Scribd Logo
Upload

Welcome to Scribd!

  • Us 2010163778 A 1

    Uploaded by

    Ali Ali Aliali
    20 views11 pages
    dsdas

    Original Title

    Us 2010163778 a 1

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Report this Document
    dsdas

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    20 views11 pages

    Us 2010163778 A 1

    Uploaded by

    Ali Ali Aliali
    dsdas

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 11
    co») United States Zhang et al. c2) Patent Application Publication US 201001637781 (10) Pub. No.: US 2010/0163778 AL (43) Pub, Date: Jul. 1, 2010 (34). SIMPLE METHOD FOR INTRODUCING MAGNETIC PARTICLES INTO A POLYMER (75) Inventors) Congyun Zhang, Beijing (CN); Weidong Zhou, Beijing (CN) Correspondence Address: DAVIS WRIGHT TREMAINE, LLP/Seattle 1201 Third Avenue, Suite 2200 SEATTLE, WA 98101-3045 (US) (13) Assignee: BEWING DINGGUOCHANGSHENG BIOTECH, CO. LTD., Beijing (cn) (21) Appl. No. 121600,647 (22) PCT Filed May 18,2007 (86) PCT No. PCTICN2007/001622 $371 (0X0) (2),(4)Date: Feb. 1, 2010 Publication Clas Cl HOLE ior (2006.01) a. 25216255 ABSTRACT The present invention provides simple method fr introduc ing magnetic particles into a polymer for further preparing a ‘magnetic polymer, the methad using the capability of poy mer to absorb Fe and other divalent metal ons M-", adding alkali immediately each time after absorbing Fe" or M™ thereby generating hydrated oxide ofthe Fe and hydrated ‘oxide of the divalent metal ions in sequence inside the poy. ‘met, and then heating, so thatthe hydrated oxide ofthe Fe™= an! the hydrated oxie ofthe divalent metal ions are trans ‘ormed into magnetic particles MFexOy, where M may be Fe, Za, Me", Cu", Ca, Bat, Si, Ni, Coe, Min and the ike, and x-1.0°2.0; y-3.0-40. Compared with the prior art method, the presen one is simpler, wider in appli ation, and more operable US 2010/0163778 Al SIMPLE METHOD FOR INTRODUCING MAGNETIC PARTICLES INTO A POLYMER FIELD OF THE INVENTION 10001] The present invention relates to a method for pre= Paring a magnetic polymer, and in particular, relates to simple method for preparing a magnetic polymer by intro- ducing magnetic particles into polymer, BACKGROUND OF THE INVENTION [0002] A magoetic polymers a composite material com- posed of polymer and magnetic inorganic compound. Cur rely, mest magnete polymers in fastest development ae rogue ina particle fon ands tween nanomtersand milimetr. Since magnetic polymers ae capable of rapidly tnoving ina certain dieton in an external mgt eld they are widely applied in fields soch as biochemistry, tmolectlar biology, medical scence, phamaceutial science and chemical eaalysis, ete, for example, they may act as powerful isolation and purification tools in studies on purifi- ationand isolation of clei acids nd proteins, cell sereen- ing, immune ealsis and cinial diagnosis, and may sho sd in ating raps, The magnetic polymer isnt mite twsphercl shape, which ean be any gsomete spe, and it inay assume various kinds, icloing solid, oll, porous, dumb bell-shaped, onion-shaped, micro capsular, flaky or ‘ther imegalar shapes, et [0003] "A magnetic polymer mainly comprises two pa ‘one isthe magnetic part mainly aking of inorganic patil, for example metal particles such a ron, cobalt and nickel, ce, oF magnetic frie particles, for example FeO, and Mre,0,, where May be Fe, Zn. Mg, Ca, Ca, Ba Sc N.Co, Ma, ete. Anothe part of the magnetic polymere poyane, and typically the magetie particles are encapsulate inside the polymer [0004] Carey the known meted for preparing o meg ttc polymer are to asemble th ing parile part and the polymer pact sequently, which can he summaries in the following kinds i preparing in advance the mapoetic partite and polymers, plysially mixing he polymers and magnetic atc. This mnths simple end ss demanding, bathe prod is oor in shape, with wide dtrbutions of pale ameter. 