CN105601550B - Stimuli-sensitive multifunctional polyisocyanates having reactive groups - Google Patents

Stimuli-sensitive multifunctional polyisocyanates having reactive groups Download PDF

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CN105601550B
CN105601550B CN201511000158.XA CN201511000158A CN105601550B CN 105601550 B CN105601550 B CN 105601550B CN 201511000158 A CN201511000158 A CN 201511000158A CN 105601550 B CN105601550 B CN 105601550B
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丁明明
汪锐
傅强
谭鸿
张琴
李洁华
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Sichuan University
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C265/00—Derivatives of isocyanic acid
    • C07C265/02—Derivatives of isocyanic acid having isocyanate groups bound to acyclic carbon atoms
    • C07C265/04—Derivatives of isocyanic acid having isocyanate groups bound to acyclic carbon atoms of a saturated carbon skeleton
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
    • C07C323/40—Y being a hydrogen or a carbon atom
    • C07C323/41—Y being a hydrogen or an acyclic carbon atom
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    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • C08G18/77—Polyisocyanates or polyisothiocyanates having heteroatoms in addition to the isocyanate or isothiocyanate nitrogen and oxygen or sulfur
    • C08G18/775—Polyisocyanates or polyisothiocyanates having heteroatoms in addition to the isocyanate or isothiocyanate nitrogen and oxygen or sulfur sulfur
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/81—Unsaturated isocyanates or isothiocyanates
    • C08G18/8133—Unsaturated isocyanates or isothiocyanates having acetylenic groups

Abstract

The invention discloses a stimulation sensitive multifunctional polyisocyanate with active groups, which is characterized in that the structural general formula of the polyisocyanate is as follows:
Figure DDA0000890755660000011
wherein A is a stimuli-sensitive group; r1And R2Is a compound group containing or not containing an active group and having 1-20 carbon atoms, R1And R2May be the same or different, but at least one of them contains a reactive group. The polyisocyanate provided by the invention contains pH, oxidation, reduction, enzyme or photosensitive groups, and the side chain contains active groups such as ester groups, azido groups, alkynyl groups, alkenyl groups, halogenated hydrocarbon groups, sulfenyl groups, tertiary amino groups or isocyanate groups, so that the polyisocyanate can meet the use requirements of different occasions, obtain intelligent high polymer materials which can respond to or degrade under various stimulation environments, and can introduce various active sites into the side chain of a polymer to endow the materials with the potential of further functional modification, thereby having wide application prospects in the fields of functional high polymer materials and biomedical materials.

Description

Stimuli-sensitive multifunctional polyisocyanates having reactive groups
Technical Field
The invention belongs to the technical field of polyisocyanates, and particularly relates to a stimulation-sensitive multifunctional polyisocyanate with active groups.
Background
The polymer material with stimulus sensitivity is a novel intelligent material, can sense the change of the surrounding environment and respond, and has unique functions of feedback, bionics, information transmission and the like compared with common functional materials. When the environment such as external temperature, pressure, pH, electromagnetic field, light, oxidation-reduction potential and the like changes, the properties such as molecular structure, phase behavior, assembly behavior, mechanical property and the like of the polymer can change along with the change, so the polymer has wide application prospect in the fields of biosensors, tissue engineering, artificial muscles, medicines, gene transmission and the like. Especially in the field of drug slow release and controlled release, the micro-environment of the focus part is obviously different from the normal tissue, and the stimulation sensitive polymer drug carrier can respond to the complex internal environment and focus signals in the organism and realize the release of the drug in a specific time and space, thereby improving the curative effect of the drug and reducing the toxic and side effect.
Besides responding to environmental stimuli, the intelligent polymer material also has more functionality according to different application fields so as to meet the requirements of development of modern industry and medical fields on the material. For example, the surface of a polymer product applied to a humid environment such as a marine facility, an industrial water cooling system, food processing equipment and the like needs to have certain antifouling, antibacterial, self-cleaning and other performances; medical polymers used as implant materials are required to have good performances such as histocompatibility, blood compatibility, low protein adsorption, platelet adhesion and the like; polymer carriers used for gene and Drug Delivery need to have properties of long cycling, targeting, cell internalization, and controlled Drug release (z. cheng, et al, Science,2012,338, 903-. The realization of such multiple functionalities often requires the use of certain chemical means to functionally modify the bulk or surface of the material. However, conventional polymeric materials generally lack reactive sites and are difficult to modify or introduce functional groups.
