US4806337A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Erodible matrix for sustained release bioactive composition
Assignee: Actavis Laboratories UT Inc
•
Filing: 1986-10-14
•
Granted: 1989-02-21
•
Expires: 2006-10-14
Abstract
Abstract A sustained release composition for releasing a biologically active compound into an aqueous liquid environment comprises said biologically active compound dispersed in a bioerodible matrix, the matrix comprising a mixture of (a.) 5% to 95% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000K selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in the aqueous liquid. Dosage forms comprising the erodible matrix are prepared by molding, particularly by injection molding.
Inventors
- 👤 Wallace C. Snipes
- 👤 Stephen J. Wagner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 22:54
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/20; A61K9/2004; A61K9/2022; A61K9/2031; A61K9/2013; B; B29; B29K; B29K2105/00; B29K2105/0005; B29K2105/0035; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2913; Y10T428/2933; Y10T428/294; Y10T428/298; Y10T428/2982; Y10T428/2989
Claims Analysis
Total Claims: 103
Claim 1
Independent Claim
82 words
A composition erodible by an aqueous liquid comprising (a.) 5% to 99.5% by weight of a solid water dispersible polyether dio having a molecular weight from about 1000 to about 20,000 selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 2
Dependent Claim
82 words
A composition erodible by an aqueous liquid comprising (a.) 5% to 99.5% by weight of a solid water dispersible polyether dio having a molecular weight from about 1000 to about 20,000 selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 3
Dependent Claim
20 words
The composition of claim 1 wherein said polyether diol is a polyethylene glycol having a molecular weight of about 8000.
Claim 4
Dependent Claim
20 words
The composition of claim 1 wherein said water-dispersible polyether diol is a block copolymer of ethylene oxide and propylene oxide.
Claim 5
Dependent Claim
62 words
The composition of claim 3 wherein said polyether diol is a block copolymer having the formula HO(CH.sub.2 CH.sub.2 O).sub.a (CH(CH.sub.3)CH.sub.2 O).sub.b (CH.sub.2 CH.sub.2 O).sub.c H wherein b has a value of 15 or greater and the sum of a and c is selected so that the terminal portions of the molecule comprise from 20% to 90% by weight of the polymer molecule.
Claim 6
Dependent Claim
22 words
The composition of claim 3 wherein a has a value of about 30 and a and c have values of about 75.
Claim 7
Dependent Claim
18 words
The composition of claim 1 wherein said erosion rate modifier is a C 12 -C 20 fatty acid.
Claim 8
Dependent Claim
21 words
The composition of claim 6 wherein said fatty acid is selected from the group consisting of myristic acid and stearic acid.
Claim 9
Dependent Claim
19 words
The composition of claim 1 wherein said erosion rate modifier is a combination of stearyl alcohol and stearic acid.
Claim 10
Dependent Claim
39 words
The composition of claim 9 wherein said stearyl alcohol is present in an amount of about 4% to about 13% by weight and said stearic acid is present in an amount of about 4% to about 15% by weight.
Claim 11
Dependent Claim
22 words
The composition of claim 1 additionally comprising a substance which increases the compatibility of the polyethylene glycol and the erosion rate modifier.
Claim 12
Dependent Claim
41 words
The composition of claim 10 wherein said substance is a polyethylene glycol having a molecular weight from about 200 to about 10000 and having at least one of its terminal OH groups esterified with a C 12 -C 20 fatty acid.
Claim 13
Dependent Claim
13 words
The composition of claim 11 wherein said polyethylene glycol is polyethylene glycol 400.
Claim 14
Dependent Claim
25 words
The composition of claim 12 wherein said substance is polyethylene glycol 400 having at least one of its terminal OH groups esterified with stearic acid.
Claim 15
Dependent Claim
9 words
The composition of claim 1 additionally comprising a disintegrant.
Claim 16
Dependent Claim
10 words
The composition of claim 14 wherein said disintegrant is starch.
Claim 17
Dependent Claim
10 words
The composition of claim 1 additionally comprising a molding adjuvant.
Claim 18
Dependent Claim
20 words
The composition of claim 16 wherein said molding adjuvant is polyethylene oxide having a molecular weight of 100,000 to 5,000,000.
