein the formulation is in a vaporizer or a vapor inhaler or a device selected from the group consisting of a metered dose inhaler including HFA propellant, a metered dose inhaler with non-HFA propellant, a nebulizer, a pressurized can, and a continuous sprayer and is selected from the group consisting of a vapor including osmotically active excipient, a vapor that changes surface tension, a vapor that changes viscosity, a vapor that changes surface pressure, and a vapor that changes surface energy.  
     
     
         20 . The formulation of  claim 1  comprising a suspension selected from the group comprising an isotonic suspension, a hypertonic suspension, a hypotonic suspension, an aqueous suspension including osmotically active excipient, an aqueous suspension of an excipient that changes surface tension, an aqueous suspension of an excipient that changes surface pressure and aqueous suspension of an excipient that changes surface energy, wherein the formulation is delivered as an aerosol with particles having a diameter between approximately 0.1 and 30 microns, most preferable between approximately 1 and 10 microns in a device selected from the group consisting of metered dose inhaler including HFA propellant, a metered dose inhaler with non-HFA propellant, a nebulizer, a pressurized can, and a continuous sprayer.  
     
     
         21 . The formulation of  claim 1  comprising a solution or suspension selected from the group consisting of a non-toxic organic solution or suspension including an osmotically active excipient, a non-toxic organic solution or suspension of an excipient that changes surface tension, a non-toxic organic solution or suspension of an excipient that changes viscosity, a non-toxic organic solution or suspension of an excipient that changes surface pressure, a non-toxic organic solution or suspension of an excipient that changes surface energy, and non-toxic organic solution or suspension delivered as an aerosol in a device selected from the group consisting of metered dose inhaler including HFA propellant, a metered dose inhaler with non-HFA propellant, a nebulizer, a pressurized can, and a continuous sprayer with particles having a diameter most preferably between approximately 1 and 10 microns.  
     
     
         22 . An inert substrate comprising an effective amount of a particulate composition for administration to the nose or mouth to dilute endogenous surfactant fluid, to alter surface tension, surface elasticity, or bulk viscosity, thereby decreasing aerosol exhalation.  
     
     
         23 . The substrate of  claim 22  wherein the composition comprises a material selected from the group consisting of salts, sugars and other osmotically active materials.  
     
     
         24 . The substrate of  claim 23  wherein the concentration of composition on or in the substrate ranges from about 0.01% to about 20% by weight, preferably between 0.9% to about 10%.  
     
     
         25 . The substrate of  claim 22  wherein the substrate comprises a biodegradable or disposable woven or non-woven fabric.  
     
     
         26 . The substrate of  claim 25  wherein the fabric is formed of a cellulose type material  
     
     
         27 . The substrate of  claim 22  further comprising at least one bioactive compound.  
     
     
         28 . The substrate of  claim 27  wherein the bioactive agent is selected from the group consisting of an antiviral, an antibiotic, a bronchodilator, a steroid, and a vaccine.  
     
     
         29 . The substrate of  claim 22  further comprising a lotion or lubricant for application to the skin.  
     
     
         30 . The substrate of  claim 22  comprising particulate surfactant in an effective amount to limit infectivity of an infectious agent.  
     
     
         31 . A method of decreasing exhalation of particles in an individual having a respiratory disease comprising administering to the individual an effective amount of a biocompatible non-surfactant formulation that dilutes endogenous surfactant fluid, to alter surface tension, surface elasticity, or bulk viscosity, thereby decreasing aerosol exhalation.  
     
     
         32 . The method of  claim 31  wherein the respiratory disease is an infection with an agent selected from the group consisting of the agents causing tuberculosis, SARS, influenza, cytomegalovirus, respiratory syncytial virus, African swine fever, coronavirus, rhinovirus, tularemia, bubonic plague, anthrax, and foot and mouth disease.  
     
     
         33 . The method of  claim 13  wherein the respiratory disease is selected from the group consisting of allergy, asthma, cystic fibrosis, chronic bronchitis, emphysema, and acute respiratory distress syndrome.  
     
     
         34 . The method of  claim 31  wherein the formulation alters physical properties selected from the group consisting of the surface tension of respiratory tract lining fluid, the viscosity of the respiratory tract lining fluid, the surface elasticity of the respiratory tract lining fluid, the surface pressure of the respiratory tract lining fluid, the surface energy of the respiratory tract lining fluid, the osmolarity of the respiratory tract lining fluid, the osmotic activity of respiratory tract cell types, the production of airway lining fluid, transport of bioaerosols within an individual from sites of upper airway deposition to lung parenchyma.  
     
     
         35 . The method of  claim 31  where the formulation creates a coating on the respiratory tract lining fluid.  
     
     
         36 . The method of  claim 31  wherein the formulation is applied as a solution or suspension parenterally, orally, rectally, vaginally, topically, or by and inhalation.  
     
     
         37 . The method of  claim 36  wherein the solution or suspension is administered to the ocular space.  
     
     
         38 . The method of  claim 33  wherein the formulation is administered in a building, tent, or other facility.  
     
     
         39 . A method for the diagnosis of animals or humans who have an enhanced propensity to exhale aerosols comprising screening for at least one characteristic selected from the group consisting of the measurement of expired air and inspired air, assessment of exhaled particle numbers, assessment of exhaled particle size, assessment of tidal volume and respiratory frequency during sampling.  
     
     
         40 . The method of  claim 39  comprising assessing exhaled particle numbers at a respiratory flow rate of about 10 to about 120 LPM.  
     
     
         41 . The method of  claim 39  comprising assessment of infectivity of exhaled aerosol.  
     
     
         42 . The method of  claim 39  comprising measuring bacterial or viral infectivity.  
     
     
         43 . A device for the measurement of exhaled particle number and particle size according to the method of  claim 39.