JP5081401B2 - Sulfated sugar-containing polyurethane derivative and process for producing the same - Google Patents

Description

  The present invention relates to a sulfated 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 an affinity for influenza virus and AIDS virus, and development of a new material capable of capturing the virus using this principle and a method for producing the same are desired.
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 glycan clusters by using a repeating unit in which a plurality of sulfated glycans are introduced, and to have excellent film-forming ability and biocompatibility. It is to provide a sulfated oligosaccharide-containing polyurethane derivative that is expected to have high blood compatibility and a simple and inexpensive production method thereof.

  As a result of intensive studies in view of the above problems, the inventors of the present invention 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. The present inventors have found that a sulfated oligosaccharide-containing polyurethane derivative can be obtained by reacting with a activating reagent, and the present invention has been completed.

That is, the present invention includes the following (1) to (3).
(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,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
M represents a hydrogen atom, an alkali metal atom, an ammonium group or an organic amino group,
s represents the number of secondary hydroxyl groups of the oligosaccharide modified with a sulfuric acid-containing group, and represents an integer in the range of 1 ≦ s ≦ r,
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 oligosaccharide-containing polyurethane represented by:
(2) The sulfated oligosaccharide-containing polyurethane according to the above (1), wherein the OLS is a skeleton of trehalose, maltose or lactose.
(3) 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,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
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 method for producing a sulfated oligosaccharide-containing polyurethane according to (1), wherein the oligosaccharide-containing polyurethane represented by the formula (1) is reacted with a sulfating reagent.

  The sulfated oligosaccharide-containing polyurethane of the present invention is thermoplastic, soluble in a solvent and excellent in film forming ability. Since the film is composed of an oligosaccharide-containing polyurethane, it has excellent biocompatibility and blood compatibility, and in addition to the increased sugar chain cluster density, the oligosaccharide is sulfated. Affinities with specific cells, proteins and viruses are 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 oligosaccharide-containing polyurethane of the present invention is

[Wherein R ¹ , R ² , r, s, m, n and OLS are as defined above]
A sulfated 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.

M in the general formula [1] represents a hydrogen atom, an alkali metal atom, an ammonium group or an organic amino group.
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], s represents the number of secondary hydroxyl groups of the oligosaccharide modified with a sulfuric acid-containing group, and is an integer in the range of 1 ≦ s ≦ r. Here, the “sulfuric acid-containing group” is a group represented by the formula (OSO ₃ M) in the general formula [1] (wherein M is as defined above).
In general formula [1], m and n are the number of repeating units, m is an integer of 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is in the range of 0.01 to 1.00. From the viewpoint of balance between water absorption, polymer strength, and polymer moldability, the number is preferably in the range of 0.02 to 0.80. Note that the arrangement of the repeating units in the general formula [1] may be regular or irregular.

(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 [2]:

[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 [2] 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 [2], 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, an oligosaccharide-containing polyurethane represented by the general formula [2] 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.

(Method for producing sulfated oligosaccharide-containing polyurethane)
Next, the oligosaccharide-containing polyurethane represented by the general formula [2] can be reacted with a sulfating reagent to obtain the sulfated oligosaccharide-containing polyurethane represented by the general formula [1] of the present invention.
As the sulfating reagent, trimethylamine sulfur trioxide complex, triethylamine sulfur trioxide complex, dimethylformamide sulfur trioxide complex, pyridine sulfur trioxide complex, chlorosulfonic acid and the like are used.
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 oligosaccharide-containing polyurethane represented by the general formula [1] of the present invention has an excellent physiological function (eg, a function of capturing viruses, proteins, etc.) and can be used as various physiological functional materials. it can. 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 compounds used for polymerization are abbreviated as follows.
OLS = oligosaccharide skeleton TRE = trehalose LAC = lactose MAL = maltose MDI = diphenylmethane diisocyanate PPG4 = polypropylene glycol (molecular weight 400)
PPG7 = polypropylene glycol (molecular weight 700)
Py = pyridyl group