Claim 19
Dependent Claim
111 words
A sustained release composition for releasing a biologically active compound into its surrounding environment comprising said biologically active compound dispersed in a matrix which, when contacted wth an aqueous liquid, erodes progressively, said matrix comprising a mixture of (a.) 5% to 99.5% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 20
Dependent Claim
111 words
A sustained release composition for releasing a biologically active compound into its surrounding environment comprising said biologically active compound dispersed in a matrix which, when contacted wth an aqueous liquid, erodes progressively, said matrix comprising a mixture of (a.) 5% to 99.5% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 21
Dependent Claim
20 words
The composition of claim 18 wherein said polyether diol is a polyethylene glycol having a molecular weight of about 8000.
Claim 22
Dependent Claim
20 words
The composition of claim 18 wherein said water-dispersible polyether diol is a block copolymer of ethylene oxide and propylene oxide.
Claim 23
Dependent Claim
62 words
The composition of claim 20 wherein said polyether diol is a block copolymer having the formula HO(CH.sub.2 CH.sub.2 O).sub.a (CH(CH.sub.3)CH.sub.2 O).sub.b CH.sub.2 CH.sub.2 O).sub.c H wherein b has a value of 15 or greater and the sum of a and c is selected so that the terminal portions of the molecule comprise from 20% to 90% by weight of the polymer molecule.
Claim 24
Dependent Claim
22 words
The composition of claim 21 wherein a has a value of about 30 and a and c have values of about 75.
Claim 25
Dependent Claim
18 words
The composition of claim 18 wherein said erosion rate modifier is a C 12 -C 20 fatty acid.
Claim 26
Dependent Claim
21 words
The composition of claim 23 wherein said fatty acid is selected from the group consisting of myristic acid and stearic acid.
Claim 27
Dependent Claim
19 words
The composition of claim 18 wherein said erosion rate modifier is a combination of stearyl alcohol and stearic acid.
Claim 28
Dependent Claim
39 words
The composition of claim 25 wherein said stearyl alcohol is present in an amount of about 4% to about 13% by weight and said stearic acid is present in an amount of about 4% to about 15% by weight.
Claim 29
Dependent Claim
22 words
The composition of claim 18 additionally comprising a substance which increases the compatibility of the polyethylene glycol and the erosion rate modifier.
Claim 30
Dependent Claim
41 words
The composition of claim 27 wherein said substance is a polyethylene glycol having a molecular weight from about 200 to about 10000 and having at least one of its terminal OH groups esterified with a C 12 -C 20 fatty acid.
Claim 31
Dependent Claim
13 words
The composition of claim 28 wherein said polyethylene glycol is polyethylene glycol 400.
Claim 32
Dependent Claim
25 words
The composition of claim 29 wherein said substance is polyethylene glycol 400 having at least one of its terminal OH groups esterified with stearic acid.
Claim 33
Dependent Claim
9 words
The composition of claim 18 additionally comprising a disintegrant.
Claim 34
Dependent Claim
10 words
The composition of claim 31 wherein said disintegrant is starch.
Claim 35
Dependent Claim
10 words
The composition of claim 18 additionally comprising a molding adjuvant.
Claim 36
Dependent Claim
20 words
The composition of claim 33 wherein said molding adjuvant is polyethylene oxide having a molecular weight of 100,000 to 5,000,000.
Claim 37
Dependent Claim
121 words
A sustained release composition for releasing a biologically active compound into its surrounding environment comprising a pharmaceutically active compound or non-toxic pharmaceutically acceptable salt of said pharmaceutically active compound dispersed in a matrix which, when contacted with an aqueous liquid, erodes progressively, said matrix comprising a mixture of (a.) 5% to 99.5% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 38
Dependent Claim
121 words
A sustained release composition for releasing a biologically active compound into its surrounding environment comprising a pharmaceutically active compound or non-toxic pharmaceutically acceptable salt of said pharmaceutically active compound dispersed in a matrix which, when contacted with an aqueous liquid, erodes progressively, said matrix comprising a mixture of (a.) 5% to 99.5% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 39
Dependent Claim
10 words
The composition of claim 35 wherein said compound is clonidine.
Claim 40
Dependent Claim
10 words
The composition of claim 35 wherein said compound is dipyridamole.
Claim 41
Dependent Claim
10 words
The composition of claim 35 wherein said compound is hydrochlorothiazide.
Claim 42
Dependent Claim
10 words
The composition of claim 35 wherein said compound is furosemide.
Claim 43
Dependent Claim
10 words
The composition of claim 35 wherein said compound is indomethacin.
