CN105440222A - Polyamino acid non-ionic macro-molecular cross-linking agent and preparation method thereof - Google Patents
Polyamino acid non-ionic macro-molecular cross-linking agent and preparation method thereof Download PDFInfo
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- 239000002253 acid Substances 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 239000003431 cross linking reagent Substances 0.000 title claims abstract description 16
- 238000007151 ring opening polymerisation reaction Methods 0.000 claims abstract description 13
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims abstract description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 36
- 229920002521 macromolecule Polymers 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 239000003795 chemical substances by application Substances 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- 238000004132 cross linking Methods 0.000 claims description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 18
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 12
- NPSSWQJHYLDCNV-UHFFFAOYSA-N prop-2-enoic acid;hydrochloride Chemical compound Cl.OC(=O)C=C NPSSWQJHYLDCNV-UHFFFAOYSA-N 0.000 claims description 11
- 239000003999 initiator Substances 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 229920005604 random copolymer Polymers 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 238000005915 ammonolysis reaction Methods 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 150000003141 primary amines Chemical class 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 239000000017 hydrogel Substances 0.000 abstract description 23
- 239000001257 hydrogen Substances 0.000 abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 6
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 abstract 1
- 238000007098 aminolysis reaction Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 229920001308 poly(aminoacid) Polymers 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- 239000000499 gel Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 238000001291 vacuum drying Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000005119 centrifugation Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000004821 distillation Methods 0.000 description 9
- LJCWONGJFPCTTL-UHFFFAOYSA-N 4-hydroxyphenylglycine Chemical compound OC(=O)C(N)C1=CC=C(O)C=C1 LJCWONGJFPCTTL-UHFFFAOYSA-N 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 229920000835 poly(gamma-benzyl-L-glutamate) polymer Polymers 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000006837 decompression Effects 0.000 description 4
- 239000011261 inert gas Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 3
- 239000004160 Ammonium persulphate Substances 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 3
- 235000019395 ammonium persulphate Nutrition 0.000 description 3
- 238000002983 circular dichroism Methods 0.000 description 3
- 238000001142 circular dichroism spectrum Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000002594 sorbent Substances 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
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
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- PQUXFUBNSYCQAL-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1F PQUXFUBNSYCQAL-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000024287 Areas Species 0.000 description 1
- 238000012425 Freezing-thawing process Methods 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
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- 150000001413 amino acids Chemical class 0.000 description 1
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- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
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- 229920005615 natural polymer Polymers 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to the technical field of polyamino acids, specifically to a polyamino acid non-ionic macro-molecular cross-linking agent and a preparation method thereof. The method comprises the following steps: reacting gamma-benzyl-L-benzyl glutamate with triphosgene so as to obtain N-carboxylanhydride compound (NCA); then carrying out ring-opening polymerization so as to obtain poly(gamma-benzyl-L-benzyl glutamate) (PBLG); subjecting PBLG and 3-aminopropanol to aminolysis reaction so as to obtain poly(N-5-(3-hydroxypropyl)-L-glutamine (PHPG); and reacting PHPG with acryloyl chloride so as to obtain the polyamino acid non-ionic macro-molecular cross-linking agent. The cross-linking agent provided by the invention has biocompatibility and multiple hydrogen bonds and can improve mechanical strength and toughness of hydrogel when applied to preparation of the hydrogel, so the hydrogel prepared by using the cross-linking agent can better applied to the field of biological supporting systems.
Description
Technical field
The present invention relates to technical field of polyamino acid, be specifically related to a kind of polyamino acid non-ionic type macromolecules cross-linking agent and preparation method thereof.
Background technology
Materials science is intersected with life science, has promoted the fast development of biomaterial.Hydrogel (Hydrogel) take water as the gel of dispersion medium.Have in the water-soluble polymer of cross-linked network and introduce a part of hydrophobic grouping and hydrophilic residue, hydrophilic residue and water molecules, water molecules is connected to netted inside, and the cross-linked polymer of hydrophobic residue water-swellable.Be a kind of macromolecule network system, character is soft, can keep certain shape, a large amount of water can be absorbed, and after water suction, there is certain softness and elasticity, it is the specific dispersion system be made up of wetting ability tridimensional network and large water gaging, can be swelling and do not dissolve in water.
