CN1379053A - Tree-type high-molecular polyamide-amine compound and its preparing process and application - Google Patents
Tree-type high-molecular polyamide-amine compound and its preparing process and application Download PDFInfo
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Abstract
A tree-type polyamide-amine material series includes G1.5, G2.0, G2.5, G3.5...G8.0 three-type high-molecular materials. The above-mentioned half generation tree-type polyamid-amine material is prepared through Michael addition reaction of integer generation one on methyl acrylate under the catalysis of sodium methoxide. The above-mentioned integer generation tree-type polyamide-amine material is prepared through amidation reaction of half generation one on ethanediamine. Its advantages are biodegradability and low poison. It can be used as gene transfer carrier and release controlling carrier of medicine.
Description
Technical field
The present invention relates to a kind of tree-type high-molecular polyamide-amine compound and its production and use.
Background technology
Tree type polymer is a class novel high polymer, has definite structure, high branch degree, monodispersity, profile is spherical, and molecular surface can have a large amount of functional groups and High Density Charge, can be combined into mixture by electrostatic interaction with dna molecular, enter cell (Jonathan.D.Eichman by pinosome again, et al, PSTT, 2000,3 (7), 232-245).Its another attracting characteristic can form master-object (host-guest) composite structure with small molecules exactly, can hold small molecules in the inner chamber of tree type molecule.So just can control molecular size and surface tissue by molecular designing, thereby research tree type molecule and gene, medicine bonded mechanism, exploitation tree type molecular gene transfer vector, tree type molecular medicine carrier (Renxi Zhuo, Bo Du, et al, Journal of Controlled Release, 1999,57,249-257).Tree type molecule also can be used for aspect (a:K.Inoue such as nano-catalytic, little reaction carriers, bunch shape macromole simulation, magnetic resonance imaging contrast, chemical sensor, information media material, immunodiagnosis, Progress in Polymer Science, 2000,25 (4), 453-571; B:F.V gtle, S.Gestermann, et al, Progress in Polymer Science, 2000,25 (7), 987-1041).Problem is, the biodegradability that existing tree type polymer has is relatively poor, and the toxicity that has is higher and limit its application.
Summary of the invention
The present invention provides a kind of polymeric amide-amine tree-type polymer at the problems referred to above exactly, this polymer high-efficiency low-toxicity and have biodegradability preferably.The inventor is a nuclear with the 1,3,5-Benzenetricarboxylic acid, by esterification, has prepared half for tree G0.5, then by Michael addition and amidated reaction repeated process, synthesizes the polymeric amide-amine tree-type polymer of different algebraically.
Technical scheme provided by the invention is: a kind of tree-type high-molecular polyamide-amine compound, they be following be the three-way type tree-type high-molecular polyamide-amine compound of nuclear with the 1,3,5-Benzenetricarboxylic acid: 1.5 generation tree type polymers (G1.5), 2.0 generation tree type polymers (G2.0), 2.5 generation tree type polymers (G2.5), 3.0 generation tree type polymers (G3.0) ..., 8.0 generation tree type polymers (G8.0); Wherein, the high molecular structural formula of 1.5 generation tree types
2.0 structural formula for tree type polymer (G2.0)
2.5 structural formula for tree type polymer (G2.5)
And the like can to draw follow-up half and half generation and each whole for tree type macromolecular structure formula, up to 8.0 generation tree type macromolecular structure formula, promptly use-CH
2CH
2COOCH
3Substitute whole for tree type polymer branch end-NH
2On-H is follow-up partly for tree type polymer, usefulness-NHCH
2CH
2NH
2Substitute half on the tree type polymer branch end-OCH
3Be follow-up whole for tree type polymer.
The preparation method of above-mentioned tree-type high-molecular polyamide-amine compound, with 0.5 generation the intermolecular benzene tricarboxylic acid trimethyl of (G0.5) tree type and excessive quadrol make 1.0 generations (G1.0) tree type polymer through amidate action; 1.5 generation (G1.5) tree type polymer by 1.0 generation tree type polymer under the katalysis of sodium methylate, carry out the Michael addition reaction with excessive methyl acrylate and prepare; 2.0 generation (G2.0) tree type polymer by 1.5 generation tree type polymer and excessive quadrol make through amidate action; 7.5 generation (G7.5) tree type polymer by 7.0 generations (G7.0) tree type polymer under the katalysis of sodium methylate, carry out the Michael addition reaction with excessive methyl acrylate and prepare; 8.0 generation (G8.0) tree type polymer by 7.5 generation tree type polymer and excessive quadrol make through amidate action.
