# US 2010/0167991 A1 · Polysaccharides comprising carboxyl functional groups substituted by a hydrophobic alcohol derivative

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- Number: US 2010/0167991 A1
- Document ID: US20100167991A1
- Status: Published application
- Kind: A1
- Application number: 12/588,149
- Filed: 2009-10-06
- Published: 2010-07-01
- Earliest claimed: 2008-10-06
- Assignees: Adocia
- Inventors: Remi Soula; Olivier Soula; Gerard Soula; Richard Charvet
- Web page: https://patentgrep.com/patent/US20100167991A1

## CPC

- C08B 37/0021: {Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran}
- A61K 31/715: Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K 31/721: Dextrans
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- C08B 37/00: Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof (cellulose D21; {microbiological processes C12P})
- C08B 37/0006: {Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid}
- C08B 37/0018: {Pullulan, i.e. (alpha-1,4)(alpha-1,6)-D-glucan; Derivatives thereof}
- C08B 37/0024: {beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof}
- C08B 37/0045: {alpha-D-Galacturonans, e.g. methyl ester of (alpha-1,4)-linked D-galacturonic acid units, i.e. pectin, or hydrolysis product of methyl ester of alpha-1,4-linked D-galacturonic acid units, i.e. pectinic acid; Derivatives thereof}
- C08B 37/0054: {Inulin, i.e. beta-2,1-D-fructofuranan; Derivatives thereof}
- C08B 37/0057: {beta-D-Xylans, i.e. xylosaccharide, e.g. arabinoxylan, arabinofuronan, pentosans; (beta-1,3)(beta-1,4)-D-Xylans, e.g. rhodymenans; Hemicellulose; Derivatives thereof}
- C08B 37/0072: {Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates}
- C08B 37/0084: {Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates}
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to a polysaccharide comprising carboxyl functional groups, one at least of which is substituted by a derivative of a hydrophobic alcohol. The invention also relates to a pharmaceutical composition comprising one of the polysaccharides according to the invention and at least one active principle. It also relates to a pharmaceutical composition, wherein the active principle is chosen from the group consisting of proteins, glycoproteins, peptides and nonpeptide therapeutic molecules. The invention also relates to the use of the functionalized polysaccharides according to the invention in the preparation of pharmaceutical compositions as described above.

## Claims

### Claim 1

A polysaccharide comprising carboxyl functional groups, one at least of which is substituted by a derivative of a hydrophobic alcohol, denoted HA:
said alcohol being grafted or bonded to the anionic polysaccharide via a coupling arm R, said coupling arm being bonded to the anionic polysaccharide via a functional group F, said function F resulting from the coupling between the amine function of the connecting arm R and a carboxyl function of the anionic polysaccharide, and said coupling arm being bonded to the hydrophobic alcohol via a function G resulting from the coupling between a carboxyl, isocyanate, thioacid or alcohol function of the coupling arm and a function of the hydrophobic alcohol, the unsubstituted carboxyl functions of the anionic polysaccharide being in the cationic carboxylate form, the cation preferably being that of an alkali metal, such as Na+ or K+,
F being an amide function,
G being either an ester, thioester, carbonate or carbamate function,
R being a chain comprising between 1 and 18 carbons which is optionally branched and/or unsaturated, which optionally comprises one or more heteroatoms, such as O, N and/or S, and which has at least one acid function,
HA being a residue of a hydrophobic alcohol, the product of the coupling between the hydroxyl function of the hydrophobic alcohol and at least one electrophilic function carried by the group R,
said polysaccharide comprising carboxyl functional groups being amphiphilic at neutral pH.

### Claim 2 (depends on 1)

The polysaccharide as claimed in claim 1, which is chosen from polysaccharides comprising carboxyl functional groups, at least one of which is substituted by a derivative of a hydrophobic alcohol, of general formula I:
in which n represents the molar fraction of the carboxyl functions of the polysaccharide substituted by F R G HA and is between 0.01 and 0.7,
F, R, G and HA corresponding to the definitions given above, and, when one or more carboxyl functions of the polysaccharide are not substituted by F R G HA, then the carboxyl function or functions of the polysaccharide are cation carboxylates, the cation preferably being that of an alkali metal, such as Na+ or K+.

### Claim 3 (depends on 1)

The polysaccharide as claimed in claim 1, the anionic polysaccharide naturally carrying acid functions and being chosen from the group consisting of alginate, hyaluronan and galacturonan.

### Claim 4 (depends on 1)

The polysaccharide as claimed claim 1, the anionic polysaccharide being a synthetic anionic polysaccharide obtained from an anionic or nonanionic (neutral) natural polysaccharide to which at least one acid function has been grafted, of general formula II:
the natural polysaccharide being chosen from the group of the polysaccharides predominantly composed of glycoside monomers bonded via glycoside bonds of (1,6) and/or (1,4) and/or (1,3) and/or (1,2) type,
L being a bond resulting from the coupling between the connecting arm Q and an —OH function of the neutral or anionic polysaccharide, being either an ester, thioester, carbonate, carbamate or ether function,
Q being a chain comprising between 1 and 18 carbons which is optionally branched and/or unsaturated, which comprises one or more heteroatoms, such as O, N and/or S, and which comprises at least one acid function CO2H.

