CN1760227A - Nano granules possessing hydrophobic core and hydrophilic surface, preparation method and application - Google Patents
Nano granules possessing hydrophobic core and hydrophilic surface, preparation method and application Download PDFInfo
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- CN1760227A CN1760227A CN 200510027609 CN200510027609A CN1760227A CN 1760227 A CN1760227 A CN 1760227A CN 200510027609 CN200510027609 CN 200510027609 CN 200510027609 A CN200510027609 A CN 200510027609A CN 1760227 A CN1760227 A CN 1760227A
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Abstract
A nanoparticle with hydrophobic core and hydrophilic surface used for medicine, food, or cosmetics features that it contains hydrophobic polymer block and hydrophilic polymer block. Its preparing process includes such steps as generating the free amino of chitosan under action of trigger, and combining with hydrophilic unsaturated monomer and alkyl acrylata (or methylacrylate) to obtain triblock copolymer.
Description
Technical field
The invention belongs to amphiphilic nano material technology field, be specifically related to a kind of block copolymer nano grain and its production and application with hydrophobic core, water-wetted surface.
Background technology
Modern nanotechnology and nano science are meant the science of research size in the physics that material had, chemical property and the function of 1～100nm, and it can be by manipulating single atom directly, molecule is assembled and creating the material of specific function.Nanoparticle is material with the polymer substance, and activeconstituents can dissolve, adsorbs or be wrapped in the material.Usually nanoparticle has slowly-releasing, target and the effect of protection activeconstituents, can improve curative effect and reduce toxic side effect etc.Nanoparticle is difficult for occluding vascular, can by in the cell or iuntercellular pass endothelial wall and arrive target site, also can play a role again by the capillary vessel even the hemato encephalic barrier (BBB) of human body.Nanoparticle has the dispersiveness of height and huge surface-area, and its size reduces by 3 orders of magnitude, and then surface-area improves 6 orders of magnitude, has higher carrying active principle and improve activeconstituents and absorbs the effect of enhanced activity composition.Nanoparticle can effectively be controlled the release rate of activeconstituents.The nanoparticle bag carries activeconstituents can also shield contacting of activeconstituents and body endoenzyme liquid or acid ﹠ alkali liquid, and the protection activeconstituents is by enzyme or soda acid degraded.
Before the nineties in 20th century, the material of nanoparticle is acrylic acid derivative mostly, and these materials are hydrophobic mostly, and bag year hydrophilic active composition ability is low.After the nineties, Akashi etc. have developed the engrafted nanometer grain of a series of hydrophobic cores, water-wetted surface, the wetting ability of nanoparticle and ability (the Oral peptide usingnanoparticles composed of novel graft copolymers having hydrophobic backbone andhydrophilic branches that bag carries the hydrophilic active composition have been improved, Int.J.Pharm., 1997,149:93-106).Stieneker etc. have developed the hydrophilic nanoparticle of amino alkane METH oleic series, there are several nanoparticles to have stronger positive charge, the hydrophilic DNA and the pharmaceutical grade protein of easy adsorption zone negative charge, improve the ability (Preparation of carrying hydrophilic active composition, characterization and cytotoxicityof methylmethacrylate copolymer nanoparticles with a permanent positive surface charge, Int.J.Pharm., 1997,157:189-198).Existing nanoparticle exists and carries that active principle is low, prominent to be released and shortcoming such as poor stability.
Summary of the invention
What the object of the present invention is to provide a kind of year active principle height, good stability has block copolymer nano grain of hydrophobic core, water-wetted surface and preparation method thereof, and the application of the block copolymer nano grain of this hydrophobic core, water-wetted surface is provided, to overcome the deficiencies in the prior art and defective.
Design of the present invention is as follows:
Select for use hydrophobic methyl methacrylate and hydrophilic methacrylic acid derivative copolymerization to obtain the multipolymer of diblock, after the purification process, be scattered in the water, form amphipathic nanoparticle, its hydrophilic chain is shorter.Chitosan has excellent biological compatibility, security, is the good material of preparation nanoparticle, but chitosan nano easily produces precipitation, coacervation under the physiological environment condition, have a strong impact on the absorption of activeconstituents.For stability that improves chitosan nano and the nanoparticle that obtains to have longer hydrophilic chain, the present invention adopts the free radical reaction principle earlier with acrylic acid derivative or methacrylic acid derivative beautify chitosan, obtain the multipolymer of three blocks then by copolymerization, promptly get nanoparticle behind the purifying.
