US4897268A
Expired / Lapsed
US
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Drug delivery system and method of making the same
Assignee: SOUTHERN RESEARCH INSTITUTE PO BOX 55305 BIRMINGHAM ALABAMA 35255-5305
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Filing: 1987-08-03
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Granted: 1990-01-30
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Expires: 2007-08-03
Abstract
Abstract A compatible, biodegradable microcapsule delivery system for active ingredients, including hormonally active peptides, proteins, or other bioactive molecules, and a method of making the same. The ingredients are encapsulated in biodegradable copolymer excipients of varying mole ratios and the blend of the microcapsules are administered to an animal. Delivery of the ingredient occurs over a prolonged period of time at a constant rate as a result of the varying break-down rates of the copolymer excipients.
Inventors
- 👤 Thomas R. Tice
- 👤 Richard M. Gilley
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:23
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/5084; A61K38/00; A61K38/04; A61K38/08; A61K38/09; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/1647
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
118 words
A method of preparing a composition for delivering a an effective amount of a constant dose of an active ingredient to an animal over a preselected, prolonged period of time, comprising the steps of: (a) encapsulating effective amounts of said ingredient in first and second separate biodegradable and biocompatible copolymer excipients having different monomers ratios to form first and second microcapsules, each of said microcapsules having of a different rate of release therefrom of said ingredient; and (b) combining an effective amount of said first and second microcapsules to form said composition having a delivery profile wherein the release of said ingredient through said second microcapsule begins as the release of said ingredient through said first microcapsule declines.
Claim 2
Independent Claim
118 words
A method of preparing a composition for delivering a an effective amount of a constant dose of an active ingredient to an animal over a preselected, prolonged period of time, comprising the steps of: (a) encapsulating effective amounts of said ingredient in first and second separate biodegradable and biocompatible copolymer excipients having different monomers ratios to form first and second microcapsules, each of said microcapsules having of a different rate of release therefrom of said ingredient; and (b) combining an effective amount of said first and second microcapsules to form said composition having a delivery profile wherein the release of said ingredient through said second microcapsule begins as the release of said ingredient through said first microcapsule declines.
Claim 3
Dependent Claim
22 words
A method as claimed in claim 1, further including the step of administering an effective amount of said composition to the animal.
Claim 4
Dependent Claim
34 words
A method as claimed in claim 1, wherein said excipient is selected from the group consisting of polyacetal polymers, polyorthoesters, polyesteramides, polycaprolactone and copolymers thereof, polycarbonates, polyhydroxybuterate and copolymers thereof, polymaleamides, copolyaxalates, and polysaccharides.
Claim 5
Dependent Claim
13 words
The method as claimed in claim 1, wherein a copolymer excipient is poly(D,L-lactide-co-glycolide).
Claim 6
Dependent Claim
23 words
The method as claimed in claim 5, wherein the copolymer excipients have mole ratios of lactide to glycolide of 40:60 to 85:15, respectively.
Claim 7
Dependent Claim
15 words
The method as claimed in claim 1, wherein said active ingredient is a bioactive molecule.
Claim 8
Dependent Claim
14 words
The method as claimed in claim 1, wherein said active ingredient is a peptide.
Claim 9
Dependent Claim
11 words
The method of claim 7, wherein said peptide is hormonally active.
Claim 10
Dependent Claim
20 words
The method as claimed in claim 7, wherein said peptide is a luteinizing hormone releasing hormone or an analogue thereof.
Claim 11
Dependent Claim
12 words
The method of claim 1, wherein said active ingredient is a protein.
Claim 12
Dependent Claim
18 words
The method as claimed in claim 7, wherein said peptide is [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide.
Claim 13
Dependent Claim
76 words
The method as claimed in claim 1, wherein said first microcapsule comprises 3 percent by weight loaded [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide encapsulated in a copolymer excipient having a mole ratio of 52 percent lactide to 48 percent glycolide and wherein said second microcapsule comprises 10 percent by weight loaded [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide encapsulated in a copolymer excipient having a mole ratio of 68 percent lactide to 32 percent glycolide.
Claim 14
Dependent Claim
50 words
The method as claimed in claim 12, wherein said combining step further comprises adding to said composition an effective amount of 8 percent by weight loaded [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide encapsulated in a copolymer excipient having a mole ratio of 85 percent lactide to 15 percent glycolide.
Claim 15
Dependent Claim
34 words
The method as claimed in claim 13, wherein [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide is delivered at a constant rate ranging from 50 μg to 250 μg per day for approximately 180 days.
Claim 16
Dependent Claim
20 words
The method as claimed in claim 7, wherein said peptide is [D-N-Ac-4-Cl-Phe 2 , D-Trp 6 , D-Ala 10 ]-LHRH.
Claim 17
Dependent Claim
38 words
The method as claimed in claim 15, wherein said [D-N-Ac-4-Cl-Phe 2 , D-Trp 6 , D-Ala 10 ]-LHRH is delivered at a constant rate of about 200 μg to 500 μg per day for at least 90 days.
Claim 18
Dependent Claim
13 words
The method as claimed in claim 1, wherein said administering step is parenterally.
