US4713448A
Expired / Lapsed
US
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Chemically modified hyaluronic acid preparation and method of recovery thereof from animal tissues
Assignee: Sanofi Biosurgery Inc
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Filing: 1985-03-12
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Granted: 1987-12-15
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Expires: 2005-03-12
Abstract
Abstract Disclosed is hylan, a chemically modified hyaluronic acid preparation characterized by the presence of small amounts (0.005-0.05% by weight) of aldehyde cross-linking groups covalently bonded to the hyaluronic acid molecular chains. Also disclosed is a method of obtaining hylan comprising treating hyaluronic acid in situ in animal tissues containing same with a treatment mixture including a reagent (typically an aldehyde) which is reactive towards hyaluronic acid and the proteins contained in the animal tissue.
Inventors
- 👤 Endre A. Balazs
- 👤 Adolf Leshchiner
- 👤 Adelya Leshchiner
- 👤 Philip Band
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:27
CPC Classifications
C; C08; C08B; C08B37/00; C08B37/006; C08B37/0063; C08B37/0072; A; A61; A61P; A61P7/00; A61P7/02
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
89 words
A method of obtaining a chemically modified hyaluronic acid preparation comprising: (a) treating animal tissue containing hyaluronic acid with an aqueous treating mixture including, an aldehyde to effect chemical modification of the hyaluronic acid contained in the tissue, in situ, (b) removing excess treating mixture from the reaction mixture, (c) extracting the chemically modified hyaluronic acid from the treated animal tissue with water, (d) separating the extract containing the chemically modified hyaluronic acid from the treated animal tissue, and (e) recovering the chemically modified hyaluronic acid from the extract.
Claim 2
Independent Claim
89 words
A method of obtaining a chemically modified hyaluronic acid preparation comprising: (a) treating animal tissue containing hyaluronic acid with an aqueous treating mixture including, an aldehyde to effect chemical modification of the hyaluronic acid contained in the tissue, in situ, (b) removing excess treating mixture from the reaction mixture, (c) extracting the chemically modified hyaluronic acid from the treated animal tissue with water, (d) separating the extract containing the chemically modified hyaluronic acid from the treated animal tissue, and (e) recovering the chemically modified hyaluronic acid from the extract.
Claim 3
Dependent Claim
14 words
A method according to claim 1 wherein the aldehyde is formaldehyde, glutaraldehyde or glyoxal.
Claim 4
Dependent Claim
22 words
A method according to claim 1 wherein the aqueous treating mixture includes a water-miscible solvent which does not react with the aldehyde.
Claim 5
Dependent Claim
20 words
A method according to claim 3 wherein the solvent is a lower ketone, a lower alcohol or an aprotic solvent.
Claim 6
Dependent Claim
23 words
A method according to claim 4 wherein the solvent is acetone, methyl ethyl ketone, ethanol, isopropanol, dimethyl formamide, dimethyl acetamide or dimethyl sulfoxide.
Claim 7
Dependent Claim
20 words
A method according to claim 3 wherein the aqueous treating mixture includes an electrolyte and a water insoluble organic solvent.
Claim 8
Dependent Claim
20 words
A method according to claim 6 wherein the electrolyte is sodium acetate and the water insoluble organic solvent is chloroform.
Claim 9
Dependent Claim
31 words
A method according to claim 3 wherein the weight ratio of water to water-miscible solvent in the treating mixture is 1-5:4-8.5 and the weight ratio of water to aldehyde is 1-5:0.02-1.
Claim 10
Dependent Claim
30 words
A method according to claim 6 wherein the treating mixture comprises, in parts by weight: ______________________________________
water 10-50
water-miscible solvent
40-85
aldehyde 0.2-10
water insoluble solvent
0.5-10
electrolyte 0-20.
______________________________________
Claim 11
Dependent Claim
44 words
A method according to claim 1 wherein the treating mixture has a pH of 4-10, the weight ratio of treating mixture to tissue to be treated is at least 10:1, and treatment is effected for about 4-24 hours at or below about room temperature.
Claim 12
Dependent Claim
25 words
A method according to claim 1 wherein the animal tissue is rooster combs and the combs are cut into slices of about 1-3 mm thickness.
Claim 13
Dependent Claim
28 words
A method according to claim 1 wherein excess treating mixture is removed from the reaction mixture by washing the treated tissue with a solvent or a solvent/water mixture.
Claim 14
Dependent Claim
26 words
A method according to claim 12 wherein the solvent used for washing the treated tissue is the same solvent as is used in the treating mixture.
Claim 15
Dependent Claim
50 words
A method according to claim 1 wherein the extraction of the chemically modified hyaluronic acid is effected at a temperature below about 25° C. for about 6 hours to several days, the weight ratio of water to treated tissue being about 2-5:1 based on the weight of the untreated tissue.
Claim 16
Dependent Claim
23 words
A method according to claim 14 wherein the treated tissue is dried to about 25-50% of its treated weight before the extraction step.
Claim 17
Dependent Claim
20 words
A method according to claim 1 wherein the extract is separated from the animal tissue by filtration, centrifugation or decantation.
Claim 18
Dependent Claim
12 words
A method according to claim 16 wherein separation is effected by filtration.
Claim 19
Dependent Claim
40 words
A method according to claim 17 wherein the filtration is a two step procedure, a first, or gross filtration through a wide mesh to remove the pieces of animal tissue and a second, or fine filtration through a cellulosic material.
Claim 20
Dependent Claim
34 words
A method according to claim 1 wherein the chemically modified hyaluronic acid is recovered from the extract by precipitation with a solvent, followed by washing and drying the resulting precipitated chemically modified hyaluronic acid.
Claim 21
Dependent Claim
18 words
A method according to claim 19 wherein the solvent used for the precipitation is acetone, ethanol or isopropanol.
Claim 22
Dependent Claim
19 words
A method according to claim 20 wherein a mineral acid or an electrolyte is added during the precipitation step.
Claim 23
Dependent Claim
29 words
A method according to claim 21 wherein the mineral acid is HCl, H 2 SO 4 or H 3 PO 4 and the electrolyte is sodium acetate or NaCl.
Claim 24
Dependent Claim
19 words
A method according to claim 1 wherein the chemically modified hyaluronic acid is removed from the extract by lyophilization.
Claim 25
Dependent Claim
42 words
A method of cross-linking the chemically modified hyaluronic acid obtained according to the method of claim 1, which comprises subjecting said chemically modified hyaluronic acid to a cross-linking reaction with divinyl sulfone under alkaline conditions at room temperature for about one hour.
Claim 26
Dependent Claim
10 words
A product produced by the method according to claim 1.
Claim 27
Dependent Claim
10 words
A product produced by the method according to claim 24.
Claim 28
Dependent Claim
29 words
A chemically modified hyaluronic acid preparation characterized by the presence of about 0.005 to 0.05% by weight of aldehyde cross-linking groups covalently bonded to the hyaluronic acid polymer chains.
Claim 29
Dependent Claim
29 words
A chemically modified hyaluronic acid preparation characterized by the presence of about 0.005 to 0.05% by weight of aldehyde cross-linking groups covalently bonded to the hyaluronic acid polymer chains.
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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) | 1990-12-14 | 1991-06-15 | 1991-12-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-12-14 | 1995-06-15 | 1995-12-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-12-14 | 1999-06-15 | 1999-12-15 | $7700.00 | Window Closed / Lapsed |