Hydrogel has various sorting technique, according to the difference of hydrogel network bonding, can be divided into physical gel and chemical gel.Physical gel is that this gel is volatile, can change solution into by heated gel, so be also referred to as pseudo-gels or heat reversible gel by physical force as the winding of electrostatic interaction, hydrogen bond, chain etc. is formed.Many natural polymers are stable gel state at normal temperatures, as k2 type carrageenin, agar etc.; In synthetic polymer, polyvinyl alcohol (PVA) is a typical example, through freezing thawing process, can obtain hydrogel stable below 60 DEG C.Chemical gel is the three-dimensional network polymkeric substance be cross-linked to form by chemical bond, is permanent, is also called true gel.
Hydrogel is as the high water-keeping material of a kind of high water suction, be widely used in multiple fields, as: the drought resisting of arid area, water blockoff in condensation preventing agent in facial mask in makeup, defervescence plaster used, pain easing plaster, agricultural film, building, humextant, petrochemical complex is adjusted, the dehydration of crude oil or processed oil, dust-inhibitor in mining industry, the preservation agent in food, thickening material, pharmaceutical carrier in medical treatment etc.It should be noted that different Application Areass should select different macromolecule raw materials, to meet the different needs.
Usually can use linking agent in the preparation process of hydrogel, but the mechanical strength of the hydrogel adopting linking agent preparation common at present to synthesize is more weak, toughness is not enough and absorption speed slow, these defects hamper the application in the fields such as its biologic strut system.In order to improve the over-all properties of hydrogel, to meet its application in fields such as biologic strut systems, just need to improve its linking agent, and lack the relevant linking agent for the preparation of the hydrogel of better performances at present.
Summary of the invention
The object of the invention is to solve the problem, providing the agent of a kind of polyamino acid non-ionic type macromolecules cross-linking, another object of the present invention is to provide a kind of preparation method preparing this macromolecules cross-linking agent simultaneously.
In order to reach foregoing invention object, the present invention by the following technical solutions:
The agent of a kind of polyamino acid non-ionic type macromolecules cross-linking, its structural formula is as follows:
Wherein: n is the integer of 30-500.
As preferably, x and y is respectively the ratio of repeating unit in random copolymers, x+y=1.
As preferably, x is 0.5-1.
A preparation method for polyamino acid non-ionic type macromolecules cross-linking agent, comprises the following steps:
(1) adopt γ-phenmethyl-Pidolidone benzyl ester and triphosgene to react, obtain N-carboxyl-ring inner-acid anhydride compound (NCA);
Synthetic route is as follows:
Adopt γ-phenmethyl-Pidolidone benzyl ester and triphosgene to be dissolved in solvent to react, after reaction terminates, with Rotary Evaporators except desolventizing, by thick product by recrystallization purifying, underpressure distillation obtains final product;
(2) under initiator effect, described NCA carries out ring-opening polymerization, is gathered (γ-phenmethyl-Pidolidone benzyl ester) (PBLG);
NCA and initiator are being dissolved in solvent; and react under certain temperature and protection of inert gas condition; after reaction terminates; by solution decompression distillation except desolventizing; then the solution after concentrated is precipitated in poor solvent; obtain solid by centrifugation, vacuum drying obtains final product white solid PBLG.Synthetic route is as follows:
Described rare gas element refers to the gas not participating in reacting, and following gas is especially applicable to rare gas element: nitrogen, helium, neon and argon gas;
(3) by described poly-(γ-phenmethyl-Pidolidone benzyl ester) and 3-aminopropanol generation ammonolysis reaction, (nitrogen is gathered
5-(3-hydroxypropyl) L-glutaminate) (PHPG);
First PBLG is dissolved in 3-aminopropanol, reacts, after reaction terminates, added in poor solvent by solution and be precipitated out, centrifugal separation obtains solid, and vacuum drying obtains final product white solid PHPG.Synthetic route is as follows:
Described poor solvent is ether; Centrifuge speed is 9000 revs/min;
(4) by described poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) react with acrylate chloride, obtain the agent of polyamino acid non-ionic type macromolecules cross-linking.
