US4582865A
Expired / Lapsed
US
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Cross-linked gels of hyaluronic acid and products containing such gels
Assignee: Sanofi Biosurgery Inc
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Filing: 1984-12-06
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Granted: 1986-04-15
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Expires: 2004-12-06
Abstract
Abstract Disclosed are cross-linked gels of hyaluronic acid, alone or mixed with other hydrophilic polymers and containing various substances or covalently bonded low molecular weight substances and processes for preparing them. These products are useful in numerous applications including cosmetic formulations and as drug delivery systems.
Inventors
- 👤 Endre A. Balazs
- 👤 Adolf Leshchiner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 11:25
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0014; A61K47/00; A61K47/30; A61K47/36; A61K8/00; A61K8/18; A61K8/72; A61K8/73; A61K8/731; A61K8/735; A61P; A61P43/00; A61Q; A61Q19/00; C; C08; C08B; C08B37/00; C08B37/006; C08B37/0063; C08B37/0072; C08L; C08L5/00; C08L5/08
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
68 words
A method of preparing a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone, said method comprising subjecting a mixture of sodium hyaluronate and said other hydrophilic polymer in a dilute aqueous alkaline solution at a pH of not less than about 9 to a cross-linking reaction with divinyl sulfone at about 20° C.
Claim 2
Independent Claim
68 words
A method of preparing a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone, said method comprising subjecting a mixture of sodium hyaluronate and said other hydrophilic polymer in a dilute aqueous alkaline solution at a pH of not less than about 9 to a cross-linking reaction with divinyl sulfone at about 20° C.
Claim 3
Dependent Claim
57 words
A method according to claim 1 wherein the other hydrophilic polymer is a natural or synthetic polysaccharide selected from the group consisting of hydroxyethyl cellulose, carboxymethyl cellulose, xanthan gum, chondroitin sulfate and heparin, a protein selected from the group consisting of collagen, elastin, albumin, a globulin, keratin sulfate, a sulfated aminoglycosaminolgycan and a synthetic water soluble polymer.
Claim 4
Dependent Claim
21 words
A method according to claim 1 wherein sodium hyaluronate has a molecular weight of about 50,000 to about 8×10 6 .
Claim 5
Dependent Claim
36 words
A method according to claim 1 wherein the combined concentration of sodium hyaluronate and the other hydrophilic polymers in the reaction mixture is 1-8% by weight and the sodium hyaluronate comprises from 5-95% of the total.
Claim 6
Dependent Claim
23 words
A method according to claim 1 wherein the ratio of the sodium hyaluronate to divinyl sulfone is from 15:1 to 1:5 by weight.
Claim 7
Dependent Claim
38 words
A method according to claim 1 and further comprising adding an alkali metal chloride, sulfate, phosphate or acetate to the reaction mixture in an amount sufficient to provide up to about 20% by weight concentration in the mixture.
Claim 8
Independent Claim
98 words
A method of preparing a cross-linked gel of hyaluronic acid or a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone, either of which further includes an inert water insoluble substance, said method comprising subjecting sodium hyaluronate or a mixture of sodium hyaluronate and said other hydrophilic polymer in a dilute aqueous alkaline solution at a pH of not less than about 9, to which has been added an inert water insoluble substance to a cross-linking reaction with divinyl sulfone at about 20° C.
Claim 9
Independent Claim
98 words
A method of preparing a cross-linked gel of hyaluronic acid or a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone, either of which further includes an inert water insoluble substance, said method comprising subjecting sodium hyaluronate or a mixture of sodium hyaluronate and said other hydrophilic polymer in a dilute aqueous alkaline solution at a pH of not less than about 9, to which has been added an inert water insoluble substance to a cross-linking reaction with divinyl sulfone at about 20° C.
Claim 10
Dependent Claim
25 words
A method according to claim 7 wherein the inert water insoluble substance is a hydrocarbon, an oil or fat, a pigment, polyethylene or polytetrafluoro ethylene.
Claim 11
Dependent Claim
32 words
A method according to claim 8 wherein the hydrocarbon is petrolatum, the oil or fat is beeswax, coconut oil or lanolin, and the pigment is kaolin, ferric oxide or an insoluble dye.
Claim 12
Dependent Claim
21 words
A method according to claim 7 wherein sodium hyaluronate has a molecular weight of about 50,000 to about 8×10 6 .
Claim 13
Dependent Claim
54 words
A method according to claim 7 wherein the concentration of sodium hyaluronate or the mixture of sodium hyaluronate and the other hydrophilic polymer is 1-8% by weight and the inert water insoluble substance is present in an amount of 1-95% by weight based on the total weight of polymers plus inert water insoluble substance.
Claim 14
Dependent Claim
23 words
A method according to claim 7 wherein the ratio of the sodium hyaluronate to divinyl sulfone is from 15:1 to 1:5 by weight.
Claim 15
Dependent Claim
38 words
A method according to claim 7 and further comprising adding an alkali metal chloride, sulfate, phosphate or acetate to the reaction mixture in an amount sufficient to provide up to about 20% by weight concentration in the mixture.
Claim 16
Independent Claim
116 words
A method of preparing a cross-linked gel of hyaluronic acid or a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone, either of which further includes a low molecular weight substance covalently bonded to the macromolecular network, said method comprising subjecting sodium hyaluronate or a mixture of sodium hyaluronate and said other hydrophilic polymer in a dilute aqueous alkaline solution at a pH of not less than about 9, to which has been added a low molecular weight substance having a functional group with active hydrogen atoms reactive to divinyl sulfone to a cross-linking reaction with divinyl sulfone at about 20° C.
