US5252318A
Expired / Lapsed
US
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Reversible gelation compositions and methods of use
Assignee: Allergan Inc
•
Filing: 1990-06-15
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Granted: 1993-10-12
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Expires: 2010-06-15
Abstract
Abstract Reversibly gelling aqueous compositions are disclosed which undergo significant changes in viscosity in response to substantially simultaneous changes in both temperature and pH. The compositions are formed of relatively low concentrations of a stable combination of at least one pH-sensitive reversibly gelling polymer and at least one temperature-sensitive reversibly gelling polymer. The compositions can be formulated to exhibit a sol-gel transition over a wide range of conditions and viscosities and may be modified to incorporate a pharmaceutical compound for utilization as droppable or injectable drug delivery systems which will gel following administration to a physiological system for the sustained delivery of such pharmaceutical compounds.
Inventors
- 👤 Abhay Joshi
- 👤 Shulin Ding
- 👤 Kenneth J. Himmelstein
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 16:52
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0048; A61K47/00; A61K47/06; A61K47/08; A61K47/10; A61K47/16; A61K47/18; A61K47/30; A61K47/32; A61K47/36; A61K47/38; A61K9/0019; A61K9/06; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/1647
Claims Analysis
Total Claims: 41
Claim 1
Independent Claim
96 words
An aqueous pharmaceutical composition of matter exhibiting the property of reversible gelation in response to substantially simultaneous variations in both temperature and pH over predetermined ranges, said composition comprising: an aqueous solution including approximately 0.1% to 30% by weight thermally-sensitive gelling polymer and approximately 0.01% to 10% by weight pH sensitive gelling polymer whereby said aqueous composition exhibits a reversible viscosity change ranging between approximately 200 to 1,000,000 cP in response to substantially simultaneous variations in both temperature and pH over respective ranges between approximately 0° C. to 60° C. and pH 2.5 to pH 7.5.
Claim 2
Dependent Claim
96 words
An aqueous pharmaceutical composition of matter exhibiting the property of reversible gelation in response to substantially simultaneous variations in both temperature and pH over predetermined ranges, said composition comprising: an aqueous solution including approximately 0.1% to 30% by weight thermally-sensitive gelling polymer and approximately 0.01% to 10% by weight pH sensitive gelling polymer whereby said aqueous composition exhibits a reversible viscosity change ranging between approximately 200 to 1,000,000 cP in response to substantially simultaneous variations in both temperature and pH over respective ranges between approximately 0° C. to 60° C. and pH 2.5 to pH 7.5.
Claim 3
Dependent Claim
96 words
An aqueous pharmaceutical composition of matter exhibiting the property of reversible gelation in response to substantially simultaneous variations in both temperature and pH over predetermined ranges, said composition comprising: an aqueous solution including approximately 0.1% to 30% by weight thermally-sensitive gelling polymer and approximately 0.01% to 10% by weight pH sensitive gelling polymer whereby said aqueous composition exhibits a reversible viscosity change ranging between approximately 200 to 1,000,000 cP in response to substantially simultaneous variations in both temperature and pH over respective ranges between approximately 25° C. to 37° C. and pH 4.5 to pH 7.4.
Claim 4
Dependent Claim
96 words
An aqueous pharmaceutical composition of matter exhibiting the property of reversible gelation in response to substantially simultaneous variations in both temperature and pH over predetermined ranges, said composition comprising: an aqueous solution including approximately 0.1% to 30% by weight thermally-sensitive gelling polymer and approximately 0.01% to 10% by weight pH sensitive gelling polymer whereby said aqueous composition exhibits a reversible viscosity change ranging between approximately 200 to 1,000,000 cP in response to substantially simultaneous variations in both temperature and pH over respective ranges between approximately 25° C. to 37° C. and pH 4.5 to pH 7.4.
Claim 5
Dependent Claim
39 words
The composition of claim 2 wherein said at least one thermally-sensitive gelling polymer is selected from the group consisting of alkylcellulose, hydroxyalkyl cellulose, block copolymers of polyoxyethylene and polyoxypropylene, and tetrafunctional block polymers of polyoxyethylene and polyoxypropylene and ethylenediamine.
Claim 6
Dependent Claim
15 words
The composition of claim 2 wherein said at least one thermally-sensitive gelling polymer is methylcellulose.
Claim 7
Dependent Claim
17 words
The composition of claim 2 wherein said at least one pH-sensitive gelling polymer is an acidic polymer.
Claim 8
Dependent Claim
14 words
The composition of claim 5 wherein said acidic polymer is a carboxyl containing polymer.
