CN101628970B - Hyperbranched polymer and preparation method and application thereof - Google Patents
Hyperbranched polymer and preparation method and application thereof Download PDFInfo
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- CN101628970B CN101628970B CN2008101166899A CN200810116689A CN101628970B CN 101628970 B CN101628970 B CN 101628970B CN 2008101166899 A CN2008101166899 A CN 2008101166899A CN 200810116689 A CN200810116689 A CN 200810116689A CN 101628970 B CN101628970 B CN 101628970B
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Abstract
The invention provides a hyperbranched polymer and a preparation method and application thereof. The polymer has a structure shown as the following formula (I), wherein n is a positive integer from 1 to 5; B is aliphatic polyester; and the molecular weight of the polymer is between 4,000 kDa and 7,000 kDa. The invention also provides the method for preparing the polymer and a micelle formed by the polymer and a method for preparing the micelle. The micelle prepared by the polymer can be used for a medicament carrier material and has good biocompatibility; as the critical micelle concentrationCMC is quite low and the formed micelle is stable and has small particle diameter and long circulation, the polymer micelle can be used for coating various hydrophilic and hydrophobic medicaments andis a medicament carrier with development prospect.
Description
Technical field
The present invention relates to a kind of hyperbranched polymer, its preparation method, micella, micellar preparation method and application by this polymer formation.Particularly, the present invention relates to form micellar hyperbranched polyurethane-aliphatic polyester, belong to technical field of nano material.
Background technology
Dendritic macromole is the dendrimer of the high regularity of a class, three-dimensional structure, its structure and molecular dimension size have good controllability, and connect medicine and target group when can make dendritic macromole utilize differential responses by not parallel control, make it have different functional groups by the different polymkeric substance of finishing, can make surperficial possess hydrophilic property, increase biocompatibility.Can make the inside of dendritic macromole form huge hydrophobic space by making up reaction.Because dendritic macromole surface structure structure is hydrophilic, internal cavities and binding site can carry medicine, so this provides advantageous condition for dendritic macromole as pharmaceutical carrier, it can realize truly nanometer administration and medicament slow release.Thereby dendritic macromole has caused increasing scientific worker's attention as pharmaceutical carrier, becomes one of current research focus.Yet dendritic macromole is because its expensive price and loaded down with trivial details synthesis step have limited its range of application to a great extent.
Hyperbranched polymer is the polymer that a class has unique texture and performance.Because have the unexistent low viscosity of conventional linear polymkeric substance, high rheological, good solubility, a large amount of functional end-group and low-cost a series of good characteristics such as synthetic fast, hyperbranched polymer becomes the research focus of polymer subject and other cross discipline.It is the polymer that a class has unique texture and performance, because hyperbranched polymer is all very similar with performance to tree-shaped polymer architecture, and the building-up process of its single stage method is convenient, fast, be fit to produce in enormous quantities, thereby to be considered to it be the substitute of dendrimer polymkeric substance.
In the prior art, since hyperbranched polymer within it portion and outside contain a large amount of functional groups can the fixed target molecule, or hyperbranched distinctive nucleocapsid structure can be used as main body and comes the embedding guest molecule, so it has been widely used in pharmaceutical carrier and the medical material.
Aliphatic polyester is to obtain the biodegradable polymer that the drugs approved by FDA approval can enter human body as poly(lactic acid) (PLA), polymeric polyglycolide-polylactide (PLGA), polycaprolactone (PCL).They be good biocompatibility, can biodegradable in vivo polymkeric substance, therefore be suitable for very much as drug carrier material, be widely used at aspects such as artificial skin and organizational project, controlled delivery of pharmaceutical agents releases.Yet the wetting ability difference of these aliphatic polyesters and have high crystalline, thereby reduced their degradation rate, cause reducing with the consistency of soft organ, the effective ways that overcome these problems are exactly to introduce biocompatibility and blood compatibility hydrophilic segment in the aliphatic polyester segment, and the performance of aliphatic polyester is had greatly improved.This grafting or block polymer are amphipathic because of having, so have bigger superiority as the carrier of drug release, wound dressing.
As everyone knows, if having hydrophilic and hydrophobic two portions in the polymkeric substance simultaneously forms, so this amphipathic nature polyalcohol just can self-assembly form polymer nano micelle in the aqueous solution, polymer nano micelle is developed the nineties in 20th century as pharmaceutical carrier, be by amphipathic nature polyalcohol spontaneous a kind of self-assembled structures that forms in the aqueous solution, the wetting ability fragment forms shell, and the hydrophobicity fragment forms kernel, constitutes unique nucleocapsid structure.Have that drug loading height, medicine carrying scope are wide, distribute in long, the unique body of residence time in the good stability, body and increase stability of drug, improve bioavailability and reduce characteristics such as toxic side effect.Characteristics such as nucleocapsid structure, micelle-forming concentration are low, Heat stability is good are with a wide range of applications in fields such as drug delivery systems the amphipathic nature polyalcohol micella because of having.
