US6344488B1
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US
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Temperature-controlled pH-dependent formation of ionic polysaccharide gels
Assignee: Biosyntech Ltd
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Filing: 1999-02-12
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Granted: 2002-02-05
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Expires: 2019-02-12
Abstract
Abstract The present invention relates a temperature-controlled pH-dependant formation of ionic polysaccharide gels, such as chitosan/organo-phosphate aqueous systems, and methods of preparation thereof. While chitosan aqueous solutions are pH-dependant gelating systems, the addition of a mono-phosphate dibasic salt of polyol or sugar to a chitosan aqueous solutions leads to further temperature-controlled pH-dependant gelation. Solid organo-phosphate salts (1-20% w/v) are added and dissolved at low temperature (10° C.) within 0.5 to 4.0% w/v chitosan in aqueous acidic solutions. Aqueous chitosan/organo-phosphate solutions are initially stored at low temperatures (4° C.), then endothermally gelated within the temperature range of 30 to 60° C. Chitosan/organo-phosphate solutions rapidly turn into gels at the desired gelation temperature. Gelation can be ex vivo within any receivers or molds, or in situ in animals or humans (in vivo) so as to fill a tissue defect or cavity.
Inventors
- 👤 Abdellatif Chenite
- 👤 Cyril Chaput
- 👤 Christele Combes
- 👤 Amine Selmani
- 👤 Fayrouze Jalal
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 12:50
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024; A61K47/00; A61K47/30; A61K47/36; A61L; A61L24/00; A61L24/04; A61L24/08; A61L26/00; A61L26/0009; A61L26/0052; A61L26/0061; A61L26/008; A61L27/00; A61L27/14; A61L27/20; A61L27/26; A61L27/50; A61L27/52; C; C08; C08L; C08L5/00; C08L5/08
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
74 words
A polysaccharide based gel solution which comprises: a) 0.1 to 5.0% by weight of chitosan; and b) 1.0 to 20% by weight of a salt of polyol or sugar selected from the group consisting of monophosphate dibasic salt of polyol or sugar; wherein said gel solution is a solution at pH between 6.5 and 7.4 at a temperature below 20° C., and forms a gel within a temperature range from 20 to 70° C.
Claim 2
Dependent Claim
74 words
A polysaccharide based gel solution which comprises: a) 0.1 to 5.0% by weight of chitosan; and b) 1.0 to 20% by weight of a salt of polyol or sugar selected from the group consisting of monophosphate dibasic salt of polyol or sugar; wherein said gel solution is a solution at pH between 6.5 and 7.4 at a temperature below 20° C., and forms a gel within a temperature range from 20 to 70° C.
Claim 3
Dependent Claim
32 words
A gel solution according to claim 1 , wherein said salt is a mono-phosphate dibasic salt of glycerol selected from the group consisting of glycerol-2-phosphate salts, sn-glycerol 3-phosphate salts and L-glycerol-3-phosphate salts.
Claim 4
Dependent Claim
40 words
A gel solution according to claim 1 , wherein said salt is a mono-phosphate dibasic salt of polyol selected from the group consisting of histidinol, acetol, diethylstilbestrol, indole-glycerol, sorbitol, ribitol, xylitol, arabinitol, erythritol, inositol, mannitol, glucitol and a mixture thereof.
Claim 5
Dependent Claim
54 words
A gel according to claim 1 , wherein said salt is a mono-phosphate dibasic salt and said sugar is selected from the group consisting of fructose, galactose, ribose, glucose, xylose, rhamnulose, sorbose, erythrulose, deoxy-ribose, ketose, mannose, arabinose, fuculose, fructopyranose, ketoglucose, sedoheptulose, trehalose, tagatose, sucrose, allose, threose, xylulose. hexose, methylthio-ribose, methylthio-deoxy-ribulose, and a mixture thereof.
Claim 6
Dependent Claim
32 words
A gel solution according to claim 1 , wherein said salt is a mono-phosphate dibasic salt of polyol selected from the group consisting of palmitoyl-glycerol, linoleoyl-glycerol, oleoyl-glycerol, arachidonoyl-glycerol, and a mixture thereof.
Claim 7
Dependent Claim
24 words
A gel solution according to claim 1 , wherein said gel solution is selected from the group consisting of chitosan-β-glycerophosphate, chitosan-α-glycerophosphate, chitosan-glucose-1-glycerophosphate, and chitosan-fructose-6-glycerophosphate.
Claim 8
Dependent Claim
23 words
A gel solution according to claim 1 , wherein solid particulate or water-soluble additives are incorporated within said polysaccharide gel prior to gelation.
Claim 9
Dependent Claim
24 words
A gel solution according to claim 1 , wherein drugs, polypeptides or non-living pharmaceutical agents are incorporated within said polysaccharide gel prior to gelation.
Claim 10
Dependent Claim
27 words
A gel solution according to claim 1 , wherein living microorganisms, plant cells, animal cells or human cells are encapsulated within said polysaccharide gel prior to gelation.
Claim 11
Dependent Claim
155 words
A method for producing a solution of a polysaccharide based gel according to claim 1 , which comprises the steps of: a) dissolving a chitosan within an aqueous acidic solution of a pH from about 2.0 to about 5.0 to obtain an aqueous polysaccharide composition having a concentration of 0.1 to 5.0% by weight of a chitosan; b) dissolving 1.0 to 20% by weight of a salt of polyol or sugar, wherein said salt is selected from the group consisting of mono-phosphate dibasic salt, in said aqueous polysaccharide composition of step a) to obtain a solution of said polysaccharide based gel, wherein said solution of the polysaccharide based gel has a concentration of 0.1 to 5.0% by weight of a chitosan, and a concentration of 1.0 to 20% by weight of a salt of a polyol or sugar, and said solution of the polysaccharide based gel has a pH from about 6.5 to about 7.4.