Technical scheme of the present invention is as follows:
The nanoparticle with hydrophobic core, water-wetted surface that the present invention proposes is made up of following two kinds of polymkeric substance: the hydrophilic polymer block of the hydrophobic polymer block of polyalkyl acrylate or polyalkyl methacrylate and wetting ability unsaturated monomer or the polymer-modified chitosan that formed by this wetting ability unsaturated monomer.
Wherein the part by weight of wetting ability unsaturated monomer and chitosan is in 20: 80 to 80: 20 scope, and the part by weight of alkyl acrylate or alkyl methacrylate and wetting ability unsaturated monomer-chitin copolymer or polymkeric substance-chitin copolymer of being formed by this wetting ability unsaturated monomer is in 90: 10 to 50: 50 scope.
Said alkyl methacrylate is one or more in methyl methacrylate, Jia Jibingxisuanyizhi, propyl methacrylate, butyl methacrylate, Propenoic acid, 2-methyl, isobutyl ester and the N-Hexyl methacrylate.
Said alkyl acrylate is one or more in methyl acrylate, ethyl propenoate, propyl acrylate, butyl acrylate, isobutyl acrylate and the Ethyl acrylate.
Said wetting ability unsaturated monomer is a vinylformic acid, methacrylic acid, the vinylformic acid salt, the methacrylic acid salt, the salt of acrylate or acids, the salt of methacrylic ester or acids, acrylic acid amides, the amides of methacrylic acid, acrylic acid N-alkylamide, the N-alkylamide of methacrylic acid, the salt and the acids of vinylformic acid N-alkylamide, the salt and the acids of methacrylic acid N-alkylamide, acrylamide, acrylamide derivative, Methacrylamide, in the methacrylamide derivatives one or more.
Usually used wetting ability unsaturated monomer is one or more in methacrylic acid, acrylamide, N-N-isopropylacrylamide, methylacryoyloxyethyl trimethyl ammonium chloride (TMAEMC), dimethylaminoethyl methacrylate (DMAEMC), the 3-sulfopropyl-vinylformic acid sylvite.
Nanoparticle with hydrophobic core, water-wetted surface of the present invention, particle diameter are 100-250nm.
Nanoparticle with hydrophobic core, water-wetted surface of the present invention, its preparation method is as follows:
(1) chitosan is dissolved in 1% the acetate, is heated to 60～75 ℃, add initiator, add the wetting ability unsaturated monomer after 10～60 minutes, form graft copolymer;
Add hydrophobic alkyl acrylate or alkyl methacrylate after (2) 10～90 minutes, reacted 2～24 hours, obtain the amphoteric triblock copolymer;
(3), promptly get three block amphiphilic nano grains with hydrophobic core, water-wetted surface with above-mentioned triblock copolymer purifying.
Wherein the part by weight of wetting ability unsaturated monomer and chitosan is in 20: 80 to 80: 20 scope, and the part by weight of alkyl acrylate or alkyl methacrylate and wetting ability unsaturated monomer-chitin copolymer or polymkeric substance-chitin copolymer of being formed by this wetting ability unsaturated monomer is in 90: 10 to 50: 50 scope.
Said alkyl methacrylate is one or more in methyl methacrylate, Jia Jibingxisuanyizhi, propyl methacrylate, butyl methacrylate, Propenoic acid, 2-methyl, isobutyl ester and the N-Hexyl methacrylate.
Said alkyl acrylate is one or more in methyl acrylate, ethyl propenoate, propyl acrylate, butyl acrylate, isobutyl acrylate and the Ethyl acrylate.
Said wetting ability unsaturated monomer is a vinylformic acid, methacrylic acid, the vinylformic acid salt, the methacrylic acid salt, the salt of acrylate or acids, the salt of methacrylic ester or acids, acrylic acid amides, the amides of methacrylic acid, acrylic acid N-alkylamide, the N-alkylamide of methacrylic acid, the salt and the acids of vinylformic acid N-alkylamide, the salt and the acids of methacrylic acid N-alkylamide, acrylamide, acrylamide derivative, Methacrylamide, in the methacrylamide derivatives one or more.
