Patent US2656509A successfully refreshed from Google Patents.
US4937270A
Expired / Lapsed
US
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Water insoluble derivatives of hyaluronic acid
Assignee: Genzyme Corp
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Filing: 1987-09-18
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Granted: 1990-06-26
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Expires: 2007-09-18
Abstract
Abstract A method for making a water insouble bicompatible gel includes activating HA with an activating agent to form activated HA, and reacting the activated HA with a nucleophile, under conditions producing the water insoluble bicompatible gel. Also, a method for making a water insoluble biocompatible film includes providing a biocompatible gel made according to the above method, and drying the gel or compressing the gel under conditions permitting escape of water from the gel. Also, a water insoluble composition including HA is prepared without the use of any bifunctional or polyfunctional nucleophile.
Inventors
- 👤 Raymond Hamilton
- 👤 Ellen M. Fox
- 👤 Raksha A. Acharya
- 👤 Alan E. Walts
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 01:20
CPC Classifications
C; C08; C08B; C08B37/00; C08B37/006; C08B37/0063; C08B37/0072; A; A61; A61K; A61K47/00; A61K47/30; A61K47/36; A61L; A61L27/00; A61L27/14; A61L27/20; A61L27/50; A61L27/52; A61L31/00; A61L31/04; A61L31/041; A61L31/042; A61L31/14; A61L31/145
Claims Analysis
Total Claims: 45
Claim 1
Independent Claim
56 words
A method for making a water insoluble biocompatible gel, said method comprising providing an aqueous mixture comprising HA at a concentration in the range between 0.4% and 2.6% w/w, activating said HA with an activating agent to form activated HA, and reacting said activated HA with a nucleophile, under conditions producing said water insoluble biocompatible gel.
Claim 2
Independent Claim
56 words
A method for making a water insoluble biocompatible gel, said method comprising providing an aqueous mixture comprising HA at a concentration in the range between 0.4% and 2.6% w/w, activating said HA with an activating agent to form activated HA, and reacting said activated HA with a nucleophile, under conditions producing said water insoluble biocompatible gel.
Claim 3
Dependent Claim
43 words
The method of claim 1 wherein said activating comprises providing an aqueous mixture comprising said HA, lowering the pH of said aqueous mixture to between 4.0 and 5.0 by addition of an acid, and then contacting said aqueous mixture with said activating agent.
Claim 4
Dependent Claim
23 words
The method of claim 2 wherein said aqueous mixture comprises a concentration of said HA in the range between 0.4% and 2.6% w/w.
Claim 5
Dependent Claim
11 words
The method of claim 2 wherein said acid comprises hydrochloric acid.
Claim 6
Dependent Claim
41 words
The method of claim 1 wherein said HA and said activating agent are present during said activation at a molar ratio of at least 0.2 molar equivalent of activating agent to 1 molar equivalent of glucuronic acid residues of said HA.
Claim 7
Dependent Claim
43 words
The method of claim 1 wherein said activated HA and said nucleophile are present in said reacting step at a molar ratio of at least 0.2 molar equivalent of said nucleophile to 1 molar equivalent of glucuronic acid residues of said activated HA.
Claim 8
Dependent Claim
12 words
The method of claim 1 wherein said activating agent comprises a carbodiimide.
Claim 9
Dependent Claim
15 words
The method of claim 7 wherein said carbodiimide comprises 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide methiodide.
Claim 10
Dependent Claim
12 words
The method of claim 1 wherein said nucleophile comprises an amino acid.
Claim 11
Dependent Claim
13 words
The method of claim 1 wherein said nucleophile comprises an amino acid salt.
Claim 12
Dependent Claim
13 words
The method of claim 1 wherein said nucleophile comprises an amino acid ester.
Claim 13
Dependent Claim
14 words
The method of claim 11 wherein said amino acid ester comprises a methyl ester.
Claim 14
Dependent Claim
14 words
The method of claim 11 wherein said amino acid ester comprises a butyl ester.
Claim 15
Dependent Claim
13 words
The method of claim 13 wherein said butyl ester comprises a t-butyl ester.
Claim 16
Dependent Claim
28 words
The method of claim 1 wherein said nucleophile comprises a methyl ester of an amino acid from the group comprising leucine, valine, isoleucine, arginine, proline, histidine, or phenylalanine.
