Patent US3823212A successfully refreshed from Google Patents.
US4987154A
Expired / Lapsed
US
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Biocompatible, stable and concentrated fluorocarbon emulsions for contrast enhancement and oxygen transport in internal animal use
Assignee: PFC Therapeutics LLC
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Filing: 1987-08-05
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Granted: 1991-01-22
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Expires: 2007-08-05
Abstract
Abstract An up to 125% fluorocarbon emulsion for use in or with animal bodies and organs thereof, maintains emulsion stability through normal sterilization procedures with selective osmotic and buffering agents, maintains the emulsion at within predetermined osmolarity levels and, when desired, free of excessive calcium precipitation, reduces in vivo and in vitro red blood cell injury, reduces adverse anemia effects, reduces viscosity and reduces the rate of oxidation, and tends to equilibrate its distribution in major body organs thereby reducing toxicity. The osmotic agents may buffer and may provide nutrient in the form of sugars. The osmotic and buffering agents can comprise, selectively, hexahydric alcohols, namely mannitol and sorbitol; certain sugars, namely glucose, mannose and fructose; along with buffering agents that will affect osmolarity including imidazole, tris(hydroxymethyl)aminomethane, sodium chloride, sodium bicarbonate, monobasic potassium phosphate, dibasic potassium phosphate, calcium chloride, magnesium sulfate, monobasic sodium phosphate, dibasic sodium phosphate or combinations of them. The emulsion may include tocopherol. A method of emulsifying the fluorocarbon includes forced flow impingement under pressure after mixing the fluorocarbon into the discontinuous phase. The fluorocarbon emulsion can be used to deliver drugs and medicines soluble in, or transportable by the emulsion.
Inventors
- 👤 David M. Long, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:43
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0026; A61K31/00; A61K31/02; Y; Y10; Y10S; Y10S977/00; Y10S977/70; Y10S977/734; Y10S977/735; Y10S977/737; Y10S977/738; Y10S977/773; Y10S977/84; Y10S977/895; Y10S977/902; Y10S977/904; Y10S977/906; Y10S977/915
Claims Analysis
Total Claims: 49
Claim 1
Independent Claim
86 words
A fluorocarbon emulsion, prepared by: combining an aqueous phase with an effective amount of emulsifying agent and a fluorocarbon to form a mixture having from greater than 50% to about 125% weight per volume of said fluorocarbon; and passing the fluorocarbon-containing mixture through a mechanical emulsification apparatus in which said mixture is subjected to sufficiently high flow rates and pressures to form a stable, heat sterilizable fluorocarbon-in-water emulsion; wherein said emulsion is biocompatible and exhibits substantial particle size stability in the non-frozen state following heat sterilization.
Claim 2
Dependent Claim
86 words
A fluorocarbon emulsion, prepared by: combining an aqueous phase with an effective amount of emulsifying agent and a fluorocarbon to form a mixture having from greater than 50% to about 125% weight per volume of said fluorocarbon; and passing the fluorocarbon-containing mixture through a mechanical emulsification apparatus in which said mixture is subjected to sufficiently high flow rates and pressures to form a stable, heat sterilizable fluorocarbon-in-water emulsion; wherein said emulsion is biocompatible and exhibits substantial particle size stability in the non-frozen state following heat sterilization.
Claim 3
Dependent Claim
26 words
The emulsion of claim 1, wherein said emulsion further comprises an effective amount of an osmotic agent for adjusting and maintaining the osmolarity of the emulsion.
Claim 4
Dependent Claim
10 words
The emulsion of claim 1, which has been heat sterilized.
Claim 5
Dependent Claim
66 words
A storage stable, heat sterilizable fluorocarbon emulsion, comprising: an continuous aqueous phase, a discontinuous fluorocarbon phase, and an effective amount of emulsifying agent, wherein the concentration of said fluorocarbon phase in said emulsion is greater than 75% and no more than 125%, weight per volume, and wherein said emulsion exhibits substantial particle size stability on storage in the non-frozen state following heat sterilization and is biocompatible.
Claim 6
Dependent Claim
66 words
A storage stable, heat sterilizable fluorocarbon emulsion, comprising: an continuous aqueous phase, a discontinuous fluorocarbon phase, and an effective amount of emulsifying agent, wherein the concentration of said fluorocarbon phase in said emulsion is greater than 75% and no more than 125%, weight per volume, and wherein said emulsion exhibits substantial particle size stability on storage in the non-frozen state following heat sterilization and is biocompatible.
Claim 7
Dependent Claim
23 words
The emulsion of claim 4, wherein the concentration of said fluorocarbon phase in said emulsion is at least about 80%, weight per volume.
