Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Patent
1989-06-08
1992-07-28
Stoll, Robert L.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
424 11, 424405, 424417, 424431, 424445, 424447, 424450, A61L 1520, A61K 9133, A61K 3722
Patent
active
051339650
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to the art of enclosing passenger molecules in a amphipathic carrier structure.
BACKGROUND OF THE INVENTION
There have been numerous attempts in the prior art to develop lipid-based vesicles which are capable of entrapping various materials of interest ("passenger molecules"). The known methods have generally resulted in generally spherical vesicles known as liposomes which are composed of a lipid bilayer having an inner space in which the entrapped material is held. These vesicles have been formed by methods employing mechanical agitation, for example, sonication or extrusion. After lipids in organic solvents were mixed, the resulting mixture was dried, followed by mechanical agitation and rehydration with the passenger molecule to be entrapped to encourage the lipid bilayer to enclose around the passenger molecule.
The liposomes formed by this method were generally heterogeneous in size and difficult to sterilize for in vivo applications. The stability or shelf-life of these liposomes was often very limited. The entrapment efficiency of passenger molecules was generally limited. The methods required, in general, toxic non-biocompatible solvents. The prior procedures were not applicable to aerosolization or formation of liposomes in situ. The vehicles formed by this method generally could be sterilized only by filtration as they exhibited heat lability. Moreover, prior methodology was not acceptably adaptable to the entrapment of certain passenger molecules.
SUMMARY OF THE INVENTION
It has now been found that an amphipathic vehicle (hereinafter referred to as "Solvent Dilution Micro-Carriers" or "SDMCs") can be made using a method which leads to entrapping the passenger molecule in the bilayer itself, or in association with a component of the bilayer, rather than inside the space created by a spherical bilayer. In this method, a solvent is mixed with an amphipathic material and a passenger molecule. A small amount of water is then added to form a turbid solution. Additional solvent is then added to form an optically clear solution, also referred to as the "formed solution." An organization step is performed either immediately or at a time remote from the previous steps. The organization may involve aerosolization, dilution into aqueous materials or drying and rehydrating. The amphipathic vehicles or solvent dilution microcarriers (SDMCs) are formed upon employment of the organization method. The vehicles formed by this method exhibit substantial size homogeneity and are capable of being sterilized by sterile filtration, heating or u.v. irradiation.
The process may be put on hold after the formed solution is made and that solution held until it is desired to perform the organization step.
The SDMCs formed by this new method are unique in that they entrap a wide range of passenger molecules. The SDMCs have a wide range of applications. Aerosols containing SDMCs may be advantageously applied to large surface areas, such as for example when the passenger molecule is a pesticide. On the other hand, aerosols are also applicable to delivery of medicaments and cosmetics such as antibiotics or hair sprays. The methodology of this invention is also useful for SDMC formation in situ. The formed solution or SDMCs may be adsorbed on a surface such as bandage material and dried. Hydration allows the SDMC to deliver the passenger molecule to the desired site.
A sustained-release wound dressing material comprised of a foam bandage material and SDMCs has also been found.
DETAILED DESCRIPTION OF THE INVENTION
In the examples which follow, Solvent Dilution Microcarriers (SDMCs) were prepared by solubilizing at least one amphipathic material such as a surfactant (for example a biocompatible surfactant with good miscibility such as, but not limited to, Tween, Triton, sodium dodecyl sulfate (SDS), sodium laurel sulfate, and sodium octyl glucoside), a phospholipid, a mixture of phospholipids, polar lipids, sterols, sterol esters, neutral lipids, fatty acids, or other bilayer form
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Fountain Pharmaceuticals, Inc.
Metzmaier D.
Stoll Robert L.
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