Be dissolved in by PHPG in solvent, add sour sorbent material, under ice-water bath condition, slowly drip acrylate chloride, room temperature reaction is 3 hours.After reaction terminates, by underpressure distillation except desolventizing, be then precipitated out in poor solvent by the solution after concentrated, centrifugation, vacuum-drying, obtains the agent of white solid polyamino acid non-ionic type macromolecules cross-linking.Synthetic route is as follows:
Acid sorbent material is triethylamine, and the mol ratio of sour sorbent material and PHPG is 1:1; Described poor solvent is ether, and described centrifuge speed is 9000 revs/min.N is the integer of 30-500, x and y is respectively the ratio of repeating unit in random copolymers, x+y=1.
These the finished product are adopted to prepare the process of hydrogel as follows:
In ice-water bath, in acrylic acid aqueous solution, add sodium hydroxide, stir, then non-ionic type polyamino acid double-bond functionalized for linking agent is added in solution, stir, by ammonium persulphate and N, N, N, N-Tetramethyl Ethylene Diamine is added in mixed solution respectively, after stirring, mixed solution is poured in the middle of mould, react 2 hours at 25 DEG C.
Described acrylic acid solution is made up of 5g vinylformic acid and 20ml deionized water, and through purifying before described vinylformic acid uses, described alkali is oxyhydroxide, and preferred as one, described alkali is sodium hydroxide.
As preferably, in step (1), the mol ratio of described γ-phenmethyl-Pidolidone benzyl ester and triphosgene is 1:(0.30-0.50).
As preferably, the solvent of step (1) described reaction is tetrahydrofuran (THF), ethyl acetate or methylene dichloride; The temperature of described reaction is 35-55 DEG C; Reaction times is 4-6 hour.
As preferably, in step (2), the initiator of ring-opening polymerization is primary amine, secondary amine, tertiary amine or hmds, and the solvent of ring-opening polymerization is dimethyl formamide, N,N-DIMETHYLACETAMIDE, tetrahydrofuran (THF) or dioxane.
As preferably, in step (2) ring-opening polymerization, the mol ratio of initiator and N-carboxyl-ring inner-acid anhydride compound is 1:50-200.
As preferably, in step (2), the temperature of ring-opening polymerization is 20-50 DEG C, and the time of ring-opening polymerization is 24-36 hour.
As preferably, in above-mentioned preparation method, step (3) described poly-(γ-phenmethyl-Pidolidone benzyl ester) can be 1:(10-30 with the mol ratio of 3-aminopropanol), the temperature of reaction of step (3) is 50-80 DEG C, and the reaction times is 12-36 hour.
As preferably, step (4) anti-solvent-applied is tetrahydrofuran (THF) or methylene dichloride; Temperature of reaction is-5-5 DEG C; Reaction times is 2-5 hour; Poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) with acrylate chloride mole amount than for 1:(0.2-2).
The raw material sources of preparation method provided by the invention are extensive, and can obtain from existing commercial sources, with low cost, synthetic method is simple; Double bond is incorporated in α helix poly amino acid molecular, the synergy of many hydrogen bonds makes this supermolecular mechanism power should not be underestimated, when not destroying its covalent linkage, and stretching α helical polypeptide, its hydrogen bond has reversibility, can be used for the recoverable hydrogel of preparation high strength.Polyamino acid is the polymkeric substance with good biocompatibility, adopts the hydrogel of this materials synthesis, and its biocompatibility is significantly increased compared to single-component polyacrylic acid hydrogel, can as bio-tissue engineering and renovating bracket material etc.
The present invention compared with prior art, beneficial effect is: the macromolecules cross-linking agent that the present invention prepares is the agent of polyamino acid non-ionic type macromolecules cross-linking, this linking agent has biocompatibility and multiple hydrogen bonding, the mechanical strength of hydrogel can be strengthened in for the preparation of hydrogel process, improve the toughness of hydrogel, thus make the hydrogel utilizing this linking agent to prepare can be applied to biologic strut system field better.
Accompanying drawing explanation
Fig. 1 is polyamino acid non-ionic type macromolecules cross-linking agent shown in embodiment 1 Chinese style (II)
1hNMR spectrogram;
Fig. 2 is the circular dichroism spectrogram of embodiment 1;
Fig. 3 is the circular dichroism spectrogram of embodiment 2;
Fig. 4 is the circular dichroism spectrogram of embodiment 3.