2 preparing in vance the magnetic parle, and polymer izing organic monomers atthe periphery of the magnetic paris. Since the inorgni parle andthe organi mono ters havea poor fin the grates fc for preparing ‘compost poymers sing theongnie monomer polymerize tion method on magnetic particles i that the monomers re ha to be polymerized at te mire of inorgnie prices, tor form spheres sparta, which roy reel in scant spheres, an the magnetic partes are unevenly distributed between spheres either. To overcome this draback, ts noes to procesthe uric of nongane pails but he poet sill ean not mest the eqirmeat 3 preparing in advance the polymer isl iatrodueing meg netic patils into the polymer, For example, U.S. at No 4,774,265 cselosesa method of preparing the polymer pret substanse with very even pace diameters fist an then iniadicng the magnetic sibstanes into the inside of the polymer The method requires the plymerto have functional Erpups capable ofinng metal ins sich as Fe, Co, and Ni fndonly nthe case wher the nabs ons inthe ction Jul. 1, 2010 ae eliminated after absorbing suficient divalent meta ions and Fe"* ions withswitable proportions, and alkaline reagents tare added finally, the magnetic particles can be generated inside the polymer in stu. Ifa polymer has no absorption capability to the above meta ions, such polymer ean not he used to prepare magnetic polymer. {0005} "The method disclosed by the U.S. Pat, No. 4774, 26S is toad a solution ofa mixture oftwo metal ionsinto the polymer mircosphere. This method requires the polymer microsphere o absorb divalent metal ions and Fe" ons with 8 suitable proportion at the same time, and for oxiation- reduction reaction, the amount ofthe oxidization agent or reducing azent may be controlled such that the final propor- tion between the divalent metal ons and Fe" fons s 1:2, and thereby generating magnetic Fe,0,, [0006] "However, tothe polymer Which has no oxidable or reducible group, use of such mixed iron sat doesnot have a ood effet inthe following aspects: fil, its nt easy to contol the absorption proportion ofthe divalent metal ions andl Fe" ions inside the polymer to be exactly 1:2; secondly, «proportion of metal ions in mixed ion sal, which is suite able for one polymer, may not be suitable for another polymer B; thinly, it may require times of repetitive operations 10 obtain the magnetic transfer effect and moreover, magnetic polymer ean often not be obtained for micron or smuller polymer. [0007] Besides, intrvtetion of magnetic particles to ear- boxylicresinis disclosed inthe literature “Study on Preparing “Magnetic Cation Exchange Resin by Chemical Transforma- tion Method”, by Zhang Mei, Wang Busen, Zhang Yuge, He BBinglin, et, Zon Exchange and Absorpion, 1995, 11 (4), 302-308, wherein in case the mol rato between two ion sats being 2:1, or even 1:1, itis unable to introdoce magnetic particles into the polymer, whichanonly be suecessfalunder tte mol ati being :5-1:50 andthe polymer can only exhibit strong magnetism after repeating the introduction throe times or more. It is speculated that weak acid type ion exchange resin has a clear selectivity, which has a strong sorption capability to Fe" but weak io absorb Fe", thusit needs a greatly excessive amount of Fe™ salt in the mixed ironsalt Besides, when magnetic transferring, theineresse of ‘magnetism is not proportional, and there may have more complex affecting factors besides the selectivity. {0008} Besides, the information as disclosed in Example 2 ofthe U.S. Pat. No. 4783,102 also shows similar situation, ‘wherein when using a 1:1 fon salt mixture solution, a sul- fonated erosslinked polystyreneion-exchange esinhavinga strongly acidity only has a slight magnets fe the frst !magretism transformation, and only exhibits an apparent magnetism after times of magnetism transformation {0009] Thos, a method which is simpler, wider in aplica- tion and more operable is needed, SUMMARY OF THE INVENTION [0010] An object of the present invention is to provide a simple method for preparing a magnetic polymer by intro- ducing magnetic particles into the polymer. {0011} Themethod according w the present iaventioncom- prises steps of 1) putting a polymer in a container, the polymer having _roups capable of absorbing Fe" ions and Pe fons or other divalent metal ion, and having large pores within the mol- cule or boing eapable of forming a microporous gel in a solution; US 2010/0163778 Al 2) adding a Fe** salt solution into the polymer of 1), and String to make the polymer absorb Fe ons 3) washing the resultant to eliminate unabsorbed Fe ions, ‘and then ang an alkaline solution o contol the pl value in ‘range fom 9 1014, sirng, and thea washing to neutral, 4)adkinga divalent metal salt solution into the polymer of 3), stirring to make the polymer absorb divalent metal ions, ') washing the resultant to eliminate the unabsorbed divalent metal ions; 6) introducing an ineet gas, adding an alkaline solution 19 control the pH value in 8 range from 9 to 14, sing and heating, maintaining fora period of ime, and thus the meg- netic polymer is priced. 