US4725442A
Expired / Lapsed
US
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Microdroplets of water-insoluble drugs and injectable formulations containing same
Assignee: PAUL ROYALTY FUND LP
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Filing: 1986-04-22
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Granted: 1988-02-16
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Expires: 2006-04-22
Abstract
Abstract Microdroplets of water-insoluble drugs coated with a phospholipid are prepared by sonication. As an example, microdroplets of the general anesthetic methoxyfluorane coated by a unimolecular layer of dimysistoyl phosphatidylcholine are prepared by sonication. The microdroplets so prepared remain stable in physiologically-compatible solution, and are suitable for injection, typically intradermally or intraveneously, into a patient for inducing local anesthesia. These methoxyflurane-containing microdroplets have been demonstrated to cause long-term local anesthesia when injected intradermally, giving duration of anesthesia 28 times longer than with other anesthetics, such as lidocaine and 11 times longer than with bupivacaine. The latter is considered longest acting conventional local anesthetic. The microdroplet is also capable of solubilizing and delivering benzocaine and other water-insoluble drugs, and thus represents a novel drug delivery system and general method for delivery of water-insoluble drugs, lowering the necessary dose and providing a more direct and timed release.
Inventors
- 👤 Duncan H. Haynes
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:29
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/107; A61K9/1075; A61K9/127
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
33 words
A microdroplet of from about 200 Angstroms up to one micron in diameter consisting essentially of a sphere of a substantially water-insoluble, pharmacologically acceptable liquid drug substance surrounded by a layer of phospholipid.
Claim 2
Dependent Claim
33 words
A microdroplet of from about 200 Angstroms up to one micron in diameter consisting essentially of a sphere of a substantially water-insoluble, pharmacologically acceptable liquid drug substance surrounded by a layer of phospholipid.
Claim 3
Dependent Claim
73 words
A microdroplet of from about 200 angstroms up to one micron in diameter consisting essentially of a sphere of a substantially water-insoluble drug substance dissolved in a compatible, pharmaceutically acceptable organic liquid selected from an alkane, a dialkyl ether, a long-chain ester, a hydrophobic ester, a biocompatible silicone, a biocompatible high molecular weight fluorocarbon, an oil-soluble vitamin and a volatile liquid anesthetic, the liquid plus drug being surrounded by a layer of phospholipid.
Claim 4
Dependent Claim
73 words
A microdroplet of from about 200 angstroms up to one micron in diameter consisting essentially of a sphere of a substantially water-insoluble drug substance dissolved in a compatible, pharmaceutically acceptable organic liquid selected from an alkane, a dialkyl ether, a long-chain ester, a hydrophobic ester, a biocompatible silicone, a biocompatible high molecular weight fluorocarbon, an oil-soluble vitamin and a volatile liquid anesthetic, the liquid plus drug being surrounded by a layer of phospholipid.
Claim 5
Dependent Claim
70 words
A microdroplet of from about 200 Angstroms up to one micron in diameter consisting essentially of a sphere of a liquid drug substance together with a compatible, pharmaceutically acceptable organic liquid selected from a volatile liquid anesthetic, an alkane, a dialkyl ether, a long-chain ester, a hydrophobic ester, a biocompatible silicone and a biocompatible high molecular weight fluorocarbon, the liquid plus liquid drug being surrounded by a layer of phospholipid.
Claim 6
Dependent Claim
70 words
A microdroplet of from about 200 Angstroms up to one micron in diameter consisting essentially of a sphere of a liquid drug substance together with a compatible, pharmaceutically acceptable organic liquid selected from a volatile liquid anesthetic, an alkane, a dialkyl ether, a long-chain ester, a hydrophobic ester, a biocompatible silicone and a biocompatible high molecular weight fluorocarbon, the liquid plus liquid drug being surrounded by a layer of phospholipid.
Claim 7
Dependent Claim
22 words
An injectable pharmaceutical composition consisting essentially of the microdroplets of claim 1, 2 or 3 together with a pharmaceutically acceptable injectable vehicle.
Claim 8
Dependent Claim
16 words
The injectable pharmaceutical composition of claim 4, in which the injectable vehicle is an isotonic solution.
Claim 9
Dependent Claim
20 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a general anesthetic in liquid form.
Claim 10
Dependent Claim
18 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a water-insoluble local anesthetic.
Claim 11
Dependent Claim
17 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a muscle relaxant.
Claim 12
Dependent Claim
18 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a hypnotic/sedative or analgesic.
Claim 13
Dependent Claim
18 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a non-steroidal anti-inflammatory agent.
Claim 14
Dependent Claim
18 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a steroidal anti-inflammatory agent.
Claim 15
Dependent Claim
18 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a membrane-binding, lipophilic antibiotic.
Claim 16
Dependent Claim
18 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a cardiovascularly active drug.
Claim 17
Dependent Claim
16 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a hormone.
Claim 18
Dependent Claim
18 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a cancer therapeutic agent.
Claim 19
Dependent Claim
16 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a diuretic.
Claim 20
Dependent Claim
16 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is an anticoagulant.