Embodiment
Below by specific embodiment, explanation is further described to technical scheme of the present invention.
If without specified otherwise, the raw material adopted in embodiments of the invention is the conventional raw material in this area, and the method adopted in embodiment, is the ordinary method of this area.
Embodiment 1:
The preparation of polyamino acid non-ionic type macromolecules cross-linking agent shown in formula (II)
(1) join in 200mL tetrahydrofuran (THF) by 10.00g γ-phenmethyl-Pidolidone and triphosgene, γ-phenmethyl-Pidolidone benzyl ester is 1:0.33 with the molfraction ratio of triphosgene, stirring heating 4 hours at 55 DEG C.After reaction terminates, thick product is obtained N-carboxyl-ring inner-acid anhydride compound (NCA) by recrystallization purifying.
(2) be dissolved in dimethyl formamide by 7.00gN-carboxyl-ring inner-acid anhydride compound and normal hexyl Amine, the molfraction of initiator and described N-carboxyl-ring inner-acid anhydride compound is than being 1:50, and 30 DEG C, under protection of inert gas condition, are reacted 36 hours.After reaction terminates, by solution decompression distillation except desolventizing, then precipitated in ether by the solution after concentrated, vacuum drying obtains white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) (PBLG).
(3) 4.00g white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) is dissolved in 3-aminopropanol, white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) is 1:20 with the molfraction ratio of 3-aminopropanol, under 60 DEG C of conditions, react 18 hours.After reaction terminates, added by solution in ether, precipitation also centrifugation obtains solid, and vacuum drying obtains white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) (PHPG) _.
(4) by 2.30g white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) be dissolved in methylene dichloride, in ice-water bath, drip acrylate chloride, white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) compare for 1:0.2 with the molfraction of acrylate chloride, room temperature reaction is 3 hours.After reaction terminates, by underpressure distillation except desolventizing, then precipitate in ether, centrifugation vacuum-drying obtains white solid is the agent of polyamino acid non-ionic type macromolecules cross-linking.
Nucleus magnetic hydrogen spectrum (as shown in Figure 1)
1hNMR (400MHz, DMSO): δ 4.76-4.59 (br, 1H), 4.46-4.23 (br, 2H), 4.01-3.87 (br, 4H), 3.87-3.76 (br, 2H), 3.62-3.50 (br, 3H), 2.73-2.47 (br, 2H), 2.31-1.95 (br, 2H), 1.70-1.51 (br, 3H), 1.30-1.18 (br, 8H), 0.94-0.71 (br, 2H).
1hNMR spectrogram proved response product is polyamino acid non-ionic type macromolecules cross-linking of the present invention agent, show that its polymerization degree is 50 according to nucleus magnetic hydrogen spectrum.
As shown in Figure 2, circular dichroism spectrum characterizes itself 208nm and 222nm place two obvious negative peaks, illustrates that its secondary structure is α spiral.
Embodiment 2:
The preparation of polyamino acid non-ionic type macromolecules cross-linking agent shown in formula (III)
(1) join in 200mL tetrahydrofuran (THF) by 10.00g γ-phenmethyl-Pidolidone and triphosgene, γ-phenmethyl-Pidolidone benzyl ester is 1:0.40 with the molfraction ratio of triphosgene, stirring heating 5 hours at 45 DEG C.After reaction terminates, with Rotary Evaporators except desolventizing, thick product is obtained N-carboxyl-ring inner-acid anhydride compound (NCA) by recrystallization purifying.
(2) be dissolved in dimethyl formamide by 7.00gN-carboxyl-ring inner-acid anhydride compound and normal hexyl Amine, the molfraction of initiator and described N-carboxyl-ring inner-acid anhydride compound is than being 1:100, and 50 DEG C, under protection of inert gas condition, are reacted 24 hours.After reaction terminates, by solution decompression distillation except desolventizing, then precipitated in poor solvent ether by the solution after concentrated, obtain white solid by centrifugation, vacuum drying obtains final product white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) (PBLG).
