CN101885841B - Polymer capable of performing addition reaction with thiol and having stable bonding hydrolysis - Google Patents
Polymer capable of performing addition reaction with thiol and having stable bonding hydrolysis Download PDFInfo
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- 229920000642 polymer Polymers 0.000 title abstract description 20
- 238000007259 addition reaction Methods 0.000 title abstract description 12
- 230000007062 hydrolysis Effects 0.000 title abstract description 12
- 238000006460 hydrolysis reaction Methods 0.000 title abstract description 12
- 125000003396 thiol group Chemical class [H]S* 0.000 title 1
- 125000000524 functional group Chemical group 0.000 claims abstract description 3
- 229920002521 macromolecule Polymers 0.000 claims description 14
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- -1 polyoxyethylene Polymers 0.000 claims description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 4
- 229920001577 copolymer Polymers 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 abstract description 12
- 102000004169 proteins and genes Human genes 0.000 abstract description 12
- 239000000126 substance Substances 0.000 abstract description 7
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 6
- 229920001184 polypeptide Polymers 0.000 abstract description 5
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 3
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 229920001477 hydrophilic polymer Polymers 0.000 abstract 1
- 150000003573 thiols Chemical class 0.000 abstract 1
- 238000000034 method Methods 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000499 gel Substances 0.000 description 9
- 238000004132 cross linking Methods 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000011065 in-situ storage Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 238000006957 Michael reaction Methods 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000005518 carboxamido group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
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- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- SDJHDRMYZQFJJO-UHFFFAOYSA-N ethanethioic s-acid;potassium Chemical compound [K].CC(S)=O SDJHDRMYZQFJJO-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 238000003860 storage Methods 0.000 description 1
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- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Medicinal Preparation (AREA)
- Polyethers (AREA)
Abstract
The invention discloses a polymer which can perform addition reaction with thiol and has stable hydrolysis. The polymer is formed by introducing at least one functional group shown in a formula (I) to a chain side and/or a chain end of a hydrophilic polymer, wherein X is any group or polymer chain. The polymer has the advantages that: the polymer can react with proteins or polypeptides under physiological environment without other micromolecule components, so the probably brought biotoxicity is avoided and the proteins to be modified are not influenced; and ester bonds, amido bonds, amido ester bonds and other easily hydrolytic chemical bonds are absent between the chemical bond formed after the addition reaction and a main chain, so the hydrolysis is stable.
Description
Technical field
The present invention relates to a kind ofly can and become the polymer of stable bonding hydrolysis with sulfydryl generation addition reaction.
Background technology
Characteristics become the focus of people's research in recent years because its effect is single-minded, efficient etc. for protein and polypeptide drug, but such medicine exists poor stability, lack plasma half-life and have problem such as immunogenicity, thereby have limited its application development.From the seventies in last century, people begin to utilize polymer, and (especially polyoxyethylene glycol PEG) comes protein and peptide molecule are modified, and the problems referred to above are resolved or alleviate.Nowadays this macromole modification technique not only in the exploitation of protein drug by widespread usage, also be expanded every field such as new drug carrier and controlled release preparation.For polymer (like PEG) is attached on the protein (or polypeptide), need carry out suitable modification to polymer, make it to have can with special groups on the protein (like amino, sulfydryl etc.) reactive activity group.Considering had better not damage and react protein itself in the modification reaction process to have by product or side reaction, so require the reactive group of introducing and the reaction of the generation of the group on the protein under mild conditions, to take place.Seek the reactive group and the introducing method that are fit to above-mentioned condition and also become the direction that the macromole modification technique is studied.
