Method, composition, and system to control pH in pulmonary tissue of a subject

• US 20100078014A1
• Filed: 01/08/2009
• Published: 04/01/2010
• Est. Priority Date: 09/30/2008
• Status: Active Grant

• Current Assignee: Enterprise Science Fund, LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC A Limited Liability Corporation of The State of Delaware
• Inventors: Ishikawa, Muriel Y., Wood, Lowell L. JR., Rivet, Dennis J., Hyde, Roderick A., Kare, Jordin T., Wood, Victoria Y.H.
• Granted Patent: US 8,584,670 B2
• Time in Patent Office: Days
• US Class Current: 128/200.230
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 15/0003 with means for dispensing more than one drug
• CPC Class Codes: A61M 15/02 with activated or ionised fluids, e.g. electrohydrodynamic [EHD] or electrostatic devices; Ozone-inhalators with radioactive tagged particles
• CPC Class Codes: A61M 2230/208 pH-value
• CPC Class Codes: A61P 31/12 Antivirals

Abstract

Methods, pharmaceutical compositions, and systems are provided which include a method for treating a pulmonary viral infectious disease in a subject. The method includes administering a pharmaceutical composition including at least one agent to a pulmonary tissue of the subject, wherein the pharmaceutical composition is administered as two or more distinct and non-overlapping particle size ranges configured to contact two or more levels of pulmonary tissue of the subject, wherein the at least one agent is configured to achieve a selected pH range in the two or more levels of pulmonary tissue of the subject.

Claims

1-76. -76. (canceled)

77. A system comprising:

an aerosol generator, and

a pharmaceutical composition including at least one agent configured as two or more distinct and non-overlapping particle size ranges configured to contact two or more levels of pulmonary tissue of a subject, wherein the at least one agent is configured to achieve a selected pH range in the two or more levels of pulmonary tissue of the subject.

78. The system of claim 77, wherein the at least one agent includes at least one buffering agent.

79. The system of claim 77, wherein the at least one agent includes at least one basic agent.

80. The system of claim 77, wherein the at least one agent includes at least one acidic agent.

81. The system of claim 77, wherein the pharmaceutical composition includes a first agent in first-sized particles configured to maintain a first pH range in a first level of pulmonary tissue of the subject, and a second agent in second-sized particles configured to maintain a second pH range in a second level of pulmonary tissue of the subject.

82. The system of claim 81, wherein the first-sized particles and the second-sized particles include the two or more particle size ranges of less than about 10 μ

m, less than about 6 μ

m, less than about 4 μ

m, or less than about 2 μ

m.

83. The system of claim 81, wherein at least one of the first-sized particles and the second-sized particles have the particle size ranges which include than about 4 μ

m, less than about 3 μ

m, less than about 2 μ

m, less than about 1500 nm, less than about 1 micron, less than about 800 nm, less than about 700 nm, less than about 600 nm, less than about 500 nm, less than about 400 nm, less than about 300 nm, less than about 200 nm, less than about 100 nm, less than about 75 nm, or less than about 50 nm.

84. The system of claim 81, wherein at least one of the first-sized particles and the second-sized particles have the particle size ranges which include less than about 1900 nm, less than about 1800 nm, less than about 1700 nm, less than about 1600 nm, less than about 1500 nm, less than about 1400 nm, less than about 1300 mm, less than about 1200 nm, less than about 1100 nm, less than about 1000 nm, less than about 900 nm, less than about 800 nm, less than about 700 nm, less than about 600 nm, less than about 500 nm, less than about 400 nm, less than about 300 nm, less than about 250 nm, less than about 200 nm, less than about 100 nm, less than about 75 nm, or less than about 50 nm.

85. The system of claim 81, wherein the first agent includes a buffering agent to maintain the first pH range below approximately 7.0.

86. The system of claim 81, wherein the first agent is a buffering agent configured to maintain the first pH range from approximately 7.2 to approximately 7.6.

87. The system of claim 81, wherein the second agent is a buffering agent configured to maintain the second pH range from approximately 6.4 to approximately 7.4.

88. The system of claim 77, wherein the system includes a device including the aerosol generator and the pharmaceutical composition.

89. The system of claim 77, wherein the pharmaceutical composition is administered in response to a sensed environmental condition.

