US4687762A
Expired / Lapsed
US
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Water soluble drug complex and method for production of same
Assignee: Tanabe Pharma Corp
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Filing: 1985-03-27
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Granted: 1987-08-18
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Expires: 2005-03-27
Abstract
Abstract The invention provides a method of producing a water-soluble complex comprising a water-insoluble drug and a phospholipid, comprising the steps of (1) dissolving a water-insoluble drug and a phospholipid in an organic solvent, (2) removing the solvent to leave behind a drug-containing phospholipid film, (3) suspending the resulting film in an aqueous solution, (4) ultrasonicating the film, (5) centrifuging the resulting suspension, and (6) recovering the lowermost layer of the resulting sediment to yield the water-soluble complex. The above complex can be administered parenterally as well as by the oral and other routes, and is so rich in the drug component that a remarkably increased drug activity can be realized.
Inventors
- 👤 Tsunekazu Fukushima
- 👤 Hiroshi Emoto
- 👤 Yoshio Kagitani
- 👤 Kazumasa Yokoyama
- 👤 Masayuki Nishida
- 👤 Tadakazu Suyama
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 14:22
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/10; A61K9/127; A61K9/1277; A61K47/00; A61K47/50; A61K47/51; A61K47/54; A61K47/543; A61K47/544
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
152 words
A method of producing a water-soluble complex comprising a water-insoluble drug which is a pharmacologically active compound having a molecular weight not over 1,000 and a phospholipid, comprising the steps of (1) dissolving a water-insoluble drug and a phospholipid in an organic solvent in a ratio of 0.01 to 10 parts by weight of said drug per part by weight of said phospholipid, (2) removing the solvent by evaporation to leave behind a drug-containing phospholipid film, (3) suspending the resulting film in physiologically acceptable aqueous solution, (4) ultrasonicating the film, whereby particle diameter is adjusted to 0.2 to 2 μm, (5) centrifuging the resulting suspension at 10,000× g or more for a period of 30 minutes to 2 hours to divide it into three layers comprising an upper layer, an intermediate layer and a lower most layer, and (6) recovering the lowermost layer of the resulting sediment to yield the water-soluble complex.
Claim 2
Independent Claim
152 words
A method of producing a water-soluble complex comprising a water-insoluble drug which is a pharmacologically active compound having a molecular weight not over 1,000 and a phospholipid, comprising the steps of (1) dissolving a water-insoluble drug and a phospholipid in an organic solvent in a ratio of 0.01 to 10 parts by weight of said drug per part by weight of said phospholipid, (2) removing the solvent by evaporation to leave behind a drug-containing phospholipid film, (3) suspending the resulting film in physiologically acceptable aqueous solution, (4) ultrasonicating the film, whereby particle diameter is adjusted to 0.2 to 2 μm, (5) centrifuging the resulting suspension at 10,000× g or more for a period of 30 minutes to 2 hours to divide it into three layers comprising an upper layer, an intermediate layer and a lower most layer, and (6) recovering the lowermost layer of the resulting sediment to yield the water-soluble complex.
Claim 3
Dependent Claim
26 words
The method according to claim 1, wherein said water-insoluble drug has a solubility in an organic solvent in the range of about 0.1 to 100 mg/ml.
Claim 4
Dependent Claim
13 words
The method according to claim 1, wherein said drug is an anticancer drug.
Claim 5
Dependent Claim
27 words
The method according to claim 3, wherein said drug is an anticancer drug is a member selected from the group consisting of spadicomycin, anthramycin, daunomycin and adriamycin.
Claim 6
Dependent Claim
13 words
The method according to claim 1, wherein said drug is an anti-inflammatory-analgesic drug.
Claim 7
Dependent Claim
22 words
The method according to claim 5, wherein said anti-inflammatory-analgesic drug is a member selected from the group consisting of flurbiprofen and acemetacin.
Claim 8
Dependent Claim
12 words
The method according to claim 1, wherein said water-insoluble drug is prostaglandin.
Claim 9
Dependent Claim
14 words
The method according to claim 1, wherein said water-insoluble drug is a lipoxygenase inhibitor.
Claim 10
Dependent Claim
12 words
The method according to claim 1, wherein said phospholipid is soybean phospholipid.
Claim 11
Dependent Claim
13 words
The method according to claim 1, wherein said phospholipid is egg yolk phospholipid.
Claim 12
Dependent Claim
19 words
The method according to claim 1, wherein an antioxidant for stabilizing said phospholipid is used in a stabilizing amount.
Claim 13
Dependent Claim
27 words
The method according to claim 1, wherein said ultrasonication is performed under ice-cooling until said suspension is in a particle size range of 0.2 to 2 μ.
Claim 14
Dependent Claim
26 words
The method according to claim 1, wherein said centrifugation is performed at 10,000× g to 30,000× g for a period of 30 minutes to 2 hours.
Claim 15
Dependent Claim
26 words
The method according to claim 13, wherein said centrifugation is carried out at 20,000 to 30,000× g for a period of 30 minutes to 2 hours.
Claim 16
Dependent Claim
17 words
The method according to claim 1 wherein said drug-phospholipid complex is further freeze-dried to provide a lyophilizate.
Claim 17
Dependent Claim
18 words
The method according to claim 15, wherein said freeze-drying is performed in the presence of a nonionic surfactant.
Claim 18
Dependent Claim
16 words
The method according to claim 15, wherein said lyophilizate is further processed into a dosage form.
Claim 19
Dependent Claim
18 words
A water-soluble complex comprising a water-insoluble drug and a phospholipid produced by the method according to claim 1.
Claim 20
Dependent Claim
26 words
The complex according to claim 18, wherein said water-insoluble drug has a solubility in an organic solvent in the range of about 0.1 to 100 mg/ml.
Claim 21
Dependent Claim
18 words
The complex according to claims 18 or 19, wherein said drug has a molecular weight not over 1000.
Claim 22
Dependent Claim
13 words
The complex according to claim 18, wherein said drug is an anticancer drug.
Claim 23
Dependent Claim
24 words
The complex according to claim 21, wherein said anticancer drug is a member selected from the group consisting of spadicomycin, anthramycin, daunomycin and adriamycin.
Claim 24
Dependent Claim
13 words
The complex according to claim 18, wherein said drug is an anti-inflammatory-analgesic drug.
Claim 25
Dependent Claim
22 words
The complex according to claim 23, wherein said anti-inflammatory-analgesic drug is a member selected from the group consisting of flurbiprofen and acemetacin.
Claim 26
Dependent Claim
12 words
The complex according to claim 18, wherein said drug is a prostaglandin.
Claim 27
Dependent Claim
13 words
The complex according to claim 18, wherein said drug is a lipoxygenase inhibitor.
Claim 28
Dependent Claim
12 words
The complex according to claim 18, wherein said phospholipid is soybean phospholipid.
Claim 29
Dependent Claim
13 words
The complex according to claim 18, wherein said phospholipid is egg yolk phospholipid.
Claim 30
Dependent Claim
14 words
The complex according to claim 18, which is in the form of a lyophilizate.
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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) | 1990-08-17 | 1991-02-16 | 1991-08-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-08-17 | 1995-02-16 | 1995-08-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-08-17 | 1999-02-16 | 1999-08-18 | $7700.00 | Window Closed / Lapsed |