JP5081406B2 - Sulfated sugar-containing polyurethane derivative and process for producing the same - Google Patents

Description

  The present invention relates to a novel sulfated sugar residue-modified oligosaccharide-containing polyurethane derivative and a method for producing the same.

In recent years, it has become clear that sugar chains are deeply involved in various life phenomena (cell recognition and information transmission, cell adhesion, differentiation / proliferation, canceration, virus infection, blood coagulation, immune reaction, etc.). Research and development of incorporated functional materials and pharmaceuticals has been actively conducted (for example, Non-Patent Document 1, Non-Patent Document 2, and Non-Patent Document 3).
In order to develop sugar chain-containing functional materials that express the desired physiological function, the relationship between the structure and physiological activity of sugar chains is studied at the molecular and functional group level, and sugar chains are freely modified or highly functional. Technology to be introduced into molecules is required.
Among them, sulfated sugar is known to have affinity for influenza virus, AIDS virus, etc., and development of a new material capable of capturing virus and a method for producing the same using this principle is desired. Yes.
Under such circumstances, various sugar chain-containing polymers have been reported. For example, a sulfated galactose-introduced polyacrylate type (for example, Patent Document 1), a sulfated sugar-introduced polyethylene type (for example, Patent Document 2), and a sulfated glucosamine-introduced polyethylene type (for example, Patent Document 3) are known. .
JP 11-315091 A JP-T-2004-526691 JP 2005-15451 A Design and physiological functions of glycan molecules, 2001, Academic Publishing Center Bioactive sugar chain research method, 1999, Academic Publishing Center Carbohydrate engineering and commercialization technology, 1993

Biological functions such as cell recognition and cell adhesion are expressed by the sugar chain-sugar chain interaction between sugar chain aggregates (clusters) on the surface of sugar cells and complementary sugar chain aggregates. Is known to correlate with sugar density. In the sugar chain polymer disclosed in the above patent document, since one sulfated sugar chain can be introduced only linearly per repeating unit, when such a polymer is used to form a film or the like, In order to increase the sugar chain density in the cluster and fully express the biological function of the sugar chain (cell recognition, cell adhesion, etc.), it is necessary to increase the number of repeating units into which the sugar chain is introduced in the polymer chain. However, this may reduce the original film-forming ability and mechanical strength of the skeleton polymer.
In addition, since the production process for introducing a sugar chain into a side chain requires a protection / deprotection operation, there is a problem that the production cost is complicated.
In contrast to these conventional techniques, the object of the present invention is to increase the density of sugar chain clusters and to have excellent film-forming ability by using a repeating unit in which a plurality of sulfated sugar chains are introduced into the side chain. Another object of the present invention is to provide a sulfated sugar residue-modified oligosaccharide-containing polyurethane derivative expected to have biocompatibility and blood compatibility, and a simple and inexpensive production method thereof.

  As a result of intensive studies in view of the above problems, the present inventors obtained an oligosaccharide-containing polyurethane derivative by addition polymerization of an oligosaccharide having two primary hydroxyl groups, a diisocyanate, and, if necessary, a diol compound, By reacting an acid anhydride, a carboxyl group-modified oligosaccharide-containing polyurethane derivative is obtained, and a sugar residue-modified oligosaccharide-containing polyurethane derivative having a sugar chain in the side chain obtained by further reacting with an amino sugar, It was found that by reacting with a sulfating reagent, a sugar derivative-modified oligosaccharide-containing polyurethane derivative having a sulfated sugar chain in the side chain can be obtained, and the present invention has been completed.

That is, the present invention includes the following (1) to (6).
(1) The following general formula [1]:

[Where:
R ¹ represents a C 1-16 divalent hydrocarbon group which may have a substituent,
R ² contains 1 to 100 units in total of the same or different units selected from oxyalkylene units having 2 to 12 carbon atoms and divalent hydrocarbon units having 2 to 12 carbon atoms which may have a substituent. Represents a divalent group,
R ³ represents an alkylene group having 2 to 4 carbon atoms,
R ⁴ represents a sugar residue derived from a monosaccharide or a disaccharide,
M represents a hydrogen atom, an alkali metal atom, an ammonium group or an organic amino group,
s represents the number of hydroxyl groups of the sugar residue R ⁴ modified with a sulfuric acid-containing group, and represents an integer in the range of 1 ≦ s ≦ 4,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
p and q represent integers in the range of 1 ≦ p ≦ r and 0 ≦ q ≦ r−1,
m and n are the numbers of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is a number in the range of 0.01 to 1.00. ]
A sulfated sugar residue-modified oligosaccharide-containing polyurethane represented by:
(2) The sulfated sugar residue-modified oligosaccharide-containing polyurethane according to (1), wherein R ³ is an ethylene group.
(3) The sulfated sugar residue-modified oligosaccharide-containing polyurethane according to the above (1), wherein R ⁴ is glucose, mannose, lactose or galactose.
(4) The sulfated sugar residue-modified oligosaccharide-containing polyurethane according to (1) above, wherein R ³ is an ethylene group and R ⁴ is glucose, mannose, lactose or galactose.
(5) The following general formula [2]:

[Where:
R ¹ represents a C 1-16 divalent hydrocarbon group which may have a substituent,
R ² contains 1 to 100 units in total of the same or different units selected from oxyalkylene units having 2 to 12 carbon atoms and divalent hydrocarbon units having 2 to 12 carbon atoms which may have a substituent. Represents a divalent group,
R ³ represents an alkylene group having 2 to 4 carbon atoms,
R ⁴ represents a sugar residue derived from a monosaccharide or a disaccharide,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
p and q represent integers in the range of 1 ≦ p ≦ r and 0 ≦ q ≦ r−1,
m and n are the numbers of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is a number in the range of 0.01 to 1.00. ]
A sugar residue-modified oligosaccharide-containing polyurethane represented by the following general formula [1]:

[Where:
R ¹ represents a C 1-16 divalent hydrocarbon group which may have a substituent,
R ² contains 1 to 100 units in total of the same or different units selected from oxyalkylene units having 2 to 12 carbon atoms and divalent hydrocarbon units having 2 to 12 carbon atoms which may have a substituent. Represents a divalent group,
R ³ represents an alkylene group having 2 to 4 carbon atoms,
R ⁴ represents a sugar residue derived from a monosaccharide or a disaccharide,
M represents a hydrogen atom, an alkali metal atom, an ammonium group or an organic amino group,
s represents the number of hydroxyl groups of the sugar residue R ⁴ modified with a sulfuric acid-containing group, and represents an integer in the range of 1 ≦ s ≦ 4,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
p and q represent integers in the range of 1 ≦ p ≦ r and 0 ≦ q ≦ r−1,
m and n are the numbers of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is a number in the range of 0.01 to 1.00. ]
The manufacturing method of the sulfated saccharide residue modification oligosaccharide containing polyurethane represented by these.

  The sulfated sugar residue-modified oligosaccharide-containing polyurethane of the present invention is thermoplastic and solvent-soluble, and has excellent film forming ability. Because the film is composed of oligosaccharide-containing polyurethane, it has excellent biocompatibility and blood compatibility, and in addition to the increased sugar chain cluster density, the oligosaccharide is sulfated. Affinity with cells, proteins and viruses is expected. Therefore, it is useful as a highly functional material in the fields of medical and daily necessities.

The present invention is described in detail below.
The sulfated sugar residue-modified oligosaccharide-containing polyurethane of the present invention has the following general formula [1]:

[Wherein R ¹ , R ² , R ³ , R ⁴ , M, p, q, r, s, m, n and OLS are as defined above]
A sulfated sugar residue-modified oligosaccharide-containing polyurethane represented by the formula:
In the general formulas [1] and [2], R ¹ is a C 1-16 divalent hydrocarbon group which may have a substituent.
As the “divalent hydrocarbon group having 1 to 16 carbon atoms which may have a substituent” as the “divalent hydrocarbon group having 1 to 16 carbon atoms”,
(1) A linear or branched divalent aliphatic hydrocarbon group having 1 to 16 carbon atoms [e.g., a linear or branched alkylene group having 1 to 16 carbon atoms (e.g., methylene, ethylene, tetramethylene, Pentamethylene, hexamethylene, octamethylene, hexadecamethylene, etc.), linear or branched alkenylene groups having 2 to 16 carbon atoms (eg, vinylene, propenylene, etc.), cycloalkylene having 3 to 16 carbon atoms (eg, cyclohexene). Silylene) etc.], and (2) a divalent aromatic hydrocarbon group having 6 to 14 carbon atoms [eg, arylene group having 6 to 14 carbon atoms (eg, phenylene, naphthylene, biphenylene, etc.)], and (3 ) Selected from at least one group selected from the above-mentioned linear or branched divalent aliphatic hydrocarbon groups having 1 to 16 carbon atoms and divalent aromatic hydrocarbon groups having 6 to 14 carbon atoms. At least comprises one group, a hydrocarbon group (e.g. total number of carbon atoms is in the range of 7 to 16, wherein

Groups represented by
Etc.
Examples of the “substituent” in the above “optionally substituted divalent hydrocarbon group having 1 to 16 carbon atoms” include, for example,
(1) an alkyl group having 1 to 6 carbon atoms (eg, methyl, etc.);
(2) a cycloalkyl group having 3 to 8 carbon atoms (eg, cyclohexyl, etc.);
(3) an aryl group having 6 to 14 carbon atoms (eg, phenyl, etc.);
Etc. These substituents can be substituted at the substitutable position of the above-mentioned “C1-C16 divalent hydrocarbon group” in the same or different manner, and can be substituted with 1 to 8, preferably 1 to 4.

Specific examples of R ¹ include, for example, a tetramethylene group, a pentamethylene group, a hexamethylene group, an octamethylene group, a hexadecamethylene group, a vinylene group, a propenylene group, a phenylene group, a naphthylene group, a phenylmethylene group, and a phenylethylene group. , Biphenyl group, bisphenylmethylene group, bisphenylethylene group, phenylene group (eg, paraphenylene group), xylylene group, tetramethylxylylene group, tolylene group, dicyclohexylmethylene group,
formula

Bisphenylmethylene group, phenylmethylene group and hexamethylene group are preferable.