The nearly more than ten years, the micelle administration system of being made up of the amphiphilic polymers material is with its advantage of giving prominence to and the extensive concern that has been subjected to international the world of medicine in the very big application prospect of aspects such as tumour medicine, genomic medicine, infection medicine.Amphiphilic polymers micellar system is the maximum and the most sophisticated polymeric colloid drug delivery system of research at present.Studies show that in a large number, the carrier of amphiphilic polymers drug delivery system can self aggregation becomes the micella of unique nucleocapsid structure, because " nuclear-shell " similar that polymer micelle has lipoprotein in organism has certain bio-imitability in some sense with viral structure, and the higher stability of polymer micelle has determined that it still can stable existence when concentration is extremely rare, the wetting ability shell of micellar surface can reduce identification and the phagocytic activity of scavenger cell to particle, prolong its cycling time in blood, can protect medicine to exempt from the destruction of physiological environment, slowly discharge in vivo; The micellar particle diameter is little, can directly enter organ and cell interior by the hair cell blood vessel, by more effective absorption; The extensive administering mode of micelle administration system is that other any formulation is all incomparable, and it can add remarkable advantages such as the blood of human body recycle system by modes such as oral, injection (intravenous injection, intramuscular injection, subcutaneous injection), transdermals.
2000 the 4th phases of polymer journal have been delivered " molecular designing of hyperbranched polyurethane and preparation thereof " literary composition, hyperbranched polyurethane wherein is to be that raw material makes N by the Michael addition reaction with methyl acrylate and diethanolamine, N-dihydroxy ethyl-3-amido methyl propionate monomer, use " accurate single stage method " and " dispersing method " to make it and 1 again, 1, the synthetic a kind of novel hyperbranched polyurethane of 1-TriMethylolPropane(TMP) reaction, to N, N-dihydroxy ethyl-monomeric molecular structure of 3-amido methyl propionate characterizes by nucleus magnetic resonance and elemental analysis method.GPC measures and shows synthetic hyperbranched polyurethane narrow molecular weight distribution, has monodispersity; Viscosity is less than the linear molecule with molecular weight; Resistance toheat is better, and weightless temperature is higher than 200 ℃, and formed hyperbranched polyurethane can not form micella, can't use as pharmaceutical carrier.
Summary of the invention
A purpose of the present invention provides a kind of polymkeric substance of hyperbranched polyurethane-aliphatic polyester, and this polymkeric substance can form amphipathic micella, and this polymer manufacture process good reproducibility is with a wide range of applications on pharmaceutical carrier.
Another object of the present invention provides the preparation method of this polymkeric substance.
A further object of the present invention provides a kind of micella by this polymer formation.
A further object of the present invention provides this micellar preparation method.
A further object of the present invention provides described micella as the application in the pharmaceutical carrier.
One aspect of the present invention provides a kind of hyperbranched polymer, and this polymkeric substance has as shown in the formula structure shown in (I):
(I)，
D is in the formula
Preferably, described aliphatic polyester is the aliphatic polyester with following molecular formula:
Or
, wherein m is the positive integer of 210-400, x, y are the positive integer of 50-200; Z is the positive integer of 140-250.
Be poly(lactic acid),
Be polymeric polyglycolide-polylactide,
Be polycaprolactone.
Preferably, the degree of branching of wherein said hyperbranched polyurethane is 0.5-0.7.
The present invention provides the method for preparing polymkeric substance on the other hand, and this method may further comprise the steps:
A. hyperbranched polyurethane, aliphatic ester monomer and catalyzer are mixed, described catalyzer is preferably stannous octoate;
B. under the vacuum anhydrous condition, the mixture that step a is obtained kept 8-14 hour at 100-140 ℃, obtained the polymkeric substance of hyperbranched polyurethane-aliphatic polyester.With the rac-Lactide is example, and the process of the reacting generating copolymer of hyperbranched polyurethane and rac-Lactide is as follows:
The heavy black line that links to each other with oxygen in the following formula is represented repeating unit, and the structure of the formula that provides from above (I) can be inferred its structure.
Preferably, wherein hyperbranched polyurethane and the monomeric mol ratio of aliphatic ester are 1 among the step a: 3-1: 10, and described catalyzer is the 0.3%-0.7% of hyperbranched polyurethane and the monomeric weight summation of aliphatic ester.
One side more of the present invention also provides a kind of micella, and this micella is by described hyperbranched polyurethane-aliphatic polyester polymer formation.