The Michael addition reaction in the amidate action in above-mentioned whole generation and half generation is all carried out under 0～50 ℃, nitrogen protection.
Above-mentioned amidate action and Michael addition reaction are all carried out in methyl alcohol.
In the amidate action in above-mentioned whole generation, the quadrol consumption be half generation tree type high molecular weight reactive beyond the region of objective existence enclose the ester group mole number 50-100 doubly, to stop quadrol molecule and second ester group reaction generation intramolecularly or intermolecular bridge crosslinking structure.
In the Michael in above-mentioned half generation addition reaction, the consumption of methyl acrylate is for putting in order for tree type high molecular weight reactive thing branch end-NH
2On-1.1～1.5 times of the H mole number (or being whole 2.2～3.0 times of enclosing amino mole number for tree type high molecular weight reactive beyond the region of objective existence).
Before the Michael addition reaction of carrying out above-mentioned half generation, to put in order earlier for tree type high molecular weight reactive thing 10ml anhydrous methanol, 100ml dry toluene (anhydrous methanol: dry toluene=1: 10, v/v) soak, again 30 ℃, vacuum tightness be under the 1mmHg evaporated under reduced pressure to remove the quadrol in the reactant.Because of all use excessive quadrol when the amidate action preparation is put in order for tree type polymer, removing quadrol is an important assurance guaranteeing tree type molecule regularity.The quadrol that remains in the tree type molecule will become new initiated core in subsequently synthetic, the methyl acrylate that participates in reaction can react with these quadrols and generate the tree type molecule of different IPs.These tree type molecules are because extent of reaction is different with reaction ratio, thereby resulting molecular conformation also can be different, causes the molecular weight distribution of synthetic tree type molecule to be widened, and destroy the regularity of product.
In the amidate action in above-mentioned whole generation, will partly slowly be added drop-wise in the quadrol,, avoid intramolecularly or intermolecular bridge crosslinking structure to guarantee that quadrol is all excessive in a large number at any time for tree type high molecular weight reactive thing.
Above-mentioned tree-type high-molecular polyamide-amine compound can be used as gene transfer vector, and biodegradable medicine sustained release carrier.
Polymeric amide of the present invention-amine tree-type polymer is to be the three-way type tree-type high-molecular polyamide-amine compound of nuclear with the 1,3,5-Benzenetricarboxylic acid, has the advantage of biodegradable, high-efficiency low-toxicity.Synthetic respectively can be used as the gene transfection carrier for tree type molecule and carries out the gene transfection experiment, recently change gene transfection efficient and cytotoxicity by the electric charge that changes tree type molecular conecentration, algebraically and tree type molecule and DNA formation mixture, and can carry out chemically modified to tree type molecular vehicle, thereby strengthen the carrier target, reduce cytotoxicity, improve transfection efficiency.Selecting 1,3,5-Benzenetricarboxylic acid is in order to divide the period of the day from 11 p.m. to 1 a.m to keep plane Y shape structure for the tree type low, to reach the purpose of simulated virus for nuclear.
Description of drawings
Fig. 1 is the present invention the 4th generation (G4.0) tree-type high-molecular polyamide-amine compound structural formula;
Fig. 2 is the sem photograph of the morphological analysis of the present invention the 8th generation (G8.0) product;
Fig. 3 for the present invention fourth, fifth, six, seven, eight generation tree-type high-molecular polyamide-amine compound the cytotoxicity experiment result, used cell is the HeLa cell.
Embodiment
In order to obtain with the 1,3,5-Benzenetricarboxylic acid being the tree-type high-molecular polyamide-amine compound of nuclear, the inventor has designed 1,3,5-Benzenetricarboxylic acid has been carried out esterification, carries out the technological line of Michael addition and amidated reaction repeated then, and synthetic route is as follows:
The 1,3,5-Benzenetricarboxylic acid trimethyl is prepared through esterification by 1,3,5-Benzenetricarboxylic acid and methyl alcohol, and its fusing point and document (Reynold C.Fuson, C.H.Mc Keever, J.A.C.S., 1940,60,2090) report conforms to.