In the general formulas [1] and [2], R ² is the same selected from an oxyalkylene group having 2 to 12 carbon atoms and a divalent hydrocarbon unit having 2 to 12 carbon atoms which may have a substituent. Or it is a divalent group containing 1 to 100 units of different units in total.
As such, for example, a divalent group containing 1 to 100 units of the same or different units selected from oxyalkylene having 2 to 12 carbon atoms, and optionally having 2 to 2 carbon atoms. A divalent group containing a total of 1 to 100 units of the same or different units selected from 12 divalent hydrocarbon units, or a carbon number optionally having 2 to 12 carbon atoms and a substituent. It may be a divalent group containing a total of 1 to 100 units of the same or different units selected from 2 to 12 divalent hydrocarbon units.
The above-mentioned “divalent containing a total of 1 to 100 units of the same or different units selected from a C 2-12 oxyalkylene unit and a C 2-12 divalent hydrocarbon unit optionally having a substituent” "Group" is, for example, a unit represented by the formula-(BO) _h-1 -B- and a unit represented by the formula-(E) _i- (wherein B represents at least one carbon number of 2 Represents an alkylene unit of ˜12, E represents the same or different unit selected from at least one divalent hydrocarbon unit having 2 to 12 carbon atoms which may have a substituent, h and i Are each an integer of 1 ≦ h ≦ 100 and 1 ≦ i ≦ 100.) Is a divalent group containing a total of 1 to 100 units of the same or different units selected from:
The “C2-C12 alkylene group” of B in the unit represented by the formula-(BO) _h-1 -B- may be linear or branched, and in the unit, When a plurality of B are present (2 ≦ h ≦ 100), B may be one type or two or more types. Specific examples of BO include, for example, an alkyleneoxy group such as an ethyleneoxy group, a propyleneoxy group, a trimethyleneoxy group, a butyleneoxy group, a tetramethyleneoxy group, and the _formula- (BO) _h- Specific examples of the unit represented by ₁ -B- include a unit represented by the formula -CH ₂ -CH ₂ -O-CH ₂ -CH ₂ -CH _2- .
In the unit represented by the formula-(E) _i- , the divalent hydrocarbon unit in the "divalent hydrocarbon unit having 2 to 12 carbon atoms which may have a substituent" represented by E May be linear or branched, and may be a saturated or unsaturated group. For example, alkylene having 2 to 12 carbon atoms (eg, ethylene, trimethylene, tetramethylene, hexa Methylene, nonamethylene, etc.) and alkenylene having 2 to 12 carbon atoms (eg, butadienylene, butenylene, etc.). Examples of the “substituent” that the “divalent hydrocarbon unit having 2 to 12 carbon atoms” may have include, for example, a halogen atom (eg, fluorine atom), alkyl having 1 to 6 carbon atoms. Group (eg, methyl, etc.) and the like. When a plurality of E are present in the unit (2 ≦ i ≦ 100), E may be one type or two or more types.
Specific examples of such a unit represented by the formula-(E) _i- include, for example, ethylene group, trimethylene group, tetramethylene group, hexamethylene group, nonamethylene group, -CH ₂ -CF ₂ -CF. _2- CF ₂ —CF ₂ —CH ₂ — groups, butadienylene groups, hydrogenated butadienylene groups, and divalent groups such as groups derived by removing one hydrogen atom from the carbon atoms at both chain ends of hydrogenated isoprene. Etc.

R ² is a unit represented by the formula-(BO) _h-1 -B- (wherein B and h are as defined above) and / or formula-(E) _i- (wherein , E and i are as described above), and other repeating units such as ethylene adipate group, propylene adipate group, butylene adipate group, hexamethylene adipate group, neo A repeating unit such as an alkylene ester group such as a pentyl adipate group, an alkylene carbonate group such as a hexamethylene carbonate group, a ring-opening caprolactone group, or a poly (dimethylsiloxy) dimethylsilyl group.
Specific examples of R ² containing such a unit include a divalent group obtained by removing OH at both ends from polyethylene adipate diol, a poly (dimethylsiloxy) dimethylsilyl-n-propylbisethoxy group, and the like.
Specific examples of R ² include a divalent group having a repeating unit such as an ethyleneoxy group, a propyleneoxy group, an ethylene adipate group, a propylene adipate group, a hexamethylene carbonate group, and a ring-opening caprolactone group, a trimethylene group, and a tetramethylene group. , —CH ₂ —CF ₂ —CF ₂ —CF ₂ —CF ₂ —CH ₂ —, a hydrogenated butadienylene group, and a hydrogenated isoprene. A valent group, polydimethylsiloxydimethylsilyl-n-propylbisethoxy group and the like are preferable.

R ³ in the general formulas [1] and [2] is an alkylene group having 2 to 4 carbon atoms. Specific examples include an ethylene group, a trimethylene group, and a tetramethylene group. Among these, an ethylene group and a trimethylene group are preferable, and an ethylene group is more preferable.

R ⁴ in the general formulas [1] and [2] represents a sugar residue derived from a monosaccharide or a disaccharide. A sugar residue is a residue obtained by removing a part of hydroxyl groups from sugar. Examples of monosaccharides or disaccharides used for R ⁴ include glucose, mannose, galactose, and lactose.
Among these, R ⁴ is preferably a sugar residue derived from glucose, mannose and galactose, more preferably a sugar residue derived from glucose.

M in the general formula [1] represents a hydrogen atom, an alkali metal atom, an ammonium group or an organic amino group, s represents the number of hydroxyl groups of the sugar residue R ⁴ modified with a sulfuric acid-containing group, and 1 ≦ s ≦ Represents an integer in the range of 4.
Examples of the alkali metal atom in M include a sodium atom, a potassium atom, and a lithium atom, and a sodium atom and a potassium atom are preferable.
Examples of the organic amino group include an amino group having 1 to 3 alkyl groups having 1 to 6 carbon atoms (eg, mono C _1-6 alkylamino group (eg, monomethylamino group, monoethylamino group, monopropylamino group). Group, monobutylamino group, monopentylamino group, monohexylamino group), diC _1-6 alkylamino group [eg, dimethylamino group, diethylamino group, dipropylamino group (eg, di n-propylamino group, Diiso-propylamino group), dibutylamino group], tri-C _1-6 alkylamino group (eg, trimethylamino group, triethylamino group)], aromatic amino group having 6 to 14 carbon atoms [eg, C _{6-6 14} aralkylamino group (e.g., benzylamino _{group), C 6-14} aromatic heterocyclic amino group (e.g., pyridyl group) and the like, preferably dimethyl Amino group, trimethyl amino, triethyl amino group, a pyridyl group, a benzylamino group.

  OLS in the general formulas [1] and [2] represents an oligosaccharide skeleton. An oligosaccharide skeleton is a residue obtained by removing all hydroxyl groups from an oligosaccharide. The oligosaccharide used in the present invention is not particularly limited as long as it has two primary hydroxyl groups, and may be any of disaccharide, trisaccharide, and tetrasaccharide. For example, specific examples include trehalose, Examples thereof include disaccharides such as maltose, lactose, and cellobiose. Among them, disaccharides such as trehalose, maltose, and lactose are preferable from the viewpoint of price and reactivity. In general formulas [1] and [2], r represents the total number of secondary hydroxyl groups of the oligosaccharide. For example, when OLS is a disaccharide or a trisaccharide, r is 6 or 9, respectively.