Preferably, the micelle-forming concentration of described polymer micelle is 1.40 * 10
-4-8.40 * 10
-4Mg/ml.
More preferably, the micella particle of described polymer micelle is spherical, and diameter is 110-215nm.
One side more of the present invention also provides a kind of preparation micellar method, and this method may further comprise the steps:
A. the polymkeric substance of hyperbranched polyurethane-aliphatic polyester of obtaining of purifying;
B. the polymkeric substance behind the purifying forms described polymer micelle in water.
Preferably, wherein step a may further comprise the steps: at first with the polymer dissolution of hyperbranched polyurethane-aliphatic polyester in methylene dichloride, then in methylene dichloride, add sherwood oil, remove insolubles, revaporization is removed the sherwood oil in the solution.
Preferably, wherein step b may further comprise the steps: at first the polymkeric substance behind the purifying is dissolved in the acetone, the polymer drops that then will be dissolved in the acetone is added in the deionized water, forms band blue light emulsion, removes acetone again, obtains described polymer micelle.
Further aspect of the present invention also provides described micella as the application in the pharmaceutical carrier.
Because in the hyperbranched polyurethane-aliphatic poly ester polymer of the present invention's preparation, hyperbranched polyurethane end possess hydrophilic property wherein, the aliphatic polyester end has hydrophobicity, so can assemble the formation nano-micelle as pharmaceutical carrier as the amphipathic nature polyalcohol of basic material preparation with hyperbranched polyurethane and aliphatic ester monomer, can avoid being caught by reticuloendothelial cell, prolong drug effect effectively, improved bioavailability and biological activity.
The invention has the beneficial effects as follows: (1) polymkeric substance of the present invention wherein hyperbranched polyurethane end and the aliphatic polyester end of dissaving structure has excellent biological compatibility; (2) this polymer micelle has kept the form and the structure of hyperbranched polyurethane, the wetting ability of hyperbranched polyurethane and hyperbranched special construction can be avoided being caught by reticuloendothelial cell effectively, prolonged drug effect effectively, can improve drug encapsulation and improve bioavailability and biological activity; (3) polymer micelle of the present invention is because micelle-forming concentration CMC is very low, and the micella of formation is stable, and particle diameter is little, has long cyclicity, and can be used for bag and carry various hydrophilic, hydrophobic medicines, be pharmaceutical carrier with development prospect; (4) polymer micelle preparation method of the present invention is simple, and good reproducibility is with a wide range of applications on pharmaceutical carrier.
Description of drawings
Fig. 1 represents the 4th generation hyperbranched polyurethane-polylactic acid polymer micellar photo.
Fig. 2 represents to be loaded with the 4th generation hyperbranched polyurethane-polylactic acid polymer micellar photo of bovine serum albumin (BSA).
Fig. 3 represent among the embodiment 7 the 4th generation hyperbranched polyurethane infrared spectrum.
Fig. 4 represent among the embodiment 7 the 4th generation hyperbranched polyurethane-polylactic acid polymer infrared spectrum.
Fig. 5 represent among the embodiment 7 the 4th generation hyperbranched polyurethane nmr spectrum.
Fig. 6 represent among the embodiment 7 the 4th generation hyperbranched polyurethane-polylactic acid polymer nmr spectrum.
Embodiment
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
In there-necked flask, add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml carbinol mixture, at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, remove excessive methyl acrylate and methyl alcohol through underpressure distillation then, obtain a kind of water white oily liquids promptly, N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the preparation of s-generation hyperbranched polyamine ester polymer
In there-necked flask, add 1.342 g 1,1,1-TriMethylolPropane(TMP), 5.93g N, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.017g four isobutoxy titaniums are catalyzer, reaction system is at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then obtains s-generation hyperbranched polyurethane.Its molecular formula is as follows:
Heavy black line in the superincumbent structural formula is partly represented the multiple structural unit, the chemical structure that is connected on the Sauerstoffatom of another hydroxyethyl that links to each other with nitrogen-atoms with the symmetric Sauerstoffatom of this hydroxyethyl on the chemical structure that is connected be identical, represent this part with heavy black line in the superincumbent structural formula.
With 1,1, the structure that the Sauerstoffatom on the another one methylol of representing among the structure that the Sauerstoffatom on two other methylol of 1-TriMethylolPropane(TMP) links to each other and the last figure links to each other is identical, in the superincumbent structural formula also the thick line with black represent.
2. s-generation hyperbranched polyurethane-polylactic acid polymer is synthetic
The s-generation hyperbranched polyamine ester products that obtains is placed on drying in the vacuum drying oven, 1.512g s-generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.020g again, then with plug tight and sealing the single port bottle stopper.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.The polymkeric substance of the product s-generation hyperbranched polyurethane-poly(lactic acid) that obtains after the filtration in vacuum drying oven 25 ℃ dry 2 days down.Characterizing the polymkeric substance that confirms s-generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism generates; Molecular weight is 4000kDa.