Claim 19
Dependent Claim
13 words
The method as claimed in claim 1, wherein said administering step is intramuscularly.
Claim 20
Dependent Claim
97 words
A composition capable of delivering an effective amount of a constant dose of an active ingredient to an animal over a preselected, prolonged period of time, comprising a blend of effective amounts of an active ingredient encapsulated in at least two biodegradable and biocompatible copolymer excipients having different monomers ratios to form first and second microcapsules, each excipient having of a different rate of release of said ingredient therethrough, said composition having a delivery profile wherein the release of said ingredient through said second microcapsule begins as the release of said ingredient through said first microcapsule declines.
Claim 21
Dependent Claim
97 words
A composition capable of delivering an effective amount of a constant dose of an active ingredient to an animal over a preselected, prolonged period of time, comprising a blend of effective amounts of an active ingredient encapsulated in at least two biodegradable and biocompatible copolymer excipients having different monomers ratios to form first and second microcapsules, each excipient having of a different rate of release of said ingredient therethrough, said composition having a delivery profile wherein the release of said ingredient through said second microcapsule begins as the release of said ingredient through said first microcapsule declines.
Claim 22
Dependent Claim
13 words
A composition as claimed in claim 19, wherein said copolymer excipients are poly(D,L-lactide-co-glycolide).
Claim 23
Dependent Claim
23 words
A composition as claimed in claim 20, wherein said copolymer excipients have mole ratios of lactide to glycolide of 40:60 to 85:15 respectively.
Claim 24
Dependent Claim
15 words
A composition as claimed in claim 19, wherein said active ingredient is a bioactive molecule.
Claim 25
Dependent Claim
14 words
A composition as claimed in claim 19, wherein said active ingredient is a peptide.
Claim 26
Dependent Claim
13 words
A composition as claimed in claim 23, wherein said peptide is hormonally active.
Claim 27
Dependent Claim
20 words
A composition as claimed in claim 23, wherein said peptide is a luteinizing hormone releasing hormone or an analog thereof.
Claim 28
Dependent Claim
21 words
A composition as claimed in claim 25, wherein said luteinizing hormone releasing hormone is [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide.
Claim 29
Dependent Claim
14 words
A composition as claimed in claim 19, wherein said active ingredient is a protein.
Claim 30
Dependent Claim
72 words
A composition as claimed in claim 19, wherein said blend of microencapsulated peptide is comprised of appropriate amounts of 3% by weight loaded [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide encapsulated in a copolymer excipient having a mole ratio of 52% lactide to 48% glycolide, and 10% by weight loaded [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide encapsulated in a copolymer excipient having a mole ratio of 68% lactide to 32% glycolide.
Claim 31
Dependent Claim
44 words
A composition as claimed in claim 28 and further comprising an appropriate amount of 8% by weight loaded [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide encapsulated in a copolymer excipient having a mole ratio of 85% lactide to 15% glycolide added to said blend.
Claim 32
Dependent Claim
34 words
A composition as claimed in claim 29, wherein said blend delivers [D-Trp 6 , des-Gly 10 ]-LHRH ethylamide at a constant rate of about 50 μg to 250 μg per day for 180 days.
Claim 33
Dependent Claim
20 words
A composition as claimed in claim 23, wherein said peptide is [D-N-Ac-4-Cl-Phe 2 , D-Trp 6 , D-Ala 10 ]-LHRH.
Claim 34
Dependent Claim
38 words
A composition as claimed in claim 31, wherein said blend delivers [D-N-Ac-4-Cl-Phe 2 , D-Trp 6 , D-Ala 10 ]-LHRH at a constant rate of about 200 μg to 500 μg per day for at least 90 days.
References Cited (Backward Citations)
FR615662A
Cited
US3887699A
Cited
US3773919A
Cited
DE2051580A1
Cited
US3737337A
Cited
GB1332505A
Cited
ZA718150B
Cited
US3835108A
Cited
US3853837A
Cited
US3826796A
Cited
US3824227A
Cited
US3991766A
Cited
US4490291A
Cited
US4008209A
Cited
US4003846A
Cited
US4033938A
Cited
US3892723A
Cited
US3972859A
Cited
US3896105A
Cited
US4093709A
Cited
US4180646A
Cited
US4131648A
Cited
US4076798A
Cited
US4010125A
Cited
US4011312A
Cited
US4010196A
Cited
US4066568A
Cited
US4118470A
Cited
US4145410A
Cited
US4107071A
Cited
US4211769A
Cited
US4166800A
Cited
US4148871A
Cited
GB2026976A
Cited
GB2034182A
Cited
US4234571A
Cited
US4622244A
Cited
US4293539A
Cited
US4439199A
Cited
US4318905A
Cited
US4341767A
Cited
EP0052510B1
Cited
US4675189A
Cited
EP0058481A1
Cited
US4767628A
Cited
US4767628B1
Cited
US4568559A
Cited
US4760053A
Cited
US4775660A
Cited
EP0202065A2
Cited
WO1987006129A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-01-29 | 1993-07-31 | 1994-01-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-01-29 | 1997-07-31 | 1998-01-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-01-29 | 2001-07-31 | 2002-01-30 | $7700.00 | Window Closed / Lapsed |