(3) 4.00g white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) is dissolved in 3-aminopropanol, white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) is 1:10 with the molfraction ratio of 3-aminopropanol, under 60 DEG C of conditions, react 18 hours.After reaction terminates, added by solution in ether, precipitation also centrifugation obtains solid, and vacuum drying obtains white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) (PHPG).
(4) by 2.30g white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) be dissolved in methylene dichloride, in ice-water bath, drip acrylate chloride, white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) compare for 1:0.5 with the molfraction of acrylate chloride, room temperature reaction is 3 hours.After reaction terminates, by underpressure distillation except desolventizing, then precipitate in ether, centrifugation vacuum-drying obtains white solid is the agent of polyamino acid non-ionic type macromolecules cross-linking.As shown in Figure 3, circular dichroism spectrum characterizes itself 208nm and 222nm place two obvious negative peaks, illustrates that its secondary structure is α spiral.
Embodiment 3:
The preparation of polyamino acid non-ionic type macromolecules cross-linking agent shown in formula (IV)
(1) join in 200mL tetrahydrofuran (THF) by 10.00g γ-phenmethyl-Pidolidone and triphosgene, γ-phenmethyl-Pidolidone benzyl ester is 1:0.48 with the molfraction ratio of triphosgene, stirring heating 6 hours at 35 DEG C.After reaction terminates, with Rotary Evaporators except desolventizing, thick product is obtained N-carboxyl-ring inner-acid anhydride compound (NCA) by recrystallization purifying.
(2) be dissolved in dimethyl formamide by 7.00gN-carboxyl-ring inner-acid anhydride compound and normal hexyl Amine, the molfraction of initiator and described N-carboxyl-ring inner-acid anhydride compound is than being 1:200, and 50 DEG C, under protection of inert gas condition, are reacted 36 hours.After reaction terminates, by solution decompression distillation except desolventizing, then precipitated in poor solvent ether by the solution after concentrated, obtain white solid by centrifugation, vacuum drying obtains final product white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) (PBLG).
(3) 4.00g white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) is dissolved in 3-aminopropanol, white solid-poly-(γ-phenmethyl-Pidolidone benzyl ester) is 1:30 with the molfraction ratio of 3-aminopropanol, under 60 DEG C of conditions, react 18 hours.After reaction terminates, added by solution in ether, precipitation also centrifugation obtains solid, and vacuum drying obtains white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) (PHPG).
(4) by 2.30g white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) be dissolved in methylene dichloride, in ice-water bath, drip acrylate chloride, white solid-poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate) compare for 1:0.5 with the molfraction of acrylate chloride, room temperature reaction is 3 hours.After reaction terminates, by underpressure distillation except desolventizing, then precipitate in ether, centrifugation vacuum-drying obtains white solid is the agent of polyamino acid non-ionic type macromolecules cross-linking.As shown in Figure 4, circular dichroism spectrum characterizes itself 208nm and 222nm place two obvious negative peaks, illustrates that its secondary structure is α spiral.
By embodiment 1 gained polyamino acid non-ionic type macromolecules cross-linking agent (0.277g) under ice-water bath condition, join in 5.00g sodium acrylate and 20mL water mixed liquid, then 0.50g ammonium persulphate is added, then 300uLN is added fast, N, N, N-Tetramethyl Ethylene Diamine, mix, pour in silica gel piece mould, react 2 hours at 25 DEG C.Tension test finds that the rupture stress of hydrogel and elongation at break reach 0.20MPa and 3000% respectively, has good toughness.After stretching through three times, its tensile strength still has 91% of original value, illustrates that the mechanical property of gel has reversibility.
Meanwhile, in order to contrast, under ice-water bath condition, to in 5.00g vinylformic acid and 20mL water mixed liquid, add 2.08g sodium hydroxide, then add 0.050gN, N '-methylene-bisacrylamide, 0.50g ammonium persulphate, adds 300uLN fast, N, N, N-Tetramethyl Ethylene Diamine, mixes, pour in silica gel piece mould, react 2 hours at 25 DEG C.The rupture stress of hydrogel and elongation at break are respectively 0.22MPa and 150%.After one-off drawing, gel fracture cannot be replied.
Claims (10)
1. a polyamino acid non-ionic type macromolecules cross-linking agent, is characterized in that, its structural formula is as follows:
Wherein: n is the integer of 30-500.
