US4816247A
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Emulsion compositions for administration of sparingly water soluble ionizable hydrophobic drugs
Assignee: Wyeth Holdings LLC
•
Filing: 1985-09-11
•
Granted: 1989-03-28
•
Expires: 2005-09-11
Abstract
Abstract Lipid emulsion form compositions have been formulated and presented to eliminate adverse injection site reactions associated with the intravenous administration of certain sparingly water soluble, hydrophobic, ionizable drugs in mammals and to provide a solubilized drug form for oral, parenteral or intraarticular administration which enhances drug absorption and the therapeutic efficacy of the drug.
Inventors
- 👤 Narendra R. Desai
- 👤 Edward C. Shinal
- 👤 Madurai Ganesan
- 👤 Eugene A. Carpentier
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 19:52
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/0012; A61K9/0019; A61K47/00; A61K47/50; A61K47/51; A61K47/54; A61K47/541; A61K9/107; A61K9/1075
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
108 words
A composition of matter for delivery by intravenous, intramuscular or intraarticular routes of hydrophobic drugs comprising: (a) a hydrophobic drug; (b) a pharmaceutically acceptable oleaginous vehicle or oil selected from the group consisting of (i) naturally occurring vegetable oils and (ii) semisynthetic mono, di or triglycerides said oil or oleaginous vehicle being free of BHT or BHA; (c) a surfactant or emulsifier; (d) a co-surfactant or auxiliary emulsifier; (e) an ion-pair former selected from C 6 -C 20 saturated or unsaturated aliphatic or aromatic acids when the hydrophobic drug is basic and a pharamaceutically acceptable aliphatic or aromatic amine when the hydrophobic drug is acidic; and (f) water.
Claim 2
Dependent Claim
108 words
A composition of matter for delivery by intravenous, intramuscular or intraarticular routes of hydrophobic drugs comprising: (a) a hydrophobic drug; (b) a pharmaceutically acceptable oleaginous vehicle or oil selected from the group consisting of (i) naturally occurring vegetable oils and (ii) semisynthetic mono, di or triglycerides said oil or oleaginous vehicle being free of BHT or BHA; (c) a surfactant or emulsifier; (d) a co-surfactant or auxiliary emulsifier; (e) an ion-pair former selected from C 6 -C 20 saturated or unsaturated aliphatic or aromatic acids when the hydrophobic drug is basic and a pharamaceutically acceptable aliphatic or aromatic amine when the hydrophobic drug is acidic; and (f) water.
Claim 3
Dependent Claim
111 words
The composition of matter as recited in claim 1 comprising: ______________________________________
Percent
Ingredient Range W/V
______________________________________
Basic Hydrophobic Drug 0.01-5.0
Soybean Oil 3.0-20.0
Sesame Oil (super-refined)
0.0-5.0
Oleic Acid N.F. 0.2-4.0
Hexanoic Acid ˜short or long chain fatty
0.0-0.50
acid to form an ion-pair
Polyvinylpyrrolidone 0.0-0.2
Soy or Egg Lecithin-emulsifier
0.25-2.0
Polyoxyethylated hydrocarbon
0.0-1.0
dl-α-Tocopherol 0.0-0.05
Glycerine U.S.P. 0.5-2.25
Water qs ad 100
______________________________________ wherein the hydrophobic drug comprises a sparingly water soluble ionizable solid or a water insoluble viscous oily liquid and/or comprises a basic drug which has a pK' lower or nearer the physiological pH or an acidic drug which has a pK' higher or nearer the physiological pH.
Claim 4
Dependent Claim
87 words
The composition of matter as recited in claim 1 comprising: ______________________________________
Percent
Ingredient Range W/V
______________________________________
Acidic Hydrophobic Drug
0.01-5.0
.sub.--N--Methyl-D-glucamine or
0.1-5.0
R--NH--CH.sub.2 (CHOH).sub.4 CH.sub.2 OH
where R is alkyl(C.sub.1 -C.sub.6)
Soybean Oil 3.0-20.0
Soy or Egg Lecithin 0.2-2.0
Benzyl Alcohol 0.1-1.0
Glycerine U.S.P. 0.5-5.0
Water for Injection qs
______________________________________ wherein the hydrophobic drug may be a sparingly water soluble ionizable solid or a water insoluble viscous oily liquid and/or may be an acidic drug which has an ionization constant higher or nearer the physiological pH.
Claim 5
Dependent Claim
15 words
The composition of matter as recited in claim 2 where the hydrophobic drug is bis(2-imidazolin-2-ylhydrazone)-9,10-anthracenedicarboxaldehyde.
Claim 6
Dependent Claim
15 words
The composition of matter as recited in claim 2 where the hydrophobic drug is 3-[4,6-bis[(1,1-2,2-tetramethylpropyl)amino]-s-triazin-2-yl]-3-azabicyclo[3.2.2]nonane.
Claim 7
Dependent Claim
17 words
The composition of matter as recited in claim 3 where the hydrophobic drug is 4-biphenyl acetic acid.
Claim 8
Dependent Claim
44 words
The composition of matter as recited in claim 1 comprising: ______________________________________
Ingredient Amount % W/V
______________________________________
Hydrophobic Drug 0.2
Soybean Oil 10.0
Oleic Acid N.F. 1.2
Soy Lecithin 95% P.C.
