Classifications

• • 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
  • A61K31/74—Synthetic polymeric materials
  • A61K31/80—Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
• • 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
  • A61K31/695—Silicon compounds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
  • C07F7/02—Silicon compounds
  • C07F7/08—Compounds having one or more C—Si linkages
  • C07F7/0834—Compounds having one or more O-Si linkage
  • C07F7/0838—Compounds with one or more Si-O-Si sequences
  • C07F7/0872—Preparation and treatment thereof
  • C07F7/089—Treatments not covered by a preceding group
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
  • C07F7/02—Silicon compounds
  • C07F7/08—Compounds having one or more C—Si linkages
  • C07F7/20—Purification, separation
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
  • C08G77/04—Polysiloxanes
  • C08G77/32—Post-polymerisation treatment
  • C08G77/34—Purification
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
  • Y02P20/00—Technologies relating to chemical industry
  • Y02P20/50—Improvements relating to the production of bulk chemicals
  • Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids

Definitions

• the present invention relates to a novel, highly effective method to purify vitreofluid silicone oils or fluids using supercritical fluid extraction. More particularly, the present invention relates to a method for purifying vitreofluid silicone oils or fluids that is contaminant-free and, in most cases, does not require the disposal of organic solvents.
• Ocular tamponades are vitreous substitutes that are used to reposition the retina of an eye in instances where a reattachment is not achievable by natural healing or by laser coagulation.
• the purpose of a vitreous substitute is to provide long-term tamponade of the retina, i.e., exhibit an ideal pressure (force/area) to position and maintain the retina in place.
• Current commercially used tamponades include perfluorocarbon-liquids, balanced salt solutions, silicone oil or fluid and gases, such as air, sulfur hexafluoride (SF 6 ) and perfluorocarbons (PFCs). Silicone oil or fluid is the preferred tamponade in cases of severe retina detachment, where the tamponade is used six months or longer.
• Silicone oil or fluid is prepared by a ring-opening polymerization of strained cyclic silicones.
• the final product consists of relatively high molecular weight silicone fluid and unreacted relatively low molecular weight cyclic siloxanes and oligomers.
• the unreacted relatively low molecular weight cyclics and oligomers are cytotoxic and have been implicated in an undesirable emulsification phenomenon that sometimes occurs in silicone-based fluids. Accordingly, the unreacted relatively low molecular weight cyclics and oligomers must be removed from the silicone fluid product to be useful as an ocular tamponade.
• the preferred current method of purifying relatively high molecular weight silicone oil, or silicone fluid involves the use of a lengthy solvent extraction process whereby the silicone fluid is slowly added to a non-solvent, such as acetone, and allowed to separate.
• a non-solvent such as acetone
• the unreacted low molecular weight cyclics and oligomers are soluble in the non-solvent or acetone phase.
• the unreacted low molecular weight cyclics and oligomers are thus removed with the non-solvent or acetone phase upon separation thereof from the high molecular weight silicone fluid.
• the non-solvent phase with the low molecular weight cyclics and oligomers becomes an undesirable waste product of the purification method and requires disposal.
• controls are necessary to ensure the final silicone oil or fluid product is free of non-solvent contamination.
• the present invention is an economical, highly effective process for the purification of relatively high molecular weight vitreofluid silicone oils or fluids using carbon dioxide supercritical fluid (SCF) extraction.
• a fluid with its temperature and pressure simultaneously higher than its critical temperature and pressure is in the supercritical state.
• SCF supercritical fluid
• carbon dioxide is a gas at ambient conditions. In a supercritical state, it is essentially a compressed, high density fluid.
• Carbon dioxide is relatively innocuous, economical, and non-reactive under most operating conditions.
• the density, solvent power or selectivity of a SCF is easily altered with relatively small changes in pressure or by addition of small amounts of an organic solvent. The change in carbon dioxide density with pressure at 35 degrees Celsius does not increase linearly with increasing pressure.
• Another object of the present invention is to provide a process for the purification of relatively high molecular weight silicone fluid that is economical.
• Another object of the present invention is to provide a process for the purification of relatively high molecular weight silicone fluid that is reproducible.
• Another object of the present invention is to provide a process for the purification of relatively high molecular weight silicone fluid that is contaminant-free.
• Another object of the present invention is to provide a process for the purification of relatively high molecular weight silicone fluid for use as an ocular tamponade.