Claim 8
Dependent Claim
23 words
The emulsion of claim 4, wherein the concentration of said fluorocarbon phase in said emulsion is at least about 100%, weight per volume.
Claim 9
Dependent Claim
13 words
The fluorocarbon emulsion of claim 1 wherein the emulsifying agent is a phospholipid.
Claim 10
Dependent Claim
11 words
The fluorocarbon emulsion of claim 7 wherein the phospholipid is lecithin.
Claim 11
Dependent Claim
14 words
The fluorocarbon emulsion of claim 1 wherein the emulsifying agent is an anionic surfactant.
Claim 12
Dependent Claim
13 words
The fluorocarbon emulsion of claim 1 wherein the fluorocarbon is a mono-brominated perfluorocarbon.
Claim 13
Dependent Claim
12 words
The fluorocarbon emulsion of claim 10 wherein the mono-brominated perfluorocarbon is 1-bromoseptadecafluoroctane.
Claim 14
Dependent Claim
12 words
The fluorocarbon emulsion of claim 10 wherein the mono-brominated perfluorocarbon is 1-bromotridecafluorohexane.
Claim 15
Dependent Claim
12 words
The fluorocarbon emulsion of claim 10 wherein the mono-brominated perfluorocarbon is 1-bromopentadecafluoroseptane.
Claim 16
Dependent Claim
11 words
The fluorocarbon emulsion of claim 1 wherein the fluorocarbon is C4F9CH-CHC4F9.
Claim 17
Dependent Claim
11 words
The fluorocarbon emulsion of claim 1, wherein the fluorocarbon is F-decalin.
Claim 18
Dependent Claim
15 words
The fluorocarbon emulsion of claim 1 wherein the emulsifying agent comprises a biocompatible fluorinated surfactant.
Claim 19
Dependent Claim
37 words
The fluorocarbon emulsion of claim 16 wherein the fluorocarbon emulsion and fluorinated surfactant have a sufficient elimination rate that the fluorocarbon emulsion and fluorinated cosurfactant are substantially eliminated from the animal body or organ before carcinosis occurs.
Claim 20
Dependent Claim
37 words
The fluorocarbon emulsion of claim 16 wherein the fluorocarbon emulsion and fluorinated surfactant have a sufficient elimination rate that the fluorocarbon emulsion and fluorinated cosurfactant are substantially eliminated from the animal body or organ before teratogenesis occurs.
Claim 21
Dependent Claim
37 words
The fluorocarbon emulsion of claim 16 wherein the fluorocarbon emulsion and fluorinated surfactant have a sufficient elimination rate that the fluorocarbon emulsion and fluorinated cosurfactant are substantially eliminated from the animal body or organ before embryotoxicity occurs.
Claim 22
Dependent Claim
15 words
The fluorocarbon emulsion of claim 16 wherein the fluorinated cosurfactant comprises a fluorinated polyhydroxylated surfactant.
Claim 23
Dependent Claim
22 words
The fluorocarbon emulsion of claim 1 further comprising a buffering agent selected from the group consisting of imidazole, tris(hydroxymethyl)aminomethane, and combinations thereof.
Claim 24
Dependent Claim
41 words
The fluorocarbon emulsion of claim 21 wherein said buffering agent group further consists of sodium bicarbonate, monobasic sodium phosphate, dibasic sodium phosphate, magnesium sulfate, magnesium chloride, sodium chloride, potassium chloride, monobasic potassium phosphate, dibasic potassium phosphate and non-calcium precipitating combinations thereof.
Claim 25
Dependent Claim
27 words
The fluorocarbon emulsion of claim 21 wherein the pH of the emulsion is maintained at from approximately 4.0 to approximately 8.4 after sterilization and before use intravenously.
Claim 26
Dependent Claim
29 words
The fluorocarbon emulsion of claim 21 for use wherein the pH of the emulsion is maintained at from approximately 7.0 to approximately 7.8 before use in the coronary arteries.
Claim 27
Dependent Claim
12 words
The fluorocarbon emulsion of claim 21 wherein said buffering agent is imidazole.
Claim 28
Dependent Claim
10 words
The fluorocarbon emulsion of claim 1 further comprising an anti-oxidant.
Claim 29
Dependent Claim
11 words
The fluorocarbon emulsion of claim 26 wherein said anti-oxidant comprises mannitol.
Claim 30
Dependent Claim
12 words
The fluorocarbon emulsion of claim 26 wherein the anti-oxidant comprises a tocopherol.
Claim 31
Dependent Claim
13 words
The fluorocarbon emulsion of claim 26 wherein the anti-oxidant comprises mannitol and tocopherol.
Claim 32
Dependent Claim
12 words
The fluorocarbon emulsion of claim 28 wherein the tocopherol comprises alpha-tocopherol acetate.