Claim 44
Dependent Claim
10 words
The composition of claim 35 wherein said compound is scopolamine.
Claim 45
Dependent Claim
11 words
The composition of claim 35 wherein said compound is a bronchodilator.
Claim 46
Dependent Claim
10 words
The composition of claim 42 wherein said bronchodilator is theophylline.
Claim 47
Dependent Claim
10 words
The composition of claim 35 wherein said compound is quinidine.
Claim 48
Dependent Claim
10 words
The composition of claim 35 wherein said compound is naproxen.
Claim 49
Dependent Claim
10 words
The composition of claim 35 wherein said compound is propranolol.
Claim 50
Dependent Claim
11 words
The composition of claim 35 wherein said compound is a salicylate.
Claim 51
Dependent Claim
10 words
The composition of claim 47 wherein said salicylate is aspirin.
Claim 52
Dependent Claim
10 words
The composition of claim 35 wherein said compound is nitroglycerin.
Claim 53
Dependent Claim
11 words
The composition of claim 35 wherein said compound is isosorbide dinitrate.
Claim 54
Dependent Claim
111 words
A sustained release composition for releasing an ecologically active compound into its surrounding environment comprising said ecologically active compound dispersed in a matrix which, when contacted with an aqueous liquid, erodes progressively, said matrix comprising a mixture of (a.) 5% to 99.5% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 55
Dependent Claim
111 words
A sustained release composition for releasing an ecologically active compound into its surrounding environment comprising said ecologically active compound dispersed in a matrix which, when contacted with an aqueous liquid, erodes progressively, said matrix comprising a mixture of (a.) 5% to 99.5% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 56
Dependent Claim
13 words
The composition of claim 51 wherein said ecologically active compound is a fertilizer.
Claim 57
Dependent Claim
13 words
The composition of claim 51 wherein said ecologically active compound is a pesticide.
Claim 58
Dependent Claim
13 words
The composition of claim 51 wherein said ecologically active compound is an insecticide.
Claim 59
Dependent Claim
13 words
The composition of claim 51 wherein said ecologically active compound is an herbicide.
Claim 60
Dependent Claim
108 words
A sustained release dosage form for releasing a biologically active compound into an aqueous liquid environment comprising a non-porous solid erodible matrix having dispersed therein a biologically active compound, said matrix comprising a mixture of (a.) 5% to 99.5% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 61
Dependent Claim
108 words
A sustained release dosage form for releasing a biologically active compound into an aqueous liquid environment comprising a non-porous solid erodible matrix having dispersed therein a biologically active compound, said matrix comprising a mixture of (a.) 5% to 99.5% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, and (b.) 95 to 0.5% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in said aqueous liquid, the molecular structure of said amphiphilic compound having a lipophilic portion and a hydrophilic portion.
Claim 62
Dependent Claim
21 words
The dosage form of claim 56 wherein said polyether diol is a polyethylene glycol having a molecular weight of about 8000.
Claim 63
Dependent Claim
21 words
The dosage form of claim 56 wherein said water-dispersible polyether diol is a block copolymer of ethylene oxide and propylene oxide.
Claim 64
Dependent Claim
63 words
The dosage form of claim 58 wherein said polyether diol is a block copolymer having the formula HO(CH.sub.2 CH.sub.2 O).sub.a (CH(CH.sub.3)CH.sub.2 O).sub.b (CH.sub.2 CH.sub.2 O).sub.c H wherein b has a value of 15 or greater and the sum of a and c is selected so that the terminal portions of the molecule comprise from 20% to 90% by weight of the polymer molecule.
Claim 65
Dependent Claim
23 words
The dosage form of claim 59 wherein a has a value of about 30 and a and c have values of about 75.
Claim 66
Dependent Claim
19 words
The dosage form of claim 56 wherein said erosion rate modifier is a C 12 -C 20 fatty acid.
Claim 67
Dependent Claim
22 words
The dosage form of claim 61 wherein said fatty acid is selected from the group consisting of myristic acid and stearic acid.
Claim 68
Dependent Claim
20 words
The dosage form of claim 56 wherein said erosion rate modifier is a combination of stearyl alcohol and stearic acid.
Claim 69
Dependent Claim
40 words
The dosage form of claim 63 wherein said stearyl alcohol is present in an amount of about 4% to about 13% by weight and said stearic acid is present in an amount of about 4% to about 15% by weight.