Polyurethanes and polyureas are a class of classical block polymers that are widely used in the industrial and biomedical fields due to their excellent mechanical properties, good biocompatibility, and excellent molecular tailorability. They can be used as concrete forms of foamed plastics, elastomers, adhesives, coatings and the like in various aspects of packaging, construction, automobiles, national defense, aviation and the like, and can also be used as implant materials in the medical fields of cardiac pacemakers, artificial blood vessels, interventional catheters and the like. In addition, the biodegradable polyurethane/polyurea can also be applied to absorbable surgical sutures, implants, bone screws, bone plates, drug slow-release and controlled-release systems, tissue engineering, artificial organs and the like. However, multifunctional polyurethanes and polyureas with stimuli-sensitive properties have only begun to attract academic interest in recent years (M.Ding, et al., Soft Matter,2012,8, 5414-. For example, Zhou introduces a pH-sensitive hydrazone bond into polycaprolactone diol (PCL), and synthesizes pH-sensitive degradable polyurethane by using the bond as a soft segment (l.zhou, et al, Macromolecules,2011,44, 857-116 864); paramonov and Huang et al synthesized a series of pH sensitive polyureas and polyurethanes using diols containing ketal and acetal linkages, respectively (S.E. Paramonov, et al, Bioconjugate Chemistry,2008,19, 911-. Ding et al synthesized a multi-stimulus sensitive multifunctional polyurethane material (CN102335435A) by using dithiodiethanol containing redox sensitivity as a chain extender and polyethylene glycol (PEG) containing a hydrazone bond as a soft segment, and the multifunctional drug carrier prepared from the material can accurately and safely deliver chemotherapeutic drugs to tumor sites, thereby achieving good anti-tumor effects in vivo and in vitro (M.Ding, et al, Advanced Materials,2012,24, 3639-. Song et al synthesized a multifunctional chain extender containing disulfide bonds and alkynyl groups, and prepared a clickable polyurethane with a disulfide bond in the main chain and active groups in the side chain from the chain extender (N.Song, et al, Biomacromolecules,2013,14, 4407-4419). However, these researches have been carried out to realize the multi-functionalization of the polymer by designing and synthesizing chain extenders or soft segments with different functions, not only the synthesis process is complicated, but also the obtained polymer is usually a complex multi-block structure, which brings great challenges to the precise control of the high molecular structure and the industrial and clinical approval and application of the polymer product.
It is well known that polyisocyanates are one of the important raw materials for the synthesis of polyurethanes and polyureas, and the development history thereof has profound effects on the progress of the entire polyurethane industry. In the biomedical field, the early medical polyurethane material mainly adopts aromatic polyisocyanate, and the formed hard segment thereof can generate carcinogenic and teratogenic products after being degraded in vivo, so that the polyurethane material can only be used as an inert implant material in the fields of cardiac pacemakers, artificial blood vessels, interventional catheters and the like for a long time. Since the advent of aliphatic polyisocyanates has attracted increasing attention to biodegradable polyurethane materials, scientists in various countries have developed a series of biodegradable polyurethanes based on degradable polyester soft segments and aliphatic polyisocyanates and explored their potential for use as scaffolds, hydrogels and gene vectors for tissue engineering (X.J.Loh, et al, Biomaterials,2008,29, 2164-. However, there has been no report on the stimulus-sensitive type of multifunctional polyisocyanate so far.
Disclosure of Invention
The present invention aims at providing one kind of multifunctional irritation sensitive polyisocyanate with active groups.
The stimulation sensitive multifunctional polyisocyanate with the active group provided by the invention has the following structural general formula:
Figure BDA0000890755650000021
wherein A is a stimuli-sensitive group; r1And R2Is a compound group containing or not containing an active group and having 1-20 carbon atoms, R1And R2May be the same or different, but at least one of them contains a reactive group.
The stimulus-sensitive group a in the above polyisocyanate is any of a thio group, a selenylene group, a dithiolene group, a diselenylene group, an acetal group, a ketal group, a ketalene group, a hydrazone group, a benzoylimine group, an oxime group, an orthoester group, an o-nitrophenylene group, or an azophenylene group, and preferably a dithiolene group, a diselenylene group, an orthoester group, an o-nitrophenylene group, or an azophenylene group.
R in the structural general formula of the polyisocyanate1And R2Preferably any of the compound groups having 4 to 19 carbon atoms, which may or may not contain an active group.
R in the structural general formula of the polyisocyanate1And R2The active group is at least one of ester group, azido group, alkynyl group, alkenyl group, halogenated hydrocarbon group, sulfenyl group, tertiary amine group and isocyanate group, and ester group, azido group and alkynyl group are preferred. When the reactive group is a sulfenyl group, the group is located on a side chain of the polyisocyanate molecule.
In the above polyisocyanate, when the active group is an alkenyl group or an alkynyl group, the stimulus-sensitive group a is any one of a thio group, a seleno group, a dithiolene group, a diselenide group, a ketalthiol group, a hydrazone group, a benzoylimine group, an oximo group, an orthoester group, an o-nitrophenylene group or an azophenylene group, and preferably a dithiolene group, a diselenide group, an orthoester group, an o-nitrophenylene group or an azophenylene group.
An exemplary method for preparing the stimuli-sensitive multifunctional polyisocyanate having an active group according to the present invention is to react a polyamine having at least one active group selected from the group consisting of a thio group, a seleno group, a dithio group, a diseleno group, an acetal group, a ketal group, a hydrazone group, a benzoylimine group, an oxime group, an orthoester group, an o-nitrophenylene group and an azophenylene group, with phosgene, diphosgene and triphosgene in a solvent at a reaction temperature to prepare the polyisocyanate.
In the method, the molar ratio of polyamine containing any one stimulus-sensitive group of sulfenyl, selenylene, dithiolene, diselenylene, acetal group, ketal group, ketolidene thiol group, hydrazone group, benzoylimine group, oximino group, orthodoxe group, o-nitrophenylene group and azophenylene group and at least one active group of ester group, azide group, alkynyl group, alkenyl group, halogenated hydrocarbon group, sulfenyl and tertiary amine group to phosgene, diphosgene or triphosgene is 0.1-1.5; the solvent is at least one of dichloromethane, chloroform, benzene, toluene, ethyl acetate, pyridine and inorganic alkali aqueous solution, wherein the inorganic alkali is preferably sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate; the reaction temperature is-20 ℃ to reflux temperature, and the reaction time is at least 10 minutes.