Claim 17
Dependent Claim
40 words
The method of claim 1 wherein said nucleophile comprises L-leucine methyl ester hydrochloride, L-valine methyl ester hydrochloride, L-isoleucine methyl ester hydrochloride, L-arginine methyl ester hydrochloride, L-proline methyl ester hydrochloride, L-histidine methyl ester hydrochloride, L-phenylalanine hydrochloride, or L-leucine t-butyl ester hydrochloride.
Claim 18
Dependent Claim
13 words
The method of claim 1 wherein said nucleophile comprises an amino acid amide.
Claim 19
Dependent Claim
13 words
The method of claim 17 wherein said amino acid amide comprises leucinamide hydrochloride.
Claim 20
Dependent Claim
12 words
The method of claim 1 wherein said nucleophile comprises a monofunctional amine.
Claim 21
Dependent Claim
11 words
The method of claim 19 wherein said monofunctional amine comprises aniline.
Claim 22
Dependent Claim
13 words
A water insoluble biocompatible gel made according to the method of claim 1.
Claim 23
Dependent Claim
23 words
A method for making a water insoluble biocompatible film, said method comprising providing the biocompatible gel of claim 21, and drying said gel.
Claim 24
Dependent Claim
9 words
The film made by the method of claim 22.
Claim 25
Dependent Claim
32 words
A method for making a water insoluble biocompatible film, said method comprising providing the biocompatible gel of claim 21, and compressing said gel under conditions permitting escape of water from said gel.
Claim 26
Dependent Claim
9 words
The film made by the method of claim 24.
Claim 27
Dependent Claim
13 words
The method of claim 1 wherein said activating and said reacting occur concurrently.
Claim 28
Dependent Claim
13 words
The method of claim 1, said method further comprising admixing a detectable marker.
Claim 29
Dependent Claim
16 words
The method of claim 22 wherein said detectable marker comprises a dye that stains amino acids.
Claim 30
Dependent Claim
13 words
The method of claim 27 wherein said detectable marker comprises "Brilliant Blue R".
Claim 31
Dependent Claim
13 words
A water insoluble composition comprising HA, said composition being substantially free of crosslinking.
Claim 32
Dependent Claim
13 words
A water insoluble composition comprising HA, said composition being substantially free of crosslinking.
Claim 33
Dependent Claim
28 words
The composition of claim 30, said composition being substantially free of any bifunctional or polyfunctional nucleophile and said composition being substantially free of any bifunctional or polyfunctional electrophile.
Claim 34
Dependent Claim
10 words
The composition of claim 30, further comprising a monofunctional nucleophile.
Claim 35
Dependent Claim
10 words
The composition of claim 30, further comprising a monofunctional amine.
Claim 36
Dependent Claim
10 words
The composition of claim 30, further comprising a detectable marker.
Claim 37
Dependent Claim
13 words
The composition of claim 34, wherein said detectable marker comprises "Brilliant Blue R".
Claim 38
Dependent Claim
11 words
The composition of claim 30, further comprising a pharmaceutically active substance.
Claim 39
Dependent Claim
16 words
The composition of claim 36 wherein said pharmaceutically active substance is covalently bonded to said HA.
Claim 40
Dependent Claim
23 words
The composition of claim 36 wherein said pharmaceutically active substance is dispersed within said composition and is not covalently bonded to said composition.
Claim 41
Dependent Claim
16 words
A water insoluble composition comprising the reaction product of HA, an activating agent, and a nucleophile.
Claim 42
Dependent Claim
16 words
A water insoluble composition comprising the reaction product of HA, an activating agent, and a nucleophile.
Claim 43
Dependent Claim
12 words
The composition of claim 34, wherein said activating agent is a carbodiimide.
Claim 44
Dependent Claim
10 words
The composition of claim 40, wherein said carbodiimide is EDC.
Claim 45
Dependent Claim
16 words
The composition of claim 41, wherein said nucleophile is a methyl ester of an amino acid.
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Cited
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1993-06-25 | 1993-12-25 | 1994-06-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-06-25 | 1997-12-25 | 1998-06-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-06-25 | 2001-12-25 | 2002-06-26 | $7700.00 | Window Closed / Lapsed |