EP0640647A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Ionically crosslinked glycosaminoglycan gels for soft tissue augmentation and drug delivery
Assignee: Collagen Aesthetics Inc
•
Filing: 1994-08-18
•
Granted: —
•
Expires: 2014-08-18
Abstract
Abstract The present invention pertains to the use of glycosaminoglycans, chemically derivatized glycosaminoglycans, and optionally, chemically derivatized collagens to form ionically crosslinked gels useful in mammal soft tissue augmentation and in drug delivery systems. The derivatized glycosaminoglycans can be used to form an ionically homogeneous gel comprising one or more species of glycosaminoglycan derivative or can be used to form an ionically crosslinked heterogeneous gel comprising one or more negatively charged species of glycosaminoglycan or collagen derivative in combination with one or more positively charged species of glycosaminoglycan derivative or collagen derivative. The ionically crosslinked homogeneous or ionically crosslinked heterogeneous gels are produced from liquid solutions which upon adjusting pH in situ form a gel.
Inventors
- 👤 Richard A. Berg
- 👤 Woonza M. Rhee
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-26 10:16
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K47/00; A61K47/30; A61K47/36; A61L; A61L27/00; A61L27/14; A61L27/26; A61L27/50; A61L27/54; C; C08; C08L; C08L5/00; C08L5/08; C08L5/10; A61L2300/00; A61L2300/40; A61L2300/404; A61L2300/406; A61L2300/412; A61L2300/414; A61L2300/416; A61L2300/426
Claims Analysis
Total Claims: 56
Claim 1
Independent Claim
28 words
An ionically homogeneous gel comprising one or more species of glycosaminoglycan derivative having a net neutral charge within the pH range of between about 6 and about 9.
Claim 2
Dependent Claim
19 words
The gel of claim 1, wherein the glycosaminoglycan derivative contains free carboxyl and amino groups capable of ionic interaction.
Claim 3
Dependent Claim
38 words
The gel of claim 1, wherein the glycosaminoglycan derivative is selected from the group consisting of deacetylated hyaluronic acid, deacetylated desulfated chondroitin sulfate A, deacetylated desulfated dermatan sulfate, deacetylated desulfated chondroitin sulfate C, desulfated heparin, and combinations thereof.
Claim 4
Dependent Claim
13 words
The gel of claim 3, wherein the glycosaminoglycan derivative is deacetylated hyaluronic acid.
Claim 5
Dependent Claim
33 words
The gel of claim 1, further comprising a therapeutically effective amount of a pharmaceutically active agent selected from the group consisting of a cytokine, a growth factor, a chemotherapeutic agent, and an antibiotic.
Claim 6
Dependent Claim
54 words
An ionically heterogeneous gel comprising one or more negatively charged species of glycosaminoglycan and one or more positively charged species of glycosaminoglycan derivative, wherein the negatively charged species and the positively charged species interact to form a gel having a net neutral charge within the pH range of between about 6 and about 9.
Claim 7
Dependent Claim
40 words
The gel of claim 6, wherein the negatively charged species of glycosaminoglycan is selected from the group consisting of sodium hyaluronate, keratan sulfate, keratosulfate, sodium chondroitin sulfate A, sodium dermatan sulfate B, sodium chondroitin sulfate C, heparin, and combinations thereof.
Claim 8
Dependent Claim
53 words
The gel of claim 6, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of esterified deacetylated hyaluronic acid, esterified deacetylated desulfated chondroitin sulfate A, esterified deacetylated desulfated chondroitin sulfate C, deacetylated desulfated keratan sulfate, deacetylated desulfated keratosulfate, esterified desulfated heparin, chitosan 1, chitosan 2, and combinations thereof.
Claim 9
Dependent Claim
35 words
The gel of claim 6, wherein the negatively charged species of glycosaminoglycan is sodium hyaluronate and the positively charged species of glycosaminoglycan derivative is selected from the group consisting of chitosan 1 and chitosan 2.