It should be noted that the above-mentioned method for preparing the stimuli-sensitive multifunctional polyisocyanate having reactive groups is only used for illustrative purposes of the present invention and is not to be construed as limiting the scope of the present invention. Other methods known to those skilled in the art can be used to obtain the stimuli-sensitive multifunctional polyisocyanates with reactive groups having the structures described herein, and still fall within the scope of the present invention.
Compared with the prior art, the invention has the following advantages:
1. the main chain of the stimulation-sensitive multifunctional polyisocyanate with the active groups contains groups sensitive to pH, oxidation, reduction, enzyme, light and the like, and the side chain contains active groups such as ester groups, azido groups, alkynyl groups, alkenyl groups, halogenated hydrocarbon groups, tertiary amino groups, isocyanate groups and the like, so that the use requirements of different occasions can be met, materials capable of responding or degrading under various stimulation environments can be obtained, and meanwhile, the active sites of the materials can endow the materials with the potential of further functional modification, thereby providing a novel polyisocyanate with a wide application range for the field.
2. The stimulus-sensitive multifunctional polyisocyanate with the active group can form stimulus-sensitive multifunctional polyurea or polyurethane with the reactive active group with micromolecule amines or alcohols through gradual addition polymerization, and can also obtain modifiable stimulus-sensitive multifunctional block copolymers with other polymer chain segments containing active hydrogen through simple coupling reaction, thereby providing a new thought, a new method and starting materials for the preparation of intelligent and multifunctional macromolecules.
3. The molecular chain terminal of the stimulation-sensitive multifunctional polyisocyanate with the active groups provided by the invention has active isocyanate groups, and the stimulation-sensitive multifunctional polyisocyanate with the active groups can be used as a multifunctional coupling agent or a crosslinking agent to realize reversible coupling of active molecules such as targeting groups, drugs, proteins, saccharides and nucleic acids, and can also realize the multifunction and reversible crosslinking stability of systems such as polymer emulsion, micelle and gel.
4. The stimulation-sensitive multifunctional polyisocyanate with active groups is used for preparing the stimulation-sensitive multifunctional polymer material, so that the synthesis of monomers such as complex soft segments, chain extenders and the like can be avoided, the structure of a product macromolecule is greatly simplified, and stimulation-sensitive multifunctional homopolymers or copolymers with relatively regular structures are obtained, so that the industrialization and the clinic of the intelligent polymer are easier.
5. The stimuli-sensitive multifunctional polyisocyanate with active groups and the polymer thereof provided by the invention can be widely applied to the biomedical field and the industrial field.
Detailed Description
The following examples are given to illustrate the present invention, but it should be noted that the following examples are only for further illustration of the present invention and should not be construed as limiting the scope of the present invention.
Example 1
This example synthesizes a stimuli-sensitive multifunctional polyisocyanate I having reactive groups.
14.5 g of cystine dimethyl ester are dissolved in 400 ml of ethyl acetate, 10.7 g of triphosgene are added under nitrogen protection, and the mixture is reacted at room temperature for 1 hour and then heated under reflux for 4 hours. The reaction solution was washed twice with dilute hydrochloric acid after cooling, and once with saturated sodium chloride solution and distilled water. The organic phase was dried over anhydrous magnesium sulfate for 4 hours, filtered with suction and concentrated under reduced pressure. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000041
the infrared spectrum data are as follows:
FTIR(KBr,cm-1):2957(s,ν CH),1441(m,δCH)，2272(s,v N＝C＝O),1746(s,v C＝O)。
nuclear magnetic hydrogen spectrum data are as follows:
1H NMR(400MHz,CDCl3):δ4.40(q,J＝4.2,NCO-CH-,2H),3.86(s,CH3O-,6H),3.20(dd,J＝4.2,9.8,-CH2-S-,2H),3.10(dd,J＝7.4,6.6,-CH2-S-,2H)。
nuclear magnetic carbon spectral data are as follows:
13C NMR(400MHz,CDCl3):δ167(-C＝O),127.5(-N＝C＝O),56.6(-CH-NCO),53.6(CH3-O-),42.9(-S-CH2)。
example 2
This example synthesizes a stimuli-sensitive multifunctional polyisocyanate II having reactive groups.
8.41 g of dibenzyl homocystine was dissolved in a mixed solvent of 200 ml of methylene chloride and 200 ml of saturated aqueous sodium bicarbonate solution, and cooled to 0 ℃ and vigorously stirred for 10 minutes. Stirring was then stopped and 41 ml of a toluene solution of phosgene (1.93 mol/l) were injected into the organic phase and stirred for 10 minutes with ice-cooling. The reaction solution was separated into layers, the organic phase was washed twice with 0.5 mol/l brine, once with distilled water, the aqueous phase was backwashed once with dichloromethane, the organic phases were combined and dried with anhydrous sodium sulfate for 10 hours, filtered and concentrated under reduced pressure. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000051
the infrared spectrum data are as follows:
FTIR(KBr,cm-1):2957(s,ν CH)，2275(s,v N＝C＝O),1740(s,v C＝O)。
nuclear magnetic hydrogen spectrum data are as follows:
1H NMR(400MHz,DMSO-d6):δ7.05-7.5(m,C6H5-),4.05(t,CHCOO-),2.25(m,-CH2CH2-S-),2.50(t,-CH2-S-)。
example 3
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate III having reactive groups.