The G1.0 product is prepared through amidate action by G0.5 product and a large amount of excessive quadrol.(Raif?Wrl?and?HubertKster，Tetrahedron，1999，55，2951)
The G1.5 product under the katalysis of sodium methylate, carries out Michael addition reaction preparation by G1.0 product and a small amount of excessive methyl acrylate in methanol solution.
Above-mentioned half obtains whole for product for product and a large amount of excessive quadrol through amidate action, obtain half for product and put in order through the Michael addition reaction, so repeat to obtain the polymeric amide-amine tree-type polymer of G0.5 to 16 different algebraically such as G8.0 for product and a small amount of excessive methyl acrylate.
The used organic solvent of above-mentioned preparation method is preferably methyl alcohol.Used quadrol CaH
2Steam after refluxing, methyl acrylate is attached most importance to and was steamed reagent, and methyl alcohol steams after magnesium chips refluxes, and toluene steams after the sodium silk refluxes.
The experiment of the vitro cytotoxicity of above-mentioned G4.0 (its structural formula is seen Fig. 1)-G8.0 product be reference literature (N.Malik, etal, Journal of Controlled Release, 2000,65,133-148) carry out.
The present invention is from 1,3,5-Benzenetricarboxylic acid, and having designed and synthesized is the three-way type polymeric amide-amine tree-type polymer of nuclear with the 1,3,5-Benzenetricarboxylic acid.The structure of compound is through infrared spectra (FT-IR) (seeing Table one), proton NMR spectrum (
1H NMR) (see Table two), (seeing Table three) confirmed in ultimate analysis (EA).Each is measured by gel chromatography (GPC) for weight-average molecular weight, number-average molecular weight and the polydispersity index of product, and eluting solvent is 0.1M potassium dihydrogen phosphate buffer solution (seeing Table four).Each morphological analysis and size distribution for product obtain (see figure 2) by the scanning electron microscope experiment.Synthetic respectively can be used as the gene transfection carrier for tree type molecule and carries out the gene transfection experiment, recently change gene transfection efficient and cytotoxicity by the electric charge that changes tree type molecular conecentration, algebraically and tree type molecule and DNA formation mixture, and can carry out chemically modified to tree type molecular vehicle, thereby strengthen the carrier target, reduce cytotoxicity, improve transfection efficiency.
Table one: infrared result
Generation IR
G0.5 V
C＝O1731cm
-1；V
C-O-C1274cm
-1，1249cm
-1
G1.0 V
NH23414cm
-1；V
C＝O1655cm
-1
G1.5 V
NH3291cm
-1；V
C＝O1667cm
-1，1733cm
-1；V
C-O-C1203cm
-1，1262cm
-1
G2.0 V
NH3283cm
-1；V
C＝O1652cm
-1
G2.5 V
NH3306cm
-1；V
C＝O1658cm
-1，1737cm
-1；V
C-O-C1261cm
-1
G3.0 V
NH23402cm
