Polysaccharide derivative having membrane-permeable peptide chain

Patent metadata

Field	Value
Publication number	US-10793603-B2
Application number	US-201615547595-A
Country	US
Kind code	B2
Filing date	Feb 23, 2016
Priority date	Feb 27, 2015
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

A polysaccharide derivative has a partial structure represented by Formula (1) below. It is preferable that at least one of the amino acids that constitute X 2 in Formula (1) below is a basic amino acid.

(In the formula, X 1 represents a residue obtained by removing the terminal amino group and the terminal carboxyl group from a neutral amino acid or an ω-aminoalkanoic acid, X 2 represents a residue obtained by removing the terminal amino group and the terminal carboxyl group from a membrane-permeable peptide, X 3 represents a hydroxyl group, an amino group, an alkoxyl group having 1 to 4 carbon atoms, or a benzyloxy group, a represents a number of 0 or 1, and b represents a number of from 0 to 50.)

First claim

The invention claimed is:

1. A polysaccharide derivative having a structure represented by one of Formulae (3) to (5) below:

wherein X 1 represents a residue obtained by removing a terminal amino group and a terminal carboxyl group from a neutral amino acid or an ω-aminoalkanoic acid, X 2 represents a residue obtained by removing a terminal amino group and a terminal carboxyl group from a membrane-permeable peptide, X 3 represents a hydroxyl group, an amino group, an alkoxyl group having 1 to 4 carbon atoms, or a benzyloxy group, and b represents a number of from 0 to 50;
c and d represent numbers satisfying the condition that c+d is such that the polysaccharide derivative represented by Formula (3) has a weight-average molecular weight of 5,000 to 50,000,000 and d/(c+d) is such that a ratio of the partial structures represented by Formula (2) below to the total saccharide units in said polysaccharide derivative is from 0.29 to 0.8;

wherein X 1 to X 3 and b are as defined in Formulae (3) to (5) and * represents a bonding hand;
e, f and g represent numbers satisfying the condition that e+f+g is such that the polysaccharide derivative represented by Formula (4) has a weight-average molecular weight of 5,000 to 50,000,000 and g/(e+f+g) is such that a ratio of the partial structures represented by Formula (2) to the total saccharide units in said polysaccharide derivative is from 0.29 to 0.8; and
h, j, k and m represent numbers satisfying the condition that h+j+k+m is such that the polysaccharide derivative represented by Formula (5) has a weight-average molecular weight of 5,000 to 50,000,000 and (k+m)/(h+j+k+m) is such that a ratio of the partial structures represented by Formula (2) to the total saccharide units in said polysaccharide derivative is from 0.29 to 0.8.

2. The polysaccharide derivative according to claim 1 , wherein at least one of the amino acids that constitute X 2 in Formula (1) is a basic amino acid.

3. The polysaccharide derivative according to claim 1 , wherein the polysaccharide derivative is a polysaccharide derivative represented by Formula (3), provided that the c units and the d units are bound to one another in a random manner.

4. An introducing agent for introducing a poorly membrane-permeable compound into a cell or a mucous membrane, the introducing agent comprising the polysaccharide derivative according to claim 1 .

5. A method for introducing a poorly membrane-permeable compound into a cell, the method comprising:
contacting the cell with an aqueous solution containing the introducing agent according to claim 4 and the poorly membrane-permeable compound or an aqueous dispersion containing the introducing agent and the poorly membrane-permeable compound, or
attaching, on a skin surface, a microprojection array in which the mixture containing the introducing agent according to claim 4 and the poorly membrane-permeable compound is applied to the surface or a microprojection array having microprojections including the mixture containing the introducing agent and the poorly membrane-permeable compound, passing minute projections of the microprojection array through the skin, and infiltrating the introducing agent and the poorly membrane-permeable compound under the skin.

6. A method for introducing a poorly membrane-permeable compound into a mucous membrane, the method comprising contacting the mucous membrane with a mixture containing the introducing agent according to claim 4 and the poorly membrane-permeable compound.

7. An introducing agent for introducing a poorly membrane-permeable compound into a cell or a mucous membrane, the introducing agent comprising the polysaccharide derivative according to claim 2 .

8. The method according to claim 5 ,
wherein the poorly membrane-permeable compound is a protein drug, an enzyme, an antibody or a glycoprotein.

9. The method according to claim 6 ,
wherein the poorly membrane-permeable compound is a protein drug, an enzyme, an antibody or a glycoprotein.

10. The polysaccharide derivative according to claim 1 ,
wherein b represents a number of from 2 to 50;
and
wherein X 1 is the residue of a neutral amino acid selected from the group consisting of asparagine, glutamine, glycine, methionine, phenylalanine, proline, threonine and hydroxyproline.

11. The polysaccharide derivative according to claim 1 ,
wherein b represents a number of from 2 to 50; and
wherein X 1 is the residue of a neutral amino acid selected from the group consisting of alanine, asparagine, cysteine, glutamine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, valine and hydroxyproline.

Assignees

• Josho Gakuen Educational Found
• Adeka Corp

Inventors

• Sakuma Shinji
• Mohri Kohta
• Hiwatari Ken-Ichiro
• Ochiai Kyohei

Classifications

• C08B37/0072

  Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates · CPC title

• C08B37/00 Primary

  Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof (cellulose D21; {microbiological processes C12P}) · CPC title

• C07K9/00

  Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof · CPC title

• A61K47/30

  Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title