4.4 g of N, N '-di-tert-butoxycarbonyl-L-cystine is dissolved in 50 ml of dichloromethane, 4.33 g of N, N' -dicyclohexylcarbodiimide and 4.05 g of 1-hydroxybenzotriazole are added under ice-bath cooling, 1.38 g of propargylamine is added, and the mixture is naturally returned to room temperature for reaction for 24 hours. After the reaction was complete, the precipitate was removed by filtration, the product was evaporated to dryness and dissolved in ethyl acetate, washed three times with saturated sodium bicarbonate solution, washed once with saturated sodium chloride solution and once with distilled water, and dried overnight with anhydrous magnesium sulfate. After suction filtration, the filtrate was concentrated under reduced pressure and recrystallized from ethyl acetate. The dried crystals were dissolved in 20 ml of dichloromethane, and 20 ml of trifluoroacetic acid was added under ice-bath, stirred at room temperature for 2 hours and then dried under reduced pressure to obtain a product a.
Dissolving 4.72 g of the product A in a mixed solvent of 70 ml of dichloromethane and 9 ml of pyridine, cooling to-15 ℃, dropwise adding 3.92 g of triphosgene in dichloromethane solution 60 ml for reaction for 4 hours, washing the reaction solution twice with dilute hydrochloric acid, washing the saturated sodium chloride solution and distilled water once respectively, drying the organic phase with anhydrous magnesium sulfate overnight, and concentrating under reduced pressure after suction filtration. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000061
the infrared spectrum data are as follows:
FTIR(KBr,cm-1):3304(s,νNH),2962(s,ν CH),2259(s,v N＝C＝O),1663(s,v C＝O),1547(m,δNH)。
nuclear magnetic hydrogen spectrum data are as follows:
1H NMR(400MHz,CDCl3):δ4.46(m,NCO-CH-,2H),3.75(t,C≡C-CH2,4H),3.18-3.40(m,-CH2-S-,C≡CH,6H)。
example 4
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate IV having reactive groups.
3.36 g of N, N, N, N-tetrakis (8-aminooctyl) diaminoethanol acetonide was dissolved in a mixed solvent of 100 ml of dichloromethane and 20 ml of pyridine, cooled to-20 ℃, 26 ml of a toluene solution of phosgene (1.93 mol/l) was added dropwise, and the reaction was continued for 6 hours under cooling. The reaction solution was washed once with saturated sodium chloride solution and distilled water, and the organic phase was dried over anhydrous sodium sulfate for 12 hours, filtered and concentrated under reduced pressure. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000071
nuclear magnetic hydrogen spectrum data are as follows:
1H NMR(400MHz,DMSO-d6):δ3.52(t,-OCH2-),3.40(t,-CH2-NCO),3.02(t,-CH2-N-),1.2-1.6(m,-CH2in octane and–CH3in ketal).
example 5
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate V having reactive groups.
6.7 g of selenocysteine di-tert-butyl ester is dissolved in a mixed solvent of 80 ml of dichloromethane and 8 ml of pyridine, cooled to-15 ℃, added with 2.97 g of diphosgene toluene solution (50 ml) dropwise, and reacted for 5 hours under the cooling condition. The reaction solution was washed twice with dilute hydrochloric acid, saturated sodium chloride solution and distilled water, and the organic phase was dried over anhydrous magnesium sulfate for 12 hours, filtered, and concentrated under reduced pressure. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000072
example 6
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate VI having reactive groups.
Adding 2.25 g of cystamine dihydrochloride into a reaction bottle, adding 50 ml of dichloromethane and 4.2 ml of triethylamine, stirring and dissolving, then adding 4.33 g of N, N' -dicyclohexylcarbodiimide and 4.05 g of 1-hydroxybenzotriazole, then adding 6 g of N-tert-butoxycarbonylmethionine, and naturally returning to room temperature for reacting for 24 hours. After the reaction was complete, the precipitate was removed by filtration, the product was evaporated to dryness and dissolved in ethyl acetate, washed three times with saturated sodium bicarbonate solution, washed once with saturated sodium chloride solution and once with distilled water, and dried overnight with anhydrous magnesium sulfate. After suction filtration, the filtrate was concentrated under reduced pressure and recrystallized from ethyl acetate. The dried crystals were dissolved in 20 ml of dichloromethane, and 20 ml of trifluoroacetic acid was added under ice-bath, stirred at room temperature for 2 hours and then dried under reduced pressure to obtain a product a.
Dissolving 4.15 g of the product A in a mixed solvent of 100 ml of dichloromethane and 20 ml of pyridine, cooling to-15 ℃, dropwise adding 80 ml of a dichloromethane solution of 2.38 g of triphosgene for reaction for 6 hours, washing the obtained product twice with dilute hydrochloric acid, washing the obtained product once with a saturated sodium chloride solution and distilled water respectively, drying an organic phase with anhydrous magnesium sulfate, filtering, and concentrating under reduced pressure. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000081
example 7
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate VII having reactive groups.
