Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
  • A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/02—Halogenated hydrocarbons
  • A61K31/025—Halogenated hydrocarbons carbocyclic
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P11/00—Drugs for disorders of the respiratory system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• the present invention is in the field of biological gas exchange in e mammals using C-10 perfluorinated hydrocarbons (perfluorocarbons) as 7 a medium of the exchange. More particularly, the present invention is ⁇ directed to use of those C-10 perfluorinated hydrocarbons in biological
• liquid ventilation is a term used for describing gas
• total liquid ventilation is unlikely to become a
• one of the present inventors is “low volume” or “alveolar” ventilation
• HNCL hyperinflated non-collapsible lung syndrome
• the rate of loss due to is exhalation/evaporation is also related to the volatility (vapor pressure at
• HNCL hyperinflated non-collapsible lung syndrome
• the ⁇ o present invention provides perfluorocarbons which avoid the ⁇ hyperinflated lung syndrome and other problems associated with the
• 19 artificial blood are liquids at ambient temperature and have a vapor
• 27 compounds is in the range of approximately 144 to 146°C.
• Figure 1 is a graph showing the rate of exhalation of F- 1,2,3,5-
• 29 exchange is their ability to dissolve a large quantity of gases, including ⁇ oxygen and carbon dioxide.
• Formulas 3, 4 and 5 represent a total of 18
• F- s-decalin which at ⁇ o atmospheric pressure has a boiling point of 141°C.
• the mixture of the ⁇ two liquids is maintained in a closed container and the "headspace"
• pentyl, butyl and propyl groups represent all possible positional isomers of said groups, for example “propyl” represents «-propyl and ir ⁇ -propyl as well, and “butyl” represents «-butyl, f-butyl and 1-methylpropyl and 2-methylpropyl groups.
• propyl represents «-propyl and ir ⁇ -propyl as well
• butyl represents «-butyl, f-butyl and 1-methylpropyl and 2-methylpropyl groups.
• the preferred compounds of Formulas 6 - 9 and 11 - 16 are single positional isomers and cis and trans isomerism for these compounds is not possible.
• the compound of Formula 8 and some of the compounds within the scope of Formulas 14 and 15 have one or more chiral centers and therefore exist in enantiomeric and some in diasteromeric forms. Enantiomers, however are not expected to give rise in the testing and regulatory approval process to problems of the same magnitude as positional isomers, because a racemic mixture of compounds is often considered acceptable for regulatory purposes. Also in chromatographic and many other analytical techniques, unless the chromatography involves a "chiral column", a racemic mixture is not resolved.
• the C 10 F 20 compounds which are presently most preferred in accordance with the present invention are: F-t-butylcylohexane (Formula 9); F-l,l-diethylcyclohexane (Formula 11), and F-neopentylcyclopentane (Formula 17)
• the C 10 F 20 compounds used within the scope of the present invention, and particularly the preferred compounds shown in Formulas 6 - 9 and 11 - 16 can be synthesized from homologous hydrocarbons by well-known techniques, such as reaction with cobalt trifluoride in a furnace.
• a method of manufacture of F- tt ⁇ ry-butylcyclohexane is described in United States Patent No. 4,453,028, incorporated herein by reference.
• Further procedures for the synthesis of C 10 F 20 cyclohexane derivatives are described in United States Patent Nos. 5,300,528, 4,105,798, and 5,093,432 which are also specifically incorporated herein by reference.
• the compounds can be used for example as described in United States
• the nonfasted rat is weighted and anesthetized with a volatile is anesthetic such as enflurane, halothane or similar agent.
• a volatile is anesthetic such as enflurane, halothane or similar agent.
• the neck area is shaved, and the skin is cleaned with
• the rat is positioned on her back on a padded surgical platform
• a heat lamp is used to maintain body temperature 2 ⁇ between 35 and 37 degrees Celsius.
• Sterilized instruments are used for the surgical procedure. A 2 ⁇ cm midline incision is made in the neck over the trachea. The
• the surgical platform is elevated about 30-40° to facilitate the ⁇ gravity flow of perfluorocarbon neat liquid into the lungs.
• Oxygen is concomitantly delivered.
• the rat can also be is rotated to the left and right during dosing to help distribute the liquid.
• PROTOCOL 2 Intratracheal administration of perfluorocarbon neat
• Topical 2% Lidocaine may facilitate the cannulation.
• the animal is administered humidified, 100% oxygen during the
• the rat is placed in a specially designed chamber consisting of a
• PROTOCOL 4 Test of intratracheal neat liquid perflurocarbons for
• 29 cannula was removed, the incision closed and the animal allowed to recover in USDA-approved, air conditioned quarters. The rabbits were observed frequently until sacrifice on the fourth day after infusion.
• Table 2 above shows the results obtained with five separate C 10 F 20 perfluorocarbons that are utilized in accordance with the present invention.
• the chemical name of each of the perfluorocarbons measured is indicated by the superscripts over the numerical data.
• the data of Table 2 clearly demonstrate that the vapor pressure of the 5 C 10 F 20 compounds are significantly lower than that of F cis decalin.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Medicinal Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Engineering & Computer Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Hematology (AREA)
• Dermatology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Pulmonology (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicinal Preparation (AREA)

Priority Applications (4)

Applications Claiming Priority (2)

Publications (2)

Family

ID=25523336

Family Applications (1)

Country Status (6)

Cited By (2)

Families Citing this family (10)

Family Cites Families (11)

• 1997
  • 1997-11-21 US US08/975,743 patent/US6167887B1/en not_active Expired - Lifetime
• 1998
  • 1998-11-18 CA CA002311122A patent/CA2311122C/en not_active Expired - Fee Related
  • 1998-11-18 WO PCT/US1998/024632 patent/WO1999026604A2/en not_active Ceased
  • 1998-11-18 JP JP2000521806A patent/JP2003522094A/ja active Pending
  • 1998-11-18 AU AU14184/99A patent/AU759557B2/en not_active Expired
  • 1998-11-18 EP EP19980958073 patent/EP1037619A4/en not_active Withdrawn

Also Published As

Similar Documents

Legal Events