• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
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  • 优先权
    • 专利摘要:
    Novel polymers having a linear backbone which is free from both branching and cross-linking, comprising either tertiary or quaternized nitrogen atoms linked to each other through ethylene groups. These polymers are useful as antimicrobials, flocculating agents, antistatic agents, electroconductive agents for coating paper, chelating agents and bile acid binding agents, as well as in similar applications where their high charge to weight ratio and fully accessible nitrogen atoms can be employed. The polymers are obtained by the polymerization of an oxazoline, hydrolysis or direct reduction, nitrogen substitution, and optional quaternization of the resulting polymer.
    公开号:SU727150A3
    申请号:SU762408605
    申请日:1976-09-28
    公开日:1980-04-05
    发明作者:Грайер Натаниэль；Франклин Вагнер Артур
    申请人:Мерк Энд Ко.,Инк (Фирма)；
    IPC主号:
    专利说明:

    1 The invention relates to the field of the chemistry of high molecular weight compounds specifically to the preparation of linear polyamines possessing biologically active properties for binding bile acids. A known method for producing linear polyamines containing quaternary nitrogen atoms by reacting tritic amines with cores l. Polymers of the general formula Wn "fN- (CH,)., (CH,) A are obtained. The resulting polymers have biological activity. A disadvantage of the known method is that the processable polymer is partially crosslinked. The known method provides a limited opportunity for the introduction of substituents attached to the polymer chain. The chain of the invention is to broaden the range of biologically active polyamines for binding bile acid. The goal is accomplished by reacting the polymer containing the repeating unit | N- (. Where} Q is ethylene or trimethylene, Rf, R2 is the lowest, lowest alkvl substituted by one hydroxy group, (, is an alkyl noticed by several hydroxyl groups). groups, Cj-41-cycloalkyl, substituted with several alkyl groups, Such; cycloalkyl, -cycloalkyl-substituted lower alkyl, ammonium lower alkyl, lower alkyl ammonium lower alkyl, lower alkyl ammonium, lower trialkyl ammonium lower alkyl, carboxy lower alkyl, carboxy lower alkyl, lkilo, cjk with two alkylating RX and Rj, X, where R, R - hydrogen, lower alkyl, monohydroxy-substituted lower alkyl, polyhydroxy-substituted - cycloalkyl, - cycloalkyl, cycloalkyl-substituted lower alkyl, lower alkyl substituted - cycloalkyl yl, ammonium lower alkyl, lower alkylammonium lower alkyl, di-lower al-: cylammonium lower alkyl, trin-lower alkyl ammonium lower alkyl; carboxy-lower alkyl; carbon is lower alkoxy lower alkyl; - alkeiil; alkynyl; aralkyl; carbamyl lower alkyl; Fluoro-substituted lower alkyl cyanza -substituted lower alkyl; guanidine lower alkyl; carba-, synthetic lower alkyl; N is a lower alkylcarbamidine lower alkyl; lower alkoxy lower alkyl; lower alkylthioalkyl; furanosyl; pyranosyl and lower alkanoyl lower alkyl, Example 1, A polymer in which R is 3-hydroxypropyl and R. is methyl (random distribution, 5:05 ratio). A solution of 462 mg (6 μs of equivalents) of polymethyl-1P | trimethylene and 41 mg (300 µmol) of 3-bromopropanol in 12 ml of dimethlformamide were kept at s for 24 hours. The mixture was cooled and 2.9 g of methyl bromide was added to it. The reaction mixture was held at 50 ° C for 3 hours. The product was concentrated by condensing the reaction mixture under reduced pressure and washed with ether and then dried under reduced pressure. The exchange of bromine counterion for chlorine ion was carried out; the usual way. using an ion exchange resin. Example 2. A polymer in which R is hydroxyP13opil and R is methyl (random distribution, 50:50 ratio). A solution of 213 mg (3 millisquivaleNta) of poly- (methyleneamino) trimethylene7 and 209 mg (1.5 mmol) of 3-bromopropanol Was isolated at 75 ° C for 24 hours. Reactionary; the mixture was cooled and 1.5 g of methyl bromide was added to it. The reaction mixture was then kept at 50 ° C.
    3 hours and was processed by the method described above.
    PRI me R 3.
    Polymer; in which R is 3-hydroxypropyl and R4 is methyl (random distribution, 95: 5 ratio).