1.8 g of 3, 6-dithia-1, 8-octanediamine are dissolved in 50 ml of tetrahydrofuran, cooled in an ice bath and magnetically stirred. 4.33 g of N, N' -dicyclohexylcarbodiimide and 4.05 g of 1-hydroxybenzotriazole were added, and 7.57 g of N-t-butoxycarbonyl-L-glutamic acid-. gamma. -azidoethylamide were then added to the mixture, and the mixture was allowed to naturally return to room temperature and reacted for 24 hours. After the reaction was complete, the precipitate was removed by filtration, the product was evaporated to dryness and dissolved in ethyl acetate, washed three times with saturated sodium bicarbonate solution, washed once with saturated sodium chloride solution and once with distilled water, and dried overnight with anhydrous magnesium sulfate. After suction filtration, the filtrate is decompressed and concentrated, dissolved in 25 ml dichloromethane, and then reacted for 4 hours at room temperature after 20 ml ethyl acetate saturated solution of hydrogen chloride in ice bath, and decompressed and dried, thus obtaining the product A.
Dissolving 2.87 g of the product A in a mixed solvent of 50 ml of dichloromethane and 8 ml of pyridine, cooling to-15 ℃, dropwise adding 2.38 g of triphosgene in a dichloromethane solution of 50 ml, reacting for 5 hours, washing the obtained product twice with dilute hydrochloric acid, washing the obtained product once with saturated sodium chloride solution and distilled water, drying the organic phase with anhydrous magnesium sulfate, filtering, and concentrating under reduced pressure. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000082
example 8
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate VIII having reactive groups.
1.2 g of 4-seleno-lysine ethyl ester is dissolved in a mixed solvent of 60 ml of dichloromethane and 60 ml of saturated potassium bicarbonate water solution, and is cooled to 0 ℃ and stirred vigorously for 10 minutes. Stirring was then stopped and 1.34 g of triphosgene in dichloromethane (20 ml) was injected into the organic phase and stirred for 15 minutes with ice-cooling. The reaction solution is separated into layers, the organic phase is washed twice by dilute hydrochloric acid and saturated sodium chloride solution respectively, the organic phase is washed once by distilled water, the aqueous phase is backwashed once by dichloromethane, the organic phase is combined and dried for 12 hours by anhydrous sodium sulfate, and the pressure reduction and concentration are carried out after the filtration. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000091
example 9
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate IX having reactive groups.
2.18 g of N-trifluoroacetyl-L-serine propargylamide are dissolved in 125 ml of anhydrous dichloromethane and 125 mg of pyridinium p-toluenesulfonate are added. The mixture was cooled to 0 ℃ in an ice bath, and 25 ml of a dichloromethane solution of 0.92 g of 2,2, 2-trifluoro-N- (2-ethyleneoxyethyl) acetamide was slowly added dropwise thereto. After 30 minutes of reaction, 30 ml of a 5% by mass sodium carbonate solution was added. The reaction solution was diluted with 100 ml of dichloromethane, washed twice with distilled water and saturated sodium chloride solution, and the aqueous phase was back-washed once with dichloromethane. The organic phases were combined, dried over anhydrous magnesium sulfate overnight, filtered and concentrated under reduced pressure. The resulting oil was dissolved in 40 ml of tetrahydrofuran, 40 ml of 1.6 mol/l sodium hydroxide solution was added thereto, the mixture was stirred overnight, and then extracted with diethyl ether, the organic phase was dried over anhydrous magnesium sulfate, filtered under suction and concentrated under reduced pressure, and the resulting oil was purified by silica gel column chromatography (chloroform/methanol: 8/1) to obtain product a.
Dissolving 0.97 g of the product A in a mixed solvent of 40 ml of dichloromethane and 5 ml of pyridine, cooling to-15 ℃, dropwise adding 40 ml of a dichloromethane solution of 0.83 g of triphosgene for reaction for 4 hours, washing the obtained product once by using a saturated sodium chloride solution and distilled water respectively, drying an organic phase by using anhydrous magnesium sulfate, and concentrating under reduced pressure after suction filtration. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000092
example 10
This example synthesizes a stimuli-sensitive multifunctional polyisocyanate X having reactive groups.
1.72 g of N-trifluoroacetyl-L-cysteine propargylamide and 0.15 g of p-toluenesulfonic acid monohydrate were dissolved in 20 ml of benzene and stirred for 10 minutes. 10 g of 5A molecular sieve was added and stirring was continued for 10 minutes. 0.2 g of 2, 2-dimethoxypropane was added thereto, and the mixture was stirred at room temperature for 24 hours. The molecular sieves were removed by filtration and the product was purified by silica gel column chromatography (ethyl acetate/petroleum ether: 1/6) to give product a.
1 g of the product A is dissolved in 20 ml of tetrahydrofuran, 20 ml of sodium hydroxide solution (6 mol/l) is added, the mixture is stirred for 4 hours at room temperature, the product is extracted five times by ethyl acetate, the organic phase is dried by anhydrous magnesium sulfate, and the product is concentrated under reduced pressure after suction filtration to obtain a product B.
Dissolving 1.07 g of the product B in a mixed solvent of 40 ml of dichloromethane and 5 ml of pyridine, cooling to-15 ℃, dropwise adding 0.59 g of triphosgene in dichloromethane solution of 40 ml for reaction for 4 hours, washing the obtained product once by using saturated sodium chloride solution and distilled water respectively, drying an organic phase by using anhydrous magnesium sulfate, filtering by suction, and concentrating under reduced pressure. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000101
example 11
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate XI having reactive groups.