Claim 10
Dependent Claim
33 words
The gel of claim 6, further comprising a therapeutically effective amount of a pharmaceutically active agent selected from the group consisting of a cytokine, a growth factor, a chemotherapeutic agent, and an antibiotic.
Claim 11
Dependent Claim
55 words
An ionically heterogeneous gel comprising one or more species of glycosamino glycan derivative and one or more species of collagen derivative, wherein the gel was formed by reaction of a negatively charged glycosaminoglycan species with a positively charged collagen derivative within the pH range of between about 6 and about 9 to form a gel.
Claim 12
Dependent Claim
40 words
The gel of claim 11, wherein the negatively charged species of glycosaminoglycan is selected from the group consisting of sodium hyaluronate, keratan sulfate, keratosulfate, sodium chondroitin sulfate A, sodium dermatan sulfate B, sodium chondroitin sulfate C, heparin, and combinations thereof.
Claim 13
Dependent Claim
16 words
The gel of claim 11, wherein the positively charged species of collagen derivative is methylated collagen.
Claim 14
Dependent Claim
15 words
The gel of claim 13, wherein the negatively charged species of glycosaminoglycan is sodium hyaluronate.
Claim 15
Dependent Claim
33 words
The gel of claim 11, further comprising a therapeutically effective amount of a pharmaceutically active agent selected from the group consisting of a cytokine, a growth factor, a chemotherapeutic agent, and an antibiotic.
Claim 16
Dependent Claim
54 words
An ionically heterogeneous gel comprising one or more species of glycosaminoglycan derivative and one or more species of collagen derivative, wherein the gel was formed by reaction of a positively charged glycosaminoglycan derivative with a negatively charged collagen derivative within the pH range of between about 6 and about 9 to form a gel.
Claim 17
Dependent Claim
53 words
The gel of claim 16, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of esterified deacetylated hyaluronic acid, esterified deacetylated desulfated chondroitin sulfate A, esterified deacetylated desulfated chondroitin sulfate C, deacetylated desulfated keratan sulfate, deacetylated desulfated keratosulfate, esterified desulfated heparin chitosan 1, chitosan 2, and combinations thereof.
Claim 18
Dependent Claim
16 words
The gel of claim 16, wherein the negatively charged species of collagen derivative is succinylated collagen.
Claim 19
Dependent Claim
25 words
The gel of claim 18, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of chitosan 1 and chitosan 2.
Claim 20
Independent Claim
55 words
A method of preparing an ionically homogeneous glycosaminoglycan gel comprising the steps of: chemically derivatizing a solution comprising one or more species of glycosaminoglycan to produce an ionically homogeneous solution of one or more charged species; and affecting the pH of the solution so that the derivatized glycosaminoglycan species ionically interact to form a gel.
Claim 21
Dependent Claim
25 words
The method of claim 20, wherein the glycosaminoglycan is chemically derivatized by a method selected from the group consisting of deacetylation, desulfation, and combinations thereof.
Claim 22
Dependent Claim
21 words
The method of claim 21, wherein the chemical derivatization is effected by combining the glycosaminoglycan solution with a strong basic solution.
Claim 23
Dependent Claim
15 words
The method of claim 22, wherein the strong basic solution comprises a sodium hydroxide solution.
Claim 24
Dependent Claim
32 words
The method of claim 20, wherein the glycosaminoglycan is selected from the group consisting of sodium hyaluronate, sodium chondroitin sulfate A, sodium dermatan sulfate, sodium chondroitin sulfate C, heparin, and combinations thereof.
Claim 25
Independent Claim
84 words
A method of preparing an ionically heterogeneous gel comprising the steps of: providing a first solution comprising one or more negatively charged species of glycosaminoglycan or collagen derivative; providing a second solution comprising one or more positively charged species of glycosaminoglycan derivative or collagen derivative; combining the first solution and the second solution; and allowing the negatively charged species in the first solution and the positively charged species in the second solution to ionically interact to form a gel having a net neutral charge.