### Claim 5 (depends on 4)

The polysaccharide as claimed in claim 4, the polysaccharide being predominantly composed of glycoside monomers bonded via glycoside bonds of (1,6) type.

### Claim 6 (depends on 5)

The polysaccharide as claimed in claim 5, the polysaccharide predominantly composed of glycoside monomers bonded via glycoside bonds of (1,6) type being dextran.

### Claim 7 (depends on 4)

The polysaccharide as claimed in claim 4, the polysaccharide being predominantly composed of glycoside monomers bonded via glycoside bonds of (1,4) type.

### Claim 8 (depends on 7)

The polysaccharide as claimed in claim 7, the polysaccharide predominantly composed of glycoside monomers bonded via glycoside bonds of (1,4) type being chosen from the group consisting of pullulan, alginate, hyaluronan, xylan, galacturonan or a water-soluble cellulose.

### Claim 9 (depends on 4)

The polysaccharide as claimed in claim 4, the polysaccharide being predominantly composed of glycoside monomers bonded via glycoside bonds of (1,3) type.

### Claim 10 (depends on 9)

The polysaccharide as claimed in claim 9, the polysaccharide predominantly composed of glycoside monomers bonded via glycoside bonds of (1,3) type being a curdlan.

### Claim 11 (depends on 4)

The polysaccharide as claimed in claim 4, the polysaccharide being predominantly composed of glycoside monomers bonded via glycoside bonds of (1,2) type.

### Claim 12 (depends on 11)

The polysaccharide as claimed in claim 11, the polysaccharide predominantly composed of glycoside monomers bonded via glycoside bonds of (1,2) type being an inulin.

### Claim 13 (depends on 4)

The polysaccharide as claimed in claim 4, the polysaccharide being predominantly composed of glycoside monomers bonded via glycoside bonds of (1,4) and (1,3) type.

### Claim 14 (depends on 13)

The polysaccharide as claimed in claim 13, the polysaccharide predominantly composed of glycoside monomers bonded via glycoside bonds of (1,4) and (1,3) type being a glucan.

### Claim 15 (depends on 4)

The polysaccharide as claimed in claim 4, the polysaccharide being predominantly composed of glycoside monomers bonded via glycoside bonds of (1,4) and (1,3) and (1,2) type.

### Claim 16 (depends on 15)

The polysaccharide as claimed in claim 15, the polysaccharide predominantly composed of glycoside monomers bonded via glycoside bonds of (1,4) and (1,3) and (1,2) type being mannan.

### Claim 17 (depends on 4)

The polysaccharide as claimed in claim 4, wherein the group Q is chosen from the following groups:

### Claim 18 (depends on 1)

The polysaccharide as claimed in claim 1, wherein the group R is chosen from amino acids.

### Claim 19 (depends on 1)

The polysaccharide as claimed in claim 1, wherein the group R is chosen from a amino acids.

### Claim 20 (depends on 19)

The polysaccharide as claimed in claim 19, the a amino acids being chosen from natural a amino acids, including leucine, alanine, isoleucine, glycine, phenylalanine, tryptophan or valine.

### Claim 21 (depends on 1)

The polysaccharide as claimed in claim 1, the hydrophobic alcohol being chosen from fatty alcohols.

### Claim 22 (depends on 21)

The polysaccharide as claimed in claim 21, the hydrophobic alcohol being chosen from the alcohols composed of a saturated or unsaturated and branched or unbranched alkyl chain comprising from 4 to 18 carbons.

### Claim 23 (depends on 1)

The polysaccharide as claimed in claim 1, the fatty alcohol being chosen from myristyl alcohol, cetyl alcohol, stearyl alcohol, cetearyl alcohol, butyl alcohol, oleyl alcohol or lanolin.

### Claim 24 (depends on 21)

The polysaccharide as claimed in claim 21, the hydrophobic alcohol being cholesterol.

### Claim 25 (depends on 21)

The polysaccharide as claimed in claim 21, the hydrophobic alcohol being menthol.

### Claim 26 (depends on 21)

The polysaccharide as claimed in claim 21, the hydrophobic alcohol being chosen from tocopherols, preferably a tocopherol.

### Claim 27 (depends on 21)

The polysaccharide as claimed in claim 21, the hydrophobic alcohol being chosen from alcohols carrying an aryl group.

### Claim 28 (depends on 27)

The polysaccharide as claimed in claim 27, the alcohol carrying an aryl group being chosen from benzyl alcohol or phenethyl alcohol.

### Claim 29 (depends on 1)

The use of a functionalized polysaccharide as claimed in claim 1 in the preparation of pharmaceutical compositions as described above.

### Claim 30 (depends on 1)

A pharmaceutical composition comprising a polysaccharide as claimed in claim 1 and at least one active principle.

### Claim 31 (depends on 30)

The pharmaceutical composition as claimed in claim 30, which can be administered by the oral, nasal, vaginal or buccal route.

### Claim 32 (depends on 30)

The pharmaceutical composition as claimed in claim 30, wherein the active principle is chosen from the group consisting of proteins, glycoproteins, peptides and nonpeptide therapeutic molecules.