1.7 g of 5-hydroxy-2-nitrophenylethanol and 4.3 g of potassium carbonate were dispersed in 20 ml of N, N' -dimethylformamide, heated to 60 ℃ and stirred for 1 hour. A solution of 2.82 g of N-benzyloxycarbonyl bromoethylamine in methylene chloride (5 ml) was slowly added dropwise thereto, and the reaction was carried out at 60 ℃ for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, the product was dissolved with ethyl acetate, washed twice with a saturated sodium bicarbonate solution, a saturated sodium chloride solution and each with distilled water, the organic phase was dried with anhydrous magnesium sulfate for 8 hours, filtered, concentrated under reduced pressure, and recrystallized twice in ethyl acetate/cyclohexane to obtain a product a.
1.56 g of product A are dissolved in 50 ml of anhydrous dichloromethane, 1.25 g of N-benzyloxycarbonylmethionine, 1.33 g of N, N' -dicyclohexylcarbodiimide and 0.2 g of 4-dimethylaminopyridine are added under cooling in an ice bath and stirred at room temperature overnight. After the reaction, the mixture was washed twice with frozen dilute hydrochloric acid, a saturated sodium bicarbonate solution and a saturated sodium chloride solution, once with distilled water, and dried over anhydrous sodium sulfate overnight. The solvent was removed under reduced pressure with suction and recrystallized twice from ethyl acetate. The obtained crystals were dissolved in 20 ml of chloroform, and 20 ml of a saturated ethyl acetate solution of hydrogen chloride was added under ice-bath, reacted at room temperature for 6 hours, and then dried under reduced pressure to obtain a product B.
0.687 g of the product B was dissolved in a mixed solvent of 50 ml of methylene chloride and 8 ml of pyridine, cooled to-18 ℃ and reacted with dropwise addition of 10 ml of a toluene solution of phosgene (1.93 mol/l) for 6 hours. The reaction solution was washed twice with dilute hydrochloric acid and saturated sodium bicarbonate solution, and once with saturated sodium chloride solution and distilled water. The organic phase was dried over anhydrous magnesium sulfate overnight, filtered off with suction and concentrated under reduced pressure. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000102
example 12
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate XII having reactive groups.
Dissolving 16.57 g of N-tert-butoxycarbonyl-5-azidopropyl-L-glutamine in 100 ml of dichloromethane, cooling to 0 ℃ in an ice bath, adding 4.33 g of dicyclohexylcarbodiimide and 4.05 g of 1-hydroxybenzotriazole, then dropwise adding 2.4 g of dichloromethane solution (40 ml) of 4, 4-diaminomethylazobenzene, and naturally returning to room temperature for reacting for 24 hours; after the reaction is finished, carrying out suction filtration on the reaction solution, carrying out reduced pressure concentration, adding 100 ml of 0.5 mol/L diluted hydrochloric acid, extracting with ethyl acetate, washing an organic layer with a saturated sodium bicarbonate solution, a saturated sodium chloride solution and distilled water for 2 times respectively, adding anhydrous magnesium sulfate, drying for 8 hours, carrying out suction filtration, carrying out reduced pressure concentration on the organic layer, dissolving the obtained oily substance in 50 ml of chloroform, adding 50 ml of an ethyl acetate saturated solution of hydrogen chloride, carrying out room temperature reaction for 2 hours, and carrying out reduced pressure concentration to obtain a product A.
Dissolving 3.3 g of the product A in a mixed solvent of 60 ml of dichloromethane and 6 ml of pyridine, cooling to-15 ℃, dropwise adding 40 ml of a dichloromethane solution of 1 g of triphosgene, naturally returning to room temperature for reaction for 4 hours, washing the obtained product once by using dilute hydrochloric acid, a saturated sodium chloride solution and distilled water respectively, drying an organic phase by using anhydrous magnesium sulfate, and concentrating under reduced pressure after suction filtration. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000111
example 13
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate XIII having reactive groups.
4.86 g of 2,2, 2-trifluoro-N- (2-methoxy-2-methyl- [1,3] -dioxolan-4-methyl) acetamide, 6.6 g of 4-trifluoroacetyl-3- (3, 4-dichlorophenyl) -1-butanol and 50 mg of pyridinium p-toluenesulfonate were mixed and heated to 130 ℃ and the reaction was stirred until no volatile substance appeared in the reaction system, the reaction was cooled to room temperature, and the resulting oil was purified by silica gel column chromatography (ethyl acetate/petroleum ether ═ 1/2) to obtain product a.
8.12 g of the product a was dissolved in 50 ml of tetrahydrofuran, 50 ml of 1.6 mol/l sodium hydroxide solution was added thereto, the mixture was stirred overnight, and then extracted with diethyl ether, the organic phase was dried over anhydrous magnesium sulfate, filtered under suction and concentrated under reduced pressure, and the resulting oil was purified by silica gel column chromatography (chloroform/methanol: 10/1) to obtain a product B.
Dissolving 3.5 g of the product B in a mixed solvent of 60 ml of dichloromethane and 6 ml of pyridine, cooling to-15 ℃, dropwise adding 40 ml of a dichloromethane solution of 2.97 g of triphosgene, naturally returning to room temperature for reaction for 4 hours, washing the obtained product once by using a saturated sodium chloride solution and distilled water respectively, drying an organic phase by using anhydrous magnesium sulfate, and concentrating under reduced pressure after suction filtration. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000121
example 14
This example synthesizes a stimulus-sensitive multifunctional polyisocyanate XIV having reactive groups.
