US5603961A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Sustained release multi-core microsphere preparation and method for producing the same
Assignee: Tanabe Pharma Corp
•
Filing: 1993-09-30
•
Granted: 1997-02-18
•
Expires: 2013-09-30
Abstract
Abstract Sustained release multi-core microsphere preparation which shows high incorporation efficiency of medicament and can release the medicament at a specific rate, which comprises two or more biodegradable polymers and a pharmaceutically active ingredient, and has the medicament incorporated into microregions which are produced by one of these polymers (the first polymer), and these microregions are distributed in other biodegradable polymers (the second polymer), or a method for producing the same.
Inventors
- 👤 Takehiko Suzuki
- 👤 Yukiko Nishioka
- 👤 Yasuhisa Matsukawa
- 👤 Akihiro Matsumoto
- 👤 Masao Kobayashi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 19:26
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/14; A61K9/16; A61K9/1682; A61K9/1694; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/1647; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984; Y10T428/2985
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
169 words
A sustained release multi-core microsphere preparation, which comprises (1) microregions comprising a first biodegradable polymer, (2) a continuous region comprising a second biodegradable polymer, in which the microregions are distributed, and (3) a therapeutically effective amount of at least one pharmaceutically active ingredient selectively retained in the microregions of said first biodegradable polymer; said microsphere preparation being obtained by (i) preparing an oil-in-oil emulsion comprising water immiscible organic solvent, the first biodegradable polymer, the second biodegradable polymer and the pharmaceutically active ingredient having higher affinity for the first biodegradable polymer than for the second biodegradable polymer, the biodegradable polymers being selected from the group consisting of polylactic acid and a copolymer of lactic acid and glycolic acid, and the oil-in-oil emulsion having microdroplets of the first biodegradable polymer dispersed in a continuous oil phase of the second biodegradable polymer, (ii) dispersing the oil-in-oil emulsion in an aqueous solution to give an oil-in-oil-in-water emulsion, and (iii) removing the water-immiscible organic solvent from the oil phases of the resulting oil-in-oil-in-water emulsion.
Claim 2
Dependent Claim
169 words
A sustained release multi-core microsphere preparation, which comprises (1) microregions comprising a first biodegradable polymer, (2) a continuous region comprising a second biodegradable polymer, in which the microregions are distributed, and (3) a therapeutically effective amount of at least one pharmaceutically active ingredient selectively retained in the microregions of said first biodegradable polymer; said microsphere preparation being obtained by (i) preparing an oil-in-oil emulsion comprising water immiscible organic solvent, the first biodegradable polymer, the second biodegradable polymer and the pharmaceutically active ingredient having higher affinity for the first biodegradable polymer than for the second biodegradable polymer, the biodegradable polymers being selected from the group consisting of polylactic acid and a copolymer of lactic acid and glycolic acid, and the oil-in-oil emulsion having microdroplets of the first biodegradable polymer dispersed in a continuous oil phase of the second biodegradable polymer, (ii) dispersing the oil-in-oil emulsion in an aqueous solution to give an oil-in-oil-in-water emulsion, and (iii) removing the water-immiscible organic solvent from the oil phases of the resulting oil-in-oil-in-water emulsion.
Claim 3
Dependent Claim
29 words
The microsphere preparation according to claim 1, wherein said first biodegradable polymer is a copolymer of lactic acid and glycolic acid and said second biodegradable polymer is polylactic acid.
Claim 4
Dependent Claim
29 words
The microsphere preparation according to claim 1, wherein said first biodegradable polymer is polylactic acid and said second biodegradable polymer is a copolymer of lactic acid and glycolic acid.
Claim 5
Dependent Claim
29 words
The microsphere preparation according to claim 2, wherein said pharmaceutically active ingredient in a member selected from the group consisting of cisplatin, TRH, LHRH, and vitamin B 12 .
Claim 6
Dependent Claim
26 words
The microsphere preparation according to claim 3, wherein said pharmaceutically active ingredient is a member selected from the group consisting of calcitonin and (4S)-3-{(2S)-N-{(1S)-1-ethoxycarbonyl-3-phenylpropyl}alanyl}-1-methyl-2-oxo-4-imidazolidinecarboxylic acid hydrochloride.