In the general formula [1], p is a secondary hydroxyl group of a sulfated oligosaccharide modified with a dibasic acid and an amino sugar (formula —O ₂ C—R ³ —CO—NH—R ⁴ — (SO ₃ M) represents the number of groups represented by _s ; R ³ , R ⁴ and s are as defined above, and in general formula [2], p is modified with a dibasic acid and an amino sugar Represents the number of secondary hydroxyl groups (groups represented by the formula —O ₂ C—R ³ —CO—NH—R ⁴ ; R ³ and R ⁴ are as defined above) of the oligosaccharide, Is also an integer in the range of 1 ≦ p ≦ r.
In the general formulas [1] and [2], q is a secondary hydroxyl group of an oligosaccharide modified with a dibasic acid (a group represented by the formula HO ₂ C—R ³ —CO ₂ —; R ³ is As defined, and represents an integer in the range of 0 ≦ q ≦ r−1.

  In the general formulas [1] and [2], m and n are the number of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is 0.01 to 1. From the viewpoint of the balance of water absorption, polymer strength and polymer moldability, the number is preferably in the range of 0.02 to 0.80. In addition, the arrangement of the repeating units in the general formulas [1] and [2] may be regular or irregular.

Next, a method for producing a sulfated sugar residue-modified oligosaccharide-containing polyurethane represented by the general formula [1] and a sugar residue-modified oligosaccharide-containing polyurethane represented by the general formula [2] will be described.
(Method for producing oligosaccharide-containing polyurethane)
General formula [3]:

[Wherein OLS and p are as defined above]
And, if necessary, the following general formula [4]:

[Wherein R ² is as defined above]
Is represented by the following general formula [5]:

[Wherein R ¹ is as defined above]
Is reacted with a diisocyanate represented by the following general formula [6]:

[Wherein R ¹ , R ² , m, n and r are as defined above]
Can be obtained.
At this time, the oligosaccharide represented by the general formula [3] is mixed with the diol represented by the general formula [4] as necessary, and this is reacted with the diisocyanate represented by the general formula [5]. Alternatively, the diisocyanate represented by the general formula [5] may be reacted with a diol represented by the general formula [7] as necessary to form a prepolymer, and then the general formula [5]. 3] may be reacted (prepolymer method 1), or first, the oligosaccharide represented by the general formula [3] is reacted with the diisocyanate represented by the general formula [5]. It may be made into a prepolymer and then reacted with a diol represented by the general formula [4] as necessary (prepolymer method 2).
In the above reaction, the oligosaccharide represented by the general formula [3], the diol represented by the general formula [4], and the diisocyanate represented by the general formula [5] may each be one kind, A mixture of two or more kinds may be used.

Examples of the diisocyanate of the general formula [5] used in the present invention include tetramethylene diisocyanate, pentamethylene diisocyanate, hexamethylene diisocyanate, octamethylene diisocyanate, hexadecamethylene diisocyanate, vinylene diisocyanate, propenylene diisocyanate, naphthylene diisocyanate, and phenyl. Methane diisocyanate, diphenylmethane diisocyanate, phenylethane diisocyanate, diphenylethane diisocyanate, phenylene diisocyanate (eg, paraphenylene diisocyanate), biphenyl diisocyanate, xylylene diisocyanate, tetramethylxylylene diisocyanate, tolylene diisocyanate, isophorone diisocyanate, dicyclo Hexyl diisocyanate and the like.
The diol represented by the general formula [4] is not particularly limited as long as it is a diol having a primary hydroxyl group. Specifically, for example, ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,9-nonanediol, 2,2,3,3,4,4, Low molecular weight diols such as 5,5-octafluoro-1,6-hexanediol; and polyethylene glycol, polytetramethylene ether glycol, polypropylene glycol, ethylene oxide-propylene oxide copolymer, tetrahydrofuran-ethylene oxide copolymer, tetrahydrofuran- Polyether-based diols such as propylene oxide copolymer, polyethylene adipate glycol, polydiethylene adipate glycol, polypropylene adipate glycol, polybutylene adipate glycol, polyhexamethylene adipate Polyester glycols such as recall, polyneopentyl adipate glycol, polycaprolactone glycol, polycarbonate diols such as polyhexamethylene carbonate glycol, polyolefin glycols such as polybutadiene glycol, hydrogenated polybutadiene glycol, hydrogenated polyisoprene glycol, bis (hydroxy And high molecular weight diols such as silicone-based diols such as ethoxy-n-propyldimethylsilyl) polydimethylsiloxane.

The solvent for producing the polyurethane represented by the general formula [6] may be any solvent that can dissolve the reaction product and the polyurethane to be produced. Specifically, for example, organic solvents such as dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc) alone or the like The mixed solvent is mentioned.
When producing the polyurethane represented by the general formula [6], for example, the oligo of the general formula [3] is introduced into a solution containing the diisocyanate of the general formula [5] through a dry inert gas such as nitrogen. Sugar and, if necessary, diol of general formula [4] are added.
The charged molar ratio of the reaction components is, for example, from 3: 0.01 to 2.99: 0.01 to the compound of the general formula [5]: the compound of the general formula [4]: the compound of the general formula [3]. 3 is preferable, and 3: 0.2 to 2.5: 0.5 to 2.8 is more preferable.
The reaction temperature for the above reaction is preferably 10 to 150 ° C., more preferably 20 to 120 ° C., and the reaction time is preferably 1 to 10 hours, more preferably 2 to 6 hours.
After completion of the reaction, a polyurethane represented by the general formula [6] can be obtained. In the polyurethane, for example, a reaction solution is added to a solvent such as methanol, acetone, water or the like alone or a mixed solvent thereof, and a solid content obtained by repeating filtration, washing, and reprecipitation purification as necessary is room temperature to 100 ° C. And can be purified by drying under reduced pressure for about 1 to 24 hours.