    A solution of 1.42 mg (2 milliequivalents) of poly- (methylamino) trimetshlen and 264 mg (1.9 mmol) of 3-bromopropanol was held at 75 C for 16 hours. After cooling the mixture, 1 g of methyl bromide was added and the mixture was kept at 50 ° C for 12 hours. The reaction mixture was processed according to the method described above.
    PRI me R 4,
    Poly- {methyl- (3-methoxypropyl-imins trimethylene chloride3.
    A solution of 284 mg (4 milliequivalents) of poly (methylimino) trimethylene1 and 2.45 g (16 mmol) of 3-methoxypropyl bromide in 15 ml of dimethylformamide was crushed at a temperature of 75 ° C for 16 hours. The product was filtered, washed with ethyl ether and dried under reduced pressure. The product was dissolved in 25 ml of water and the bromine counterion was exchanged for chlorine ion. As a result, 450 mg of polymethyl (3-methoxypropyl) imino triethylene chloride was obtained.
    In the synthesis of polymers in which K. and RJ, respectively, 3-meth 6 hydroxypropyl and methyl, with a ratio of 5:95 to 95: 5, the procedure used is similar to that described above. Poly (methylimino) trimethylene interacts with a limited amount of 3-methoxyproduct bromide, and then with an excess of methyl bromide.
    PRI me R 5. Poly- {methyl- (3-methylthiopropyl imino trimethylene chloroRVD.
    A solution of 426 mg (6 milli-equivalents) of poly - {(methylimino) trimethylene and 4.06 g of methyl 3-methylthiopropyl in 15 ml of dimethylformamide was maintained at temperature for 24 hours. The product was separated by filtration, dissolved in 30 ml of water and passed through a 45 ml column filled with ion exchange resin (36 mmol of chlorine ions). The concentration of the aqueous eluate gave 650 m of poly-methyl- (3-methylthiopropyl) imino trimethylene chloride.
    In the synthesis of polymers, in which P. and P. are, respectively, 3-methylthiopropyl and methyl and their ratio varies from 5:95 to 95: 5, the procedure described above is repeated, according to which poly - {(methylamino ) trimetylen reacts with a limited amount of 3-methylthio. propyl bromide, and then with an excess of methyl bromide.
    Example
    Poly- {methyl- (3-ammoniopropyl) imino trimethylene-chlorine.
    A solution of 568 mg (8 ml) of poly- (methylimino) -trimethylene} and 8.6 g (30 mmol) of 3-phthalimidopropane methyl bromide in 25 ml of dimethylformamide was maintained at 18 hours for a period of 18 hours. The product was filtered, suspended in 10 ml of methyl alcohol and treated with 1 g of anhydrous hydrazine at 3 hours. The mixture was concentrated under reduced pressure, acidified with dilute hydrochloric acid, triturated with sulfuric ether and filtered. The product was washed with water and passed through a 45 m ion exchange resin column (36 mmol chlorine ions). Concentration of the aqueous aluate gave poly- {methyl- (3-ammonium propyl) amino trimethylene dichloride.
    On the other hand, a solution of 568 mg (8 ppm of equivalents) of poly- {(methylimino) trimethylene and 6.3 g (40 mmol) of 1-bromo-3-chloropropane in 20 ml of dimethyl forma was maintained at ~ 75 ° C for 18 hours. The reaction mixture was concentrated under reduced pressure and heated with 30 ml of liquid ammonia for 5 hours. Ammonia Evaporation and passage through a 45 MP ion exchange resin column, the product was converted to a compound containing a chlorine ion.