Usually used wetting ability unsaturated monomer is one or more in methacrylic acid, acrylamide, N-N-isopropylacrylamide, methylacryoyloxyethyl trimethyl ammonium chloride (TMAEMC), dimethylaminoethyl methacrylate (DMAEMC), the 3-sulfopropyl-vinylformic acid sylvite.
Said initiator is ammonium persulphate or Potassium Persulphate.Its consumption is 0.01～0.2% (g/ml) of reaction system.
When reacting, the adding order of chitosan, alkyl methacrylate and wetting ability unsaturated monomer can be in no particular order.
The molecular weight of triblock copolymer of the present invention can be by dropping into amount of monomer, reaction times and initiator concentration decision.Other parameter as temperature of reaction, the adding mode of hydrophilic polymer, use nitrogen, reaction times etc., can be adjusted as required.
The present invention has investigated the influence to nanoparticle such as hydrophilic monomer concentration, hydrophobic monomer concentration, total monomer, initiator concentration, pH, reaction times, has prepared several stabilized nano grains.
Purification step comprises technology well known by persons skilled in the art in the preparation of nanoparticle.After dialysis or ultrafiltration, the suspension of the nanoparticle that obtains, it can directly use, perhaps also can separate or collect by known any suitable physics mode itself, for example: by filter, concentrate, density gradient centrifugation, precipitation, adding salt or lyophilize etc.
Impurity (salt) and solvent can be removed by any suitable physical separation processes, for example by dialysis, filtration, pH change, chromatogram or distillation etc.
Triblock polymer of the present invention is spontaneous formation nanoparticle in the aqueous solution, and this nanoparticle can form powdery solid or form stable suspension colloid in Physiological Medium.
The carrier that nanoparticle of the present invention can be used as activeconstituents uses.Contain nanoparticle suspension colloid of the present invention and/or powdery solid and can comprise at least a following activeconstituents:
(1) protein and polypeptide: condition somatomedins such as Regular Insulin, oxyphorase, albumin, cytopigment, Interferon, rabbit, antigen, antibody, erythropoietin, tethelin, interleukin, G CFS etc.
(2) vaccine: combine separately or with at least a antigen.
(3) polysaccharide: particularly select heparin.
(4) nucleic acid: RNA, DNA, oligonucleotide and polynucleotide.
(5) belong to non-peptide-protein molecule, particularly anthracycline, Zorubicin, colchicine, the taxanes etc. of different anticancer chemotherapy types.
(6) mixture of above-mentioned various activeconstituentss.
Nanoparticle suspension colloid of the present invention can filter by sterilising filter, obtains sterile injectable or oral medicinal fluid, and is convenient and economical.The nanoparticle of carrying active composition is used to produce for example medicinal product of sustained release activeconstituents system type.They can be the medicinal products of administration such as in per os or nose, vagina, eye, subcutaneous, intravenously, intramuscular, intradermal, intraperitoneal, the brain.
Nanoparticle of the present invention can be used for production nutrition, plant protection or makeup special product.The application examples of makeup such as nanoparticle and composition of active components can be used by transdermal.
The invention has the advantages that:
(1) nanoparticle of the present invention is more stable under physiological condition, avoided the easy flocculation sediment of chitosan nano, and the hydrophilic chain of nanoparticle of the present invention is longer, helps improving the amount of carrying the hydrophilic active composition.
(2) triblock copolymer synthetic route of the present invention is easily capable, purge process is easy, the monomer material convenient sources.
(3) the synthetic multipolymer can spontaneous formation nanoparticle in the aqueous solution, does not need to add organic solvent, tensio-active agent etc.
(4) particle diameter of nanoparticle of the present invention is all less than 250nm, and heterogeneity index shows that all less than 0.1 the particle diameter of nanoparticle is less, and distribution range is narrower.Nanoparticle of the present invention all has stronger surface charge (Zeta potential), and is more stable under the physiological environment condition, is difficult for producing cohesion and precipitation.