-1；V
NH3307cm
-1；V
C＝O1652cm
-1
G3.5 V
NH3368cm
-1；V
C＝O1646cm
-1，1734cm
-1；V
C-O-C1267cm
-1
G4.0 V
NH3291cm
-1；V
C＝O1657cm
-1
G4.5 V
NH3291cm
-1；V
C＝O1658cm
-1，1738cm
-1；V
C-O-C1260cm
-1
G5.0 V
NH23400cm
-1；V
NH3281cm
-1；V
C＝O1646cm
-1
G5.5 V
NH3304cm
-1；V
C＝O1646cm
-1，1734cm
-1；V
C-O-C1260cm
-1
G6.0 V
NH3282cm
-1；V
C＝O1644cm
-1
G6.5 V
NH3307cm
-1；V
C＝O1647cm
-1，1734cm
-1；V
C-O-C1260cm
-1
G7.0 V
NH3301cm
-1；V
C＝O1645cm
-1
G7.5 V
NH3307cm
-1；V
C＝O1658cm
-1，1733cm
-1；V
C-O-C1261cm
-1
G8.0 V
NH3275cm
-1V
C=O1638cm
-1Table two: (ppm, whole be DMSO-d for the product solvent to the nuclear-magnetism result
6, be CDCl partly for the product solvent
3) Generation H
Ar-CONHCH
2--CONHCH
2--OCH
3All the other-CH
2-0.5 8.8 (s, 3H) 3.9 (s, 9H) 1.0 8.4 (s, 3H) 8.6 (t, 3H) 3.3 (t, 6H) 2.7 (t, 6H) 1.5 8.4 (s, 3H) 7.4 (t, 3H) 2.9 (m, 6H) 3.6 (s, 18H) 2.3-2.8 (m, 30H) 2.0 8.4 (s, 3H) 7.9-8.6 (t, 9H), 3.0-3.4 (t, 18H) 2.2-3.0 (m, 42H) 2.5 8.5 (s, 3H) 7.0-7.9 (t, 9H) 3.1-3.5 (m, 18H) 3.7 (s, 36H) 2.4-2.9 (m, 90H) 3.0 8.4 (s, 3H) 7.9-8.8 (t, 21H) 3.1-3.4 (t, 42H) 2.2-3.0 (m, 114H) 3.5 8.4 (s, 3H) 7.1-8.2 (m, 21H) 3.2-3.5 (m, 42H) 3.7 (s, 72H) 2.1-2.9 (m, 210H) 4.0 8.4 (s, 3H) 7.9 (m, 45H) 3.0-3.3 (t, 90H) 2.2-2.7 (m, 258H) 4.5 8.5 (s, 3H) 7.1-7.8 (m, 45H) 3.3-3.5 (m, 90H) 3.7 (s, 144H) 2.2-2.9 (m, 450H) 5.0 8.4 (s, 3H) 7.9 (m, 93H) 3.0-3.2 (t, 186H) 2.2-2.8 (m, 546H) 5.5 7.2 (m, 93H) 3.3-3.5 (m, 186H) 3.7 (s, 288H) 2.3-2.8 (m, 930H) 6.0 7.9-8.2 (m, 172H) 3.0-3.2 (m, 344H) 2.2-2.7 (m, 1163H) 6.5 7.2-7.4 (m, 175H) 3.2-3.5 (m, 366H) 3.7 (s, 576H) 2.3-2.8 (m, 2017H) 7.0 7.8-8.6 (m, 381H) 3.0-3.4 (m, 762H) 2.2-2.9 (m, 2027H) 7.5 7.2-7.8 (m, 371H) 3.2-3.5 (m, 762H) 3.7 (s, 1152H) 2.3-2.8 (m, 4089H) 8.0 7.6-8.2 (m, 765H) 3.0-3.2 (m, 1530H) 2.2-2.7 (m, 4590H) notes: along with algebraically increases, the peak of benzene ring hydrogen on spectrogram is more and more littler, disappears at last.
Table three: results of elemental analyses
N％ N％ C％ C％ H％ H％Generation M
w
(Calc.) (Found) (Calc.) (Found) (Calc.) (Found)
0.5 252.24 0 0 57.14 58.37 4.80 5.57
1.0 336.45 24.98 21.99 53.54 52.17 7.20 9.77
1.5 853.05 9.85 10.76 54.91 57.82 7.10 13.17
2.0 1021.47 24.69 22.93 52.91 53.46 8.31 14.52
2.5 2054.67 12.27 12.47 54.36 62.61 7.67 7.30
3.0 2391.51 24.60 24.37 52.73 52.88 8.62 18.94
3.5 4457.91 13.20 12.46 54.15 54.90 7.88 5.07
4.0 5131.59 24.57 20.95 52.66 49.25 8.74 6.55
4.5 9264.39 13.61 13.88 54.06 54.15 7.98 12.68
5.0 10611.75 24.56 22.38 52.63 52.17 8.79 16.23
5.5 18877.35 13.80 13.95 54.01 54.98 8.03 13.65
6.0 21572.07 24.55 23.38 52.61 52.82 8.82 13.70
6.5 38103.27 13.90 14.39 53.99 54.22 8.05 15.00
7.0 43492.71 24.55 23.89 52.60 49.94 8.83 14.02
7.5 76555.11 13.95 13.63 53.98 53.39 8.06 13.15
8.0 87333.99 24.54 23.73 52.60 53.15 8.84 13.99 annotate: H% (Found) is higher to be because the sample moisture absorption very easily.