The reaction system that can take place under the above-mentioned mild conditions on the other hand, still is an importance of in-situ crosslinking aquogel research.Macromolecule hydrogel is because its superior biocompatibility and the three-dimensional structure similar with extracellular matrix form fields such as being widely used in organizational project and medicine controlled releasing.Especially in the appearance of injection aquagel (being in-situ crosslinking aquogel) in recent years; Thereby numerous advantages that it has such as its can be implanted with the method for Wicresoft and reduce less patient suffering and medical treatment cost; Can adhere to organizing very closely; Medicine, protein even cell can wrap up etc. through simply mixing with gel component, more make it to become the focus that people pay close attention to.In-situ crosslinking aquogel has physical gel and chemical gel two big classes usually.The cross-linking set of physical gel connects with the non covalent bond mode usually, comprises ionic linkage, hydrogen bond, Van der Waals force and hydrophobic interaction etc.The crosslinking method of chemical gel is a covalent linkage, so have better stable with respect to physical gel.The preparation method of in-situ chemical gel has methods such as radical polymerization, addition, condensation usually at present.The method that is formed gel by monomer polymerization may make monomer and initiator bring certain toxicity, realizes that crosslinked method application is more extensive so utilize high molecular group to react to each other.The radical reaction under mild conditions (or physiological condition) that the range of application of situ-gel also requires to use in the system can take place.
At present; The reaction system type that above-mentioned mild conditions can take place down is still less; The Michael reaction, the amber sulphur polyurethane-amino coupling reaction based on amino, aldehyde radical-amino reaction and the nonmetal catalytic nitrine-alkynyl that generally include based on sulfydryl are clicked (click) reaction etc., and be wherein extensive with the Michael reaction based on sulfydryl especially.The group that is generally used for generating with sulfydryl reaction and no coupling product is maleimide and esters of acrylic acid, and this type group exists the problem of facile hydrolysis usually.And stability to hydrolysis for macromole modify the back medicine to be easy to purifying and prolonged storage stable (especially injectable drug) etc. all extremely important, also need to become key be hydrolysis-stable and be used for long-lasting requirement like the hydrogel of tissue substitutes such as vitreum.And have at present report can under mild conditions, react with sulfydryl and group that no coupling product generates only has the ethene sulfuryl, introducing the ethene sulfuryl like PEG can carry out protein modification (Morpurgo, M.; Bioconjugate Chemistry, 1996,7:363); Multi-arm PEG introduces macromole precursor (Lutolf, M.P., the Advanced Materials that the ethene sulfuryl can be used as the original position hydrogel; 2003,15:888).But the introducing process of ethene sulfuryl is loaded down with trivial details, and the production building-up process introduces the toxicity small molecules easily, thereby range of application unusual limitation still at present.
Summary of the invention
The purpose of this invention is to provide and a kind ofly can and become polymer of stable bonding hydrolysis and preparation method thereof with sulfydryl generation addition reaction.
Provided by the present invention can with the polymer of sulfydryl generation addition reaction and hydrolysis-stable, its chain side and/or the end of the chain have the functional group shown at least one formula (I):
Formula (I)
Wherein, X is any group or macromolecular chain, is preferably :-O-R;-NH-R, wherein R is an alkyl; Said high molecular main chain is a hydrophilic macromolecule.
Hydrophilic macromolecule described in the present invention comprises natural hydrophilic high mol and synthetic hydrophilic high mol, and its wetting ability is from hydrophilic radicals such as the carboxyl in the macromolecular structure, carboxamido-group, amido, ethers.Said natural hydrophilic high mol comprises polyose (like starch, Mierocrystalline cellulose, Lalgine, mucinase, chitosan etc.) and polypeptide class (like collagen, gather L-Methionin, gather L-L-GLUTAMICACID etc.).Said synthetic hydrophilic high mol comprises vinylformic acid and derivatives class thereof etc. (SEPIGEL 305 gathers N-and gathers for acrylic amide etc. for ROHM, polymethyl acrylic acid).