(5) the charged nanoparticle of surface hydrophilic of the present invention is difficult for being engulfed system identification by endothelium, can increase activeconstituents cycling time in vivo, enhanced activity effect.Epithelial cell as diseased regions such as tumours is in a kind of seepage state, because the long in vivo circulation of nanoparticle, the chance that the medicine that its bag carries enters diseased region increases.
(6) chitosan in the nanoparticle of the present invention has the effect of sticking, and the activity component concentration difference of mucous membrane surface and mucous membrane internal layer is increased, and helps the diffusion of activeconstituents, improves the effect of activeconstituents.
(7) some group (as carboxyl) on acrylic acid derivative or the methacrylic acid derivative can combine with some enzymes, the active centre of destructive enzyme, thereby protection nucleic acid and pharmaceutical grade protein.
(8) the amphiphilic nano grain among the present invention has long hydrophilic chain, and acrylic acid derivative, methacrylic acid derivative and chitosan have certain electric charge, hydrophilic activeconstituents need not pass through special processing the such as high speed centrifugation, supersound process, organic solvent, tensio-active agent, emulsification, evaporation just can freely be adsorbed on the nanoparticle surface, can not destroy the activity of activeconstituents.
(9) medicine combines more firmly with nanoparticle, can not take place in vivo prominent to release phenomenon, and activeconstituents can slowly release from nanoparticle, plays slowly-releasing, reduces the toxic effect of activeconstituents.
(10) by changing the structure of multipolymer, can control the combination and the release of activeconstituents effectively.
Embodiment
Embodiment 1
0.75 gram chitosan is added in the acetate of 70ml 1%, be heated to 60 ℃, being stirred to chitosan dissolves fully, add 1.5 gram methyl methacrylates, 0.0175 gram ammonium persulphate, reacted 2 hours, dialysed 48 hours, the lyophilize powdered, be scattered in the water, form diblock nanoparticle (CM nanoparticle), particle diameter is 152.6nm.
Embodiment 2
0.75 gram chitosan is added in the acetate of 70ml 1%, be heated to 65 ℃, being stirred to chitosan dissolves fully, add 1.5 gram n-BMAs, 0.02 gram ammonium persulphate, reacted 3 hours, dialysed 72 hours, the lyophilize powdered, be scattered in the water, form the diblock nanoparticle, particle diameter is 187.4nm.
Embodiment 3
1 gram chitosan is added in the acetate of 95ml 1%, be heated to 70 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.1 gram Potassium Persulphate, add 1 gram methacrylic acid quaternary ammonium salt after 10 minutes, add 1.5 gram methyl methacrylates after 30 minutes again, reacted 18 hours, dialysed 96 hours, the lyophilize powdered is scattered in the water, form three block nanoparticles (CTM nanoparticle), particle diameter is 169.2nm.
Embodiment 4
0.75 gram chitosan is added in the acetate of 70ml 1%, be heated to 70 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.06 gram ammonium persulphate, add 1 gram methacrylic acid tertiary amine salt after 20 minutes, add 1.2 gram methyl methacrylates after 30 minutes again, reacted 24 hours, dialysed 56 hours, the lyophilize powdered is scattered in the water, form three block nanoparticles (CDM nanoparticle), particle diameter is 139.4nm.
Embodiment 5
0.5 gram chitosan is added in the acetate of 95ml 1%, be heated to 75 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.1 gram ammonium persulphate, add 0.5 gram methacrylic acid quaternary ammonium salt after 10 minutes, add 0.75 gram methyl methacrylate after 60 minutes again, reacted 16 hours, dialysed 72 hours, the lyophilize powdered is scattered in the water, form three block nanoparticles (CTM nanoparticle), particle diameter is 154.7nm.
Embodiment 6
1 gram chitosan is added in the acetate of 95ml 1%, be heated to 65 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.1 gram ammonium persulphate, add 1 gram methacrylic acid quaternary ammonium salt after 20 minutes, add 1.8 gram Propenoic acid, 2-methyl, isobutyl esters after 30 minutes again, reacted 24 hours, dialysed 96 hours, the lyophilize powdered, be scattered in the water, form three block nanoparticles, particle diameter is 189.5nm.