Claim 17
Independent Claim
116 words
A method of preparing a cross-linked gel of hyaluronic acid or a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone, either of which further includes a low molecular weight substance covalently bonded to the macromolecular network, said method comprising subjecting sodium hyaluronate or a mixture of sodium hyaluronate and said other hydrophilic polymer in a dilute aqueous alkaline solution at a pH of not less than about 9, to which has been added a low molecular weight substance having a functional group with active hydrogen atoms reactive to divinyl sulfone to a cross-linking reaction with divinyl sulfone at about 20° C.
Claim 18
Dependent Claim
15 words
A method according to claim 14 wherein the low molecular weight substance is a drug.
Claim 19
Dependent Claim
16 words
A method according to claim 14 wherein the low molecular weight substance is a carminic acid.
Claim 20
Dependent Claim
21 words
A method according to claim 14 wherein sodium hyaluronate has a molecular weight of about 50,000 to about 8×10 6 .
Claim 21
Dependent Claim
54 words
A method according to claim 14 wherein the concentration of sodium hyaluronate or the mixture of sodium hyaluronate and the other hydrophilic polymer is 1-8% by weight and the low molecular weight substance is present in an amount of 1-95% by weight based on the total weight of polymers plus inert water insoluble substance.
Claim 22
Dependent Claim
23 words
A method according to claim 14 wherein the ratio of the sodium hyaluronate to divinyl sulfone is from 15:1 to 1:5 by weight.
Claim 23
Dependent Claim
38 words
A method according to claim 14 and further comprising adding an alkali metal chloride, sulfate, phosphate or acetate to the reaction mixture in an amount sufficient to provide up to about 20% by weight concentration in the mixture.
Claim 24
Dependent Claim
50 words
A mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone, wherein the combined concentration of sodium hyaluronate and the other hydrophilic polymer is 1-8% by weight and the sodium hyaluronate comprises from 5-95% of the total.
Claim 25
Dependent Claim
50 words
A mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone, wherein the combined concentration of sodium hyaluronate and the other hydrophilic polymer is 1-8% by weight and the sodium hyaluronate comprises from 5-95% of the total.
Claim 26
Dependent Claim
57 words
A gel according to claim 21 wherein the other hydrophilic polymer is a natural or synthetic polysaccharide selected from the group consisting of hydroxyethyl cellulose, carboxymethyl cellulose, xanthan gum, chondroitin sulfate and heparin, a protein selected from the group consisting of collagen, elastin, albumin, a globulin, keratin sulfate, a sulfated aminoglycosaminoglycan and a synthetic water soluble polymer.
Claim 27
Dependent Claim
87 words
A cross-linked gel of hyaluronic acid or a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone and further comprising an inert water insoluble substance, wherein the concentration of sodium hyaluronate or the mixture of sodium hyaluronate and the other hydrophilic polymer is 1-8% by weight and the inert water insoluble substance is present in an amount of 1-95% by weight based on the total weight of polymers plus inert water insoluble substance.
Claim 28
Dependent Claim
87 words
A cross-linked gel of hyaluronic acid or a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone and further comprising an inert water insoluble substance, wherein the concentration of sodium hyaluronate or the mixture of sodium hyaluronate and the other hydrophilic polymer is 1-8% by weight and the inert water insoluble substance is present in an amount of 1-95% by weight based on the total weight of polymers plus inert water insoluble substance.
Claim 29
Dependent Claim
24 words
A gel according to claim 23 wherein the inert water insoluble substance is a hydrocarbon, an oil or fat, a pigment, polyethylene or polytetrafluoroethylene.
Claim 30
Dependent Claim
32 words
A gel according to claim 24 wherein the hydrocarbon is petrolatum, the oil or fat is beeswax, coconut oil or lanolin, and the pigment is kaolin, ferric oxide or an insoluble dye.
Claim 31
Dependent Claim
89 words
A cross-linked gel of hyaluronic acid or a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone and further comprising a low molecular weight substance covalently bonded to the macromolecular network, wherein the concentration of sodium hyaluronate or the mixture of sodium hyaluronate and the other hydrophilic polymer is 1-8% by weight and the low molecular weight substance is present in an amount of 1-95% by weight based on the total weight of the polymer.
Claim 32
Dependent Claim
89 words
A cross-linked gel of hyaluronic acid or a mixed cross-linked gel of hyaluronic acid and at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone and further comprising a low molecular weight substance covalently bonded to the macromolecular network, wherein the concentration of sodium hyaluronate or the mixture of sodium hyaluronate and the other hydrophilic polymer is 1-8% by weight and the low molecular weight substance is present in an amount of 1-95% by weight based on the total weight of the polymer.
Claim 33
Dependent Claim
15 words
A gel according to claim 26 wherein the low molecular weight substance is a drug.
Claim 34
Dependent Claim
15 words
A gel according to claim 26 wherein the low molecular weight substance is carminic acid.
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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) | 1989-04-14 | 1989-10-14 | 1990-04-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-04-14 | 1993-10-14 | 1994-04-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-04-14 | 1997-10-14 | 1998-04-15 | $7700.00 | Window Closed / Lapsed |