JP2008501639A5

JP2008501639A5 -

Info

Publication number: JP2008501639A5
Application number: JP2007508984A
Authority: JP
Filing date: 2005-04-25
Publication date: 2008-05-15

Claims

A method for stabilizing a protein, comprising contacting a protein with a sugar polymer derivative, wherein the sugar polymer derivative is not α-, β-, or γ-cyclodextrin . Stabilizing against change and / or degradation .

For stabilizing a protein in an aqueous solution, method of claim 1.

For stabilizing the protein in dry form, The method of claim 1.

The sugar polymer derivative is selected from the group consisting of erythrose, threose, ribose, arabinose, xylose, lyxose, allose, altrose, glucose, mannose, gulose, idose, galactose, talose, psicose, fructose, sorbose, tagotose, xylulose and ribulose one or a plurality of sugar, methods who described 請 Motomeko 1 that.

The method according to claim 1 , wherein the sugar polymer derivative is fructosan or glucosan.

The method according to claim 1 , wherein the sugar polymer derivative is an inulin derivative.

The method according to claim 1 , wherein the sugar polymer derivative is a glucoside derivative.

Sugar polymer derivative is derivatized by one or more types nonpolar hydrocarbyl group of A process according to 請 Motomeko 1.

Inulin derivatives, linear alkyl derivatives, branched alkyl derivatives, aromatic groups, are derivatized by one or more types nonpolar hydrocarbyl group is selected from the group consisting of polyols and fatty acids, in claim 6 The method described.

An inulin derivative is a compound of formula (I),
G (O—CO—NH—R ¹ ) _a- [F (O—CO—NH—R ² ) _b ] _n (I)
Where
G is a terminal glucosyl unit, the one or more hydroxyl groups of which may be substituted with one or more groups of formula (O—CO—NH—R ¹ );
R ¹ is selected from the group consisting of an alkyl group, an alkenyl group, an alkynyl group, a haloalkyl group, a cycloalkyl group, an aryl group, and an aralkyl group, and two or more (O—CO—NH—R ¹ ) on the glucosyl unit. When groups are present, each R ¹ group may be the same or different;
a is an integer of 0 to 4;
F is a fructosyl unit whose one or more hydroxyl groups may be substituted with one or more groups of the formula (O—CO—NH—R ² );
R ² is selected from the group comprising an alkyl group, an alkenyl group, an alkynyl group, a haloalkyl group, a cycloalkyl group, an aryl group and an aralkyl group, and two or more (O—CO—NH—R ² ) on the fructosyl unit. When groups are present, each R ² group may be the same or different;
b is an integer from 0 to 3 and from 0 to 4 with respect to the terminal fructosyl unit;
n is an integer of 2 to 499, preferably 2 to 249, 2 to 99, 2 to 49, 9 to 49, 14 to 39, 19 to 29, or 19 to 24,
Formula ^{F (O-CO-NH-} R 2) each unit of _b is the formula ^{F (O-CO-NH-} R 2) _b may or different and the same as any other units, and glucosyl units Or the method of Claim 6 which is a compound whose average substitution degree per fructosyl unit is 0.01-3.0.

11. A process according to claim 10, wherein the compound of formula (I) is a polydisperse linear or slightly branched inulin N-alkyl urethane.

Protein A method of stabilizing with a characterized by contacting the protein and glucoside hydrocarbyl derivative, aggregation of the protein, a method for stabilizing against change and / or degradation of the conformation.

A kit for carrying out the method or use according to claim 1 .