3. prepare s-generation hyperbranched polyurethane-polylactic acid polymer micella
The polymkeric substance of the s-generation hyperbranched polyurethane-poly(lactic acid) behind the 0.2g purifying is dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains the hyperbranched amine ester of the s-generation-polylactic acid polymer micella.Then micella being carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry observes.The result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 110nm, and dispersion index is 0.05; Transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 1.42 * 10
-4Mg/ml.
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
Add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml methyl alcohol in there-necked flask, mixture is at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer after excessive methyl acrylate and methyl alcohol are removed in the process underpressure distillation then.
B. the preparation of s-generation hyperbranched polyurethane
In there-necked flask, add 1.342 g 1,1,1-TriMethylolPropane(TMP), 15.93g N, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.017g four isobutoxy titaniums are catalyzer, reaction system is at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then obtains s-generation hyperbranched polyurethane.
2. s-generation hyperbranched polyurethane-polylactic acid polymer is synthetic
The s-generation hyperbranched polyamine ester products that obtains is placed on drying in the vacuum drying oven, 0.648g s-generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.020g again, with plug tight and sealing the single port bottle stopper.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 100 ℃ and kept 8 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.The polymkeric substance of the product s-generation hyperbranched polyurethane-poly(lactic acid) that obtains after the filtration in vacuum drying oven 25 ℃ dry 2 days down.Characterize the polymkeric substance that confirms s-generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism and generate, molecular weight is 4700kDa.
3. prepare s-generation hyperbranched polyurethane-polylactic acid polymer micella
S-generation hyperbranched polyurethane-poly(lactic acid) behind the 0.2g purifying is dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains s-generation hyperbranched polyurethane-polylactic acid polymer micella.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows that it is 124nm that the diffusing look of dynamic light is penetrated its particle diameter of mensuration, and dispersion index is 0.07; Transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 2.31 * 10
-4Mg/ml.
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
In there-necked flask, add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml carbinol mixture, at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, after excessive methyl acrylate and methyl alcohol are removed in the process underpressure distillation then, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the preparation of s-generation hyperbranched polyamine ester polymer
In there-necked flask, add 1.342 g 1,1,1-TriMethylolPropane(TMP), 15.93g N, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.017g four isobutoxy titaniums are catalyzer, answer system at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then obtains s-generation hyperbranched polyurethane.
2. s-generation hyperbranched polyurethane-polylactic acid polymer is synthetic
The s-generation hyperbranched polyamine ester products that obtains is placed on drying in the vacuum drying oven, 0.454g s-generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.020g again, then with plug tight and sealing the single port bottle stopper.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 14 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.The polymer product of the s-generation hyperbranched polyurethane-poly(lactic acid) that obtains after the filtration in vacuum drying oven 25 ℃ dry 2 days down.Characterize the polymkeric substance that confirms s-generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism and generate, molecular weight is 5100kDa.
3. prepare s-generation hyperbranched polyurethane-polylactic acid polymer micella
S-generation hyperbranched polyurethane-polylactic acid polymer behind the 0.2g purifying is dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains s-generation hyperbranched polyurethane-polylactic acid polymer micella.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 144nm, and dispersion index is 0.08, and transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 3.02 * 10
-4Mg/ml.
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
In there-necked flask, add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml carbinol mixture at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, after excessive methyl acrylate and methyl alcohol are removed in the process underpressure distillation then, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the preparation of third generation hyperbranched polyamine ester polymer
Add 5g s-generation hyperbranched polyurethane 7.32g, N in there-necked flask, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.017g four isobutoxy titaniums are catalyzer, answer system at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then obtains third generation hyperbranched polyurethane;
2. third generation hyperbranched polyurethane-polylactic acid polymer is synthetic
The third generation hyperbranched polyamine ester products that obtains is placed on drying in the vacuum drying oven, 1.677g third generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.030g again, then with plug tight and sealing the single port bottle stopper.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.The polymkeric substance of the product third generation hyperbranched polyurethane-poly(lactic acid) that obtains after the filtration in vacuum drying oven 25 ℃ dry 2 days down.Characterize the polymkeric substance that confirms third generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism and generate, molecular weight is 4850kDa.