The preferred synthetic hydrophilic high mol of hydrophilic macromolecule described in the present invention specifically can be selected from the following polymer any one: polyoxyethylene glycol (PEG), Z 150PH (PVA), Vinylpyrrolidone polymer (PVP), SEPIGEL 305 (PAM), poly hydroxy ethyl acrylate (PHEMA), ethylene glycol copolymer, polyvinyl alcohol copolymer, Vinylpyrrolidone polymer multipolymer, polyacrylamide copolymer and poly hydroxy ethyl acrylate multipolymer; Further be preferably polyoxyethylene glycol and multipolymer thereof.
The number-average molecular weight of said hydrophilic high mol is 500Da-10
7Da is preferably 10
3Da-10
5Da.
Polymer according to the invention can further be expressed as the compound shown in formula (IV) or the formula V:
Formula (IV)
Formula V
In formula (IV) and the formula V, n is the integer greater than 1; R
1, R
2Be any group or macromolecular chain; R
2Be preferably-C
2H
5
Provided by the present inventionly can and become in the polymer of stable bonding hydrolysis with sulfydryl generation addition reaction; Because the suction of carbonyl electricity conjugation in the formula (I); Make two bonding electron cloud density reduce, thereby easily by the sulfydryl nucleophilic addition(Adn), the addition reaction type can be but be not limited to reversal of the Michael addition.
Experiment showed, that polymer shown in the formula of the present invention (I) (specifically suc as formula the polymer shown in (II)) and four arm end sulfydryl PEG can (or physiological condition) form in-situ crosslinking aquogel under mild conditions.
High molecular advantage provided by the present invention is: its under physiological environment (37 ℃; PH=7.4; The aqueous solution) can react with the sulfydryl on protein (or polypeptide) or the other materials; And need not add any other small molecule component, thereby the bio-toxicity of having avoided these small molecule components to bring can not impact yet to the adorned protein of needs; And do not have the chemical bond of facile hydrolysiss such as ester bond, amido linkage, amine ester bond between chemical bond that forms after the generation addition reaction and the main chain, thereby be hydrolysis-stable.
Description of drawings
Fig. 1 is a high molecular proton nmr spectra spectrogram prepared among the embodiment 1.
Fig. 2 is a high molecular proton nmr spectra spectrogram prepared among the embodiment 2.
Embodiment
For a better understanding of the present invention, below in conjunction with embodiment the present invention is done further detailed description.But protection scope of the present invention is not limited to the scope that embodiment explains.
Experimental technique described in the following embodiment like no specified otherwise, is ordinary method; Said reagent and material like no specified otherwise, all can obtain from commercial sources.
Embodiment 1, preparation can and become the linear PEG of stable bonding hydrolysis with sulfydryl generation addition reaction
With terminal hydroxy group PEG (number-average molecular weight is about 2000, and Alfa-Aesar provides, article No. B22181) is raw material, compound shown in the preparation formula (II), and wherein n is less than 60 integer greater than 30.
Formula (II)
Concrete preparation method is following:
Terminal hydroxy group PEG 20.0g is dissolved in the 500mL exsiccant methylene dichloride; Add triethylamine 8.3mL, Tosyl chloride 11.4g; Reaction is 24 hours under the room temperature, with products therefrom and thioacetic acid potassium 4.5g 85 ℃ of refluxed 4 hours, then with the methanol solution of products therefrom and 2M ammonia; Under nitrogen protection, stirred 4 hours, promptly obtain holding sulfydryl PEG.
9.0g methylol ethyl propenoate (TCI provides, article No. H0916) is dissolved in the 75mL anhydrous diethyl ether, splashes into the 2.3mL phosphorus tribromide under the ice bath, ice bath reaction down continued reaction 24 hours in room temperature after 3 hours, obtained the brooethyl ethyl propenoate.
Hold sulfydryl PEG to be dissolved in the 300mL methylene dichloride 20.0g, add the 3mL triethylamine, and under ice bath, splash into 8mL brooethyl ethyl propenoate, reaction is 24 hours under the room temperature, promptly obtains the finished product (compound shown in the formula II).
The structure of gained compound can obtain from the nucleus magnetic hydrogen spectrum of Fig. 1 confirming.