10012] Instep 1) ofthe method ofthe present invention, the polymer isa wet cross-linked polymer with water content \weight being 0.1-100 times 10013] Instep 1) ofthe method ofthe present invention, the polymer is a water-soluble natural polymer and derivatives thereof, including pectne, heparin, animal serum albumin, selose, glocan and their derivatives. 10014] instep 1) ofthe method ofthe present invention, the polymer isa synthetic polymer having cation exchange capa- bility, the synthetic polymer i formed by homapolymeriza- tionor copolymerization of monomers having soups suchas —SO3H (sulfonic group), —COOH (carboxy! group), —POH, (phosphate group), —CONH—OH (hydroximie ‘acid group) in the molecule ora polymer introdoced with the above groups by chemical modifeation 10015] Instep 1) ofthe method ofthe present invention, the polymers asynthete polymer having single coordination or chelation capobility, including polyacrylamide, polyvinyl aleohols, polyvinyl pyridine, polyvinyl amine, or imine cr- boxylic acids bearing both amino group and carboxyl group in @ molecule (-NHCH,COOH, —N(CH,COOH),, ete), phosphoramidie aid stracture (-NECH,PO,H,), proline structure i) 0016] _Instep2) of temethod ofthe present invention, the Fe salt includes FeCl, and is hydrates, Fe(NO3}y and its hytrates, (NE, )FeSO,). and its hydrates, (NH)s{F(C0.) sJand is hydrates, Fe(CI0,):XH0, eric eta, an ferie ‘ammonium citrate. 0017] In step 3) and step 6) ofthe method o the present invention, the alkaline solution includes any one of KOH, NeOH, and ammonia 0018} instep) ofthe method ofthe present invention, the divalent metal salt is a divalent metal compound which is capable of forming magnetic MFe,O, particles with Fe” ions, wherein Mincludes Fe", Za", Me? Se*, NP*, CoP, Mn?*; x=1.0-2.0¢ and y=3 10019] instep ofthe method ofthe present invention, the divalent metal salt includes FeCl, and its hydrates, ferrous ‘oxalate, (NH,),Fe(S0,), and its hydrates, FeSO, and its hydrates, MgCl, and its hydrates, MnSO, and its hydates, (CoC, and its yates, NiCI, and its hydrates Jul. 1, 2010 {0020} Instep 3) and step 6) of the method ofthe prseat Jnventon, the alkaline soltion ines any one of KOH, N20, and ammonia, {0021} Themethod provdedby the present invention needs 10 consideration of the absorption proportion of MP*IFe* inside the polymer, and after separately aldng Fe" and MW, 8 magnetic polymer can be obtained by only performing ‘magnetism tansfonation for one time. The method ofthe present invention is parteuary advantageous to sll sized polymers for example in nanometers or micros DESCRIPTION OF THE PREFERRED EMBODIMENTS {0022} Themethod ofthe present invention sto iatoduce ‘magnetic particles into a shaped polymer, by utilizing the capability ofthe polymer o absorb Fe" ons and other diva- Jent metal ions M™, the method comprises: adding Fe* ions and divalent metal ions i sequence, adding alkaline inme- diately after each time of absorbing a cation, thereby gener- ating hydrated oxide ofthe Fe ions and hydrated oxide of divalent metal ins inside the polymee in sequence: and then heating, so that the hydrated oxide ofthe Fe ions and hydrated oxide of divalent metal ions ae tansfoemed into magnetic particles MFe,0,, M may be, Fe, Zn”, Mp, Ce Cae Bars Se" NE, Core, Ma and, when 310-20; 9-30-40, {0023} The polymer applicable to the present invention is fisly a cross-linked water soluble polymer or @ strongly lydrophiie polymer. Lhe polymer have a weak hydophil fy, the ions are hard to be dispersed into the inside ofthe polymer, andthe polymer absorbs very small amount of ans br the absorption balance