Claim 7
Dependent Claim
33 words
The microsphere preparation according to any one of claims 2, 3, 1, 4, or 5 wherein said microsphere preparation has an average particle size in the range of 0.01 μm to 500 μm.
Claim 8
Dependent Claim
68 words
A sustained release multi-core microsphere preparation having an average particle size in the range of 0.01 μm to 500 μm, which comprises (1) microregions comprising a copolymer of lactic acid and glycolic acid, (2) a continuous region comprising polylactic acid, in which the microregions are distributed, and (3) a therapeutically effective amount of cisplatin selectively retained in said microregions comprising a copolymer of lactic acid and glycolic acid.
Claim 9
Dependent Claim
68 words
A sustained release multi-core microsphere preparation having an average particle size in the range of 0.01 μm to 500 μm, which comprises (1) microregions comprising a copolymer of lactic acid and glycolic acid, (2) a continuous region comprising polylactic acid, in which the microregions are distributed, and (3) a therapeutically effective amount of cisplatin selectively retained in said microregions comprising a copolymer of lactic acid and glycolic acid.
Claim 10
Independent Claim
131 words
A method of producing a multi-core microsphere preparation which comprises the steps of: (1) preparing an oil-in-oil emulsion comprising a water immiscible organic solvent, a first biodegradable polymer, a second biodegradable polymer and at least one pharmaceutically active ingredient having higher affinity for the first biodegradable polymer than for the second biodegradable polymer, said biodegradable polymers being selected from the group consisting of polylactic acid and a copolymer of lactic acid and glycolic acid, (2) dispersing said oil-in-oil emulsion in an aqueous solution to give an oil-in-oil-in-water emulsion, and (3) removing said water-immiscible organic solvent from the oil phases of the resulting oil-in-oil-in-water emulsion to obtain a multi-core microsphere comprising microregions distributed in a continuous region and a pharmaceutically active ingredient retained selectively in the microregions or in the continuous region.
Claim 11
Independent Claim
131 words
A method of producing a multi-core microsphere preparation which comprises the steps of: (1) preparing an oil-in-oil emulsion comprising a water immiscible organic solvent, a first biodegradable polymer, a second biodegradable polymer and at least one pharmaceutically active ingredient having higher affinity for the first biodegradable polymer than for the second biodegradable polymer, said biodegradable polymers being selected from the group consisting of polylactic acid and a copolymer of lactic acid and glycolic acid, (2) dispersing said oil-in-oil emulsion in an aqueous solution to give an oil-in-oil-in-water emulsion, and (3) removing said water-immiscible organic solvent from the oil phases of the resulting oil-in-oil-in-water emulsion to obtain a multi-core microsphere comprising microregions distributed in a continuous region and a pharmaceutically active ingredient retained selectively in the microregions or in the continuous region.
Claim 12
Dependent Claim
25 words
A method according to claim 8, wherein the first polymer and the second polymer are used in a ratio of 1:2 to 4 by weight.
Claim 13
Dependent Claim
30 words
The microsphere preparation according to claim 1, wherein the polylactic acid and the copolymer of lactic acid and glycolic acid are those having a molecular weight of 1,000 to 500,000.
Claim 14
Dependent Claim
20 words
The microsphere preparation according to claim 1, wherein the first polymer is a mixture of two or more biodegradable polymers.
Claim 15
Dependent Claim
20 words
The microsphere preparation according to claim 1, wherein the second polymer is a mixture of two or more biodegradable polymers.
Claim 16
Dependent Claim
33 words
The microsphere preparation according to any one of claims 2, 3, 1, 4, 5, wherein the first polymer and the second polymer are used in a ratio of 1:2 to 4 by weight.
Claim 17
Dependent Claim
30 words
The microsphere preparation according to any one of claims 2, 3, 1, 4, 5, wherein a content of the pharmaceutically active ingredient is in a range of 0.01 to 40%.
References Cited (Backward Citations)
EP0052510B1
Cited
EP0145240A2
Cited
US4940588A
Cited
EP0190833A2
Cited
EP0263490A2
Cited
WO1988008300A1
Cited
EP0330180A1
Cited
US5100669A
Cited
WO1989007935A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-02-18 | 2000-08-19 | 2001-02-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-02-18 | 2004-08-19 | 2005-02-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-02-18 | 2008-08-19 | 2009-02-18 | $7700.00 | Window Closed / Lapsed |