Embodiment 7
0.75 gram chitosan is added in the acetate of 95ml 1%, be heated to 72 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.09 gram Potassium Persulphate, add 1.2 gram methacrylic acid quaternary ammonium salts after 30 minutes, add 2 gram methyl acrylates after 30 minutes again, reacted 14 hours, dialysed 60 hours, the lyophilize powdered, be scattered in the water, form three block nanoparticles, particle diameter is 166.8nm.
Embodiment 8
1 gram chitosan is added in the acetate of 95ml 1.5%, be heated to 65 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.12 gram ammonium persulphate, add 0.5 gram methacrylic acid tertiary amine salt after 20 minutes, add 1 gram n-BMA after 50 minutes again, reacted 15 hours, dialysed 80 hours, the lyophilize powdered is scattered in the water, form three block nanoparticles, particle diameter is 192.3nm.
Embodiment 9
0.75 gram chitosan is added in the acetate of 95ml 1.5%, be heated to 75 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.1 gram ammonium persulphate, add 0.75 gram methacrylic acid tertiary amine salt after 20 minutes, add 1 gram Propenoic acid, 2-methyl, isobutyl ester after 30 minutes again, reacted 12 hours, dialysed 96 hours, the lyophilize powdered is scattered in the water, form three block nanoparticles, particle diameter is 154.2nm.
Embodiment 10
0.75 gram chitosan is added in the acetate of 95ml 1%, be heated to 70 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.09 gram ammonium persulphate, add 0.5 gram methacrylic acid tertiary amine salt after 20 minutes, add 1.2 gram methyl acrylates after 30 minutes again, reacted 8 hours, dialysed 60 hours, the lyophilize powdered, be scattered in the water, form three block nanoparticles, particle diameter is 147.9nm.
Embodiment 11
0.375 gram chitosan is added in the acetate of 70ml 1%,, be heated to 75 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.06 gram ammonium persulphate, add 0.5 gram methacrylic acid tertiary amine salt after 40 minutes, add 0.6 gram methyl methacrylate after 60 minutes again, reacted 8 hours, dialysed 72 hours, the lyophilize powdered, be scattered in the water, form three block nanoparticles (CDM nanoparticle), particle diameter is 133.6nm.
Embodiment 12
1 gram chitosan is added in the acetate of 95ml 1%, be heated to 68 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.1 gram ammonium persulphate, add 1 gram methacrylic acid quaternary ammonium salt after 20 minutes, add 2 gram methyl methacrylates after 30 minutes again, reacted 24 hours, dialysed 68 hours, the lyophilize powdered, be scattered in the water, form three block nanoparticles (CTM nanoparticle), particle diameter is 176.4nm.
Embodiment 13
0.75 gram chitosan is added in the acetate of 70ml 1%, be heated to 75 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.06 gram ammonium persulphate, add 1 gram methacrylic acid tertiary amine salt after 30 minutes, add 1.8 gram methyl methacrylates after 40 minutes again, reacted 12 hours, dialysed 56 hours, the lyophilize powdered is scattered in the water, form three block nanoparticles (CDM nanoparticle), particle diameter is 145.2nm.
Embodiment 14
1.2 gram chitosans are added in the acetate of 95ml 1%, be heated to 65 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.1 gram ammonium persulphate, add 1.2 gram methacrylic acid quaternary ammonium salts after 30 minutes, add 1.5 gram methyl methacrylates after 30 minutes again, reacted 24 hours, dialysed 80 hours, the lyophilize powdered, be scattered in the water, form three block nanoparticles (CTM nanoparticle), particle diameter is 149.8nm.
Embodiment 15
1 gram chitosan is added in the acetate of 95ml 1%, be heated to 70 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.075 gram ammonium persulphate, add 1 gram methacrylic acid quaternary ammonium salt after 30 minutes,, add 1.5 gram methyl methacrylates after 30 minutes again, reacted 24 hours, dialysed 75 hours, and formed three block nanoparticles (CTM nanoparticle), particle diameter is 171.5nm.
Embodiment 16
0.75 gram chitosan is added in the acetate of 70ml 1%, be heated to 72 ℃, be stirred to chitosan and dissolve fully, feed nitrogen, add 0.06 gram ammonium persulphate, add 0.75 gram methacrylic acid tertiary amine salt after 20 minutes, add 1.2 gram methyl methacrylates after 40 minutes again, reacted 16 hours, dialysed 96 hours, form three block nanoparticles (CDM nanoparticle), particle diameter is 141.8nm.