Claim 33
Dependent Claim
39 words
The fluorocarbon emulsion of claim 26 including an anti-oxidant for reduction of oxidation of components of said emulsion comprising an effective amount of an anti-oxidant selected from the group consisting of ascorbyl palmitate, mannitol, tocopherol, imidazole and combinations thereof.
Claim 34
Dependent Claim
42 words
The fluorocarbon emulsion of claim 26 including an anti-oxidant for reduction of oxidation of tissues of animal bodies and organs thereof comprising an effective amount of an anti-oxidant selected from the group consisting of ascorbyl palmitate, mannitol, tocopherol, imidazole and combinations thereof.
Claim 35
Dependent Claim
32 words
The fluorocarbon emulsion of claim 1 for application to tissue of animal bodies and organs thereof, further comprising mannitol and tocopherol in an effective amount for reduction of oxidation in said emulsion.
Claim 36
Dependent Claim
38 words
The fluorocarbon emulsion of claim 1 for application to tissue of animal bodies and organs thereof, further comprising mannitol and tocopherolan in an effective amount for reduction of oxidation in said tissue of animal bodies and organs thereof.
Claim 37
Dependent Claim
30 words
The fluorocarbon emulsion of claim 1 for application to tissue of animal bodies and organs thereof, further comprising mannitol in an effective amount for reduction of oxidation in said emulsion.
Claim 38
Dependent Claim
36 words
The fluorocarbon emulsion of claim 1 for application to tissue of animal bodies and organs thereof, further comprising mannitol in an effective amount for reduction of oxidation in said tissue of animal bodies and organs thereof.
Claim 39
Dependent Claim
38 words
The fluorocarbon emulsion of claim 31 for application to tissue of animal bodies and organs thereof for reduction of oxidation therein wherein said anti-oxidant group further includes ascorbic acid, salts and complexes thereof and non-calcium precipitating combinations thereof.
Claim 40
Dependent Claim
26 words
The fluorocarbon emulsion of claim 1 wherein the fluorocarbon in emulsion is in an amount of from 80% weight per volume to 125% weight per volume.
Claim 41
Dependent Claim
23 words
The fluorocarbon emulsion of claim 2, wherein the osmolarity of the emulsion is maintained between from about 240 milliosmols to about 650 milliosmoles.
Claim 42
Dependent Claim
23 words
The fluorocarbon emulsion of claim 2, wherein the osmolarity of the emulsion is maintained between from about 300 milliosmols to about 450 milliosmols.
Claim 43
Dependent Claim
21 words
The fluorocarbon emulsion of claim 39 or 40, wherein the osmolarity is maintained, at least in part, by a hexahydric alcohol.
Claim 44
Dependent Claim
20 words
The fluorocarbon emulsion of claim 41, wherein the hexahydric alcohol is selected from the group consisting of mannitol and sorbitol.
Claim 45
Dependent Claim
29 words
The fluorocarbon emulsion of claim 42, wherein the hexahydric alcohol is mannitol, present at a concentration of from about 0.25% weight per volume to about 1.5% weight per volume.
Claim 46
Dependent Claim
20 words
The fluorocarbon emulsion of claim 39 or 40, wherein the osmolarity is maintained, at least in part, by a sugar.
Claim 47
Dependent Claim
23 words
The fluorocarbon emulsions of claim 44, wherein the sugar is selected from the group consisting of glucose, mannose and fructose, or combinations thereof.
Claim 48
Dependent Claim
21 words
The fluorocarbon emulsion of claim 39 or 40, wherein the osmolarity is maintained, at least in part, by a buffering agent.
Claim 49
Dependent Claim
22 words
The fluorocarbon emulsion of claim 39 or 40, wherein the osmolarity is maintained, at least in part, by chloride or sulfate salts.
References Cited (Backward Citations)
FR2105287A1
Cited
US3818229A
Cited
US3975512A
Cited
US3962439A
Cited
US4073879A
Cited
US4105798A
Cited
US4146499A
Cited
EP0023109A1
Cited
JPS5658032A
Cited
JPS5759067A
Cited
JPS5759046A
Cited
US4343797A
Cited
US4439424A
Cited
JPS5896061A
Cited
US4451251A
Cited
US4613708A
Cited
US4397870A
Cited
US4423077A
Cited
US4497829A
Cited
US4654337A
Cited
JPS5960166A
Cited
JPS5967229A
Cited
US4605786A
Cited
US4640833A
Cited
EP0220153A1
Cited
EP0231070A2
Cited
US4895876A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-01-21 | 1994-07-23 | 1995-01-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-01-21 | 1998-07-23 | 1999-01-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-01-21 | 2002-07-23 | 2003-01-22 | $7700.00 | Window Closed / Lapsed |