Fluosol emulsion development

A PFC emulsion with an oxygen-carrying capacity 4-5 times greater than Fluosol was developed by Alliance Pharmaceutical Corporation (San Diego, CA). This compound, called Oxygent, did not receive approval in phase III trials due to increased incidence of stroke in treated patients. 

Medical appHcations of PFC emulsions for organ perfusion and intravenous uses have received much attention in recent years. The first commercial blood substitute (Fluosol DA 20%, trademark of the Green Cross Corp.) employed perfluorodecalin, and improved, second generation products based on this PFC, or perfluorooctylbromide, are now under development (20,21). The relatively high oxygen dissolving capabiHty of PFCs undedies these appHcations (see Blood, artificial). 

The first commercially developed PFC emulsion, Fluosol, consisted of a mixture of F-decalin and F-tiipropylamine emulsified with Pluronic F-68 [a poly(oxyethy-lene) poly(oxypropylene) block co-polymer] as the main surfactant. It gained... 

For many years, the perfluorocarbons seemed to present insurmountable hurdles to further development. However, newer emulsions are being developed that allow higher concentrations of dissolved oxygen and interest in perfluorocarbon products has been renewed (31). One product, Fluosol-DA, a 20% by weight emulsion, has been licensed for use in coronary angioplasty. As of 1991, this product was available through the U.S. Food and Drug Administration (FDA) for compassionate use. 

Intravenous infusion of the plasma-insoluble PFCs into animals results in fatal embolisms. However, following extensive research with a large number of PFCs and emulsifiers, the development of several PFC emulsions dispersed in isotonic solution has produced promising results. The first commercial product, Fluosol-DA 20% (F-DA), available in 1978, consists of perfluorodecalin (14%) and perfluorotripropylamine (6%) in emulsifiers260. 

The first commercially developed emulsion, Fluosol-DA (Green Cross Corp. Osaka, Japan), was stabilized using a mixture of 6 and F-tripropylamine (FTPA, 7, 30% of total PFC) (Table 2). However, the product s stability was still poor Fluosol had to be frozen for shipment and storage, and reconstituted prior to use. Fluosol utilized a surfactant system that included poloxamer-188 (Pluronic F-68) with smaller amounts of EYP and potassium oleate. The poloxamer provided steric stabilization, and potassium oleate introduced negative charges on the droplets, likely to oppose flocculation. 

Another 20 /o w/v emulsion, trade-name Perftoran, based on an FDC and F-[l-(4-methylcyclohexyl)piper-idine] (FMCP, 8) mixture emulsified with a poloxamer was developed in Russia (Russian Academy of Sciences/ Perftoran Company, Pushshino, Russia). " Perftoran is filter-sterilized and stable for about 1 month at 4-8°C but requires freezing for longer storage. The Russian health authorities licensed it in 1997 for a wide range of indications. A highly stable 20 /o w/v F-tributyl-amine/Pluronic F-68 emulsion, Fluosol-43 (later renamed Oxypherol), was commercially available for many years for experimental use. 

The first successful development of an injectable perfluorocarbon-based commercial product was achieved by the Green Cross Corporation in Japan, when it made Fluosol-DA , a dilute (20 /o w/v) emulsion based on perfluorodecalin and perflurotripropylamine emulsified... 

Atto-engineering for more than a whole century is in permanent and almost infinite development. Theoretical background is related to the surface physics and chemistry, quantum and wave mechanics, and quantum electrodynamics. Discrete and constrained discrete models are convenient for describing related events. Tools and equipment are nano- and atto-dispersions and beams (demons, ions, phonons, infons, photons, electrons), ultra-thin films and membranes, fullerenes and bucky tubules, Langmuir-Blodgett systems, molecular machines, nano-electronic devices, and various beam generators. Output is, generally, demonstrated as finely dispersed particles (plasma, fluosol-fog, fluosol-smoke, foam, emulsion, suspension, metal, vesicle, dispersoid). 

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