3. prepare third generation hyperbranched polyurethane-polylactic acid polymer micella
The polymkeric substance of the third generation hyperbranched polyurethane-poly(lactic acid) behind the 0.2g purifying is dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains the polymer micelle of third generation hyperbranched polyurethane-poly(lactic acid).Then micella being carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry observes, the result shows that the diffusing look of dynamic light is penetrated and measured its particle diameter is 153nm, and dispersion index is 0.06, transmission electron microscope observation particle is regular spheroidal, and its micelle-forming concentration of fluorescence spectrometry is 4.15 * 10
-4Mg/ml.
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
In there-necked flask, add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml carbinol mixture, at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, remove excessive methyl acrylate and methyl alcohol through underpressure distillation then, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the preparation of third generation hyperbranched polyamine ester polymer
Add 5g s-generation hyperbranched polyurethane, 7.32g N in there-necked flask, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.03g four isobutoxy titaniums are catalyzer, answer system at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then obtains third generation hyperbranched polyurethane;
2. third generation hyperbranched polyurethane-polylactic acid polymer is synthetic
The third generation hyperbranched polyamine ester products that obtains is placed on drying in the vacuum drying oven, 0.719g third generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.030g again, then with plug tight and sealing the single port bottle stopper.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.The product third generation hyperbranched polyurethane-polylactic acid polymer that obtains after the filtration in vacuum drying oven 25 ℃ dry 2 days down.Characterize the polymkeric substance that confirms third generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism and generate, molecular weight is 5310kDa.
3. prepare third generation hyperbranched polyurethane-polylactic acid polymer micella
Third generation hyperbranched polyurethane-polylactic acid polymer behind the 0.2g purifying is dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains third generation hyperbranched polyurethane-polylactic acid polymer micella.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows that the diffusing look of dynamic light is penetrated and measured its particle diameter is 168nm, and dispersion index is 0.09, and transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 5.36 * 10
-4Mg/ml.
Embodiment 6
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
In there-necked flask, add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml carbinol mixture at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, after excessive methyl acrylate and methyl alcohol are removed in the process underpressure distillation then, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the preparation of third generation hyperbranched polyamine ester polymer
Add 5g s-generation hyperbranched polyurethane, 7.32g N in there-necked flask, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.030g four isobutoxy titaniums are catalyzer, answer system at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then obtains third generation hyperbranched polyurethane;
2. third generation hyperbranched polyurethane-polylactic acid polymer is synthetic
The third generation hyperbranched polyamine ester products that obtains is placed on drying in the vacuum drying oven, 0.503g third generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.030g again, then with plug tight and sealing the single port bottle stopper.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.Third generation hyperbranched polyurethane that obtains after the filtration and polylactic acid polymer product are following dry 2 days 25 ℃ of vacuum drying ovens.Characterize the polymkeric substance that confirms third generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism and generate, molecular weight is 5800kDa.
3. prepare third generation hyperbranched polyurethane-polylactic acid polymer micella
Third generation hyperbranched polyurethane-polylactic acid polymer behind the 0.2g purifying is dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains third generation hyperbranched polyurethane-polylactic acid polymer micella.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 172nm, and dispersion index is 0.05, and transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 6.14 * 10
-4Mg/ml.
Embodiment 7
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
Add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml methyl alcohol in there-necked flask, mixture is at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, after excessive methyl acrylate and methyl alcohol are removed in the process underpressure distillation then, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the 4th generation the hyperbranched polyamine ester polymer preparation
Add 5g third generation hyperbranched polyurethane, 6.60g N in there-necked flask, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.050g four isobutoxy titaniums are catalyzer, and reaction system is at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then, obtain the 4th generation the hyperbranched polyamine ester polymer.
2. the 4th generation hyperbranched polyurethane-polylactic acid polymer synthesizes
With obtain the 4th generation the hyperbranched polyamine ester products be placed in the vacuum drying oven dryly, 1.760g the 4th generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.040g again, with plug that the single port bottle stopper is tight and seal then.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.The 4th generation hyperbranched polyurethane-polylactic acid polymer product that obtains after the filtration in vacuum drying oven 25 ℃ dry 2 days down.The polymkeric substance that characterizes confirmation the 4th generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism generates, and molecular weight is 5250kDa.
The 4th generation hyperbranched polyurethane infrared spectrum can be referring to accompanying drawing 3, in this accompanying drawing, 3369.084cm
-1O-H peak, 1727.933cm on the expression polyurethane
-1Represent the C=O peak on this polyurethane, 1614.152cm
-1Represent the C-N peak on this polyurethane, 1457.944cm
-1Represent the CH on this polyurethane
2The peak.