Claim 21
Dependent Claim
17 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is an oil-soluble vitamin.
Claim 22
Dependent Claim
16 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is a prostaglandin.
Claim 23
Dependent Claim
17 words
The microdroplet of claim 1, 2 or 3 in which the drub substance is a tricyclic antidepressant.
Claim 24
Dependent Claim
16 words
The microdroplet of claim 1, 2 or 3 in which the drug substance is an antiepileptic.
Claim 25
Dependent Claim
53 words
A microdroplet, produced by sonification, of from about 200 Angstroms to one micron in diameter and consisting of a water-insoluble liquid drug core stabilized against coalescence and surrounded by a phospholipid layer in which the ratio of volume of drug substance to the weight of the phospholipid layer is at least 1.0 ml/g.
Claim 26
Dependent Claim
53 words
A microdroplet, produced by sonification, of from about 200 Angstroms to one micron in diameter and consisting of a water-insoluble liquid drug core stabilized against coalescence and surrounded by a phospholipid layer in which the ratio of volume of drug substance to the weight of the phospholipid layer is at least 1.0 ml/g.
Claim 27
Dependent Claim
13 words
The microdroplet of claim 22, having a diameter of up to 10,000 Angstroms.
Claim 28
Dependent Claim
47 words
A timed release drug delivery vehicle composed of microdroplets of from about 200 Angstroms up to one micron in diameter consisting essentially of a substantially water-insoluble drug substance, itself a liquid or dissolved in a water-insoluble liquid, stabilized against coalescence and surrounded by a layer of phospholipid.
Claim 29
Dependent Claim
47 words
A timed release drug delivery vehicle composed of microdroplets of from about 200 Angstroms up to one micron in diameter consisting essentially of a substantially water-insoluble drug substance, itself a liquid or dissolved in a water-insoluble liquid, stabilized against coalescence and surrounded by a layer of phospholipid.
Claim 30
Dependent Claim
76 words
A sterile, injectable pharmaceutical composition consisting essentially of: (1) microdroplets of from about 200 Angstroms to one micron in diameter produced by sonification and consisting of a water-insoluble local anesthetic or a solution thereof as the core stabilized against coalescence and surrounded by a phospholipid membrane layer, the ratio of the volume of liquid local anesthetic to the weight of the phospholipid membrane layer is at least 1.0 ml/g, and (2) a pharmaceutically acceptable injectable carrier.
Claim 31
Dependent Claim
76 words
A sterile, injectable pharmaceutical composition consisting essentially of: (1) microdroplets of from about 200 Angstroms to one micron in diameter produced by sonification and consisting of a water-insoluble local anesthetic or a solution thereof as the core stabilized against coalescence and surrounded by a phospholipid membrane layer, the ratio of the volume of liquid local anesthetic to the weight of the phospholipid membrane layer is at least 1.0 ml/g, and (2) a pharmaceutically acceptable injectable carrier.
Claim 32
Dependent Claim
72 words
A sterile, injectable pharmaceutical composition consisting essentially of: (1) microdroplets of from about 200 Angstroms to one micron in diameter produced by sonification and consisting of a water-insoluble general anesthetic in liquid form as the core stabilized against coalescence and surrounded by a phospholipid membrane layer, the ratio of the volume of general anesthetic to the weight of the phospholipid is at least 1.0 ml/g, and (2) a pharmaceutically acceptable injectable carrier.
Claim 33
Dependent Claim
72 words
A sterile, injectable pharmaceutical composition consisting essentially of: (1) microdroplets of from about 200 Angstroms to one micron in diameter produced by sonification and consisting of a water-insoluble general anesthetic in liquid form as the core stabilized against coalescence and surrounded by a phospholipid membrane layer, the ratio of the volume of general anesthetic to the weight of the phospholipid is at least 1.0 ml/g, and (2) a pharmaceutically acceptable injectable carrier.
Claim 34
Dependent Claim
21 words
The pharmaceutical composition of claim 26, in which a substantially water-insoluble, non-anesthetic drug substance is solubilized in the liquid general anesthetic.
Claim 35
Dependent Claim
66 words
A timed release drug delivery vehicle composed of microdroplets of from about 200 Angstroms to 10,000 Angstroms in diameter consisting essentially of a water-insoluble drug substance, itself a liquid or dissolved in a water-insoluble liquid, stabilized against coalescence and surrounded by a layer of phospholipid in which the ratio of the volume of drug substance to the weight of the phospholipid is at least 1.0 ml/g.
Claim 36
Dependent Claim
66 words
A timed release drug delivery vehicle composed of microdroplets of from about 200 Angstroms to 10,000 Angstroms in diameter consisting essentially of a water-insoluble drug substance, itself a liquid or dissolved in a water-insoluble liquid, stabilized against coalescence and surrounded by a layer of phospholipid in which the ratio of the volume of drug substance to the weight of the phospholipid is at least 1.0 ml/g.
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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) | 1991-02-15 | 1991-08-17 | 1992-02-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-02-15 | 1995-08-17 | 1996-02-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-02-15 | 1999-08-17 | 2000-02-16 | $7700.00 | Window Closed / Lapsed |