    In the synthesis of polymers, in which R is, respectively, 3-ammonio propyl and methyl and their ratio varies from 5: 9S to 95: 5, the procedure described above is used, according to which poly (methylimino) trimethylene reacts with a limited amount either 3-naphthilimidoproshshbromid L or 1-bromo-zchloropropane and then with an excess of methyl methyl. Example7, Synthesis of the proportion-J {methyl- (3-methylammoniopropyl) ymino | triethyl e dichloride. A solution of 710 mg (10 milliequivalents) of polymethylamino) trimethylene and 8 g of 1-bromo-3-chloropropane in 30 m of dimethylformamide was maintained at 75 ° C for 16 hours. The mixture was concentrated under partial pressure, suspended in 10m of methanol and Processed with 3 g of methylamine in the plugged tube. The reaction mixture was concentrated under reduced pressure, dissolved in water, and passed through a 50 ml column with ion exchange resin. As a result, the desired product was obtained. In the synthesis of polymers in which R and R, respectively, 3-methylammoniopropyl and methyl and their ratio varies from 5:95 to 95: 5, the procedure described above above is repeated substantially in accordance with its poly- (methylamino ) trimethylene first reacts with a limited amount of 1-bromo-3-chloropropane, and then with an excess of methyl bromide. Example, Synthesis of poly- {methyl- (3-dimethylammoniopropyl} imino-3-trimethyldgsporid. Solution of 710 mg (10 millisquivalents) of poly- (methylimido) trimetn-glen and 7.9 g of 1-br6m-8-chloropropane in 35 ml dimethylformamide was allowed to stand at 16 hours. The mixture was concentrated under reduced pressure, suspended in 10 ml of methyl alcohol and treated in a sealed tube of 2.3 g (3.000 mm) of dimethylamine. The reaction mixture was concentrated under reduced pressure, washed with water and passed through 50 ml column with ion exchange resin (40 yards of chlorine ions pa), giving poly {methyl- (3-D1p etilammonerprosch) imino j-trimethyl dichloride, On the other hand, a solution of 710 mg (10 milliequivalents) of poly (meth 4P imino) trimethylene in 35 ml of dimethyl formamide together with 6.6 g (AO mmol: mi) 3-dimethylaminopropyl1La bromide was kept at 50 ° C. for 6 hours. The product was filtered off, dissolved in water and passed through a 50 ml column with ion-exchange resin to obtain the 3-dimethylammoniopropyl analogue of the above compound. In the synthesis of polymers in which R.J and R are 3-dimethylammoniopropyl and methyl, respectively, and their ratio varies within 5: 9595: 5, the essentially the same procedure as described above is repeated. In accordance with this procedure, poly (methyliminC) trimethylene is treated with either a limited amount of 1-bromo-3-chloropropane, or methyl 3-dimethylaminopropyl, and then an excess of methyl bromide. Example 9. Synthesis of polymethyl- (3-trimethylammonio propyl) imino1 | trimethylenedibromide}. A solution of 710 mg (10 milliequivalents) of poly-Methylimino) trimethylene and 10.4 g (40 mmol) of 3-bromopropyltrimethylammonium bromide in 40 ml of purified dimethylformamide was held at 75 ° C; 12 hours. The product was filtered, washed with acetone and dried under reduced pressure. As a result, 1.8 g of poly- {methyl- (3-trnmethylammonioprosh) imino trimeth-shendibromide was obtained. Example 10. Synthesis of poly- {methyl- (3-trimethylammoniopropyl) imino-trimethylene dichloride. A solution of 1j66 g (5 milliequivalents) of poly- {methyl- (3-trimethylammoniopropyl) imino1-trimethyldibromide in 85 MP of water was slowly passed through a column containing 50 ml (40 mmol) gum. Then water was passed through the column until chlorine ions completely disappeared in the eluate. Concentrator combined eluate to dryness at 50 ° C, was obtained 1.1 g of poly methyl- (Z-triethylammonium) imino5 trimethylenedichlorvd. In the synthesis of polymers in which R; R, respectively, H-trimethyl-gmmonkopropil and methyl and their ratio varies from 5:95 to 95; 5, essentially the same procedure was used, which is described above in the previous example. According to it, poly- (methylimino) trimethylene was reacted with a limited count; procession of methyl bromide Z-bromopropyltri7
    methylammonium and then with an excess of methyl bromide.
    PRI me R 11.
    Polymethyl- (carboethoxymethylamine) triethylene chloride.
    A solution of 1 g (14 milliequivalent) of poly- (methylamino) trimethylene and 8.8 g (56 mmol) of A-bromoacetic acid ethyl ester in 20 ml of dimetiformamide was removed at 50 ° C.
    A significant reduction in blood cholesterol is achieved by orally administering very small doses of the polymers of the present invention. It is possible to use them in the form of various previously inaccessible forms. The polymers can be used in the form of finely divided powders or in pure form; or, more preferably, in a mixture with varying amounts of solid carriers such as colloidal silicon dioxide, starch, sucrose, talc, lactose, cellulose or modified cellulose, powdered milk powder, protein powders, such as soy flour, and the like. It is desirable to make them. in the form of a single dosage form, such as tablets, gelatin pills, or wrapped in paper or foil. All listed forms must include certain doses of the proposed full 50 8
    Merov. In addition, they may include additional vitamins and minerals. These forms can be easily strained and added to edible beverages, such as fruit juices or other beverages. The unit dosage compositions can include from -10 to 99% by weight of the polymer, and the rest falls to the Carriers of flavoring substances, ak fillers, substances, odor and other components. Such a single dose may include from O, f g and. up to 10 g in powder bags.