Table four: GPC result's (eluting solvent is the 0.1M potassium dihydrogen phosphate buffer solution)
G1.0 G2.0 G3.0 G4.0 G5.0 G6.0 G7.0 G8.0
M
n 800 1970 3164 5081 8774 11012 11655 12051
M
w 804 2015 3318 5694 9101 11635 13374 15441
d 1.005 1.023 1.049 1.121 1.037 1.057 1.148 1.281
G1.5 G2.5 G3.5 G4.5 G5.5 G6.5 G7.5
M
n 664 1285 2504 5270 8289 11541 16600
M
w 672 1344 2711 5607 8527 11905 19260
d 1.013 1.046 1.083 1.064 1.029 1.031 1.160
Below in conjunction with specific examples technical scheme of the present invention is further described:
The preparation of embodiment one, 1,3,5-Benzenetricarboxylic acid trimethyl G0.5: the 1,3,5-Benzenetricarboxylic acid crystal (376 ℃ of fusing points) with 2.8 gram water recrystallizations are crossed adds the 26ml anhydrous methanol, the dense H of 0.5ml
2SO
4, refluxed 2 hours, steam wherein 2/3 methyl alcohol.The methyl alcohol anhydrous K that steams
2CO
3Dry.Dried methyl alcohol is annotated back reaction flask again, refluxes 2 hours.Three times so repeatedly.When reaction mixture cools off, there are a large amount of white crystals to occur.The crystal that filters out is dissolved in the 30ml ether, filters, and filtrate is injected in the 30ml water, uses the 105ml extracted with diethyl ether again.Diethyl ether solution merges, with 100 milliliters of 10%KHCO
3Solution thoroughly washs 2 times, washes the anhydrous MgSO of the ether layer of telling again with water 2 times
4Dry.Dried diethyl ether solution filters, and filtrate decompression is drained ether, the white needle-like crystals that obtains anhydrous methanol recrystallization.Get 2.4 gram white needle-like crystals and be 1,3,5-Benzenetricarboxylic acid trimethyl (G0.5).Fusing point 144-145 ℃, productive rate 71.4%.
The preparation of embodiment two, above-mentioned G1.0: heat is dissolved in 1.4 gram G0.5 in the 70ml anhydrous methanol a little, places dropping funnel, under ice bath, nitrogen protection, induction stirring, slowly splashes in the 75ml anhydrous ethylenediamine, and lucifuge stirred 72 hours under the room temperature.30 ℃ of following pressure reducing and steaming methyl alcohol of water pump and a small amount of quadrol are the excessive quadrol of pressure reducing and steaming under the 1mmHg at 30 ℃, vacuum tightness then.The yellow oil that obtains is dissolved in the 10ml anhydrous methanol, adds the 100ml dry toluene again, and decompression steams methyl alcohol and toluene then.Three times so repeatedly, get white powder 1.6 grams and be the G1.0 product.Productive rate 85.6%.
Embodiment three, above-mentioned half preparation for product: the methanol solution that will put in order for product places three mouthfuls of round-bottomed flasks; under ice bath, nitrogen protection, induction stirring; slowly splash into mole number with syringe and be whole methyl acrylate for 2.4 times of the peripheral amido mole numbers of product; splash into the methanol solution of the sodium methylate of catalytic amount then with syringe, at room temperature lucifuge stirred 72 hours.30 ℃ of following pressure reducing and steaming methyl alcohol of water pump and excessive propene acid methyl esters with the small amount of methanol dissolving, add ether, and inclining supernatant liquid.Repeat for several times, decompressing and extracting gets yellow thick thing and is required half for tree-type high-molecular polyamide-amine compound.Productive rate is about 94%.
Embodiment four, above-mentioned whole preparation: half methanol solution for product is placed a dropping funnel for product; under ice bath, nitrogen protection, induction stirring; slowly splash in a large amount of excessive anhydrous ethylenediamines (quadrol mole number be half for the 50-100 of the peripheral ester group mole number of product doubly), lucifuge stirred 72 hours under the room temperature.30 ℃ of following pressure reducing and steaming methyl alcohol of water pump and a small amount of quadrol, under 30 ℃, vacuum tightness is to remove excessive quadrol under the 1mmHg under reduced pressure then.The yellow thick thing 10ml anhydrous methanol that obtains, the 100ml dry toluene soaks, then at 30 ℃ of following evaporated under reduced pressure methyl alcohol and toluene.Repeat so more once, get yellow thick thing after draining and be required whole for tree-type high-molecular polyamide-amine compound.Productive rate is about 98%.
