Lyophilization of synthetic liposomal pulmonary surfactant
Inventors
Cesco-Cancian, Sergio • HOY, Thomas • Trappler, Edward H. • Thomas, Michael S.
Assignees
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Publication Number
US-8748396-B2
Publication Date
2014-06-10
Expiration Date
Abstract
Lyophilized pulmonary surfactants having an increased specific surface area and porosity are described. A method of making lyophilized pulmonary surfactants is described.
Core Innovation
The invention relates to a process of making a lyophilized synthetic pulmonary surfactant having reduced or eliminated cake levitation during the process. The process provides to a lyophilizing chamber a pre-lyophilization mixture filled in a container, comprising dipalmitoyl phosphatidylcholine (DPPC), palmitoyloleoyl phosphatidylglycerol (POPG), palmitic acid, and a synthetic peptide with SEQ ID NO:1 (KL4 polypeptide) dispersed in a solvent.
The solvent contains an organic solvent between 3% (v/v) and 20% (v/v) of the total volume, with a remainder being water and/or buffer. The process includes lowering a temperature inside the lyophilizing chamber to begin a freezing phase, and an annealing phase is conducted prior to a primary drying phase, thereby reducing or eliminating cake levitation in the lyophilized synthetic pulmonary surfactant.
The lyophilized synthetic pulmonary surfactant produced has a specific surface area of at least 2.7 m2/g. The lyophilized synthetic pulmonary surfactant is characterized by specific surface area and, in some embodiments, by porosity above 40% by volume.
Claims Coverage
The partial content provides two independent claims. The claims focus on a process that reduces or eliminates cake levitation using an annealing phase prior to primary drying for a KL4/DPPC/POPG/palmitic acid formulation, and a lyophilized synthetic pulmonary surfactant composition having a required specific surface area.
Annealing to reduce or eliminate cake levitation in KL4-based lyophilized pulmonary surfactant
A process of making a lyophilized synthetic pulmonary surfactant having reduced or eliminated cake levitation during the process, comprising a pre-lyophilization mixture of DPPC, POPG, palmitic acid and a synthetic peptide with SEQ ID NO:1 (KL4 polypeptide) in a solvent having an organic solvent in a range between 3% (v/v) and 20% (v/v) of the total volume with a remainder being water and/or buffer, lowering a temperature inside the lyophilizing chamber to begin a freezing phase, and conducting an annealing phase prior to a primary drying phase, thereby reducing or eliminating cake levitation, wherein the lyophilized synthetic pulmonary surfactant has a specific surface area of at least 2.7 m2/g.
KL4/DPPC/POPG/palmitic acid lyophilized composition with minimum specific surface area
A lyophilized synthetic pulmonary surfactant composition comprising a synthetic peptide with SEQ ID NO:1 (KL4 polypeptide), dipalmitoyl phosphatidylcholine (DPPC), palmitoyloleoyl phosphatidylglycerol (POPG) and palmitic acid, wherein the lyophilized synthetic pulmonary surfactant composition has a specific surface area of at least 2.7 m2/g.
Across the independent claims, the core coverage ties the KL4-based synthetic pulmonary surfactant formulation (DPPC, POPG, palmitic acid, and SEQ ID NO:1) to lyophilized products and process outcomes characterized by reduced or eliminated cake levitation and a specific surface area requirement of at least 2.7 m2/g.
Stated Advantages
Reduced or eliminated cake levitation during the process.
The resulting lyophilized synthetic pulmonary surfactant has a specific surface area of at least 2.7 m2/g.
Documented Applications
Not explicitly described in patent.
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