(Production method of carboxyl group-modified oligosaccharide-containing polyurethane)
Next, the oligosaccharide-containing polyurethane represented by the general formula [6] is converted into the general formula [7]:

[Wherein R ³ is as defined above]
And a part or all of the secondary hydroxyl group of the oligosaccharide is modified to give the following general formula [8]:

[Wherein R ¹ , R ² , R ³ , OLS, m, n, q and r are as defined above]
Is produced by the production of a carboxyl group-modified oligosaccharide-containing polyurethane.
The above reaction is usually performed in a solvent. The solvent for the carboxyl group modification may be any solvent that can dissolve the reaction product and the polyurethane to be produced. Specifically, for example, organic solvents such as dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc) alone or the like The mixed solvent is mentioned.
As the acid anhydride represented by the general formula [7], dibasic acid anhydrides such as succinic acid anhydride, glutaric acid anhydride and adipic acid anhydride are preferably used, and succinic acid anhydride is most preferable. The acid anhydride may be used alone or as a mixture of two or more. The amount used is 1 to (r-1) moles relative to the number of secondary hydroxyl groups (r) of the oligosaccharide in the polyurethane when the hydroxyl group of the linear oligosaccharide in the polyurethane is partially modified. When the hydroxyl group is completely modified, it is r to 2r times mole, preferably 1.2r to 1.5r times mole.

In the above reaction, it is preferable to use 3 to 10 mol%, more preferably 5 mol%, of 4-dimethylaminopyridine or imidazole as a catalyst, if necessary.
The reaction temperature of the above reaction is 20 to 100 ° C., preferably 50 to 90 ° C., and the reaction time is 1 to 24 hours, preferably 2 to 20 hours.
After completion of the reaction, a carboxyl group-containing oligosaccharide-containing polyurethane represented by the general formula [8] can be obtained. The polyurethane is obtained, for example, by adding a reaction solution to methanol, acetone, water or the like alone or a mixed solvent thereof to precipitate a polymer, followed by filtration, washing, and reprecipitation purification as necessary. Can be purified by drying under reduced pressure at room temperature to 100 ° C. for about 1 to 24 hours.

(Method for producing sugar residue-modified oligosaccharide-containing polyurethane)
The oligosaccharide-containing polyurethane represented by the general formula [8] is added to the following general formula [9]:

[Wherein R ⁴ is as defined above], by reacting with an aminated sugar represented by the following general formula [2]:

[Wherein R ¹ , R ² , R ³ , R ⁴ , OLS, m, n, p, q and r are as defined above]
A sugar residue-modified oligosaccharide-containing polyurethane represented by the formula:
As the aminated sugar represented by the general formula [9], for example, glucoseamine, mannoseamine, and lactoseamine are preferable. Among these, glucoseamine and mannoseamine are more preferable, and glucoseamine is most preferable in terms of price. . Moreover, the said aminated sugar may be used individually by 1 type, and may be used as a 2 or more types of mixture.
The above reaction is usually performed in a solvent. Any solvent may be used as long as it can dissolve the reaction product and the resulting polyurethane. Specifically, for example, organic solvents such as dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc) alone or the like The mixed solvent is mentioned.
The above reaction is preferably performed in the presence of a condensing agent. As the condensing agent, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC) / N-hydroxysuccinimide (NHS) mixture, dicyclohexylcarbodiimide (DCC), or the like is used. Most preferred is an EDC / NHS mixture. The usage-amount is 0.5-1.5 times mole with respect to aminated sugar, Preferably it is 0.8-1.2 times mole.
The reaction temperature for the above reaction is 20 to 60 ° C., preferably 30 to 50 ° C., and the reaction time is 5 to 36 hours, preferably 10 to 20 hours.
After completion of the reaction, a sugar residue-modified oligosaccharide-containing polyurethane represented by the general formula [2] can be obtained. The polyurethane was obtained by, for example, distilling off the reaction solvent, adding methanol or water alone or a mixed solvent thereof to the concentrate, washing the polymer, filtering, and repeating reprecipitation purification as necessary. The solid content can be purified by drying under reduced pressure at room temperature to 100 ° C. for about 1 to 24 hours.

(Method for producing sulfated sugar residue-modified oligosaccharide-containing polyurethane)
The sugar residue-modified oligosaccharide-containing polyurethane represented by the general formula [2] is reacted with a sulfating reagent to produce a sulfated sugar residue-modified oligosaccharide-containing polyurethane represented by the general formula [1] of the present invention. Can be obtained.
Examples of the sulfating reagent include trimethylamine sulfur trioxide complex, triethylamine sulfur trioxide complex, dimethylformamide sulfur trioxide complex, pyridine sulfur trioxide complex, and chlorosulfonic acid.
The above reaction is usually performed in a solvent. As the solvent, dimethylformamide, pyridine, dimethyl sulfoxide (DMSO) and the like are usually used, the reaction temperature is usually 0 ° C. to 80 ° C., and the reaction time is usually 5 minutes to 24 hours. If necessary, M can be converted to an alkali metal atom (eg, sodium atom) by treating the resulting compound with an ion exchange resin (Na ⁺ type, etc.).

  The sulfated sugar residue-modified oligosaccharide-containing polyurethane represented by the above general formula [1] of the present invention has excellent physiological functions (eg, capture function for viruses, proteins, etc., blood compatibility, etc.), and various It can be used as a physiological functional material. The physiologically functional material is used for applications such as a contact with blood and a filter (eg, a blood separation filter, a virus separation filter, a protein separation filter, etc.).