Claim 9
Dependent Claim
12 words
The composition of claim 6 wherein said carboxyl containing polymer is polyacrylate.
Claim 10
Dependent Claim
25 words
The composition of claim 2 wherein said at least one thermally-sensitive gelling polymer is methylcellulose and said at least one pH-sensitive gelling polymer is polyacrylate.
Claim 11
Dependent Claim
23 words
The composition of claim 8 wherein said aqueous composition comprises approximately 0.1% to 5% by weight methylcellulose and approximately 0.01% to 10% polyacrylate.
Claim 12
Dependent Claim
21 words
The composition of claim 8 wherein said aqueous composition comprises approximately 1% by weight methylcellulose and approximately 0.3% by weight polyacrylate.
Claim 13
Dependent Claim
13 words
The composition of claim 2 further comprising a viscosity modifying amount of salt.
Claim 14
Dependent Claim
21 words
The composition of claim 11 wherein said salt is selected from the group consisting of univalent and divalent dissociable ionic compounds.
Claim 15
Dependent Claim
19 words
The composition of claim 11 wherein said salt is present in a slat-to-polymer ratio of approximately 0.001 to 0.5.
Claim 16
Dependent Claim
17 words
The composition of claim 2 further comprising an effective amount of a pharmaceutical medicament or diagnostic compound.
Claim 17
Dependent Claim
20 words
The composition of claim 14 wherein said pharmaceutical medicament or diagnostic compound is incorporated in a microparticulate drug delivery system.
Claim 18
Dependent Claim
71 words
The composition of claim 14 wherein said pharmaceutical medicament or diagnostic compound is selected from the group consisting of anti-bacterial substances, anti-histamines and decongestants, anti-inflammatorics, miotics and anti-cholinergics, mydriatics, anti-glaucoma compounds, anti-parasitics, anti-viral compounds, carbonic anhydrase inhibitors, diagnostic agents, ophthalmic agents, chelating agents, immunosuppressive agents, anti-metabolites, anesthetics, anti-fungal compounds, amoebacidal compounds, trichomonacidal agents, analgesics, anti-arthritics, anti-asthmatics, anti-coagulants, anti-convulsants, anti-depressants, anti-diabetics, anti-neoplastics, anti-psychotics, anti-hypertensive agents, muscle relaxants, proteins, peptides and lubricating agents.
Claim 19
Dependent Claim
23 words
The pharmaceutical composition of claim 2 further comprising a viscosity modifying effective concentration of salt in a salt-to-polymer ratio of 0.045 to 0.075.
Claim 20
Dependent Claim
19 words
A drug delivery system comprising the aqueous composition of claim 2 and an effective concentration of an ophthalmic drug.
Claim 21
Dependent Claim
19 words
The drug delivery system of claim 18 wherein said ophthalmic drug is incorporated in a microparticulate drug delivery system.
Claim 22
Dependent Claim
69 words
The drug delivery system of claim 18 wherein said drug is selected from the group consisting of anti-bacterial substances, anti-histamines and decongestants, anti-inflammatories, miotics and anti-cholinergis, mydriatics, anti-glaucoma compounds, anti-parasitics, anti-viral compounds, carbonic anhydrase inhibitors, diagnostic agents, ophthalmic agents, chelating agents, immunosuppressive agents, anti-metabolites anesthetics, anti-fungal compounds, amoebacidal compounds, trichomonacidal agents, analgesics, anti-arthritics, anti-asthmatics, anti-coagulatns, anti-convulsants, anti-depressants, anti-diabetics, anti-neoplastics, anti-psychotics, anti-hypertensive agents, muscle relaxants, proteins, peptides, and lubricating agents.
Claim 23
Dependent Claim
39 words
The composition of claim 1 wherein said at least one thermally-sensitive gelling polymer is selected from the group consisting of alkylcellulose, hydroxyalkyl cellulose, block copolymers of polyoxyethylene and polyoxypropylene, and tetrafunctional block polymers of polyoxyethylene and polyoxypropylene and ethylenediamine.
Claim 24
Dependent Claim
15 words
The composition of claim 1 wherein said at least one thermally-sensitive gelling polymer is methylcellulose.
Claim 25
Dependent Claim
17 words
The composition of claim 1 wherein said at least one pH-sensitive gelling polymer is an acidic polymer.
Claim 26
Dependent Claim
14 words
The composition of claim 23 wherein said acidic polymer is a carboxyl containing polymer.
Claim 27
Dependent Claim
12 words
The composition of claim 6 wherein said carboxyl containing polymer is polyacrylate.
