Methods and compositions for maintaining the conformation and structural integrity of biomolecules
Inventors
Seifert, Jennifer • Sood, Paul R. • Crow, Brent B. • Nelson, Kevin D. • Griffin, Nickolas B. • Patel, Alpeshkumar P. • Hubbard, Paul A.
Assignees
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Publication Number
US-11197905-B2
Publication Date
2021-12-14
Expiration Date
Abstract
A composition includes a target pharmaceutical or biological agent, a solution containing the target pharmaceutical or biological agent, and substrate that is soluble in the solution. The substrate is capable of being solidified via a solidification process and the solidification process causes the substrate to become physically or chemically cross-linked, vitrified, or crystallized. As a result of the solidification process, particles are formed. The target pharmaceutical or biological agent within the solution retains proper conformation to ultimately produce a desired effect.
Core Innovation
The disclosed invention relates to forming particles that contain a pharmaceutical or biological agent and preserve biological activity of the pharmaceutical or biological agent when exposed to an organic solvent from which protection is desired. The method includes preparing a solution, formed from water as a solvent, comprising a pharmaceutical or a biological agent and a substrate that is soluble in the solution, and combining the solution with an oil phase to form a water-in-oil emulsion in which the solution is dispersed in the oil phase.
The emulsion is lyophilized, and the particles are formed prior to or simultaneously with the lyophilizing. The pharmaceutical or biological agent is entrapped by the formed particles, and the substrate composition and the oil phase are selected so that the particles formed are suspendable in the organic solvent from which protection is desired and the biological activity of the pharmaceutical or biological agent is preserved upon suspension of the particles in the organic solvent.
One or more substances selected from surfactant, a stabilizer, an emulsifier, and combinations thereof are incorporated as part of the substrate prior to solidification to form the emulsion. The solidification process is described as occurring in different ways, including chemical or physical cross-linking, vitrified substrate formation, and crystallized substrate formation.
Claims Coverage
The provided claim content presents one main independent claim with multiple dependent refinements. The inventive features center on emulsion-based formation of lyophilized particles that entrap a pharmaceutical or biological agent and are selected for suspendability in a target organic solvent while preserving biological activity, with further refinements for additives, particle size, oil phase selection, and solidification outcome.
Water-based agent solution with soluble substrate
Preparing a solution, formed from water as a solvent, comprising a pharmaceutical or a biological agent and a substrate that is soluble in the solution.
Water-in-oil emulsion preparation with selected oil phase
Combining the solution with an oil phase to form a water-in-oil emulsion in which the solution is dispersed in the oil phase.
Lyophilizing to form entrapping particles
Lyophilizing the emulsion where the particles are formed prior to or simultaneously with the lyophilizing, and wherein the pharmaceutical or biological agent is entrapped by the formed particles.
Selection of substrate and oil phase for organic solvent suspendability and biological activity preservation
Selecting the substrate composition and the oil phase so that the particles formed are suspendable in the organic solvent from which protection is desired and the biological activity of the pharmaceutical or biological agent is preserved upon suspension of the particles in the organic solvent from which protection is desired.
Incorporated surfactant, stabilizer, or emulsifier prior to solidification
Incorporating one or more substances selected from the group consisting of a surfactant, a stabilizer, an emulsifier, and combinations thereof as part of the substrate prior to solidification in order to form the emulsion.
Lyoprotectants and cryoprotectants in the emulsion
Providing an emulsion that includes lyoprotectants and/or cryoprotectants.
Carbohydrate-containing substrate with surfactant and emulsifier
Characterizing the substrate as including one or more carbohydrate types together with a surfactant and an emulsifier.
Sub-1 µm particle diameter limitation
Characterizing the particles as having diameters less than 1 µm.
Cyclohexane or cycloheptane oil-phase solvent selection
Characterizing the oil phase as including a solvent selected from cyclohexane and cycloheptane.
Vitrified substrate formation as the solidification outcome
Characterizing the solidification process as vitrifying the substrate.
Across the provided claim set, the main inventive concept is forming lyophilized particles that entrapped a pharmaceutical or biological agent from a water-in-oil emulsion and are selected to be suspendable in a target organic solvent while preserving biological activity, with refinements specifying emulsion additives, particle size, oil-phase solvent selection, and solidification by vitrification.
Stated Advantages
Particles are suspendable in the organic solvent from which protection is desired.
Biological activity of the pharmaceutical or biological agent is preserved upon suspension of the particles in the organic solvent from which protection is desired.
Documented Applications
Protecting a pharmaceutical or biological agent from exposure to an organic solvent from which protection is desired by suspending particles formed by the disclosed method in that organic solvent while preserving biological activity.
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