Claim 70
Dependent Claim
23 words
The dosage form of claim 56 additionally comprising a substance which increases the compatibility of the polyethylene glycol and the erosion rate modifier.
Claim 71
Dependent Claim
42 words
The dosage form of claim 65 wherein said substance is a polyethylene glycol having a molecular weight from about 200 to about 10000 and having at least one of its terminal OH groups esterified with a C 12 -C 20 fatty acid.
Claim 72
Dependent Claim
14 words
The dosage form of claim 66 wherein said polyethylene glycol is polyethylene glycol 400.
Claim 73
Dependent Claim
26 words
The dosage form of claim 67 wherein said substance is polyethylene glycol 400 having at least one of its terminal OH groups esterified with stearic acid.
Claim 74
Dependent Claim
10 words
The dosage form of claim 56 additionally comprising a disintegrant.
Claim 75
Dependent Claim
11 words
The dosage form of claim 69 wherein said disintegrant is starch.
Claim 76
Dependent Claim
11 words
The dosage form of claim 56 additionally comprising a molding adjuvant.
Claim 77
Dependent Claim
21 words
The dosage form of claim 71 wherein said molding adjuvant is polyethylene oxide having a molecular weight of 100,000 to 5,000,000.
Claim 78
Dependent Claim
38 words
The dosage form of claim 56 wherein said biologically active compound is a pharmaceutically active compound or non-toxic pharmaceutically acceptable salt of said compound and said dosage form contains an effective amount of said compound or said salt.
Claim 79
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is clonidine.
Claim 80
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is dipyridamole.
Claim 81
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is hydrochlorothiazide.
Claim 82
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is furosemide.
Claim 83
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is indomethacin.
Claim 84
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is scopolamine.
Claim 85
Dependent Claim
12 words
The dosage form of claim 73 wherein said compound is a bronchodilator.
Claim 86
Dependent Claim
11 words
The dosage form of claim 80 wherein said bronchodilator is theophylline.
Claim 87
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is quinidine.
Claim 88
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is naproxen.
Claim 89
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is propranolol.
Claim 90
Dependent Claim
12 words
The dosage form of claim 73 wherein said compound is a salicylate.
Claim 91
Dependent Claim
11 words
The dosage form of claim 85 wherein said salicylate is aspirin.
Claim 92
Dependent Claim
11 words
The dosage form of claim 73 wherein said compound is nitroglycerin.
Claim 93
Dependent Claim
12 words
The dosage form of claim 73 wherein said compound is isosorbide dinitrate.
Claim 94
Dependent Claim
16 words
The dosage form of claim 56 wherein said dosage form has the shape of a cylinder.
Claim 95
Dependent Claim
20 words
The dosage form of claim 89 wherein said cylinder has a diameter from about 3 mm to about 8 mm.
Claim 96
Dependent Claim
16 words
The dosage form of claim 90 wherein said cylinder has a diameter of about 6 mm.
Claim 97
Dependent Claim
20 words
The dosage form of claim 90 wherein said cylinder has a length from about 5 mm to about 20 mm.
Claim 98
Dependent Claim
16 words
The dosage form of claim 90 wherein said cylinder has a length of about 10 mm.
Claim 99
Dependent Claim
19 words
The dosage form of claim 89 additionally comprising at least a partial coating of a liquid impermeable non-self-supporting coating.
Claim 100
Dependent Claim
18 words
The dosage form of claim 89 wherein said coating comprises a solid C 12 -C 20 fatty acid.
Claim 101
Dependent Claim
12 words
The dosage form of claim 95 wherein said coating comprises myristic acid.
Claim 102
Dependent Claim
12 words
The dosage form of claim 95 wherein said coating comprises palmitic acid.
Claim 103
Dependent Claim
27 words
The dosage form of claim 89 wherein said dosage form has a cylindrical shape and is coated on its peripheral cylindrical surface with a liquid-impervious non-self-supporting coating.
References Cited (Backward Citations)
US3336155A
Cited
US3641236A
Cited
US3634584A
Cited
US4351825A
Cited
US4333919A
Cited
US4346709A
Cited
US4629621A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-02-21 | 1992-08-22 | 1993-02-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-02-21 | 1996-08-22 | 1997-02-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-02-21 | 2000-08-22 | 2001-02-21 | $7700.00 | Window Closed / Lapsed |