US4675189A
Expired / Lapsed
US
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Microencapsulation of water soluble active polypeptides
Assignee: Syntex USA LLC
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Filing: 1985-02-08
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Granted: 1987-06-23
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Expires: 2005-02-08
Abstract
Abstract This invention concerns novel sustained release microcapsule compositions comprising water-soluble, hormonally active polypeptides and, optionally, a polymer hydrolysis modifying agent encapsulated in a biocompatible, biodegradable polymer.
Inventors
- 👤 John S. Kent
- 👤 Danny H. Lewis
- 👤 Lynda M. Sanders
- 👤 Thomas R. Tice
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:25
CPC Classifications
A; A61; A61K; A61K38/00; A61K38/04; A61K38/08; A61K38/09; A61K9/00; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/1647; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5031; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/12; Y10S930/13; Y10S930/18
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
92 words
A pharmaceutical composition designed for sustained release of a luteinizing hormone-releasing hormone (LHRH) analog, prepared in microcapsule form, wherein the composition comprises at least one luteinizing hormone-releasing hormone analog or a pharmaceutically acceptable salt thereof in an amount between 0.01 and 40.0 weight percent, and a poly(lactide-co-glycolide) polymer having a molar ratio of 75:25 to 40:60, said polymer being present in an amount between 99.9 and 60 weight percent, which composition exhibits sustained release of an effective amount of the luteinizing hormone-releasing hormone analog over a period of at least one month.
Claim 2
Dependent Claim
92 words
A pharmaceutical composition designed for sustained release of a luteinizing hormone-releasing hormone (LHRH) analog, prepared in microcapsule form, wherein the composition comprises at least one luteinizing hormone-releasing hormone analog or a pharmaceutically acceptable salt thereof in an amount between 0.01 and 40.0 weight percent, and a poly(lactide-co-glycolide) polymer having a molar ratio of 75:25 to 40:60, said polymer being present in an amount between 99.9 and 60 weight percent, which composition exhibits sustained release of an effective amount of the luteinizing hormone-releasing hormone analog over a period of at least one month.
Claim 3
Dependent Claim
12 words
The composition of claim 1 wherein said analog is an LHRH agonist.
Claim 4
Dependent Claim
12 words
The composition of claim 1 wherein said analog is an LHRH antagonist.
Claim 5
Dependent Claim
137 words
The composition of claim 2 wherein said analog is a nona-peptide or a decapeptide having the formula (pyro)Glu-His-V-Ser-W-X-Y-Aro-Pro-Z and the pharmaceutically acceptable salts thereof wherein V is tryptophyl, phenylalanyl or 3-(1-naphthyl)-L-alanyl; W is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl; X is a D-amino acid residue ##STR9## wherein R is (a) a carbocyclic aryl-containing radical selected from the group consiting of naphthyl, anthryl, fluorenyl, phenylanthryl, biphenylyl, benzhydryl and phenyl substituted with three or more straight chain lower alkyl groups; or (b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl and adamantyl; Y is leucyl, isoleucyl, non-leucyl or N-methyl-leucyl; Z is glycinamide or --NH--R 1 , wherein R 1 is lower alkyl, cycloalkyl, fluoro lower alkyl ##STR10## wherein R 2 is hydrogen or lower alkyl.
Claim 6
Dependent Claim
19 words
The composition of claim 4 wherein said analog is present in an amount between 0.1 to 10.0 weight percent.
Claim 7
Dependent Claim
16 words
The composition of claim 5 wherein said polymer has a molecular ratio of 75:25 to 50:50.
Claim 8
Dependent Claim
11 words
The composition of claim 6 in the form of injectable microcapsules.
Claim 9
Dependent Claim
55 words
The composition of claim 7 wherein the several substituents of formula I are defined as follows: said analog is defined: V is tryptophyl or phenylalanyl; W is tyrosyl; X is 3-(2-naphthyl)-D-alanyl or 3-(2,3,6-trimethylphenyl)-D-alanyl; Y is leucyl or N-methyl-leucyl; and Z is glycinamide or NMEt; and said polymer has a molar ratio between 75:25 and 50:50.
Claim 10
Dependent Claim
17 words
The composition of claim 8 wherein said analog is (pyro)Glu-His-Trp-Ser-Tyr-3-(naphthyl)-D-alanyl-Leu-Arg-Pro-Gly-NH 2 and the pharmaceutically acceptable salts thereof.
Claim 11
Dependent Claim
19 words
The composition of claim 7 wherein said microcapsules are dispersed in a pharmaceutically acceptable carrier suitable for parenteral administration.
Claim 12
Dependent Claim
21 words
The composition of claim 1 wherein said LHRH analog has the formula (pyro) Glu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH 2 and the pharmaceutically acceptable salts thereof.
Claim 13
Dependent Claim
30 words
A composition according to claim 1, wherein the LHRH analog is an analog of natural LHRH, in which modification comprises the 6-position residue changed from Gly to a D-amino acid.
Claim 14
Dependent Claim
16 words
A composition according to claim 12, wherein the D-amino acid is D-Ala, D-Leu, D-Phe or D-Trp.
Claim 15
Dependent Claim
12 words
A composition according to claim 13, wherein the D-amino acid is D-Leu.
Claim 16
Dependent Claim
12 words
A composition according to claim 13, wherein the D-Amino acid is D-Trp.
Claim 17
Dependent Claim
22 words
A composition according to claim 12, wherein the 10-position is modified to afford a nona-peptide as an alkyl-, cycloalkyl- or fluoroalkyl amine.
Claim 18
Dependent Claim
16 words
A composition according to claim 12, wherein the Gly-NH 2 is replaced by an β-azaglycine amide.
Claim 19
Dependent Claim
16 words
A composition according to claim 12, wherein N-methyl leucine is substituted for leucine in position 7.
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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) | 1990-06-22 | 1990-12-22 | 1991-06-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-06-22 | 1994-12-22 | 1995-06-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-06-22 | 1998-12-22 | 1999-06-23 | $7700.00 | Window Closed / Lapsed |