Embodiment 2, preparation can and become the linear PEG of stable bonding hydrolysis with sulfydryl generation addition reaction
With terminal hydroxy group PEG (number-average molecular weight is about 2000, and Alfa-Aesar provides, article No. B22181) is raw material, compound shown in the preparation formula (III), and wherein n is less than 60 integer greater than 30.
Formula (III)
The brooethyl ethyl propenoate can obtain through the method among the embodiment 1.
20.0g terminal hydroxy group PEG is dissolved in the 300mL methylene dichloride, adds the 2.4g sodium hydride, stirred 1 hour.Under ice bath, splash into 8mL brooethyl ethyl propenoate, reaction is 24 hours under the room temperature, promptly obtains product (compound shown in the formula III).
The structure of gained compound can obtain from the nucleus magnetic hydrogen spectrum of Fig. 2 confirming.
The in-situ crosslinking aquogel of embodiment 3, hydrolysis-stable
(number-average molecular weight is about 10000 for formula II compound that embodiment 1 is prepared and four arm end sulfydryl PEG; JenChem provides; Article No. 4ARM-SH-10K) is dissolved in the phosphate buffered saline buffer that pH=7.4 concentration is 0.1mol/L respectively; The mass concentration of both solution is 0.1g/mL, is to mix at 2: 3 both solution with volume ratio, mixes the back and in 7 hours, becomes glue.
Or the formula II compound that embodiment 1 is prepared be dissolved in the phosphate buffered saline buffer that pH=8.0 concentration is 0.1mol/L respectively with four arm end sulfydryl PEG; The mass concentration of both solution is 0.1g/mL; Is mixing in 2: 3 with both solution with volume ratio, mixes the back and in 1 hour, becomes glue.
Claims (4)
1. hydrophilic macromolecule, it is characterized in that: the chain side of said hydrophilic macromolecule and/or the end of the chain have the functional group shown at least one formula (I):
Formula (I)
Wherein, X be-O-R or-NH-R, wherein R representative-C
2H
5
The main chain of said hydrophilic macromolecule is polyoxyethylene glycol or ethylene glycol copolymer;
The number-average molecular weight of the main chain of said hydrophilic macromolecule is 500Da-10
7Da.
2. hydrophilic macromolecule according to claim 1 is characterized in that: the number-average molecular weight of the main chain of said hydrophilic macromolecule is 10
3Da-10
5Da.
3. hydrophilic macromolecule according to claim 1 and 2 is characterized in that: said hydrophilic macromolecule is the compound of formula (II) institute formula:
Formula (II)
Wherein, n is the integer greater than 1.
4. hydrophilic macromolecule according to claim 1 and 2 is characterized in that: said hydrophilic macromolecule is the compound shown in the formula (III):
Formula (III)
Wherein, n is the integer greater than 1.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1723232A (en) * | 2003-01-06 | 2006-01-18 | 尼克塔治疗亚拉巴马公司 | Thiol-selective water-soluble polmer derivatives |
| CN101111267A (en) * | 2004-12-21 | 2008-01-23 | 尼克塔治疗亚拉巴马公司 | Stabilized polymeric thiol reagents |
| CN101679625A (en) * | 2007-05-29 | 2010-03-24 | 栗村化学株式会社 | Chain-end functionalized methoxy poly(ethylene glycol)and metal nano-particles using the same |
-
2010
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1723232A (en) * | 2003-01-06 | 2006-01-18 | 尼克塔治疗亚拉巴马公司 | Thiol-selective water-soluble polmer derivatives |
| CN101111267A (en) * | 2004-12-21 | 2008-01-23 | 尼克塔治疗亚拉巴马公司 | Stabilized polymeric thiol reagents |
| CN101679625A (en) * | 2007-05-29 | 2010-03-24 | 栗村化学株式会社 | Chain-end functionalized methoxy poly(ethylene glycol)and metal nano-particles using the same |
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