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-9554999-B2
Publication Date
2017-01-31
Expiration Date
Abstract
Lyophilized pulmonary surfactants having an increased specific surface area and porosity are described. Methods of making the lyophilized pulmonary surfactants are also described.
Core Innovation
The invention relates to a lyophilized synthetic pulmonary surfactant composition comprising at least one phospholipid and a synthetic polypeptide having at least 10 amino acid residues and represented by a formula in which hydrophilic amino acid residues and hydrophobic amino acid residues occur according to specified integer-averaged subunit counts. The lyophilized synthetic pulmonary surfactant composition has a specific surface area of at least 2.2 m2/g or a porosity above 40% by volume of a total area of the lyophilized synthetic pulmonary surfactant.
The invention also 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 comprising at least one phospholipid and the same type of synthetic peptide dispersed in a solvent system containing organic solvent in a range of between 3% (v/v) and below 20% (v/v), with a remainder being water and/or buffer.
The process includes lowering a temperature inside the lyophilizing chamber to begin chilling and solidifying the pre-lyophilization mixture in a freezing phase, and conducting an annealing phase prior to a primary drying phase in order to reduce or eliminate cake levitation. The resulting lyophilized synthetic pulmonary surfactant composition is further characterized as having a specific surface area at least 2.2 m2/g or a porosity above 40% by volume.
Claims Coverage
The partial content provides two independent claims, one directed to the lyophilized synthetic pulmonary surfactant composition with specified structural and morphology performance requirements, and one directed to a lyophilization process that reduces or eliminates cake levitation using a constrained pre-lyophilization mixture and an annealing-to-primary-drying sequence. Across the independent claims, the core inventive elements are three: the specific synthetic polypeptide formula with hydrophilic and hydrophobic residue definitions and integer-averaged counts, the performance thresholds for specific surface area and/or porosity, and process features aimed at reducing or eliminating cake levitation by using a limited organic-solvent range and placing an annealing phase prior to primary drying.
Lyophilized synthetic pulmonary surfactant composition with peptide formula and morphology thresholds
A lyophilized synthetic pulmonary surfactant composition comprising at least one phospholipid and a synthetic polypeptide having at least 10 amino acid residues represented by a formula with hydrophilic amino acid residues and hydrophobic amino acid residues, and with specified integer-averaged values; wherein the lyophilized synthetic pulmonary surfactant composition has a specific surface area at least 2.2 m2/g or a porosity above 40% by volume of a total area of the lyophilized synthetic pulmonary surfactant.
Lyophilization process reducing or eliminating cake levitation using constrained pre-mixture and annealing prior to primary drying
A process of making a lyophilized synthetic pulmonary surfactant having reduced or eliminated cake levitation during the process, comprising providing to a lyophilizing chamber a pre-lyophilization mixture comprising at least one phospholipid and a synthetic peptide dispersed in a solvent having an organic solvent in a range of between 3% (v/v) and below 20% (v/v) with a remainder being water and/or buffer; lowering a temperature inside the lyophilizing chamber to begin chilling and solidifying the pre-lyophilization mixture in a freezing phase; and conducting an annealing phase prior to a primary drying phase and thereby reducing or eliminating cake levitation; wherein the lyophilized synthetic pulmonary surfactant composition has a specific surface area at least 2.2 m2/g or a porosity above 40% by volume of a total area.
The claim coverage in the partial content is centered on a lyophilized synthetic pulmonary surfactant defined by a specific synthetic polypeptide formula and at least one phospholipid, together with morphology performance requirements. The corresponding process claim links reduced or eliminated cake levitation to preparing a pre-lyophilization mixture with an organic-solvent range of 3% (v/v) to below 20% (v/v) and performing annealing prior to primary drying.
Stated Advantages
Reduced or eliminated cake levitation during the lyophilization process.
Increased or achieved specific surface area (at least 2.2 m2/g) in the lyophilized synthetic pulmonary surfactant.
Increased or achieved porosity (above 40% by volume) in the lyophilized synthetic pulmonary surfactant.
Documented Applications
No documented applications found
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