The infrared spectrum of the hyperbranched polyurethane-polylactic acid polymer in the 4th generation is seen Fig. 4, in this accompanying drawing, and 3450cm
-1Represent O-H peak, 1753cm on this polymkeric substance
-1Represent the C=O peak on the polyurethane and C=O peak, the 1648cm on the poly(lactic acid) on this polymkeric substance
-1Represent C-N peak, 1454cm on this polymkeric substance
-1Represent the CH on this polymkeric substance
2The peak, 1383cm
-1Represent the CH on this polymkeric substance
2The peak and since the 4th generation hyperbranched polyurethane and poly(lactic acid) copolymerization has taken place, so C-N peak, CH on this polymkeric substance
2Displacement has taken place in the peak.
The 4th generation hyperbranched polyurethane nmr spectrum see Fig. 5, a in this spectrogram, b, c, d, e, f, g, h, i peak all with following formula in hyperbranched polyurethane in label be that the H of a, b, c, d, e, f, g, h, i is corresponding.
The 4th generation hyperbranched polyurethane-polylactic acid polymer nmr spectrum see Fig. 6, the j peak in this spectrogram, k peak respectively with following formula in hyperbranched polyurethane-polylactic acid polymer in label be that the H of j and K is corresponding.This shows that hyperbranched polyurethane-polylactic acid polymer forms.
3. prepare the 4th generation hyperbranched polyurethane-polylactic acid polymer micella
With behind the 0.2g purifying the 4th generation hyperbranched polyurethane-polylactic acid polymer be dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, form the emulsion of band blue light at last, acetone is removed by reduction vaporization, obtains the 4th generation hyperbranched polyurethane-polylactic acid polymer micella.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 175nm, and dispersion index is that 0.07 transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 6.48 * 10
-4Mg/ml.
Embodiment 8
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
In there-necked flask, add the 8.609g methyl acrylate, 10.514g diethanolamine and 10ml methyl alcohol, mixture is at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, remove excessive methyl acrylate and methyl alcohol through underpressure distillation then, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the 4th generation the hyperbranched polyamine ester polymer preparation
In there-necked flask, add 5g third generation hyperbranched polyurethane, 6.60g N, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.050g four isobutoxy titaniums are catalyzer, answer system at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then, obtain the 4th generation hyperbranched polyurethane.
2. the 4th generation hyperbranched polyurethane-polylactic acid polymer synthesizes
With obtain the 4th generation the hyperbranched polyamine ester products be placed in the vacuum drying oven dryly, 0.754g the 4th generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.040g again, with plug that the single port bottle stopper is tight and seal then.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.The 4th generation hyperbranched polyurethane-polylactic acid polymer product that obtains after the filtration in vacuum drying oven 25 ℃ dry 2 days down.The polymkeric substance that characterizes confirmation the 4th generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism generates, and molecular weight is 6142kDa.
3. prepare the 4th generation hyperbranched polyurethane-polylactic acid polymer micella
With behind the 0.2g purifying the 4th generation hyperbranched polyurethane-polylactic acid polymer be dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains the 4th generation hyperbranched polyurethane-polylactic acid polymer micella.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 183nm, and dispersion index is 0.06; Transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 7.21 * 10
-4Mg/ml.
Embodiment 9
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
Add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml methyl alcohol in there-necked flask, mixture is at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, after excessive methyl acrylate and methyl alcohol are removed in the process underpressure distillation then, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the 4th generation the hyperbranched polyamine ester polymer preparation
Add 5g third generation hyperbranched polyurethane, 6.60g N in there-necked flask, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.050g four isobutoxy titaniums are catalyzer, answer system at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then, obtain the 4th generation hyperbranched polyurethane.
2. the 4th generation hyperbranched polyurethane-polylactic acid polymer synthesizes
With obtain the 4th generation the hyperbranched polyamine ester products be placed in the vacuum drying oven dryly, 0.528g the 4th generation hyperbranched polyamine ester products and 5g rac-Lactide are placed in the single port bottle, add the stannous octoate of 0.040g again, with plug that the single port bottle stopper is tight and seal then.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.Obtain after the filtration the 4th generation hyperbranched polyurethane and polylactic acid polymer product, in vacuum drying oven 25 ℃ dry 2 days down.The polymkeric substance that characterizes confirmation the 4th generation hyperbranched polyurethane-poly(lactic acid) by infrared and nuclear-magnetism generates, and molecular weight is 7000kDa.
3. prepare the 4th generation hyperbranched polyurethane-polylactic acid polymer micella
With behind the 0.2g purifying the 4th generation hyperbranched polyurethane-polylactic acid polymer be dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains the 4th generation hyperbranched polyurethane-polylactic acid polymer micella.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 186nm, and dispersion index is 0.07; Transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 7.53 * 10
-4Mg/ml.