EXAMPLES Next, although this invention is demonstrated still in detail based on an Example, this invention is not limited to this.
The monomer compound used for polymerization is abbreviated as follows.
OLS = oligosaccharide skeleton TRE = trehalose MDI = diphenylmethane diisocyanate PPG4 = polypropylene glycol (molecular weight 400)
PPG7 = polypropylene glycol (molecular weight 700)
SUC = succinic anhydride GluA = glucoseamine ManA = mannoseamine Py = pyridyl group

(Synthesis Example 1)
Synthesis of MDI-PPG4-TRE (molar ratio 2/1/1) polyurethane (prepolymer method 1)
Diphenylmethane diisocyanate (5.85 g) and dimethylacetamide (65 ml) are placed in a four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and stirred with polypropylene glycol (weight average molecular weight 400, 4.68 g) at room temperature. The mixture was further reacted for 1 hour. Next, trehalose (4.00 g) was added to the reaction solution and reacted at this temperature for 4 hours. The reaction solution was put into a methanol / water (volume ratio 1/3) mixed solvent to precipitate the product, filtered, washed with a methanol / water solvent, and then vacuum dried to obtain the product (yield 81%). ).
It was confirmed by proton NMR that it was the desired product.
Proton NMR (solvent: heavy dimethyl sulfoxide)
1.05, 1.20; CH ₃ −
_{3.20-3.80; -O-CH-CH 2} -O-,
—CH ₂ —, —CH—
3.86; —CH ₂ —
4.30-5.00; -O-CH-O-, -OH
7.16,7.43; _-C 6 _{H 4} -
8.65, 9.60; —NH—CO—

(Synthesis Example 2)
Synthesis of MDI-PPG7-TRE (molar ratio 2/1/1) polyurethane (prepolymer method 1)
Diphenylmethane diisocyanate (4.39 g) and dimethylacetamide (65 ml) are placed in a four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and stirred with polypropylene glycol (weight average molecular weight 700, 6.14 g) at room temperature. The mixture was further reacted for 1 hour. Next, trehalose (3.00 g) was added to the reaction solution and reacted at this temperature for 4 hours. The reaction solution was put into a methanol / water (volume ratio 1/3) mixed solvent to precipitate the product, filtered, washed with a methanol / water solvent, and then vacuum dried to obtain the product (yield 87%). ).
It was confirmed by proton NMR that it was the desired product.
Proton NMR proton (solvent: heavy dimethyl sulfoxide)
1.05, 1.20; CH ₃ −
_{3.20-3.80; -O-CH-CH 2} -O-,
—CH ₂ —, —CH—
3.86; —CH ₂ —
4.30-5.00; -O-CH-O-, -OH
7.16,7.43; _-C 6 _{H 4} -
8.65, 9.60; —NH—CO—

(Synthesis Example 3)
Synthesis of MDI-PPG7-TRE (molar ratio 3 / 2.5 / 0.5) polyurethane (prepolymer method 1)
Methane diphenyl diisocyanate (4.39 g) and dimethylacetamide (65 ml) are placed in a four-necked flask equipped with a mechanical stirrer (with nitrogen gas replaced) and stirred at room temperature with polypropylene glycol (average molecular weight 700, 6.14 g). The mixture was further reacted for 1 hour. Next, trehalose (1.00 g) was added to the reaction solution and reacted at this temperature for 4 hours. The reaction solution was put into a methanol / water (volume ratio 1/3) mixed solvent to precipitate the product, filtered, washed with a methanol / water solvent, and then vacuum dried to obtain the product (yield 86%). ).
It was confirmed by proton NMR that it was the desired product.

(Synthesis Example 4)
Synthesis of MDI-PPG4-TRE (molar ratio 2/1/1) -3SUC polyurethane A four-necked flask equipped with a mechanical stirrer (with nitrogen gas replacement) and polyurethane (1.00 g) of synthesis example 1 and dimethylacetamide (25 ml) The succinic anhydride (0.24 g) and 4-dimethylaminopyridine (0.025 g) were added at room temperature with stirring, and the mixture was reacted at 70 ° C. for 5 hours. The reaction solution was concentrated and then poured into water (75 ml) to precipitate the product. Three drops of 1M hydrochloric acid were added, filtered, washed with water, and dried in vacuo to give the product (yield 95%). .
It was confirmed by proton NMR that it was the desired product.
Proton NMR (solvent: heavy dimethyl sulfoxide)
1.05, 1.20; CH ₃ −
_{2.50-2.60; -OCO-CH 2 -CH 2} -COO-
_{3.20-3.80; -O-CH-CH 2} -O-,
—CH ₂ —, —CH—
3.86; —CH ₂ —
4.30-5.00; -O-CH-O-, -OH
7.16,7.43; _-C 6 _{H 4} -
8.65, 9.60; —NH—CO—

(Synthesis Example 5)
Synthesis of MDI-PPG4-TRE (molar ratio 2/1/1) -3SUC-1ManA polyurethane A four-necked flask equipped with a mechanical stirrer (with nitrogen gas replacement) and polyurethane (1.00 g) of synthesis example 4 and dimethylformamide ( 30 ml) at room temperature with stirring, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC, 0.57 g), N-hydroxysuccinimide (0.34 g), triethylamine (0 .59 g) was added and dissolved. Next, D-mannoseamine hydrochloride (0.53 g) was added to this solution and reacted at this temperature for 24 hours. The reaction solution was concentrated and poured into water to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product (yield 96%).
It was confirmed by proton NMR that it was the desired product.
Proton NMR (solvent: heavy dimethyl sulfoxide)
1.05, 1.20; CH ₃ −
_{2.50-2.60; -OCO-CH 2 -CH 2} -COO-
_{3.20-3.80; -O-CH-CH 2} -O-,
—CH ₂ —, —CH—
3.86; —CH ₂ —
4.30-5.00; -O-CH-O-, -OH
6.50; -NH-CO-
7.16,7.43; _-C 6 _{H 4} -
8.65, 9.60; —NH—CO—

(Synthesis Example 6)
Synthesis of MDI-PPG4-TRE (molar ratio 2/1/1) -5 SUC polyurethane A 4-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) was replaced with the polyurethane (1.00 g) of Synthesis Example 1 in dimethylacetamide (25 ml). At room temperature. Next, dimethylaminopyridine (0.025 g) was added to the reaction solution, succinic anhydride (0.966 g) was added with stirring, and the mixture was reacted at 70 ° C. for 5 hours. The reaction solution was concentrated and then poured into water (75 ml) to precipitate the product, and 1M hydrochloric acid (0.25 ml) was added. The precipitate was filtered, washed with water, and then vacuum dried at 80 ° C. to obtain the product (yield 91%).
It was confirmed by proton NMR that it was the desired product.