Claim 26
Dependent Claim
49 words
The method of claim 25, wherein the negatively charged species of glycosaminoglycan or glycosaminoglycan derivative is selected from the group consisting of sodium hyaluronate, keratan sulfate, keratosulfate, sodium chondroitin sulfate A, sodium dermatan sulfate B, sodium chondroitin sulfate C, heparin, esterified chondroitin sulfate C, esterified heparin, and combinations thereof.
Claim 27
Dependent Claim
53 words
The method of claim 25, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of esterified deacetylated hyaluronic acid, esterified deacetylated desulfated chondroitin sulfate A, esterified deacetylated desulfated chondroitin sulfate C, deacetylated desulfated keratan sulfate deacetylated desulfated keratosulfate, esterified desulfated heparin, chitosan 1, chitosan 2, and combinations thereof.
Claim 28
Dependent Claim
35 words
The method of claim 25, wherein the negatively charged species of glycosaminoglycan is sodium hyaluronate and the positively charged species of glycosaminoglycan derivative is selected from the group consisting of chitosan 1 and chitosan 2.
Claim 29
Dependent Claim
16 words
The method of claim 25, wherein the negatively charged species of collagen derivative is succinylated collagen.
Claim 30
Dependent Claim
25 words
The method of claim 29, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of chitosan 1 and chitosan 2.
Claim 31
Dependent Claim
16 words
The method of claim 25, wherein the positively charged species of collagen derivative is methylated collagen.
Claim 32
Dependent Claim
15 words
The method of claim 31, wherein the negatively charged species of glycosaminoglycan is sodium hyaluronate.
Claim 33
Independent Claim
77 words
A method of augmenting soft tissue in a mammal, comprising: injecting into a site in need of augmentation a liquid composition comprising one or more species of glycosaminoglycan derivative which exhibits both positive and negative charges at a pH within a range from about 6 to about 8.5; and permitting the liquid composition to form a gel in situ by adjustment of the liquid composition pH to within the pH range from about 6 to about 8.5.
Claim 34
Dependent Claim
38 words
The method of claim 33, wherein the glycosaminoglycan derivative is selected from the group consisting of deacetylated hyaluronic acid, deacetylated desulfated chondroitin sulfates A, deacetylated desulfated dermatan sulfate, deacetylated desulfated chondroitin sulfate C, desulfated heparin, and combinations thereof.
Claim 35
Dependent Claim
13 words
The method of claim 33, wherein the glycosaminoglycan derivative is deacetylated hyaluronic acid.
Claim 36
Independent Claim
69 words
A method of augmenting soft tissue in a meal comprising: injecting to a site in need of augmentation a liquid composition comprising one or more negatively charged species of glycosaminoglycan, glycosaminoglycan derivative or collagen derivative, and one or more positively charged species of glycosaminoglycan derivative or collagen derivative; and allowing the negatively charged species and the positively charged species to ionically interact to form a gel in situ .
Claim 37
Dependent Claim
49 words
The method of claim 36, wherein the negatively charged species of glycosaminoglycan or glycosaminoglycan derivative is selected from the group consisting of sodium hyaluronate, keratan sulfate, keratosulfate, sodium chondroitin sulfate A, sodium dermatan sulfate B, sodium chondroitin sulfate C, heparin, esterified chondroitin sulfate C, esterified heparin, and combinations thereof.
Claim 38
Dependent Claim
53 words
The method of claim 36, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of esterified deacetylated hyaluronic acid, esterified deacetylated desulfated chondroitin sulfate A, esterified deacetylated desulfated chondroitin sulfate C, deacetylated desulfated keratan sulfate, deacetylated desulfated keratosulfate, esterified desulfated heparin, chitosan 1, chitosan 2, and combinations thereof.
Claim 39
Dependent Claim
35 words
The method of claim 36, wherein the negatively charged species of glycosaminoglycan is sodium hyaluronate and the positively charged species of glycosaminoglycan derivative is selected from the group consisting of chitosan 1 and chitosan 2.
Claim 40
Dependent Claim
16 words
The method of claim 36, wherein the negatively charged species of collagen derivative is succinylated collagen.