• Still another object of the present invention is to provide a process for the purification of a relatively high molecular weight silicone fluid that lessens or eliminates the need for non-solvent waste disposal.
• a further object of the present invention is to eliminate low molecular weight silicone oligomers and cyclics from relatively high molecular weight silicone fluid in order to lessen or eliminate emulsification of the relatively high molecular weight silicone fluid in ocular tamponade uses.
• the present invention relates to a novel process for the purification of relatively high molecular weight silicone oil or fluid for use as an ocular tamponade.
• the purification process of the present invention is a novel, economical, highly effective, reproducible, contaminant-free process for removing relatively low molecular weight cyclics and oligomers from relatively high molecular weight silicone oil or fluid.
• the subject process utilizes supercritical carbon dioxide (scCO 2 ) fluid extraction to purify silicone fluid for use as an ocular tamponade.
• the supercritical carbon dioxide fluid has solvating powers comparable to those of organic solvents.
• the solvating power of the supercritical carbon dioxide fluid is adjustable through variations in pressure and temperature, or by adding modifiers to form a mixture as discussed in more detail below.
• suitable modifiers include but are not limited to methanol, isopropanol, acetonitrile and acetone.
• a 5,000 cps silicone oil tamponade was purified using supercritical carbon dioxide fluid extraction.
• the conditions of the supercritical carbon dioxide fluid extraction consisted of carbon dioxide at a pressure of approximately 3,000 pounds per square inch (psi), a temperature of approximately 55 degrees Celsius and a flow rate of approximately 52 gm per minute.
• the relatively low molecular weight cyclics and oligomers were removed from the silicone fluid to a level below size exclusion chromatography (SEC) detection limits. More particularly, SEC showed the removal of relatively low molecular weight cyclics and oligomers with no change in the silicone fluid peak height. Similar results were obtained by extracting with supercritical carbon dioxide fluid containing 10 percent acetone.
• Polydimethylsiloxane (21.01 gm) sample was loaded into a 0.7 inch tube. The loaded tube was then placed in a 3.0 inch cup. The 3.0 inch cup with the sample was placed into an extraction vessel and a lid with a 1 ⁇ 4 inch pipe attachment was placed on the extraction vessel. The lid was placed such that the 1 ⁇ 4 inch pipe attachment was inside the 0.7 inch tube.
• the extraction vessel was then pressurized to 140 bar with carbon dioxide using bottom to top flow. The extraction vessel temperature was approximately 55 degrees Celsius in an oil bath of approximately 102 degrees Celsius. A flow of 26 gm per minute carbon dioxide was begun in the extraction vessel from the top to the bottom. After one hour and 37 minutes, an increased flow rate of 52 gm per minute carbon dioxide was begun.
• Polydimethylsiloxane (21.01 gm) sample was loaded into a 0.7 inch tube. The loaded tube was then placed in a 3.0 inch cup. The 3.0 inch cup with the sample was then placed in an extraction vessel and a lid with a 1 ⁇ 4 inch pipe attachment was placed on the extraction vessel. The lid was placed such that the 1 ⁇ 4 inch pipe attachment was inside the 0.7 inch tube. The extraction vessel was then pressurized to 140 bar with carbon dioxide using bottom to top flow. The extraction vessel temperature was approximately 55 degrees Celsius in an oil bath of approximately 102 degrees Celsius. A flow of 6 gm per minute acetone and 20 gm per minute carbon dioxide was begun in the extraction vessel from the top to the bottom.
• Silicone oil or fluid ocular tamponades purified using the purification process of the present invention are used as customary in the field of ophthalmology.
• the silicone oil or fluid ocular tamponade purified in accordance with the process of the present invention is placed and maintained in the posterior segment of the eye for the desired period of time prior to the removal thereof.

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• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Organic Chemistry (AREA)
• Medicinal Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Polymers & Plastics (AREA)
• Silicon Polymers (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Extraction Or Liquid Replacement (AREA)

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• 2002
  • 2002-06-07 US US10/165,834 patent/US20030181749A1/en not_active Abandoned
• 2003
  • 2003-03-20 AU AU2003218343A patent/AU2003218343A1/en not_active Abandoned
  • 2003-03-20 DE DE60323471T patent/DE60323471D1/de not_active Expired - Lifetime
  • 2003-03-20 ES ES03714340T patent/ES2312759T3/es not_active Expired - Lifetime
  • 2003-03-20 WO PCT/US2003/008902 patent/WO2003080713A1/fr not_active Ceased
  • 2003-03-20 EP EP03714340A patent/EP1487903B1/fr not_active Expired - Lifetime
• 2004
  • 2004-03-16 US US10/801,741 patent/US7276619B2/en not_active Expired - Fee Related

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