(Synthesis Example 7)
Synthesis of MDI-PPG4-TRE (molar ratio 2/1/1) -5SUC-2GluA polyurethane A four-necked flask equipped with a mechanical stirrer (with nitrogen gas replacement) and polyurethane (1.00 g) of synthesis example 5 and dimethylacetamide ( 35 ml), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.83 g) and N-hydroxysuccinimide (0.49 g) were added at room temperature with stirring and reacted for 1 hour. I let you. Next, D-glucosamine hydrochloride (1.24 g) and triethylamine (1.45 g) were added to the reaction solution and reacted at this temperature for 24 hours. The reaction solution was concentrated and poured into water to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product (yield 96%).
It was confirmed by proton NMR that it was the desired product.
Proton NMR proton (solvent: heavy dimethyl sulfoxide)
1.05, 1.20; CH ₃ −
_{2.50-2.60; -OCO-CH 2 -CH 2} -COO-
_{3.20-3.80; -O-CH-CH 2} -O-,
—CH ₂ —, —CH—
3.86; —CH ₂ —
4.30-5.00; -O-CH-O-, -OH
6.50; -NH-CO-
7.16,7.43; _-C 6 _{H 4} -
8.65, 9.60; —NH—CO—

(Synthesis Example 8)
Synthesis of MDI-PPG7-TRE (molar ratio 2/1/1) -3 SUC polyurethane A four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and polyurethane (2.00 g) of synthesis example 2 and dimethylacetamide (50 ml) Was added, and succinic anhydride (0.79 g) and 4-dimethylaminopyridine (0.025 g) were added at room temperature with stirring, followed by reaction at 70 ° C. for 5 hours. The reaction solution was concentrated and poured into water (75 ml) to precipitate the product. Three drops of 1M hydrochloric acid were added, filtered, washed with water, and dried in vacuo to give the product (yield 84%). .
It was confirmed by proton NMR that it was the desired product.

(Synthesis Example 9)
Synthesis of MDI-PPG7-TRE (molar ratio 2/1/1) -3SUC-1ManA polyurethane A four-necked flask equipped with a mechanical stirrer (with nitrogen gas replacement) and polyurethane (1.50 g) of synthesis example 8 and dimethylacetamide ( 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.47 g), N-hydroxysuccinimide (0.28 g), triethylamine (0.62 g) at room temperature with stirring. ) Was added and allowed to react for 1 hour. Next, D-mannoseamine hydrochloride (0.53 g) was added to the reaction solution and reacted at this temperature for 24 hours. The reaction solution was concentrated and poured into water to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product (yield 78%).
It was confirmed by proton NMR that it was the desired product.

(Synthesis Example 10)
Synthesis of MDI-PPG7-TRE (molar ratio 3 / 2.5 / 0.5) -5SUC polyurethane A 4-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and polyurethane of Synthesis Example 3 (5.00 g) and dimethyl Acetamide (100 ml) was added, succinic anhydride (1.15 g) and 4-dimethylaminopyridine (0.035 g) were added at room temperature with stirring, and the mixture was reacted at 70 ° C. for 5 hours. The reaction solution was concentrated and then poured into water (75 ml) to precipitate the product. Three drops of 1M hydrochloric acid were added, filtered, washed with water, and dried in vacuo to give the product (yield 98%). .
It was confirmed by proton NMR that it was the desired product.

(Synthesis Example 11)
MDI-PPG7-TRE (molar ratio 3 / 2.5 / 0.5) -5 SUC-1 ManA Polyurethane Synthesis The polyurethane of Synthesis Example 10 (3.00 g) was placed in a 4-neck flask equipped with a mechanical stirrer (with nitrogen gas replacement). And dimethylacetamide (100 ml), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.50 g), N-hydroxysuccinimide (0.30 g), triethylamine at room temperature with stirring (0.66 g) was added and allowed to react for 1 hour. Next, D-mannoseamine hydrochloride (0.28 g) was added to the reaction solution and reacted at this temperature for 24 hours. The reaction solution was concentrated and poured into water to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product (yield 85%).
It was confirmed by proton NMR that it was the desired product.

Example 1
Synthesis of MDI-PPG4-TRE (molar ratio 2/1/1) -3SUC-1ManA- (SO ₃ Py) polyurethane A four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and the polyurethane of Synthesis Example 5 (0. 100 g) and dimethylformamide (15 ml) were added and dissolved. While stirring, pyridine sulfur trioxide complex (0.15 g) was added at room temperature and allowed to react for 8 hours. After the reaction solution was concentrated, water was added to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product.
The proton NMR and IR spectrum confirmed the desired product.
Proton NMR (solvent: heavy dimethyl sulfoxide)
1.05, 1.20; CH ₃ −
_{2.50-2.60; -OCO-CH 2 -CH 2} -COO-
_{3.20-3.80; -O-CH-CH 2} -O-,
—CH ₂ —, —CH—
3.86; —CH ₂ —
4.30-5.00; -O-CH-O-, -OH
6.50; -NH-CO-
7.16,7.43; _-C 6 _{H 4} -
8.10-9.00; -C ₅ H ₅ N · H ⁺
8.65, 9.60; —NH—CO—
IR (KBr): 1040, 1120 cm ⁻¹ (SO ₃ )

(Example 2)
MDI-PPG4-TRE (molar ratio 2/1/1) -5 SUC-2GluA-2 (SO ₃ Py) Polyurethane Synthesis Four-necked flask equipped with a mechanical stirrer (with nitrogen gas replacement) was replaced with the polyurethane of Synthesis Example 7 (1 0.000 g) and dimethylformamide (15 ml) were added and dissolved. While stirring, pyridine sulfur trioxide complex (0.30 g) was added at room temperature and allowed to react for 8 hours. After the reaction solution was concentrated, water was added to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product.
The proton NMR and IR spectrum confirmed the desired product.