Embodiment 17
The pH that regulates CM (embodiment 1), CDM (embodiment 12), CTM (embodiment 13) nanoparticle solution with HCl and NaOH solution is respectively 3,4,5,6,7,8,9,10,11,12,13 and 14, investigates the stability of nanoparticle, the results are shown in following table 1:
Table 1 when different pH, the stability of nanoparticle
| pH | CM | CDM | CTM |
| 3 | Stable | Stable | Stable |
| 4 | Stable | Stable | Stable |
| 5 | Stable | Stable | Stable |
| 6 | Stable | Stable | Stable |
| 7 | Slowly precipitate | Stable | Stable |
| 8 | Slowly precipitate | Stable | Stable |
| 9 | Slowly precipitate | Stable | Stable |
| 10 | Slowly precipitate | Stable | Stable |
| 11 | Precipitate immediately | Slowly precipitate | Stable |
| 12 | Precipitate immediately | Slowly precipitate | Stable |
| 13 | Precipitate immediately | Precipitate immediately | Stable |
| 14 | Precipitate immediately | Precipitate immediately | Slowly precipitate |
By table 1 as seen: single chitosan nano produced flocculation, precipitation at pH greater than 6 o'clock, and is unstable under physiological environment, and nanoparticle of the present invention is all more stable under physiological condition.
Embodiment 18
The Regular Insulin PBS solution of 1mg/ml is mixed with 2% CM (embodiment 1), CDM (embodiment 12), CTM (embodiment 13) nanoparticle suspension colloid, 37 ℃ vibrated 5 hours down, 15, centrifugal 50 minutes of 000rpm, get supernatant liquor, use the Lowry method to measure content of insulin in the supernatant liquor, computational envelope rate.The results are shown in following table 2.
The different nanoparticles of table 2 carry the encapsulation rate of Regular Insulin
| Nanoparticle | Encapsulation rate (%) |
| The CM nanoparticle | 65.7 |
| The CDM nanoparticle | 100 |
| The CTM nanoparticle | 100 |
Embodiment 19
Normal SD rat oral gavage is loaded with CM (embodiment 1), CDM (embodiment 12), CTM (embodiment 13) the nanoparticle suspension colloids (100U/kg) of Regular Insulin, get blood 0.2ml respectively at 0,1,2,4,6,8,10,12,14,16,18,20,22,24 hour tail vein, after treating blood coagulation, 12, centrifugal 4 minutes of 000rpm, get serum 20ul, the determination of glucose oxidase blood glucose value.
The hypoglycemic activity that carries insulin nanoparticles that table 3 is different
| Blood sugar get back to basal level time (hour) | |
| Insulin solutions | 1 |
| CM nanoparticle insulin solutions | 6 |
| CDM nanoparticle insulin solutions | 10 |
| CTM nanoparticle insulin solutions | 16 |
By table 3 as seen, CDM, CTM nanoparticle have the good slow release effect.
Embodiment 20
Superoxide-dismutase (SOD) easily loses activity, and limits its use in makeup.Nanoparticle CDM (embodiment 12), CTM (embodiment 13) are mixed with SOD, and homogenizing emulsifying was placed 1 hour for 70 ℃, utilized pyrogallol to measure the SOD activity from oxygen method (325nm).The results are shown in Table 4.
Table 4 nanoparticle is to the influence of SOD stability
| Active (%) | |
| SOD | 51.7 |
| CDM nanoparticle+SOD | 88.4 |
| CTM nanoparticle+SOD | 89.2 |
By table 4 as seen, CDM, CTM nanoparticle have the effect of stablizing SOD
Claims (11)
1, a kind of nanoparticle with hydrophobic core, water-wetted surface is characterized in that being made up of following two kinds of polymkeric substance: the hydrophilic polymer block of the hydrophobic polymer block of polyalkyl acrylate or polyalkyl methacrylate and wetting ability unsaturated monomer or the polymer-modified chitosan that formed by this wetting ability unsaturated monomer; Wherein, the part by weight of wetting ability unsaturated monomer and chitosan is in 20: 80 to 80: 20 scope, and the part by weight of alkyl acrylate or alkyl methacrylate and wetting ability unsaturated monomer-chitin copolymer or polymkeric substance-chitin copolymer of being formed by this wetting ability unsaturated monomer is in 90: 10 to 50: 50 scope.
