Title:  Fluorocarbon compositions for pulmonary therapy

United States Patent:  6,166,092

Assignee:  Alliance Pharmaceutical, Corp. (San Diego, CA)

Filed:  June 7, 1995

Biocompatible fluorocarbon compositions are provided which may be used for the delivery of bioactive agents to the pulmonary air passages of a patient. Preferred compositions comprise a fluorocarbon liquid carrier having a bioactive agent in a solid or immiscible liquid form distributed therein. The disclosed compositions allow for the selective delivery of bioactive agents in conjunction with liquid lavage and liquid ventilation for the treatment of ARDS and other pulmonary disorders.

SUMMARY OF THE INVENTION

The invention provides, in one embodiment, a hyperthermic treatment of lung cancer, which includes the steps of: temporarily filling with a liquid medium preselected pulmonary air passages adjoining pulmonary tissues containing malignant cells, circulating exogenously heated liquid medium having a temperature in the range of from about 41^o to about 50^oC. (preferably from about 42^o to about 45^oC.) through the liquid-filled pulmonary air passages for a predetermined period of time, and thereafter removing the liquid medium from the pulmonary air passages of the patient. The liquid medium may be a perfluorocarbon liquid or physiological saline solution. Suitable perfluorocarbon liquids having the requisite physical and thermal properties are characterized by an average molecular weight in the range of from about 350 to about 560 and by having: a viscosity less than about 5 CP at 25^oC., a density less than about 2.0 g/cm³ at 25^oC., a boiling point greater than about 55^oC., a vapor pressure in the range of from about 20 Torr to about 200 Torr, and a Prandtl number less than about 10 at 25^oC. Representatives of such perfluorocarbon liquids are FC-84, FC-72, RM-82, FC-75, RM-101, and perfluorodecalin. The preferred group of perfluorocarbon liquids is characterized by having an average molecular weight in the range of from about 420 to about 460, a vapor pressure less than about 100 Torr at 25^oC., and a surface tension less than about 17 dynes/cm at 25^oC.

The invention provides in another embodiment a hyperthermic treatment of lung cancer using ultrasound, including the steps of: temporarily filling with a liquid medium preselected pulmonary air passages adjoining pulmonary tissues comprising malignant cells, heating the adjoining pulmonary tissues comprising the malignant cells to a temperature in the range of from about 41^o to about 50^oC. (preferably from about 42^o to about 45^oC.) for a predetermined period of time by transmitting ultrasound through the liquid-filled pulmonary air passages, and thereafter removing the liquid medium from the pulmonary air passages of the patient. Perfluorocarbon liquids having the requisite physical, thermal, and acoustic properties for this ultrasound treatment are characterized by an average molecular weight in the range of from about 400 to about 560. Such perfluorocarbon liquids are also characterized by having: viscosity less than about 5 CP at 25^o C., density less than about 2.0 g/cm³ at 25^oC., boiling point greater than about 75^oC., vapor pressure in the range of from about 25 Torr to about 100 Torr, surface tension below about 17 dynes/cm at 25^oC., acoustic impedance in the range of from about 0.8 to about 1.6 MegaRayls at 37^oC., and acoustic attenuation less than about 1.2 dB/cm (at 1.0 MHz, 45^oC., and acoustic intensity of about 3 W/cm²). The preferred group of perfluorocarbon liquids for this purpose is characterized by an average molecular weight in the range of from about 420 to about 460, and representative of these are FC-75, RM-101, and perfluorodecalin. Operable and preferred ultrasound frequency ranges are also disclosed, for use with different liquid-filled regions of the pulmonary air passages. The ultrasound may be produced by a transducer disposed within the liquid-filled pulmonary air passages, or the transducer may be disposed exogenous to the liquid-filled pulmonary air passages. For example, the ultrasound may be transmitted through an intercostal space of the patient, or it may be transmitted from an exposed surface of the lung into the volume of same during an intra-operative application involving an "acoustic window" into the lung created by surgical means.

In yet another embodiment, the invention provides liquid infusion and isolation catheters, intracavitary ultrasound applicators, and intercostal ultrasound applicators for practicing the disclosed convection and/or ultrasound hyperthermia treatments of lung cancer.

In even another embodiment, the invention provides a means for delivering biological agents directly to at least a portion of the pulmonary system via liquid-born agents which are either recirculated in and out of the pulmonary system (e.g., by liquid lavage or liquid ventilation) or maintained static (i.e., non-recirculated) for extended periods of time. Breathable liquids are capable of providing, simultaneously, ventilation during drug delivery.

In still another embodiment, the invention provides a means to directly access cardiac output for drug infusion of biological agents, when systemic collapse precludes intravascular administration of such agents.

Other objects, aspects and embodiments of the invention will become apparent to those skilled in the art upon reading the following detailed description, when considered in conjunction with the accompanying drawings and the appended claims.

Claim 1 of 36 Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A composition for direct pulmonary delivery of at least one therapeutic or diagnostic a biological agent to at least a portion of the air passages of a patient comprising a biocompatible perfluorochemical liquid carrier having a boiling point greater than about 55^o having distributed therein at least one biological agent in the form of a solid or immiscible liquid.

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