(Example 3)
Synthesis of MDI-PPG7-TRE (molar ratio 3 / 2.5 / 0.5) -5SUC-1ManA (SO ₃ Py) polyurethane Four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas), polyurethane of Synthesis Example 11 (1.00 g) and dimethylformamide (50 ml) were added and dissolved. While stirring, pyridine sulfur trioxide complex (0.027 g) was added at room temperature and allowed to react for 8 hours. After the reaction solution was concentrated, water was added to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product.
The proton NMR and IR spectrum confirmed the desired product.

Example 4
Synthesis Example 11 MDI-PPG7-TRE (molar ratio 3 / 2.5 / 0.5) -5 SUC-1 ManA-2 (SO ₃ Py) Polyurethane Synthesis A four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) Of polyurethane (1.00 g) and dimethylformamide (50 ml) were added and dissolved. While stirring, pyridine sulfur trioxide complex (0.054 g) was added at room temperature and allowed to react for 8 hours. After the reaction solution was concentrated, water was added to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product.
The proton NMR and IR spectrum confirmed the desired product.

(Example 5)
Synthesis of MDI-PPG7-TRE (molar ratio 2/1/1) -3SUC-1ManA- (SO ₃ Py) polyurethane A four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and the polyurethane of Synthesis Example 8 (1. 00 g) and dimethylformamide (70 ml) were added and dissolved. While stirring, pyridine sulfur trioxide complex (0.078 g) was added at room temperature and allowed to react for 8 hours. After the reaction solution was concentrated, water was added to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product.
The proton NMR and IR spectrum confirmed the desired product.

<Evaluation of each sample>
Evaluation Method (1) Molecular Weight: The weight average molecular weight (Mw) of the polyurethane derivatives produced in the examples was measured using DMF (dimethylformamide) as a developing solvent with reference to standard polyethylene (PE).
(2) Softening point: The softening point of the polyurethane produced in the examples was measured at the temperature at which the sample was dissolved by heating from room temperature (5 ° C / min) using a melting point measuring device.
(3) Solvent solubility: It was examined whether or not the various polyurethanes (0.1 g) obtained in the examples were dissolved in dimethylacetamide (1 ml).
The results are shown in Table 1.

  From the above results, it was shown that the sugar residue-modified oligosaccharide-containing polyurethane has thermoplasticity and solvent solubility.

Claims (5)

The following general formula [1]:

[Where:
R ¹ represents a C 1-16 divalent hydrocarbon group which may have a substituent,
R ² contains 1 to 100 units in total of the same or different units selected from oxyalkylene units having 2 to 12 carbon atoms and divalent hydrocarbon units having 2 to 12 carbon atoms which may have a substituent. Represents a divalent group,
R ³ represents an alkylene group having 2 to 4 carbon atoms,
R ⁴ represents a sugar residue derived from a monosaccharide or a disaccharide,
M represents a hydrogen atom, an alkali metal atom, an ammonium group or an organic amino group,
s represents the number of hydroxyl groups of the sugar residue R ⁴ modified with a sulfuric acid-containing group, and represents an integer in the range of 1 ≦ s ≦ 4,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
p and q represent integers in the range of 1 ≦ p ≦ r and 0 ≦ q ≦ r−1,
m and n are the numbers of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is a number in the range of 0.01 to 1.00. ]
A sulfated sugar residue-modified oligosaccharide-containing polyurethane represented by: The sulfated sugar residue-modified oligosaccharide-containing polyurethane according to claim 1, wherein R ³ is an ethylene group. The sulfated sugar residue-modified oligosaccharide-containing polyurethane according to claim 1, wherein R ⁴ is glucose, mannose, lactose or galactose. The sulfated sugar residue-modified oligosaccharide-containing polyurethane according to claim 1, wherein R ³ is an ethylene group, and R ⁴ is glucose, mannose, lactose or galactose. The following general formula [2]:

[Where:
R ¹ represents a C 1-16 divalent hydrocarbon group which may have a substituent,
R ² contains 1 to 100 units in total of the same or different units selected from oxyalkylene units having 2 to 12 carbon atoms and divalent hydrocarbon units having 2 to 12 carbon atoms which may have a substituent. Represents a divalent group,
R ³ represents an alkylene group having 2 to 4 carbon atoms,
R ⁴ represents a sugar residue derived from a monosaccharide or a disaccharide,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
p and q represent integers in the range of 1 ≦ p ≦ r and 0 ≦ q ≦ r−1,
m and n are the numbers of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is a number in the range of 0.01 to 1.00. ]
A sugar residue-modified oligosaccharide-containing polyurethane represented by the following general formula [1]:

[Where:
R ¹ represents a C 1-16 divalent hydrocarbon group which may have a substituent,
R ² contains 1 to 100 units in total of the same or different units selected from oxyalkylene units having 2 to 12 carbon atoms and divalent hydrocarbon units having 2 to 12 carbon atoms which may have a substituent. Represents a divalent group,
R ³ represents an alkylene group having 2 to 4 carbon atoms,
R ⁴ represents a sugar residue derived from a monosaccharide or a disaccharide,
M represents a hydrogen atom, an alkali metal atom, an ammonium group or an organic amino group,
s represents the number of hydroxyl groups of the sugar residue R ⁴ modified with a sulfuric acid-containing group, and represents an integer in the range of 1 ≦ s ≦ 4,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
p and q represent integers in the range of 1 ≦ p ≦ r and 0 ≦ q ≦ r−1,
m and n are the numbers of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is a number in the range of 0.01 to 1.00. ]
The manufacturing method of the sulfated saccharide residue modification oligosaccharide containing polyurethane represented by these.