Biocompatible polymers, process for their preparation and compositions containing them

Abstract

A process for treating fibroses including administering a therapeutically effective amount of a pharmaceutical composition which includes at least one biocompatible polymer of the following general formula (I): A a X x Y y wherein: A represents a monomer selected from the group consisting of a sugar or —(O—CH 2 —CH 2 —CO)—, X represents a carboxyl group bonded to monomer A and is contained within a group according to the following formula: —R—COO—R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, Y represents a sulfate or sulfonate group bonded to monomer A and is contained within a group according to one of the following formulas: —R—O—SO 3 —R′, —R—N—SO 3 —R′, —R—SO 3 —R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, a represents the number of monomers A such that the mass of the polymers of formula (I) is greater than approximately 5,000 da, x represents a substitution rate of the monomers A by the groups X, which is between approximately 20 and 150%, and y represents a substitution rate of the monomers A by the groups Y, which is between approximately 30 and 150%.

1 . A process for treating fibroses comprising administering a therapeutically effective amount of a pharmaceutical composition which comprises at least one biocompatible polymer of the following general formula (I):
   A a X x Y y      
     wherein:
 A represents a monomer selected from the group consisting of a sugar or —(O—CH 2 —CH 2 —CO)—, 
 X represents a carboxyl group bonded to monomer A and is contained within a group according to the following formula: —R—COO—R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, 
 Y represents a sulfate or sulfonate group bonded to monomer A and is contained within a group according to one of the following formulas: —R—O—SO 3 —R′, —R—N—SO 3 —R′, —R—SO 3 —R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, 
 a represents the number of monomers A such that the mass of said polymers of formula (I) is greater than approximately 5,000 da, 
 x represents a substitution rate of the monomers A by the groups X, which is between approximately 20 and 150%, and 
 y represents a substitution rate of the monomers A by the groups Y, which is between approximately 30 and 150%. 
 
   
   
       2 . The process according to  claim 1 , wherein the fibroses are fibroses of smooth muscle tissue. 
   
   
       3 . The process according to  claim 2 , wherein the fibroses are fibroses of mesenchymal tissue. 
   
   
       4 . The process according to  claim 1 , wherein the sugar is a glucose. 
   
   
       5 . A process for reducing fibroses comprising administrating a therapeutically effective amount of a pharmaceutical composition which comprises at least one biocompatible polymer of the following general formula (I):
   A a X x Y y      
     wherein:
 A represents a monomer selected from the group consisting of a sugar or CH 2 —CH 2 —CO)—, 
 X represents a carboxyl group bonded to monomer A and is contained within a group according to the following formula: —R—COO—R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, 
 Y represents a sulfate or sulfonate group bonded to monomer A and is contained within a group to one of the following formulas: —R—O—SO 3 —R′, —R—N—SO 3 —R′, R—SO 3 —R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, 
 a represents the number of monomers A such that the mass of said polymers of formula (I) is greater than approximately 5,000 da, 
 x represents a substitution rate of the monomers A by the groups X, which is between approximately 20 and 150%, and 
 y represents a substitution rate of the monomers A by the groups Y, which is between approximately 30 and 150%. 
 
   
   
       6 . A process for treating fibroses comprising administering a therapeutically effective amount of a pharmaceutical composition which comprises at least one biocompatible polymer of the following general formula (II):
   A a X x Y y Z z      
     wherein:
 A represents a monomer selected from the group consisting of a sugar or —(O—CH 2 —CH 2 —CO)—, 
 X represents a carboxyl group bonded to monomer A and is contained within a group according to the following formula: —R—COO—R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, 
 Y represents a sulfate or sulfonate group bonded to monomer A and is contained within a group according to one of the following formulas: —R—O—SO 3 —R′, —R—N—SO 3 —R′, —R—SO 3 —R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, 
 Z represents at least one functional chemical group, which is different from X and Y, selected from the group consisting of a fatty acid, amino acid, fatty alcohol, ceramide derivative thereof and nucleotide addressing sequences and which confers supplementary biological or chemical properties, 
 a represents the number of monomers A such that the mass of said polymers of formula (I) is greater than approximately −5,000 da, 
 x represents a substitution rate of the monomers A by the groups X, which is between approximately 20 and 15.0%, 
 y represents a substitution rate of the monomers A by the groups Y, which is between approximately 30 and 150%, and 
 z represents a substitution rate of the monomers A by the group Z, which is between approximately 0 and 50%. 
 
   
   
       7 . The process according to  claim 6 , wherein Z is an amino acid. 
   
   
       8 . The process according to  claim 7 , wherein the amino acid is selected from the group comprising phenylalanine and leucine. 
   
   
       9 . The process according to  claim 6 , wherein Z is a fatty acid. 
   
   
       10 . The process according to  claim 9 , wherein the fatty acid is acetate. 
   
   
       11 . The process according to  claim 6 , wherein the fibroses are fibroses of smooth muscle tissue. 
   
   
       12 . The process according to  claim 11 , wherein the fibroses are fibroses of mesenchymal tissue. 
   
   
       13 . The process according to  claim 6 , wherein the sugar is a glucose. 
   
   
       14 . A process for reducing fibroses comprising administrating a therapeutically effective amount of a pharmaceutical composition which comprises at least one biocompatible polymer of the following general formula (II):
   A a X x Y y Z z      
     wherein:
 A represents a monomer selected from the group consisting of a sugar or —(O—CH 2 —CH 2 —CO—)—, 
 X represents a carboxyl group bonded to monomer A and is contained within a group according to the following formula: —R—COO—R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, 
 Y represents a sulfate or sulfonate group bonded to monomer A and is contained within a group according to one of the following formulas: —R—O—SO 3 —R′, —R—N—SO 3 —R′, —R—SO 3 —R′, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R′ represents a hydrogen atom or a cation, 
 Z represents at least one functional chemical group, which is different from X and Y, selected from the group consisting of a fatty acid, amino acid, fatty alcohol, ceramide derivative thereof and nucleotide addressing sequences and which confers supplementary biological or chemical properties, 
 a represents the number of monomers A such that the mass of said polymers of formula (I) is greater than approximately 5,000 da, 
 x represents a substitution rate of the monomers A by the groups X, which is between approximately 20 and 150%, 
 y represents a substitution rate of the monomers A by the groups Y, which is between approximately 30 and 150%, and 
 z represents a substitution rate of the monomers A by the group Z, which is between approximately 0 and 50%. 
 
   
   
       15 . The process according to  claim 14  wherein Z is an amino acid. 
   
   
       16 . The process according to  claim 15 , wherein the amino acid is selected from the group comprising phenylalanine and leucine. 
   
   
       17 . The process according to  claim 14 , wherein Z is a fatty acid. 
   
   
       18 . The process according to  claim 17 , wherein the fatty acid is acetate.