Claim 12
Dependent Claim
20 words
The method of claim 10 , wherein a pharmaceutical agent is added to the polysaccharide gel solution of step b).
Claim 13
Dependent Claim
42 words
The method of claim 10 , wherein said aqueous acidic solution is prepared from organic or inorganic acids selected from the group consisting of acetic acid, ascorbic acid, salicylic acid, phosphoric acid, hydrochloric acid, propionic acid, formic acid, and a mixture thereof.
Claim 14
Dependent Claim
32 words
The method of claim 10 , wherein said salt is a mono-phosphate dibasic salt of glycerol, wherein said glycerol is selected from the group consisting of glycerol-2-phosphate, sn-glycerol 3-phosphate and L-glycerol-3-phosphate salts.
Claim 15
Dependent Claim
28 words
The method of claim 10 , wherein said salt is a selected from the group consisting of glycerophosphate disodium, glycerophosphate dipotassium, glycerophosphate calcium, glycerophosphate barium and glycerophosphate strontium.
Claim 16
Dependent Claim
42 words
The method of claim 10 , wherein said salt is a mono-phosphate dibasic salt of a polyol, and said polyol is selected from a group comprising histidinol, acetol, diethylstilbestrol, indoleglycerol, sorbitol, ribitol, xylitol, arabinitol, erythritol, inositol, mannitol, glucitol, and a mixture thereof.
Claim 17
Dependent Claim
55 words
The method of claim 10 , wherein said salt is a mono-phosphate dibasic salt of a sugar, and said sugar is selected from a group comprising fructose, galactose, ribose, glucose, xylose, rhamnulose, sorbose, erythrulose, deoxy-ribose, ketose, mannose, arabinose, fuculose, fructopyranose, ketoglucose, sedoheptulose, trehalose, tagatose, sucrose, allose, threose, xylulose, hexose, methylthio-ribose, methylthio-deoxy-ribulose, and a mixture thereof.
Claim 18
Dependent Claim
35 words
The method of claim 10 , wherein said salt is a mono-phosphate dibasic salt of a polyol, and said polyol is selected from the group consisting of palmitoyl-glycerol, linoleoyl-glycerol, oleoyl-glycerol, arachidonoyl-glycerol, and a mixture thereof.
Claim 19
Dependent Claim
36 words
The method of claim 10 , wherein said salt is a mono-phosphate dibasic salt and said phosphate is selected from the group consisting of a phosphate disodium, phosphate dipotassium, phosphate calcium, phosphate barium and phosphate strontium.
Claim 20
Dependent Claim
20 words
The method of claim 10 , wherein the molecular weight of chitosan is ranging from about 10,000 to 2,000,000 Da.
Claim 21
Dependent Claim
20 words
The method of claim 10 , wherein the polysaccharide gel is thermoirreversible or thermoreversible by adjusting the polysaccharide gel pH.
Claim 22
Dependent Claim
21 words
The method of claim 20 , wherein polysaccharide gel is thermoirreversible when the pH of said polysaccharide gel solution is >6.9.
Claim 23
Dependent Claim
21 words
The method of claim 20 , wherein polysaccharide gel is thermoreversible when the pH of said polysaccharide gel solution is <6.9.
Claim 24
Dependent Claim
20 words
The method of claim 10 , wherein solid particulate additives are added to the polysaccharide gel solution of step b).
Claim 25
Independent Claim
139 words
A method for producing a polysaccharide based gel, which comprises the steps of: a) dissolving a chitosan within an aqueous acidic solution of a pH from about 2.0 to about 5.0 to obtain an aqueous polysaccharide composition having a concentration of 0.1 to 5.0% by weight of a chitosan; b) dissolving 1.0 to 20% by weight of a salt of polyol or sugar, wherein said salt is selected from the group consisting of mono-phosphate dibasic salt, in said aqueous polysaccharide corn position of step a) to obtain a solution of said polysaccharide based gel, and wherein said solution of the polysaccharide based gel has a pH from about 6.5 to about 7.4; and c) heating said polysaccharide gel solution to a temperature ranging from about 20° C. to about 80° C. to result in formation of a polysaccharide gel.
Claim 26
Independent Claim
139 words
A method for producing a polysaccharide based gel, which comprises the steps of: a) dissolving a chitosan within an aqueous acidic solution of a pH from about 2.0 to about 5.0 to obtain an aqueous polysaccharide composition having a concentration of 0.1 to 5.0% by weight of a chitosan; b) dissolving 1.0 to 20% by weight of a salt of polyol or sugar, wherein said salt is selected from the group consisting of mono-phosphate dibasic salt, in said aqueous polysaccharide corn position of step a) to obtain a solution of said polysaccharide based gel, and wherein said solution of the polysaccharide based gel has a pH from about 6.5 to about 7.4; and c) heating said polysaccharide gel solution to a temperature ranging from about 20° C. to about 80° C. to result in formation of a polysaccharide gel.
Claim 27
Dependent Claim
40 words
The method of claim 24 , which further comprises between steps b) and c) the following step, b1 dispensing for gelation the polysaccharide gel solution into a receiver, either in a mold or within a tissue, organ or body cavity.
Claim 28
Dependent Claim
35 words
The method of claim 25 , wherein said polysaccharide gel solution is introduced within an animal or human body by injection or endoscopic administration, and gelled in situ at a temperature of about 37° C.
Claim 29
Dependent Claim
18 words
The method of claim 24 , wherein said temperature ranges from about 37° C. to about 60° C.
Claim 30
Dependent Claim
13 words
The method of claim 27 , wherein said temperature is about 37° C.
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