(Synthesis Example 1)
Synthesis of MDI-PPG7-TRE (molar ratio 3 / 2.5 / 0.5) 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 (with nitrogen gas replacement), and polypropylene glycol (average molecular weight 700, 10.23 g) is added at room temperature while stirring. The reaction was performed 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.
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-LAC (molar ratio 3 / 2.5 / 0.5) polyurethane (prepolymer method 1)
Diphenylmethane diisocyanate (4.39 g), dimethylacetamide (65 ml), polypropylene glycol (average molecular weight 700, 10.23 g) and lactose (1.00 g) were used in the same manner as in Synthesis Example 1 to obtain a product (yield). Rate 90%).
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 3)
Synthesis of MDI-PPG7-MAL (molar ratio 3 / 2.5 / 0.5) polyurethane (prepolymer method 1)
Diphenylmethane diisocyanate (4.39 g), dimethylacetamide (65 ml), polypropylene glycol (average molecular weight 700, 10.23 g) and maltose (1.00 g) were used in the same manner as in Synthesis Example 1 to obtain a product (yield). 93%).
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 4)
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—

Example 1
Synthesis of MDI-PPG7-TRE (molar ratio 3 / 2.5 / 0.5)-(SO ₃ Py) polyurethane A four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) was replaced with the polyurethane (1. 00 g) and dimethylformamide (50 ml) were added and dissolved. While stirring, pyridine sulfur trioxide complex (0.06 g) was added at room temperature and reacted at room temperature for 24 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 (yield 94%).
The proton NMR and IR spectrum confirmed the desired product. Further, it was found from the integral value of the pyridyl group of proton NMR that two sulfate groups were introduced per oligosaccharide.
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 NH (pyridyl)
8.65, 9.60; —NH—CO—
IR (KBr): 1040, 1120 cm ⁻¹ (SO ₃ )

(Example 2)
Synthesis of MDI-PPG7-LAC (molar ratio 3 / 2.5 / 0.5)-(SO ₃ Py) polyurethane A four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and the polyurethane of Synthesis Example 2 (1. 00 g), dimethylformamide (50 ml) and dimethyl sulfoxide (5 ml) were added and dissolved. While stirring, pyridine sulfur trioxide complex (0.06 g) was added at room temperature and reacted at room temperature for 24 hours. After concentrating the reaction solution, water was added to precipitate the product, which was filtered, washed with water, and then vacuum dried to obtain the product (yield 98%).
The proton NMR and IR spectrum confirmed the desired product.

(Example 3)
Synthesis of MDI-PPG7-MAL (molar ratio 3 / 2.5 / 0.5)-(SO ₃ Py) polyurethane A four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and the polyurethane of Synthesis Example 3 (1. 00 g), dimethylformamide (50 ml) and dimethyl sulfoxide (5 ml) were added and dissolved. While stirring, pyridine sulfur trioxide complex (0.06 g) was added at room temperature and allowed to react at room temperature for 24 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 (yield 98%).
The proton NMR and IR spectrum confirmed the desired product.

Example 4
Synthesis of MDI-PPG4-TRE (molar ratio 2/1/1)-(SO ₃ Py) polyurethane A four-necked flask equipped with a mechanical stirrer (replaced with nitrogen gas) and polyurethane (1.00 g) of Synthesis Example 4 and dimethyl Formamide (15 ml) was added and dissolved. While stirring, pyridine sulfur trioxide complex (0.15 g) was added at room temperature and reacted at 40 ° C. for 6 hours. After concentrating the reaction solution, methanol was added to precipitate the product, which was filtered, washed with methanol, 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 NH (pyridyl)
8.65, 9.60; —NH—CO—
IR (KBr): 1040, 1120 cm ⁻¹ (SO ₃ )

<Evaluation of each sample>
Evaluation method (1) Solvent solubility: It was examined whether or not the various polyurethanes (0.1 g) obtained in the examples were dissolved in dimethylacetamide (1 ml).
(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 sulfated oligosaccharide-containing polyurethane has thermoplasticity and solvent solubility.

Claims (3)

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,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
M represents a hydrogen atom, an alkali metal atom, an ammonium group or an organic amino group,
s represents the number of secondary hydroxyl groups of the oligosaccharide modified with a sulfuric acid-containing group, and represents an integer in the range of 1 ≦ s ≦ r,
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 oligosaccharide-containing polyurethane represented by:   The sulfated oligosaccharide-containing polyurethane according to claim 1, wherein OLS is a skeleton of trehalose, maltose or lactose. 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,
OLS represents an oligosaccharide skeleton having two primary hydroxyl groups,
r represents the total number of secondary hydroxyl groups of the oligosaccharide;
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 method for producing a sulfated oligosaccharide-containing polyurethane according to claim 1, wherein the oligosaccharide-containing polyurethane represented by the formula is reacted with a sulfating reagent.