2, nanoparticle according to claim 1 is characterized in that said alkyl methacrylate is one or more in methyl methacrylate, Jia Jibingxisuanyizhi, propyl methacrylate, butyl methacrylate, Propenoic acid, 2-methyl, isobutyl ester and the N-Hexyl methacrylate; Said alkyl acrylate is one or more in methyl acrylate, ethyl propenoate, propyl acrylate, butyl acrylate, isobutyl acrylate and the Ethyl acrylate.
3, nanoparticle according to claim 1 is characterized in that said wetting ability unsaturated monomer is a vinylformic acid, methacrylic acid, the vinylformic acid salt, the methacrylic acid salt, the salt of acrylate or acids, the salt of methacrylic ester or acids, acrylic acid amides, the amides of methacrylic acid, acrylic acid N-alkylamide, the N-alkylamide of methacrylic acid, the salt and the acids of vinylformic acid N-alkylamide, the salt and the acids of methacrylic acid N-alkylamide, acrylamide, acrylamide derivative, Methacrylamide, in the methacrylamide derivatives one or more.
4, nanoparticle according to claim 3 is characterized in that used wetting ability unsaturated monomer is one or more in acrylamide, N-N-isopropylacrylamide, methylacryoyloxyethyl trimethyl ammonium chloride, dimethylaminoethyl methacrylate, the 3-sulfopropyl-vinylformic acid sylvite.
5,, it is characterized in that particle diameter is 100-250nm according to the described nanoparticle of claim 1-4.
6, a kind of preparation method with nanoparticle of hydrophobic core, water-wetted surface is characterized in that concrete steps are as follows:
(1) chitosan is dissolved in 1% the acetate, is heated to 60～75 ℃, add initiator, add the wetting ability unsaturated monomer after 10～60 minutes, form graft copolymer;
Add hydrophobic alkyl acrylate or alkyl methacrylate after (2) 10～90 minutes, reacted 2～24 hours, obtain the amphoteric triblock copolymer;
(3), promptly get three block amphiphilic nano grains with hydrophobic core, water-wetted surface with above-mentioned triblock copolymer purifying;
Wherein, the part by weight of wetting ability unsaturated monomer and chitosan is in 20: 80 to 80: 20 scope, and the part by weight of alkyl acrylate or alkyl methacrylate and wetting ability unsaturated monomer-chitin copolymer or polymkeric substance-chitin copolymer of being formed by this wetting ability unsaturated monomer is in 90: 10 to 50: 50 scope.
7, nanoparticle preparation method according to claim 6 is characterized in that said alkyl methacrylate is one or more in methyl methacrylate, Jia Jibingxisuanyizhi, propyl methacrylate, butyl methacrylate, Propenoic acid, 2-methyl, isobutyl ester and the N-Hexyl methacrylate; Said alkyl acrylate is one or more in methyl acrylate, ethyl propenoate, propyl acrylate, butyl acrylate, isobutyl acrylate and the Ethyl acrylate; Said wetting ability unsaturated monomer is a vinylformic acid, methacrylic acid, the vinylformic acid salt, the methacrylic acid salt, the salt of acrylate or acids, the salt of methacrylic ester or acids, acrylic acid amides, the amides of methacrylic acid, acrylic acid N-alkylamide, the N-alkylamide of methacrylic acid, the salt and the acids of vinylformic acid N-alkylamide, the salt and the acids of methacrylic acid N-alkylamide, acrylamide, acrylamide derivative, Methacrylamide, in the methacrylamide derivatives one or more.
8, nanoparticle preparation method according to claim 7 is characterized in that used wetting ability unsaturated monomer is one or more in acrylamide, N-N-isopropylacrylamide, methylacryoyloxyethyl trimethyl ammonium chloride, dimethylaminoethyl methacrylate, the 3-sulfopropyl-vinylformic acid sylvite.
9, nanoparticle preparation method according to claim 6 is characterized in that said initiator is a kind of of ammonium persulphate or Potassium Persulphate, and consumption is 0.01～0.2% of a reaction system, g/ml.