Embodiment five, above-mentioned each vitro cytotoxicity for tree type molecule: cultivate the HeLa cell in the 96 porocyte culture plates that contain 100 μ l nutrient solutions, cell concn is 20000/hole, places 37 ℃, 5%CO
2Cultivated 24 hours in the moist incubator.Get each 10 milligrams of above-mentioned tree type molecule G4.0-G8.0, be dissolved in respectively in 5 milliliters of nutrient solutions, ultra-fine filter filtration sterilization with 0.45 μ m, be diluted to different concns (0.001mg/ml-2mg/ml) with nutrient solution then, join in the cell of having cultivated one day and (make negative control and blank simultaneously), continue to cultivate 48 hours.When being cultured to 44 hours, every hole adds tetramethyl-azo azoles salt (MTT) solution (5mg/ml) 20 μ l, places 37 ℃, 5%CO
2Cultivated last 4 hours in the moist incubator.Inclining then supernatant liquid, and every hole adds 100 μ l DMSO.On Bio-Rad 550 microplate reader, read 570nm place light absorption value.The high molecular cytotoxicity of tree type is represented with the cell survival rate (Viability) of HeLa cell:
Viability(％)＝(A
test-A
0)/(A
control-A
0)×100％
A
TestBe the light absorption value of being surveyed under the difference tree type molecular conecentration, A
0Be the light absorption value that blank is surveyed, A
ControlThe light absorption value that negative contrast is surveyed.The result as shown in Figure 3, wherein X-coordinate is tree type polymer concentration (Dendrimerconcentration, mg/ml), ordinate zou is cell survival rate (Cell viability, %control), Fig. 3 center line 1,2,3,4 is respectively the concentration-cell survival rate relation curve of G4.0, G5.0, G6.0, G7.0, G8.0 tree-type high-molecular polyamide-amine compound.
Claims (9)
1. tree-type high-molecular polyamide-amine compound, they be following be the three-way type tree-type high-molecular polyamide-amine compound of nuclear with the 1,3,5-Benzenetricarboxylic acid: 1.5 generation tree type polymer, 2.0 generation tree type polymer, 2.5 generation tree type polymer, 3.0 generation tree type polymer ... 7.5 for tree type polymer, 8.0 generation tree type polymer; Wherein,
1.5 be for the high molecular structural formula of tree type
2.0 be for the high molecular structural formula of tree type
2.5 be for the high molecular structural formula of tree type
The rest may be inferred, and can to draw follow-up half and half generation and each whole for tree type macromolecular structure formula, up to the high molecular structural formula of 8.0 generation tree types, promptly uses-CH
2CH
2COOCH
3Substitute whole for tree type polymer branch end-NH
2On-H is later half generation tree type polymer, usefulness-NHCH
2CH
2NH
2Substitute half on the tree type polymer branch end-OCH
3Be follow-up whole for tree type polymer.
2. the preparation method of the described tree-type high-molecular polyamide-amine compound of claim 1 is characterized in that: with the 0.5 intermolecular benzene tricarboxylic acid trimethyl of generation tree type and excessive quadrol through amidate action make 1.0 generation tree type polymer; 1.5 for tree type polymer by 1.0 generation tree type polymer and excessive methyl acrylate under the katalysis of sodium methylate, carry out Michael addition reaction preparation; 2.0 for tree type polymer by 1.5 generation tree type polymer and excessive quadrol make through amidate action; 7.5 for tree type polymer by 7.0 generation tree type polymer and excessive methyl acrylate under the katalysis of sodium methylate, carry out Michael addition reaction preparation; 8.0 for tree type polymer by 7.5 generation tree type polymer and excessive quadrol make through amidate action.
3. preparation method according to claim 2 is characterized in that: the Michael addition reaction in the amidate action in above-mentioned whole generation and half generation is all carried out under 0～50 ℃, nitrogen protection.
4. according to claim 2 or 3 described preparation methods, it is characterized in that: above-mentioned amidate action and Michael addition reaction are all carried out in methyl alcohol.
5. according to claim 2 or 3 described preparation methods, it is characterized in that: in the amidate action in above-mentioned whole generation, the quadrol consumption be half generation tree type high molecular weight reactive beyond the region of objective existence enclose the ester group mole number 50-100 doubly.
