Dextran derivatives endowed, particularly with anti-coagulant properties and anti-complementary properties, their preparation and their biological uses

Claim 2

Polymers of dextran having a molecular weight higher than 5000 daltons comprising statistically, glucosyl units A with 1,6 linkages, of the formula: ##STR16## at least 35% of B units, consisting of units A substituted by a radical --O--(CH 2 ) n --R--COO - in which R represents a single bond or a --CO--NH--(CH 2 ) n' --, n is a number from 1 to 10 and ' is a numbver from 1 to 7, and at least 3% of D units, consisting of units A substituted by a chain with a group of structure ##STR17## in which: --R 1 represents a single bond, --CH 2 -- group, or a ##STR18## group, R 2 represents a physiogically acceptable anion of an inorganic or organic salt, and an inorganic or organic salt, and n is as defined above.

Claim 3

The polymers of dextran of claim 1 wherein B is at least 40%.

Claim 4

The polymers of dextran of claim 1 wherein R 2 is SO 3 31 .

Claim 5

The polymers of dextran of claim 1 wherein B is at least 40% and R 2 is SO 3 31 .

Claim 6

The polymers of dextran of claim 1 which further comprises C units consisting of A units substituted by radicals of the structure: ##STR19## in which R 1 and n are as defined in claims 1.

Claim 7

The polymers of dextran of claim 2, wherein A and B units represent at most 60% of the total number of units.

Claim 8

Polymers of dextran having the following A, B, C and D units ##STR20## wherein A and C units represent at most 50% and B and D being as defined in claim 1.

Claim 9

The polymers of dextrans of claim 1 wherein the B units are substituted by --O--CH 2 --COO - .

Claim 10

A process for making the dextran polymers of claim 1 comprising in combination bringing to a temperature of about -4° to +5° C. and reacting a dextran with units A of the formula ##STR21## with a carboxylic acid of the formula: X(CH 2 ) n --R--COOH, in which X represents a group which reacts with the --OH group of a glycosyl unit A in a ratio of carboxylic acid and dextran of 1.5 to 3.5, and bringing the temperature to between about ambient and about about 70° C., whereby there are formed B units consisting of A units substituted by a radical --O--(CH 2 ) n --R--COO - , R and n being as defined above, then reacting the dextran containing the A and B units with a derivative of formula ##STR22## in which R 1 is as defined above which causes the introduction of C units consisting of A units substituted by a chain with a group of structure: ##STR23## with n, and R 1 as defined above, and reacting the C units with an organic or inorganic salt, whereby there is obtained the D units in combination with the A, B and C units.

Claim 11

The process according to claim 9 comprising the fractionation of the dextran polymers, thereby eliminating the derivatives having a molecular weight less than 5000 daltons.

Claim 12

The process according to claim 9 wherein the units B are prepared by reacting an halogenide with the dextran consisting of units A.

Claim 13

The process according to claim 9 wherein the reaction mixture is brought to a temperature of about 0° C.

Claim 14

The process of claim 9 wherein after the mixture is brought to a temperature above ambient, the temperature is gradually raised to between about ambient ot about 55° C.

Claim 15

The process according to claim 9 wherein the dextran polymer with the A and B units is recovered by precipitation with an alcoholic solvent and by lowering the pH to about neutral.

Claim 16

The process according to claim 9 wherein the units C are prepared by coupling the units B with a compound of formula ##STR24## in the presence of a coupling agent.

Claim 17

The process according to claim 9 wherein the units C are prepared by coupling a mixed anhydride of the dextran with A and B units with a reactive compound containing R 2 which results in the formation of a radical ##STR25## wherein n, R 1 and R 2 are as defined.

Claim 18

The process according to claim 16 wherein the mixed anhydride of dextran is obtained by reacting an alkyl formate with an amine which yields a hydrochloride with HCl, at a temperature lower than 0° C., then coupling the resulting compound with the units B of the dextran.

Claim 19

A method for the preparation of plasma substitutes or expanders which comprises making an aqueous solution of a polymer which has the formula of claim 1.

Claim 20

A method for the preparation of plasma substitutes or expanders which comprises making an aqueous solution of a polymer of dextran which as the formula of claim 7.

Claim 21

A biological composition which comprises a polymer of dextran having a molecular weight higher than 5,000 daltons and comprising statistically glucosyl units A with 1,6 linkages, of the formula: ##STR26## at least 35% of B units, consisting of units A substituted by a radical --O--(CH 2 ) n --R--COO - in which R represents a single bond or a --CO--NH--(CH 2 ) n' --, n is a number from 1 to 10 and n' is a number from 1 to 7, and at least 3% of D units, consisting of units A substituted by a chain with a gorup of structure ##STR27## in which: R 1 represents a single bond, --CH 2 --group, or a --CH--CH 2 --group, R 2 respresents a physiogically acceptable anion of an inorganic or organic salt, and an inorganic or organic salt, and n is as defined above in a mixture with a biologically acceptable carrier.

Claim 22

A biological composition which comprises a polymer of dextran having a molecular weight higher than 5,000 daltons and comprising statistically glucosyl units A with 1,6 linkages, of the formula: ##STR26## at least 35% of B units, consisting of units A substituted by a radical --O--(CH 2 ) n --R--COO - in which R represents a single bond or a --CO--NH--(CH 2 ) n' --, n is a number from 1 to 10 and n' is a number from 1 to 7, and at least 3% of D units, consisting of units A substituted by a chain with a gorup of structure ##STR27## in which: R 1 represents a single bond, --CH 2 --group, or a --CH--CH 2 --group, R 2 respresents a physiogically acceptable anion of an inorganic or organic salt, and an inorganic or organic salt, and n is as defined above in a mixture with a biologically acceptable carrier.

Claim 23

The biological composition of claim 20 wherein the dextran polymer has the following A, B, C and D units ##STR28##

Claim 24

The composition of claim 20 which is a blood plasma substitute and expander.

Claim 25

The blood plasma substitute of claim 22 wherein the dextran polymer is in an aqueous concentration of about 5 to 15%.

Claim 26

The blood plasma of substitute of claim 22 wherein the solution is a saline solution.

Claim 27

The freeze-dried polymer of dextran of claim 1.

Claim 28

The freeze-dried polymer of dextran of claim 7.