time is unduly lag, which causes the amount of magnetic particles inside very small, and the preparation sep istoo comple to havea practical vale. The ‘water soluble polymer is preferably subjected toa cross linking processing, including physical cross linking. and chemical cross inking. For example, geose canbe dissolved in water ata high temperature, while it ean only be swelled, not solve, in water at rom temperature, which atypical example for physical erossfinking. What is used most is chemical crosslinking, and the reason fr preferably using chemical eros inking is that it snot alec by a general solvent and temperature changes or other conditions, thus ean ensure the material's morphological stability. Ii tu that ross linking will aflect the hydrophilty of polymer. thas boon found hat some water soluble polymers may lose water absorption capability after high level ofeross linking, butitis easy o maintain the balance between good hydrophilty and ‘mechanical strength of a polymer by adjusting the level of crosslinking, {0024} There are many kinds of water soluble polymers oF tere have een many simple methods to modify polymers to cahance theie hydrophility, and a polymer having many strongly hydrophilic gropswilalo have song sbsonytion capability to MP"7Fe™. The stongly hydrophilic groups are mostly polar groups, which away’ havea strong absorption capability to metal ions by coordination or forming ionic bonds. [0025] The water soluble polymer or strongly hydrophilic polymer in the present invention may be conveniently improved in the hydrophifty by polymerizing water soluble ionomers carried wih stogly hydrophilic groups by then- selves or introducing strongly hydrophilic groups into the polymer, Examples of chemical groupe ith sitong hydrophi- US 2010/0163778 Al lity and strong absorption capability to MP*Fe™ are, for ‘example, —SO,H (sulfonyl group), OH (alcoholic hydroxy! group, phenolic hydroxy! group), —O— (ether, ‘epoxy group), —CONR; (acylamino group, R=H orally), NH (primary amine), (secondary amine), (tontiary amine), (imine), (schitt base, \ Non (oxime), —As0,1, (arsenic cid group), S01, lene ‘cid group). —SO,H (sllsic acid group). COOH (cat- box group), -COOR (carboxylate group) —CONI—OF (hydrximic acid grup), CN (eyano group), ~CONHNE, (hyeazide), NO (nitrogen oxide), 001 (proline), —CO— (aldehyde, Ketone, quinone), —PHO (OH), —PHO(OH,, —PO(OH);, —NO, (nitro group), NO (nitroso group), —NHOCO— (carbamate group), —NHCO—NH- (ureido group), nitrogen-coatsining het- ‘erocyelic sing, —SH (thio, thiophenol), S— (thioether), $0 (sulphone and sulphoxide), Jul. 1, 2010 > (culfaldebyde, thioketone), —COSH (thiocarboxylic acid), —CSSH (carbodithivic acid), —CS-S—S—cs—, —CSNH,(thioacid amide), SCN (sulfoeyanate), — (mone, dior tally] or aryl phosphine, ec), amino car- boxslic acid series, —NHCH,PO(OH),.phosphoramiic acid series, H(NHCH,CH),.NH (polyethylene polyamine series), -N=N— (azo), (0026) Examples ofthe wate sohuble polymer with strong hydophility and bearing a chemical group having a strong absorption capability to M2*/Fe™* or strongly hydop polymer are as follows: (1) water soluble natural polymers such as modified starch, moi cellulose, pectne, heparin, some proteins (Soybean protein, fibroin, gluten), animal serum albumin, gelse, chitosan, glucan, alginic acid and their derivatives; (2) polymers which dissociates completely or parially cations nan aqueous solution, suchas poly (meth) acrylate, polyalutamic acid, hydrolysate of copolymer of polyserylate and vinyl acetate, copolymer of acrylic acid and acrylamide, polyvinysulfonte polystyrene sulfonate, poly~ maleic anhydride, polymethyl methacrylte-viny! acetate pressurized hydroiyzate, polyaerylonitrile hydrolyze, ‘wherein the strong aid type has sulfonic group, with ethyl- ne, styrene or metibond ureaformaldehyle polycondens- tion systemas the backbone; the weak acid type typically has carboxylic acid or phosphorous acid group. (3) hydrophilic polymers whieh are espable of forming simple eordination with MP*Fe™, such as polyarylamide, polyvinyl alcohol, poly alkane oxide, polyoxyethylene, polyvinyl imine, poly- Vinyl pyridine, and polyvinyl amine; (4) polymers having ‘more than two coordination site and thereby chelation capa- bility, for example, EDTA type resin with eross-linked sty- rene asthe backbone and introcing imine polyearboxylic avid, which may also be obtained by polymerization from oefine monomers with imine carboxylic acid, such resin has «strong absorption capability to most M?