Claim 28
Dependent Claim
25 words
The composition of claim 1 wherein said at least one thermally-sensitive gelling polymer is methylcellulose and said at least one pH-sensitive gelling polymer is polyacrylate.
Claim 29
Dependent Claim
23 words
The composition of claim 26 therein said aqueous composition comprises approximately 0.1% to 5% by weight methylcellulose and approximately 0.01% to 10% polyacrylate.
Claim 30
Dependent Claim
21 words
The composition of claim 26 wherein said aqueous composition comprises approximately 1% by weight methylcellulose and approximately 0.3% by weight polyacrylate.
Claim 31
Dependent Claim
13 words
The composition of claim 1 further comprising a viscosity modifying amount of salt.
Claim 32
Dependent Claim
21 words
The composition of claim 29 wherein said salt is selected from the group consisting of univalent and divalent dissociable ionic compounds.
Claim 33
Dependent Claim
19 words
The composition of claim 29 wherein said salt is present in a salt-to-polymer ratio of approximately 0.001 to 0.5.
Claim 34
Dependent Claim
17 words
The composition of claim 1 further comprising an effective amount of a pharmaceutical medicament or diagnostic compound.
Claim 35
Dependent Claim
20 words
The composition of claim 32 wherein said pharmaceutical medicament or diagnostic compound is incorporated in a microparticulate drug delivery system.
Claim 36
Dependent Claim
71 words
The composition of claim 32 wherein said pharmaceutical medicament or diagnostic compound is selected from the group consisting of anti-bacterial substances, anti-histamines and decongestants, anti-inflammatorics, miotics and anti-cholinergics, mydriatics, anti-glaucoma compounds, anti-parasitics, anti-viral compounds, carbonic anhydrase inhibitors, diagnostic agents, ophthalmic agents, chelating agents, immunosuppressive agents, anti-metabolites, anesthetics, anti-fungal compounds, amoebacidal compounds, trichomonacidal agents, analgesics, anti-arthritics, anti-asthmatics, anti-coagulants, anti-convulsants, anti-depressants, anti-diabetics, anti-neoplastics, anti-psychotics, anti-hypertensive agents, muscle relaxants, proteins, peptides and lubricating agents.
Claim 37
Dependent Claim
23 words
The pharmaceutical composition of claim 1 further comprising a viscosity modifying effective concentration of salt in a salt-to-polymer ratio of 0.045 to 0.075.
Claim 38
Dependent Claim
19 words
A drug delivery system comprising the aqueous composition of claim 1 and an effective concentration of an ophthalmic drug.
Claim 39
Dependent Claim
18 words
The drug delivery system of claim 36 wherein said drug is incorporated in a microparticulate drug delivery system.
Claim 40
Dependent Claim
70 words
The drug delivery system of claim 36 wherein said ophthalmic drug is selected from the group consisting of anti-bacterial substances, anti-histamines and decongestants, anti-inflammatorics, miotics and anti-cholinergics, mydriatics, anti-glaucoma compounds, anti-parasitics, anti-viral compounds, carbonic anhydrase inhibitors, diagnostic agents, ophthalmic agents, chelating agents, immunosuppressive agents, anti-metabolites, anesthetics, anti-fungal compounds, amoebacidal compounds, trichomonacidal agents, analgesics, anti-arthritics, anti-asthmatics, anti-coagulants, anti-convulsants, anti-depressants, anti-diabetics, anti-neoplastics, anti-psychotics, anti-hypertensive agents, muscle relaxants, proteins, peptides, and lubricating agents.
Claim 41
Dependent Claim
91 words
An aqueous injectable drug delivery composition for injection into a body to treat a condition requiring pharmacological treatment or diagnosis comprising the composition of claim 1 and an effective concentration of a drug selected from the group consisting of anti-bacterial substances, anti-histamines and decongestants, anti-inflammatorics, miotics and anti-cholinergics, mydriatics, anti-glaucoma compounds, anti-parasitics, anti-viral compounds, carbonic anhydrase inhibitors, diagnostic agents, ophthalmic agents, chelating agents, immunosuppressive agents, anti-metabolites, anesthetics, anti-fungal compounds, amoebacidal compounds, trichomonacidal agents, analgesics, anti-arthritics, anti-asthmatics, anti-coagulatns, anti-convulsants, anti-depressants, anti-diabetics, anti-neoplastics, anti-psychotics, anti-hypertensive agents, muscle relaxants, proteins, peptides and lubricating agents.
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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) | 1996-10-11 | 1997-04-12 | 1997-10-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-10-11 | 2001-04-12 | 2001-10-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-10-11 | 2005-04-12 | 2005-10-12 | $7700.00 | Window Closed / Lapsed |