    Possible use of aqueous solutions or suspensions that may be sweetened or seasoned. Although it is not always desirable, polymers can be mixed with various | and "n. In substances, such as cardamine or corn oil, when orally absorbed as such, or. in the form of aqueous emulsions. They can also be encapsulated.
    It is advisable to divide the total daily dose of the bile acid binder polymer into several single doses and take it before each meal and before bedtime. This mode provides the maximum contact time of the polymer during periods of highest concentrations in the intestine of bile acid.
    权利要求:
    Claims (1)
    [1]
    'METHOD FOR PRODUCING LINEAR POLYAMINES CONTAINING QUATERNARY NITROGEN ATOMS, characterized in that, in order to expand the range of biologically active polyamines for binding of bile acid, a polymer containing repeating units of the formula {NQ-4N-Q) - (NQ) -N- is reacted qT R t R, R 2 R f where Q is ethylene alkyl trimethylene, R {R 4 is lower alkyl, lower alkyl substituted with hydroxyl, C 3 -C 6 alkyl substituted with several hydroxyls, C 5 -C & cycloalkyl substituted several alkyls, -C, -C - cycloalkyl, C E ~ C 7 - cycloalkyl substituted lower alkyl; ammoniumalkyl *, alkylammoniumalkyl, dialkylammoniumalkyl trialkylammoniumalkyl, carboxyalkyl, carbalkocacialalkyl, where in all radicals alkyl is lower alkyl, C ^ C 7 is alkenyl, C ^ C 7 is alkynyl, aralkyl; carbamylalkyl, fluoroalkyl, cyanoalkyl, guanidinylalkyl, carbamidinylalkyl, N-alkylcarbamidinylalkyl, alkocoalkyl; furanosyl, pyranosyl alkanoylalkyl, where in all residues alkyl is lower alkyl, with an alkylating agent of the general formula R X, or sequentially with two alkylating agents of the general formula R ^ X and I 4 X, where R ^ R ^ is hydrogen, lower monohydroxy substituted lower alkyl, alkyl substituted with hydroxyl, C ^ -C 6 - cycloalkyl substituted with several hydroxyls, C, C 7 - cycloalkyl, C, -C 7 - cycloalkyl-substituted lower alkyl, lower alkyl, substituted C 3 C 7 - cycloalkyl, ij ammoniumalkyl, alkylammoniumalkyl, di-U lower alkylammonium alkyl, trialkyl- / ammoniumalkyl, carboxyalkyl, carbol- / hydroxyalkyl, where all residues al- (keel is lower alkyl, C, -C 7 alkynyl, aralkyl, carbam lalkyl, fluoroalkyl, cyanoalkyl, guanidinylalkyl, carbamidinylalkyl, N alkylcarbamidinylalkyl, alkoxyalkyl, alkylthioalkyl, furanosyl, pyranoside and alkonoylapkyl, where in all radicals alkyl represents
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    同族专利:
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2884057A|1954-02-25|1959-04-28|American Cyanamid Co|Paper of improved dry strength and method of making same|
    US3372129A|1964-10-06|1968-03-05|Nalco Chemical Co|Method of preparing polyamines|
    US3489686A|1965-07-30|1970-01-13|Procter & Gamble|Detergent compositions containing particle deposition enhancing agents|
    DE1546290A1|1966-04-30|1970-02-26|Bayer Ag|Flotation agent for fiber and filler recovery from paper machine waste water|
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    US4873293A|1986-09-30|1989-10-10|Union Carbide Chemicals And Plastics Company Inc.|Partially hydrolyzed, poly in personal care|
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    US20040053208A1|1995-08-29|2004-03-18|V. I. TECHNOLOGIES, Inc.|Methods to selectively inactivate parasites in biological compositions|
    US6093564A|1997-10-03|2000-07-25|V.I. Technologies, Inc.|Methods and compositions for the selective modification of nucleic acids|
    US6352695B1|1997-10-03|2002-03-05|V.I. Technologies, Inc.|Methods and compositions for the selective modification of nucleic acids|
    US6403359B1|1998-09-25|2002-06-11|V. I. TECHNOLOGIES, Inc.|Solid phase quenching systems|
    US6617100B2|1998-09-25|2003-09-09|V.I. Technologies, Inc.|Solid phase quenching systems|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US36904273A| true| 1973-06-11|1973-06-11|
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