90. The system of claim 89, wherein the sensed environmental condition includes a potentially infectious environment.

91. The system of claim 77, wherein the pharmaceutical composition is configured to be administered orally or intranasally.

92. The system of claim 77, wherein the pharmaceutical composition is configured to provide a timed-release of the buffering agents.

93. The system of claim 77, wherein the pharmaceutical composition is configured to provide a slow-absorbing form of the agents.

94. The system of claim 77, wherein the at least one agent is linked to a viral homing entity.

95. The system of claim 94, wherein the viral homing entity binds to a surface molecule of the virus.

96. The system of claim 94, wherein the viral homing entity binds to a cell or tissue of the subject.

97. The system of claim 78, wherein the at least one buffering agent includes phosphate buffer, citrate buffer, lactate buffer, pyruvate buffer, or an organic acid buffer.

98. The system of claim 77, wherein the aerosol generator includes a vaporizer, nebulizer, or atomizer.

99. The system of claim 80, wherein the at least one acidic agent includes a cation.

100. The system of claim 99, wherein the cation includes H⁺, K⁺, or Mg²⁺.

101. The system of claim 79, wherein the at least one basic agent includes an anion.

102. The system of claim 101, wherein the anion includes phosphate, citrate, lactate, pyruvate, or an organic acid.

103. The system of claim 77, wherein the aerosol generator is configured to administer the pharmaceutical composition to the pulmonary tissue of the subject.

104. The system of claim 77, further comprising a sensor configured to monitor a condition of the subject.

105. The system of claim 104, wherein the sensor is configured to monitor at least one of pH of the pulmonary tissue or pH of an exhalant.

106. The system of claim 104, wherein the sensor is configured to monitor at least one of humidity of an exhalant, temperature, breathing rate, peak rate of exhalation, tidal volume, vital capacity, inspiratory capacity, expiratory reserve volume, or residual volume.

107. The system of claim 104, further comprising a controller responsive to the sensor is configured to selectively deliver one or more particle size ranges.

108. The system of claim 107, wherein the controller is configured to deliver one or more particle size ranges of the selected pH.

109. The system of claim 104, wherein the monitoring sensor is in an airway passage of the subject.

110. The system of claim 109, wherein the monitoring sensor is in a sinus or a nostril of the subject.

111. The system of claim 104, wherein the monitoring sensor is integral with the system.

112. The system of claim 105, further comprising a pH-sensitive detection component configured to communicate to the pH-monitoring sensor.

113. The system of claim 112, wherein the pH-sensitive detection component releases a marker indicating a pH range, and the pH-monitoring sensor is configured to recognize the marker.

114. The system of claim 112, wherein the pharmaceutical composition including the at least one agent is administered in response to information from the pH-sensitive detection component.

115. The system of claim 77, wherein the pulmonary tissue includes epithelial tissue, mesenchymal tissue, or endothelial tissue.

116. The system of claim 77, wherein the levels of pulmonary tissue include oropharynx or nasopharynx tissue.

117. The system of claim 77, wherein the levels of pulmonary tissue include trachial tissue.

118. The system of claim 77, wherein the levels of pulmonary tissue include bronchial, bronchiole, alveolar duct, or alveoli tissue.

119. The system of claim 77, wherein the aerosol generator is configured to administer the pharmaceutical composition orally or nasally.

120. The system of claim 77, wherein the aerosol generator administers a continuous or pulsatile dose of the pharmaceutical composition.

121. The system of claim 77, wherein an aerosol dose of the pharmaceutical composition is delivered directly to an individual.

122. The system of claim 77, wherein an aerosol dose of the pharmaceutical composition is delivered to one or more individuals in an enclosed space.

123. The system of claim 77, wherein an aerosol dose of the pharmaceutical composition is delivered through a heating, ventilation, or air conditioning system.

124. The system of claim 77, wherein the pharmaceutical composition is configured to provide a timed-release of the charged ion.

125. The system of claim 77, wherein the pharmaceutical composition is configured to provide a slow-absorbing form of the charged ion.

126. The system of claim 77, wherein the pharmaceutical composition is a liquid or a powder.

127. The system of claim 77, wherein the subject is mammalian or avian.

128-167. -167. (canceled)