1.2
Polyoxyethylated hydrocarbon
1.0
dl-α-Tocopherol
0.01
Glycerine U.S.P. 2.25
Water qs ad 100
______________________________________
Claim 9
Dependent Claim
47 words
The composition of matter as recited in claim 1 comprising: ______________________________________
Ingredient Amount % W/V
______________________________________
Hydrophobic Drug 0.2
Oleic Acid U.S.P.
0.8
Hexanoic Acid 0.1
Soybean Oil 10.0
Soy Lecithin 95% P.C.
1.2
dl-α-Tocopherol U.S.P.
0.01
Polyvinylpyrrolidone
0.1
Glycerine U.S.P. 2.25
Water qs ad 100
______________________________________
Claim 10
Dependent Claim
39 words
The composition of matter as recited in claim 1 comprising: ______________________________________
Ingredient Percent W/V
______________________________________
Hydrophobic Drug 1.0
.sub.--N--Methyl-D-glucamine
0.92
Soybean Oil 7.00
Soy Lecithin 95% P.C.
1.00
Benzyl Alcohol 0.60
Glycerine U.S.P. 4.50
Water qs ad 100.
______________________________________
Claim 11
Dependent Claim
16 words
The composition of matter as recited in claim 7 where the hydrophobic drug is bis( 2-imidazolin-2-ylhydrazone)-9,10-anthracenedicarboxaldehyde.
Claim 12
Dependent Claim
15 words
The composition of matter as recited in claim 8 where the hydrophobic drug is bis(2-imidazolin-2-ylhydrazone)-9,10-anthracenedicarboxaldehyde.
Claim 13
Dependent Claim
17 words
The composition of matter as recited in claim 9 where the hydrophobic drug is 4-biphenyl acetic acid.
Claim 14
Dependent Claim
42 words
The composition of matter as recited in claim 1 comprising: ______________________________________
Percent
Ingredient Range W/V
______________________________________
Hydrophobic Drug 0.1-1.0
Soybean Oil 20.0
Oleic Acid N.F. 1.2
Soy Lecithin 95% P.C.
1.2
Polyoxyethylated hydrocarbon
1.0
dl-α-Tocopherol U.S.P.
0.01
Water qs ad 100
______________________________________
Claim 15
Dependent Claim
15 words
The composition of matter as recited in claim 3 where the hydrophobic drug is 3-[4,6-bis[(1,1-2,2-tetramethylpropyl)amino]-s-triazin-2-yl]-3-azabicyclo[3.2.2]-nonane.
Claim 16
Dependent Claim
46 words
The composition of matter as recited in claim 1, which consists essentially of: ______________________________________
Ingredient Percent W/V
______________________________________
Hydrophobic Drug 0.2
Soybean Oil 10.0
Oleic Acid N.F. 1.2
Soy Lecithin 95% P.C.
1.2
Polyoxyethylated Hydrocarbon
1.0
dl-α-Tocopherol
0.01
Glycerine U.S.P. 2.25
Water qs ad 100.
______________________________________
Claim 17
Dependent Claim
52 words
The composition of matter as recited in claim 1, which consists essentially of: ______________________________________
Ingredient Amount % W/V
______________________________________
Hydrophobic Drug 0.2
Oleic Acid U.S.P. 0.8
Hexanoic Acid 0.1
Soybean Oil 10.0
Soy Lecithin 95% P.C. 1.2
dl-α-Tocopherol U.S.P.
0.01
Polyvinylpyrrolidone Type N.P.-K-30
0.1
Glycerine U.S.P. 2.25
Water qs ad 100.
______________________________________
Claim 18
Dependent Claim
42 words
The composition of matter as recited in claim 1, which consists essentially of: ______________________________________
Ingredient Percent W/V
______________________________________
Hydrophobic Drug 1.0
.sub.--N--Methyl-D-glucamine
0.92
Soybean Oil 7.00
Soy Lecithin 95% P.C.
1.00
Benzyl Alcohol 0.60
Glycerine U.S.P. 4.50
Water qs ad 100.
______________________________________
Claim 19
Dependent Claim
44 words
The composition of matter as recited in claim 1, which consists essentially of: ______________________________________
Percent
Ingredient Range W/V
______________________________________
Hydrophobic Drug 0.1-1.0
Soybean Oil 20.0
Oleic Acid N.F. 1.2
Soy Lecithin 95% P.C.
1.2
Polyoxyethylated Hydrocarbon
1.0
dl-α-Tocopherol
0.01
Water qs ad 100.
______________________________________
Claim 20
Dependent Claim
14 words
A composition as defined in claim 15, wherein the hydrophobic drug is bis( 2-imidazolin-2-ylhydrazone)-9,10-anthracenedicarboxaldehyde.
Claim 21
Dependent Claim
13 words
A composition ad defined in claim 16, wherein the hydrophobic drug is bis(2-imidazolin-2-ylhydrazone)-9,10-anthracenedicarboxaldehyde.
Claim 22
Dependent Claim
13 words
A composition ad defined in claim 17, wherein the hydrophobic drug is bis(2-imidazolin-2-ylhydrazone)-9,10-anthracenedicarboxaldehyde.
Claim 23
Dependent Claim
13 words
A composition ad defined in claim 18, wherein the hydrophobic drug is bis(2-imidazolin-2-ylhydrazone)-9,10-anthracenedicarboxaldehyde.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-03-27 | 1992-09-26 | 1993-03-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-03-27 | 1996-09-26 | 1997-03-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-03-27 | 2000-09-26 | 2001-03-28 | $7700.00 | Window Closed / Lapsed |