Embodiment 10
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
Add 8.609g methyl acrylate, 10.514g diethanolamine and 10ml methyl alcohol in there-necked flask, mixture is at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, after excessive methyl acrylate and methyl alcohol are removed in the process underpressure distillation then, obtain a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the 4th generation the hyperbranched polyamine ester polymer preparation
Add 5g third generation hyperbranched polyurethane, 6.60g N in there-necked flask, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.050g four isobutoxy titaniums are catalyzer, answer system at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then, obtain the 4th generation hyperbranched polyurethane.
The 4th generation hyperbranched polyurethane-poly-(glycollide-rac-Lactide) polymkeric substance synthetic
With obtain the 4th generation the hyperbranched polyamine ester products be placed in the vacuum drying oven dry, 1g the 4th generation hyperbranched polyamine ester products and 0.454g rac-Lactide and 4.546g glycollide are placed in the single port bottle, the stannous octoate that adds 0.040g again is then with plug tight and sealing with the single port bottle stopper.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.Product the 4th generation hyperbranched polyurethane that obtains after the filtration-poly-(glycollide-rac-Lactide) polymkeric substance in vacuum drying oven 25 ℃ dry 2 days down.Characterize confirmation the 4th generation hyperbranched polyurethane-poly-(glycollide-rac-Lactide) polymkeric substance by infrared and nuclear-magnetism and generate, molecular weight is 5400kDa.
3. prepare the 4th generation hyperbranched polyurethane-poly-(glycollide-rac-Lactide) polymer micelle
With behind the 0.2g purifying the 4th generation hyperbranched polyurethane-poly-(glycollide-rac-Lactide) polymkeric substance be dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtain the 4th generation hyperbranched polyurethane-poly-(glycollide-rac-Lactide) polymer micelle.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 198nm, and dispersion index is 0.08; Transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 7.83 * 10
-4Mg/ml.
Embodiment 11
1. the preparation of hyperbranched polyurethane
A.N, the preparation of N-dihydroxy ethyl-3-amido methacrylate monomer
Add the 8.609g methyl acrylate in there-necked flask, 10.514g diethanolamine and 10ml carbinol mixture are at room temperature and logical N
2Be warming up to 40 ℃ of reaction 4h after stirring 30min under the situation, remove excessive methyl acrylate through underpressure distillation then and methyl alcohol obtains a kind of water white oily liquids N, N-dihydroxy ethyl-3-amido methacrylate monomer.
B. the 4th generation the hyperbranched polyamine ester polymer preparation
In there-necked flask, add 5g third generation hyperbranched polyurethane, 6.60g N, N-dihydroxy ethyl-3-amido methacrylate monomer and 0.050g four isobutoxy titaniums are catalyzer, reaction system is at N
2Under the protection, 120 ℃ of isothermal reaction 12h obtain a kind of yellow thick liquid.Crude product is dissolved in the dehydrated alcohol, suction filtration, removes ethanol with anhydrous sodium sulfate drying, suction filtration, underpressure distillation, product vacuum-drying then, obtain the 4th generation hyperbranched polyurethane.
The 4th generation hyperbranched polyurethane-polycaprolactone polymkeric substance synthetic
With obtain the 4th generation the hyperbranched polyamine ester products be placed in the vacuum drying oven dryly, 0.754g the 4th generation hyperbranched polyamine ester products and 5g caprolactone are placed in the single port bottle, add the stannous octoate of 0.040g again, with plug that the single port bottle stopper is tight and seal then.Then the single port bottle is vacuumized and heat 40 ℃ and keep anhydrous in 1 hour guarantee system, stop then vacuumizing and be heated to 140 ℃ and kept 13 hours reaction system is airtight.Product is dissolved in the methylene dichloride, gives a baby a bath on the third day after its birth time with petroleum ether precipitation and with sherwood oil, evaporates sherwood oil then.Polymer dissolution behind the purifying precipitates with deionized water in a spot of acetone.Obtain after the filtration the 4th generation hyperbranched polyurethane and the polycaprolactone polymkeric substance in vacuum drying oven 25 ℃ dry 2 days down.The polymkeric substance that characterizes confirmation the 4th generation hyperbranched polyurethane-polycaprolactone by infrared and nuclear-magnetism generates, and molecular weight is 6420kDa.
3. prepare the 4th generation hyperbranched polyurethane-polycaprolactone polymer micelle
The 4th generation hyperbranched polyurethane-polycaprolactone polymkeric substance behind the 0.2g purifying is dissolved in the acetone of 6ml, be added drop-wise to while stirring in the 14ml deionized water, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains the 4th generation hyperbranched polyurethane-polycaprolactone polymer micelle.Then micella is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 208nm, and dispersion index is 0.06; Transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 8.43 * 10
-4Mg/ml.