4.86 g of 2,2, 2-trifluoro-N- (2-methoxy-2-methyl- [1,3] -dioxolan-4-methyl) acetamide, 4.76 g of N-trifluoroacetyl-L-serine propargylamide and 50 mg of pyridinium p-toluenesulfonate were mixed and heated to 130 degrees and the reaction was stirred until no volatile substance appeared in the reaction system, the reaction was cooled to room temperature, and the resulting oil was purified by silica gel column chromatography (ethyl acetate/petroleum ether: 1/2) to obtain product a.
5 g of the product a was dissolved in 40 ml of tetrahydrofuran, 40 ml of 1.6 mol/l sodium hydroxide solution was added thereto, the mixture was stirred overnight, and then extracted with diethyl ether, the organic phase was dried over anhydrous magnesium sulfate for 12 hours, and after suction filtration and concentration under reduced pressure, the resulting oil was purified by silica gel column chromatography (chloroform/methanol: 8/1) to obtain a product B.
Dissolving 2.57 g of the product B in a mixed solvent of 60 ml of dichloromethane and 6 ml of pyridine, cooling to-15 ℃, dropwise adding 40 ml of a dichloromethane solution of 2.23 g of triphosgene, naturally returning to room temperature for reaction for 4 hours, washing the obtained product once by using a saturated sodium chloride solution and distilled water respectively, drying an organic phase by using anhydrous magnesium sulfate, and concentrating under reduced pressure after suction filtration. The structural formula of the obtained product is as follows:
Figure BDA0000890755650000122
application example 1
The application example is that the stimulation sensitive multifunctional polyisocyanate I with active groups is utilized to synthesize the polyurea homopolymer with the main chain containing disulfide bonds and the side chain containing ester groups.
2.04 g of cystine dimethyl ester and 2.30 g of multifunctional polyisocyanate I having active groups are dissolved in 100 ml of dimethylacetamide, reacted at room temperature for 34 hours, and the product is precipitated twice with distilled water and then lyophilized. The structure of the obtained product is as follows:
Figure BDA0000890755650000131
the infrared spectrum data are as follows:
FTIR(KBr,cm-1):3367(s,ν NH),1723(s,ν C＝O)，1681(s,v NHC＝O),1431(m,vC-N,δNH),1205(s,ν C-O-C)。
nuclear magnetic hydrogen spectrum data are as follows:
1H NMR(400MHz,TFA):δ8.39(s,NH),5.12(m,NH-CH-),3.93(s,CH3O),3.21-3.33(d,J＝47.4,-CH2-S-)。
the number of the polymer was determined by GPC to be 58300g/mol relative molecular mass with a narrow distribution.
The obtained polyurea has a regular structure, each structural unit of a main chain contains a reduction-sensitive disulfide bond, the polymer is endowed with excellent stimulation responsiveness, and the polyurea can be rapidly degraded into cysteine-derived small molecular substances under a reduction condition. The side chain ester group can introduce various functional groups through aminolysis, ester exchange and other reactions, or active carboxyl is obtained through saponification reaction and is used for coupling biomacromolecules.
Application example 2
The application example is that the stimulation sensitive multifunctional polyisocyanate III with active groups is utilized to synthesize the 'modifiable' block copolymer with the main chain containing disulfide bonds and the side chain containing alkynyl.
1.9 g of polyethylene glycol monomethyl ether (Mw 1900) and polycaprolactone diol (Mw 2000) are dehydrated for 2 hours at 100 ℃ in vacuum, 0.38 g of stimuli-sensitive multifunctional polyisocyanate III with active groups, 40 ml of anhydrous tetrahydrofuran solution and 0.1% of stannous octoate are sequentially added, and the reaction is carried out for 11 hours at 60 ℃. The resulting product was precipitated three times with diethyl ether and dried under vacuum at 40 ℃ for 48 hours. The structure of the product is as follows:
Figure BDA0000890755650000132
the infrared spectrum data are as follows:
FTIR(KBr,cm-1):3436(s,ν NH),2882(s,ν CH),1725(s,ν C＝O),1467(m,v C-N),1243(s,ν C-O-C of PCL),1112(s,ν C-O-C of PEG)。
nuclear magnetic hydrogen spectrum data are as follows:
1H NMR(400MHz,CDCl3):δ4.24(m,CONH-CH-),4.06(t,OCO-CH2-),3.93(t,C≡C-CH2),3.38(s,CH3O-),3.64(t,-CH2CH2O-),3.93(s,CH3O),3.20(s,C≡CH),2.89-2.96(m,-CH2-S-),2.31(t,CH2COO),1.65(m,-CH2CH2CH2-),1.38(m,-CH2CH2CH2-)。
nuclear magnetic carbon spectral data are as follows:
13C NMR(400MHz,CDCl3):δ173.5,70.5,64.1,34.2,25.5,24.5.
the number of the polymer molecules measured by GPC was 5000g/mol relative to the molecular mass and the distribution was narrow.