Claim 41
Dependent Claim
25 words
The method of claim 40, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of chitosan 1 and chitosan 2.
Claim 42
Dependent Claim
16 words
The method of claim 36, wherein the positively charged species of collagen derivative is methylated collagen.
Claim 43
Dependent Claim
15 words
The method of claim 42, wherein the negatively charged species of glycosaminoglycan is sodium hyaluronate.
Claim 44
Independent Claim
84 words
A method for administering a pharmaceutically active agent to a mammal comprising: injecting a liquid composition comprising one or more species of glycosaminoglycan derivative, which exhibits both positive and negative charges at a pH within a range from about 6 to about 8.5, in admixture with a therapeutically effective amount of a pharmaceutically active agent; and permitting the liquid composition to form a gel in situ by adjustment of the liquid composition pH to within the pH range from about 6 to about 8.5.
Claim 45
Dependent Claim
38 words
The method of claim 44, wherein the glycosaminoglycan derivative is selected from the group consisting of deacetylated hyaluronic acid, deacetylated desulfated chondroitin sulfates A, deacetylated desulfated dermatan sulfate, deacetylated desulfated chondroitin sulfate C, desulfated heparin, and combinations thereof.
Claim 46
Dependent Claim
13 words
The method of claim 44, wherein the glycosaminoglycan derivative is deacetylated hyaluronic acid.
Claim 47
Dependent Claim
28 words
The method of claim 44, wherein the pharmaceutically active agent is selected from the group consisting of a cytokine, a growth factor, a chemotherapeutic agent, and an antibiotic.
Claim 48
Independent Claim
83 words
A method for administering a pharmaceutically active agent to a mammal comprising: injecting a liquid composition comprising one or more negatively charged species of glycosaminoglycan, glycosaminoglycan derivative or collagen derivative, and one or more positively charged species of glycosaminoglycan derivative or collagen derivative, in admixture with a therapeutically effective amount of a pharmaceutically active agent; and permitting the liquid composition to form a gel in situ by adjustment of the liquid pH to within the pH range from about 6 to about 8.5.
Claim 49
Dependent Claim
49 words
The method of claim 48, wherein the negatively charged species of glycosaminoglycan or glycosaminoglycan derivative is selected from the group consisting of sodium hyaluronate, keratan sulfate, keratosulfate, sodium chondroitin sulfate A, sodium dermatan sulfate B, sodium chondroitin sulfate C, heparin, esterified chondroitin sulfate C, esterified heparin, and combinations thereof.
Claim 50
Dependent Claim
53 words
The method of claim 48, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of esterified deacetylated hyaluronic acid, esterified deacetylated desulfated chondroitin sulfate A, esterified deacetylated desulfated chondroitin sulfate C, deacetylated desulfated keratan sulfate, deacetylated desulfated keratosulfate, esterified desulfated heparin, chitosan 1, chitosan 2, and combinations thereof.
Claim 51
Dependent Claim
35 words
The method of claim 48, wherein the negatively charged species of glycosaminoglycan is sodium hyaluronate and the positively charged species of glycosaminoglycan derivative is selected from the group consisting of chitosan 1 and chitosan 2.
Claim 52
Dependent Claim
16 words
The method of claim 48, wherein the negatively charged species of collagen derivative is succinylated collagen.
Claim 53
Dependent Claim
25 words
The method of claim 52, wherein the positively charged species of glycosaminoglycan derivative is selected from the group consisting of chitosan 1 and chitosan 2.
Claim 54
Dependent Claim
16 words
The method of claim 48, wherein the positively charged species of collagen derivative is methylated collagen.
Claim 55
Dependent Claim
15 words
The method of claim 54, wherein the negatively charged species of glycosaminoglycan is sodium hyaluronate.
Claim 56
Dependent Claim
28 words
The method of claim 55, wherein the pharmaceutically active agent is selected from the group consisting of a cytokine, a growth factor, a chemotherapeutic agent, and an antibiotic.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.