* and Fe, typical imine (polyarboxylic acid chelating. groups are: imine diacetic acid, imine acetic acd propionic aid nitrbotriactic avid, N-2-hydroxyethyethylenediamine-tracetic acid eth- yen diamine tetraacetic acid, diethylene triaminepentaace- tic acd, ethylene diamine-N,N -diacetic aid type resin pro- duced "by reaction between polyethylene imine and chiloroatic acids with polyvinyl alcohol as the framework, introducing imine carboxylic acid group by reacting with epoxy-bearing amidodiaetate, chelating resin with Pike tone stricture obisined by polymerizing, methyl scroloyl acetone monoers-ketoaid ester generated by grating reae- tion between polyvinyl alcohol and ketene a chelate wth US 2010/0163778 Al structure formed by condensation reaction of polyvinyl amine as the backbone with sulicylaldehyde derivatives: ‘chelating resin with cross-linked styrene asthe backbone and introducing phosphoramidie acid on the benzene ring, or chiral chelating resin with cross-linked polyviayl alcohol as the boekbone and introducing L-proline 001 fier activation by chlorcepoxy propane. [0027] Fe" jonsandorter divalent metal ions are absorbed to the polymer via coordination bondion bond. The coor nation bondion bond formed between the absorption groups ‘onthe polymerand ihe metal ions are reversible. After adding alkali, for example, sodium hydroxide, the coordination roups or ions on the polymers will resume their original forms, andthen the metal onsar exchanged by Na fons te like, thereby forming a hydrated oxide and being depos- ited in the polymers. For example fistly a kind of metal on, for example Fe, i absorbed and after adding alkali, tans- formed ito the hyrated oxide; then another kind of divalent metal ion, for example Fe", is absorbed and also trns- formed into the hydrated oxide by adding alkali; and once hesting again, the two hydrated oxides wenerate magnetic particles MFe,O,, where M may be Fe™, Za", Ma", Cu", Gee", Bae", Se, NP*, Co®, Mn?* andthe ike, wherein 1.0-20; y-3.0~40. By using the method of the preset invention, i ypically nee only magnetism transformation ‘once to obtain strong magnetism satisfying the use require ments, and ihaher magnetism content is required, repeated reaetions are allowed. Besides, according to the preseat invention, two kinds of ions are absorbed respectively in Sequential two steps the advantege of which is thatthe absorption of any kind of ion is nt affected by oer ions, which needs no consideration of interaction between Wo kinds of ion ata further the method is applicable to poly- mers with large parle diameters or small lange diameters, ‘and tis not subject ote infiuence of mierooosmic environ: ment 10028] ‘The magnetic polymers prepared seeonting 0 the method of the present invention ore widely applicable jn fields such as eatalytie study, magnetic recording materials, magnetic resonance image, pining, cosmetics and chemical catalysis. The magnetic polymer mierospheres are also ‘widely applicable in fields such as cell biology, molecular biology, immunology, medical science and pharmacology, for example by binding antibodies to magnetic polymer microspheres, cance cell can be isolated fom an onganism, thas the magnetic polymer microspheres ae a powerl tool forisolation and purification Magnetic polymers can also be used for thermal therapy of tumor, which is a promising therapy for tumor treatment, where the treatment purpose is achieved by heating effect of magnetic polymers distributed Jul. 1, 2010 Jn the tumor tissues upon applying an extemal alternating magnetic field. Or by forming a targeting drug by loading taticancer drugs on the magnetic polymers, the anticancer drugs, under the guide of magnetic field, are enriched in the acu pat, thereby redcing noxios side effects ofthe dugs on the normal ells EXAMPLES [0029] Hereinatier, the present invention is further

    You might also like