10, a kind of application with nanoparticle of hydrophobic core, water-wetted surface as carrier for active principle, this activeconstituents is at least the one of the following kind:
(1) protein and polypeptide: a kind of in Regular Insulin, oxyphorase, albumin, cytopigment, Interferon, rabbit, antigen, antibody, erythropoietin, tethelin, interleukin and the G CFS;
(2) vaccine: combine separately or with at least a antigen;
(3) polysaccharide: particularly select heparin;
(4) nucleic acid: RNA, DNA, oligonucleotide and polynucleotide;
(5) belong to a kind of in non-peptide-protein molecule, particularly anthracycline, Zorubicin, colchicine, the taxanes of different anticancer chemotherapy types.
11, a kind of application of nanoparticle in nutrition, plant protection or makeup special product with hydrophobic core, water-wetted surface.
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007071325A3 (en) * | 2005-12-21 | 2007-07-26 | Unilever Plc | Composition containing and active agent and polymeric carrier particles comprising a copolymer of a hydrophobic monomer and a hydrophilic polysaccharide |
| EP2114377A2 (en) * | 2007-01-31 | 2009-11-11 | Rutgers, The State University of New Jersey | Controlled release of actives in skin |
| WO2011003240A1 (en) * | 2009-07-10 | 2011-01-13 | Basf (China) Company Limited | Formulation comprising terpolymer and active substance, and preparation thereof |
| CN102357079A (en) * | 2011-10-28 | 2012-02-22 | 复旦大学 | Carboxymethyl chitosan nanoparticles modified with glycyrrhizic acid, preparation method and application thereof |
| CN102300890B (en) * | 2009-01-30 | 2014-03-26 | 惠普开发有限公司 | Block copolymers and block copolymer nanoparticle compositions |
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| CN101653611B (en) * | 2009-07-23 | 2012-05-09 | 复旦大学 | Albumin-adriamycin nano preparation, preparing method and application thereof |
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2005
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| WO2007071325A3 (en) * | 2005-12-21 | 2007-07-26 | Unilever Plc | Composition containing and active agent and polymeric carrier particles comprising a copolymer of a hydrophobic monomer and a hydrophilic polysaccharide |
| EP2114377A4 (en) * | 2007-01-31 | 2012-08-01 | Univ Rutgers | Controlled release of actives in skin |
| EP2114377A2 (en) * | 2007-01-31 | 2009-11-11 | Rutgers, The State University of New Jersey | Controlled release of actives in skin |
| CN102300890B (en) * | 2009-01-30 | 2014-03-26 | 惠普开发有限公司 | Block copolymers and block copolymer nanoparticle compositions |
| WO2011003961A3 (en) * | 2009-07-10 | 2011-08-25 | Basf Se | Formulations comprising terpolymer and active substance, preparation and use thereof |
| WO2011003240A1 (en) * | 2009-07-10 | 2011-01-13 | Basf (China) Company Limited | Formulation comprising terpolymer and active substance, and preparation thereof |
| CN102002132B (en) * | 2009-09-02 | 2014-05-28 | 陈煜� | Improvement on method for preparing complex of polyvinylpyrrolidone grafted with natural polymer or water-soluble derivate thereof and iodine derivate |
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| CN105131199A (en) * | 2015-08-28 | 2015-12-09 | 吴奇 | Preparation and preparing method and application thereof |
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| CN108047455A (en) * | 2018-02-09 | 2018-05-18 | 中国人民解放军陆军军医大学 | Amphipathy hyperbranched polymer for antigen vectors and its preparation method and application |
| CN108329483A (en) * | 2018-02-09 | 2018-07-27 | 中国人民解放军陆军军医大学 | Amphipathy hyperbranched polymer and its preparation method and application |
| CN108047455B (en) * | 2018-02-09 | 2020-12-25 | 中国人民解放军陆军军医大学 | Amphiphilic hyperbranched polymer for antigen carrier and preparation method and application thereof |
| CN112915980A (en) * | 2021-01-26 | 2021-06-08 | 扬州工业职业技术学院 | Phenol adsorption film based on dual-drive self-assembly method and application thereof in wastewater purification |
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