6. according to claim 2 or 3 described preparation methods, it is characterized in that: in the Michael in above-mentioned half generation addition reaction, the consumption of methyl acrylate is for putting in order for tree type high molecular weight reactive thing branch end-NH
2On-1.1～1.5 times of H mole number.
7. preparation method according to claim 6, it is characterized in that: before the Michael addition reaction of carrying out above-mentioned half generation, to put in order earlier for tree type high molecular weight reactive thing and soak with anhydrous methanol/dry toluene mixed solvent, be evaporated under reduced pressure under the 1mmHg at 30 ℃, vacuum tightness again.
8. preparation method according to claim 5 is characterized in that: will partly slowly be added drop-wise in the quadrol for tree type high molecular weight reactive thing in the amidate action in above-mentioned whole generation.
9. the described tree-type high-molecular polyamide-amine compound of claim 1 is as gene transfer vector and biodegradable medicine sustained release carrier.
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| CN103232363A (en) * | 2013-04-18 | 2013-08-07 | 西安理工大学 | Method for continuously preparing poly(amido-amine) |
| CN103242517A (en) * | 2013-05-17 | 2013-08-14 | 中国药科大学 | Preparation of multifunctional linear-dendritic segmented copolymer and application in pharmaceutics thereof |
| CN103843808A (en) * | 2012-12-05 | 2014-06-11 | 中国科学院成都有机化学有限公司 | Macromolecular guanidinium antibacterial agent with hyperbranched structure and preparation method thereof |
| CN107474245A (en) * | 2017-07-16 | 2017-12-15 | 北京化工大学 | The preparation method of crosslinked polyamide |
| CN107722261A (en) * | 2017-11-06 | 2018-02-23 | 中国石油集团川庆钻探工程有限公司 | Suitable for the preparation method of the polyamides amine inhibitors of drilling fluid |
| EP3297637A4 (en) * | 2015-05-21 | 2019-01-23 | Ohio State Innovation Foundation | Benzene-1,3,5-tricarboxamide derivatives and uses thereof |
-
2002
- 2002-04-12 CN CNB021157081A patent/CN1174023C/en not_active Expired - Fee Related
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1293144C (en) * | 2004-07-28 | 2007-01-03 | 上海师范大学 | Inorganic-organic hybridization material of dendritic polymer of hydroxy calcium phosphate/polyamide-amine |
| CN102816331A (en) * | 2012-06-20 | 2012-12-12 | 中国人民解放军第四军医大学 | Preparation method of polyamidoamine dendritic macromolecular structure modifier and application thereof |
| CN103843808A (en) * | 2012-12-05 | 2014-06-11 | 中国科学院成都有机化学有限公司 | Macromolecular guanidinium antibacterial agent with hyperbranched structure and preparation method thereof |
| CN103232363A (en) * | 2013-04-18 | 2013-08-07 | 西安理工大学 | Method for continuously preparing poly(amido-amine) |
| CN103232363B (en) * | 2013-04-18 | 2016-01-20 | 西安理工大学 | The continuous production method of polyamide-amide |
| CN103242517A (en) * | 2013-05-17 | 2013-08-14 | 中国药科大学 | Preparation of multifunctional linear-dendritic segmented copolymer and application in pharmaceutics thereof |
| EP3297637A4 (en) * | 2015-05-21 | 2019-01-23 | Ohio State Innovation Foundation | Benzene-1,3,5-tricarboxamide derivatives and uses thereof |
| US10369122B2 (en) | 2015-05-21 | 2019-08-06 | Ohio State Innovation Foundation | Benzene-1,3,5-tricarboxamide derivatives and uses thereof |
| EP3939571A1 (en) * | 2015-05-21 | 2022-01-19 | Ohio State Innovation Foundation | Benzene-1,3,5-tricarboxamide derivatives and uses thereof |
| CN107474245A (en) * | 2017-07-16 | 2017-12-15 | 北京化工大学 | The preparation method of crosslinked polyamide |
| CN107722261A (en) * | 2017-11-06 | 2018-02-23 | 中国石油集团川庆钻探工程有限公司 | Suitable for the preparation method of the polyamides amine inhibitors of drilling fluid |
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| Publication number | Publication date |
|---|---|
| CN1174023C (en) | 2004-11-03 |
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