2. a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 1 agent, is characterized in that, x and y is respectively the ratio of repeating unit in random copolymers, x+y=1.
3. the preparation method of a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 1 agent, is characterized in that, comprise the following steps:
(1) adopt γ-phenmethyl-Pidolidone benzyl ester and triphosgene to react, obtain N-carboxyl-ring inner-acid anhydride compound;
(2) under initiator effect, described N-carboxyl-ring inner-acid anhydride compound carries out ring-opening polymerization, is gathered (γ-phenmethyl-Pidolidone benzyl ester);
(3) by described poly-(γ-phenmethyl-Pidolidone benzyl ester) and 3-aminopropanol generation ammonolysis reaction, (nitrogen is gathered
5-(3-hydroxypropyl) L-glutaminate;
(4) by described poly-(nitrogen
5-(3-hydroxypropyl) L-glutaminate and acrylate chloride react, and obtain the agent of polyamino acid non-ionic type macromolecules cross-linking.
4. the preparation method of a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 3 agent, is characterized in that, in step (1), the mol ratio of described γ-phenmethyl-Pidolidone benzyl ester and triphosgene is 1:0.30-0.50.
5. the preparation method of a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 3 agent, is characterized in that, the solvent of step (1) described reaction is tetrahydrofuran (THF), ethyl acetate or methylene dichloride; The temperature of described reaction is 35-55 DEG C; Reaction times is 4-6 hour.
6. the preparation method of a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 3 agent, it is characterized in that, in step (2), the initiator of ring-opening polymerization is primary amine, secondary amine, tertiary amine or hmds, and the solvent of ring-opening polymerization is dimethyl formamide, N,N-DIMETHYLACETAMIDE, tetrahydrofuran (THF) or dioxane.
7. the preparation method of a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 3 agent, is characterized in that, in step (2) ring-opening polymerization, the mol ratio of initiator and N-carboxyl-ring inner-acid anhydride compound is 1:50-200.
8. the preparation method of a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 3 agent, is characterized in that, in step (2), the temperature of ring-opening polymerization is 20-50 DEG C, and the time of ring-opening polymerization is 24-36 hour.
9. the preparation method of a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 3 agent, it is characterized in that, in above-mentioned preparation method, the mol ratio of the described poly-γ-phenmethyl-Pidolidone benzyl ester of step (3) and 3-aminopropanol can be 1:(10-30), the temperature of reaction of step (3) is 50-80 DEG C, and the reaction times is 12-36 hour.
10. the preparation method of a kind of polyamino acid non-ionic type macromolecules cross-linking according to claim 3 agent, is characterized in that, step (4) anti-solvent-applied is tetrahydrofuran (THF) or methylene dichloride; Temperature of reaction is-5-5 DEG C; Reaction times is 2-5 hour; Poly-(nitrogen 5-(3-hydroxypropyl) L-glutaminate and acrylate chloride mole amount than being 1:0.2-2.
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| EP0167828A1 (en) * | 1984-06-11 | 1986-01-15 | Koken Co. Ltd. | A man-made skin composed of two layers:Collagen and a poly-alpha-amino acid |
| CN102652835A (en) * | 2010-12-10 | 2012-09-05 | 邹长坪 | Sustained-release polymer retinoic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0167828A1 (en) * | 1984-06-11 | 1986-01-15 | Koken Co. Ltd. | A man-made skin composed of two layers:Collagen and a poly-alpha-amino acid |
| CN102652835A (en) * | 2010-12-10 | 2012-09-05 | 邹长坪 | Sustained-release polymer retinoic acid |
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| NOAH LOTAN ET AL.: ""Helix—Coil Transition of Poly-N5-(3-hydroxypropyl)-L-glutamine: Thermodynamic and Statistical Analysis"", 《BIOPOLYMERS》 * |
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| WO2019238090A1 (en) * | 2018-06-14 | 2019-12-19 | 华东理工大学 | Strong base-initiated n-carboxyanhydride rapid ring-opening polymerisation method |
| US11905369B2 (en) | 2018-06-14 | 2024-02-20 | East China University Of Science And Technology | Strong base-initiated N-carboxyanhydride rapid ring-opening polymerization method |
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