The sugar polymer derivative is one or more inulin derivatives of formula (I):
G (O—CO—NH—R ¹ ) _a- [F (O—CO—NH—R ² ) _b ] _n (I)
Where
G is a terminal glucosyl unit, the one or more hydroxyl groups of which may be substituted with one or more groups of formula (O—CO—NH—R ¹ );
R ¹ is a linear or branched saturated or unsaturated hydrocarbyl group having ¹ to 25 carbon atoms, and two or more (O—CO—NH—R ¹ ) groups are present on the glucosyl unit. When present, each R ¹ group may be the same or different;
a is an integer of 0 to 4;
F is a fructosyl unit whose one or more hydroxyl groups may be substituted with one or more groups of the formula (O—CO—NH—R ² );
R ² is a linear or branched saturated or unsaturated hydrocarbyl group having 1 to 25 carbon atoms, and two or more (O—CO—NH—R ² ) groups are present on the fructosyl unit. When present, each R ² group may be the same or different;
b is an integer from 0 to 3 and from 0 to 4 with respect to the terminal fructosyl unit;
n is an integer of 2 to 499, preferably 2 to 249, 2 to 99, 2 to 49, 9 to 49, 14 to 39, 19 to 29, or 19 to 24,
Formula ^{F (O-CO-NH-} R 2) each unit of _b is the formula ^{F (O-CO-NH-} R 2) _b may or different and the same as any other units; and
The average degree of substitution per glucosyl unit or fructosyl unit is 0.01 to 3.0 , and / or the sugar polymer derivative is one or more glucoside hydrocarbyl derivatives of formula (II) :
[G (O—CO—NH—R ¹ ) _a ] _n (II)
Where
G is a glucosyl unit, and one or more hydroxyl groups thereof may be substituted with one or more groups of the formula (O—CO—NH—R ¹ );
R ¹ is a hydrocarbyl group selected from the group consisting of an alkyl group, an alkenyl group, an alkynyl group, a haloalkyl group, a cycloalkyl group, an aryl group, and an aralkyl group, and two or more (O— When CO-NH-R < ¹ > ) groups are present, each R < ¹ > group may be the same or different;
a is an integer from 0 to 4 for terminal glucosyl units, 0 to 3 for non-branched, non-terminal glucosyl units, and 0 to 2 for branched, non-terminal glucosyl units;
n is an integer of 3 to 499, preferably 3 to 249, 3 to 99, 3 to 49, 9 to 49, 14 to 39, 19 to 29, or 19 to 24,
Formula ^{G (O-CO-NH-} R 1) each of the units of _a is Formula ^{G (O-CO-NH-} R 1) may or different and the same as any other unit of _a; and
The average degree of substitution per glucosyl unit is 0.01-2.0,
The kit according to claim 13 .

A protein, and an inulin derivative of formula (I), comprising:
G (O—CO—NH—R ¹ ) _a- [F (O—CO—NH—R ² ) _b ] _n (I)
Where
G is a terminal glucosyl unit, the one or more hydroxyl groups of which may be substituted with one or more groups of formula (O—CO—NH—R ¹ );
R ¹ is a linear or branched saturated or unsaturated hydrocarbyl group having ¹ to 25 carbon atoms, and two or more (O—CO—NH—R ¹ ) groups are present on the glucosyl unit. When present, each R ¹ group may be the same or different;
a is an integer of 0 to 4;
F is a fructosyl unit whose one or more hydroxyl groups may be substituted with one or more groups of the formula (O—CO—NH—R ² );
R ² is a linear or branched saturated or unsaturated hydrocarbyl group having 1 to 25 carbon atoms, and two or more (O—CO—NH—R ² ) groups are present on the fructosyl unit. When present, each R ² group may be the same or different;
b is an integer from 0 to 3 and from 0 to 4 with respect to the terminal fructosyl unit;
n is an integer of 2 to 499, preferably 2 to 249, 2 to 99, 2 to 49, 9 to 49, 14 to 39, 19 to 29, or 19 to 24,
Formula ^{F (O-CO-NH-} R 2) each unit of _b is the formula ^{F (O-CO-NH-} R 2) or different and the same as any other unit of _b may, and glucosyl unit Or the composition containing the inulin derivative whose average substitution degree per fructosyl unit is 0.01-3.0.

16. A composition according to claim 15 , wherein the compound of formula (I) is a polydisperse linear or slightly branched inulin N-alkyl urethane.

A protein and a glucoside hydrocarbyl derivative of formula (II) comprising:
[G (O—CO—NH—R ¹ ) _a ] _n (II)
Where
G is a glucosyl unit, and one or more hydroxyl groups thereof may be substituted with one or more groups of the formula (O—CO—NH—R ¹ );
R ¹ is a hydrocarbyl group selected from the group consisting of an alkyl group, an alkenyl group, an alkynyl group, a haloalkyl group, a cycloalkyl group, an aryl group, and an aralkyl group, and two or more (O— When CO-NH-R < ¹ >) groups are present, each R < ¹ > group may be the same or different;
a is an integer from 0 to 4 for terminal glucosyl units, 0 to 3 for non-branched, non-terminal glucosyl units, and 0 to 2 for branched, non-terminal glucosyl units;
n is an integer of 3 to 499, preferably 3 to 249, 3 to 99, 3 to 49, 9 to 49, 14 to 39, 19 to 29, or 19 to 24,
Formula ^{G (O-CO-NH-} R 1) each of the units of _a is Formula ^{G (O-CO-NH-} R 1) may or different and the same as any other unit of _a; and glucosyl unit A composition comprising a glucoside hydrocarbyl derivative having an average degree of substitution of 0.01 to 2.0.

The composition according to claim 15 , which is a pharmaceutical composition.