Embodiment 12
At first with the 4th generation hyperbranched polyurethane-polylactic acid polymer be dissolved in and be made into 10mg/mL solution in the acetone, bovine serum albumin (the English BSA that is called for short) is made into the aqueous solution of 2mg/mL, then 5mL the 4th generation hyperbranched polyurethane-polylactic acid polymer acetone soln is progressively progressively increased in the 10mLBSA aqueous solution, the band blue light emulsion of Xing Chenging at last, acetone is removed by reduction vaporization, obtains being loaded with the 4th generation hyperbranched polyurethane-polylactic acid polymer micella of BSA.Then carrier micelle is carried out dynamic light scattering, transmission electron microscope and fluorescence spectrometry and observe, the result shows: the diffusing look of dynamic light is penetrated and measured its particle diameter is 192nm, and dispersion index is 0.08; Transmission electron microscope observation particle is regular spheroidal; Its micelle-forming concentration of fluorescence spectrometry is 7.71 * 10
-4Mg/ml.
Claims (11)
1. hyperbranched polymer, this polymkeric substance has as shown in the formula structure shown in (I):
(I)，
D is in the formula
D
1For
N is the positive integer of 1-5, and B is an aliphatic polyester, and the molecular weight of this polymkeric substance is 4000kDa-7000kDa; Wherein, described aliphatic polyester is the aliphatic polyester with following molecular formula:
Or
Wherein m is the positive integer of 210-400; X, y are the positive integer of 50-200; Z is the positive integer of 140-250.
2. polymkeric substance according to claim 1, the degree of branching of wherein said hyperbranched polyurethane are 0.5-0.7.
3. method for preparing claim 1 or 2 described polymkeric substance, this method may further comprise the steps:
A. hyperbranched polyurethane, aliphatic ester monomer and catalyzer are mixed, described catalyzer is preferably stannous octoate;
B. under the vacuum anhydrous condition, the mixture that step a is obtained kept 8-14 hour at 100-140 ℃, obtained the polymkeric substance of hyperbranched polyurethane-aliphatic polyester.
4. method according to claim 3, wherein hyperbranched polyurethane and the monomeric mol ratio of aliphatic ester are 1 among the step a: 3-1: 10, described catalyzer is the 0.3%-0.7% of hyperbranched polyurethane and the monomeric weight summation of aliphatic ester.
5. micella, this micella is by claim 1 or 2 described polymer formation.
6. micella according to claim 5, wherein this micellar micelle-forming concentration is 1.40 * 10
-4-8.40 * 10
-4Mg/ml.
7. according to claim 5 or 6 described micellas, wherein said micellar micella particle is spherical, and diameter is 110-215nm.
8. one kind prepares each described micellar method in the claim 5 to 7, and this method may further comprise the steps:
A. the polymkeric substance of hyperbranched polyurethane-aliphatic polyester of obtaining of purifying claim 3;
B. the polymkeric substance behind the purifying forms described polymer micelle in water.
9. method according to claim 8, wherein step a may further comprise the steps: at first with the polymer dissolution of hyperbranched polyurethane-aliphatic polyester in methylene dichloride, then add sherwood oil in methylene dichloride, remove insolubles, revaporization is removed the sherwood oil in the solution.
10. according to Claim 8 or 9 described methods, wherein said step b may further comprise the steps: at first the polymkeric substance behind the purifying is dissolved in the acetone, the polymer drops that then will be dissolved in the acetone is added in the deionized water, form band blue light emulsion, remove acetone again, obtain described polymer micelle.
11. each described micella is as the application in the pharmaceutical carrier in the claim 5 to 7.
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| EP1367080A1 (en) * | 2002-05-29 | 2003-12-03 | Hycail B.V. | Hyperbranched poly(hydroxycarboxylic acid) polymers |
| WO2006128121A2 (en) * | 2005-05-27 | 2006-11-30 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications |
| CN1919893A (en) * | 2005-08-26 | 2007-02-28 | 中国科学院成都有机化学有限公司 | Hyperbranched great macromonomer, acrylate resin containing hyperbranched structure and preparation method |
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| EP1367080A1 (en) * | 2002-05-29 | 2003-12-03 | Hycail B.V. | Hyperbranched poly(hydroxycarboxylic acid) polymers |
| WO2006128121A2 (en) * | 2005-05-27 | 2006-11-30 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications |
| CN1919893A (en) * | 2005-08-26 | 2007-02-28 | 中国科学院成都有机化学有限公司 | Hyperbranched great macromonomer, acrylate resin containing hyperbranched structure and preparation method |
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| Bao-Ku Zhu, et al.Preparation and properties of hyperbranched poly(amine-ester) films using acetal cross-linking units.《Polymer International》.2005,(第55期),63-70. * |
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