The obtained two-block polymer has amphipathy, can be self-assembled into a nano-carrier in aqueous solution, and can entrap chemotherapeutic drugs, genes and imaging diagnostic reagents, the hydrophilic block and the hydrophobic block are connected through a stimulation sensitive multifunctional polyisocyanate III residue with an active group, so that the polymer has the capability of responding to reductive glutathione in tumor cells, the release control of the drugs in the cells is realized, the side chain alkynyl can be chemically modified through click reaction, and various functional groups are introduced, so that the multi-functionalization of the polymer is realized.

Claims (5)

1. A stimuli-sensitive multifunctional polyisocyanate having reactive groups, characterized in that the polyisocyanate has the general structural formula:
Figure FDF0000007975340000011
wherein A is a stimuli-sensitive group; r1And R2Is a compound group containing or not containing an active group and having 1-20 carbon atoms, R1And R2May be the same or different, but at least one of them contains a reactive group;
the R is1And R2The active group is at least one of ester group, azido group, alkynyl group, halogenated hydrocarbon group, sulfenyl group, tertiary amine group and isocyanate group, and when the active group is sulfenyl group, the group is positioned on the side chain of the polyisocyanate molecule
The stimulation sensitive group A is any one of a selenylene group, a dithiolene group, a diselenylene group, an acetal group, a propisocetone group, a pentocyclic orthoester group, an o-nitrophenylene group or an azophenylene group.
2. The multifunctional stimulus-sensitive polyisocyanate having an active group according to claim 1, wherein the stimulus-sensitive group A in the general structural formula of the polyisocyanate is any one of a dithiolene group, a diselenylene group, an acetal group, an o-nitrophenylene group or an azophenylene group.
3. Stimulus-sensitive multifunctional polyisocyanates with reactive groups according to claim 1 or 2, characterized in that the polyisocyanates have the general structural formula R1And R2Is any one of a compound group containing or not containing an active group and having 4 to 19 carbon atoms.
4. Stimulus-sensitive multifunctional polyisocyanates with reactive groups according to claim 1 or 2, characterized in that the polyisocyanates have the general structural formula R1And R2The active groups are ester groups, azide groups or alkynyl groups.
5. The device of claim 3 havingThe multifunctional stimulation sensitive polyisocyanate of the active group is characterized in that R in the structural general formula of the polyisocyanate1And R2The active groups are ester groups, azide groups or alkynyl groups.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103341177A (en) * 2013-06-08 2013-10-09 西安交通大学 Reduction sensitive type polyethylene glycol-medicament conjugate and preparation method thereof
CN103694140A (en) * 2013-12-02 2014-04-02 艾达索高新材料无锡有限公司 Degradable isocyanate and application thereof

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3627794A (en) * 1970-02-16 1971-12-14 Ashland Oil Inc Sulfur-containing compounds
JPS6026775B2 (en) * 1977-04-28 1985-06-25 東レ株式会社 Lysine ester triisocyanate
JP3229781B2 (en) * 1995-08-14 2001-11-19 三井化学株式会社 A sulfur-containing urethane-based plastic lens using a novel polythiol
JP3791973B2 (en) * 1996-07-30 2006-06-28 三井化学株式会社 Isocyanate derivatives and uses thereof
EP0976727B1 (en) * 1998-07-28 2003-01-15 Hoya Corporation Polyisocyanate compound, process for producing the same and optical resin materials using the same
CN101787047B (en) * 2010-01-22 2013-07-24 四川大学 Fluorocarbon chain or/and hydrocarbon chain containing phosphatidylcholine blocking agent with hydroxyl or amino at tail end and polyurethane material for blocking same
MY157424A (en) * 2010-08-27 2016-06-15 Inventure Internat Pte Ltd Generation of mixed diisocyanates by phosgenation of soy based methyl amino esters
US9052436B2 (en) * 2010-12-29 2015-06-09 Koc Solution Co., Ltd. Method for manufacturing resin for urethane-based optical material, resin composition for same, and optical material manufactured thereby
WO2012112014A2 (en) * 2011-02-18 2012-08-23 주식회사 케이오씨솔루션 Novel polythiol compound, preparation method therefor, and resin composition for urethane optical material using same
CN102335435B (en) * 2011-08-12 2013-12-18 四川大学 Multifunctional polyurethane medicament carrier as well as preparation method and application thereof
CN102643406A (en) * 2012-05-10 2012-08-22 四川大学 Polyester type polyurethane material with side chain containing fluorine and preparation method thereof
US9029054B2 (en) * 2012-06-29 2015-05-12 Canon Kabushiki Kaisha Electrophotographic photosensitive member, process cartridge, and electrophotographic apparatus
US20150226879A1 (en) * 2012-08-29 2015-08-13 Koc Solution Co., Ltd. Method of manufacturing thiourethane - based optical material
CN103172819B (en) * 2013-03-01 2015-01-14 中国科学院长春应用化学研究所 Biodegradable polyurethane with amino on side chain and preparation method and application thereof
CN103224607B (en) * 2013-04-10 2014-10-29 四川大学 Comb-shaped functionalized polyurethane material and preparation method thereof
CN103495203B (en) * 2013-09-09 2014-11-05 西安交通大学 Reductively biodegradable type honeycomb polyurethane support, and preparation method and application thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103341177A (en) * 2013-06-08 2013-10-09 西安交通大学 Reduction sensitive type polyethylene glycol-medicament conjugate and preparation method thereof
CN103694140A (en) * 2013-12-02 2014-04-02 艾达索高新材料无锡有限公司 Degradable isocyanate and application thereof

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