Catalytic system for (co) polymerization of lactide and glycolide

FIELD: polymerization processes and catalysts.

SUBSTANCE: invention relates to catalytic system for (co)polymerization of lactide and glycolide and to (co)polymerization process using indicated system. Catalytic system is composed of (a) trifluoromethanesulfonate of general formula (1), (b) (co)polymerization additive of general formula (2), wherein molar ratio of additive to catalyst ranges from 0.05:1 to 5:1. (Co)polymerization process of lactide and glycolide is also described as well as application of thus obtained lactide and glycolide polymer or copolymer.

EFFECT: enabled controlling chain length, nature of end units of the chain of resulting (co)polymers.

10 cl, 8 ex

 

The present invention relates to a catalytic system (co)polymerization of lactide and glycolide, and this system contains as a catalyst triftorbyenzola and (co)polymerized Supplement. The present invention also relates to a method of (co)polymerization of lactide and glycolide using this catalytic system.

Currently, increasingly focused on the synthetic polymers used for the development of artificial organs and obtain drugs [Chem.Eng.News 2001, 79(6), 30]. Such polymers must meet certain criteria and, in particular, they must be biocompatible. Biodegradable nature is an additional advantage if the polymer must be removed upon expiration of the relevant period for which it is implanted in the body. In this regard, it is of great interest are copolymers based on lactic and glycolic acid (PLGA), because they are sensitive to hydrolysis and decompose in vivo, highlighting non-toxic by-products. The scope of PLGA very wide (Adv. Mater 1996, 8, 305 and Chemosphere 2001, 43,49). In surgery they are used for the synthesis of yarn consisting of many fibers, sutures, implants, dentures. In pharmacology, they provide encapsulation, transition and modified release active substances.

For all applications, the main factor is the degradation rate of PLGA, which, of course, depends on their structure (chain length, particle size, aspect ratio, stereochemistry and bonding of monomers...). In recent years, numerous studies have been thus devoted to the development of catalysts and/or initiators (co)polymerization, i.e. the polymerization or copolymerization of lactide and glycolide providing PLGA with adjustable structure.

The use of metallic systems usually leads to contamination of the thus obtained copolymer salts of metals, in some cases severely limits their applicability. Therefore, the development of non-metallic systems, providing adjustable (co)polymerization of lactide and glycolide, is the main goal.

The applicant proposes a simple catalytic system containing a catalyst and (co)polymerizing additive, which allows you to adjust the length of the chain, as well as the nature of the final link in the chain of the obtained (co)polymer.

The object of the invention, therefore, is a catalytic system containing

(a) triftorbyenzola General formula (1)

in which

R1denotes a hydrogen atom or a deuterium or a group of formula-S14(R14)(R'14)(R14);

E14is an element of group 14;

R14, R'14and R14regardless of oznachaet a hydrogen atom, deuterium or one of the following substituted or unsubstituted radicals: alkyl, cycloalkyl or aryl, in which one or more substituents selected from halogen, alkyl, cycloalkyl and aryl,

as a catalyst and

(b) (co)polymerizing additive of General formula (2)

in which

E denotes an element of group 16;

R2denotes a hydrogen atom or deuterium;

R3denotes a hydrogen atom or a deuterium or a group of formula-E'14(T14)(T'14)(T"14);

E'14is an element of group 14;

T14T'14and T14independently represent a hydrogen atom; a deuterium atom; one of the following substituted or unsubstituted radicals: alkyl, cycloalkyl or aryl, and in which one or more substituents selected from halogen, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkene, aryl, aryloxy, carboxy, alkoxycarbonyl, cycloalkylcarbonyl and aryloxyalkyl

for (co)polymerization of lactide and glycolide.

The term halogen denotes fluorine, chlorine, bromine or iodine, preferably chlorine. The term alkyl preferably denotes a linear or branched alkyl radical containing from 1 to 6 carbon atoms, and, in particular, the alkyl radical containing from 1 to 4 carbon atoms, such as radicals: methyl, ethyl, propyl, isoprop is l, butyl, isobutyl, terbutyl and tertbutyl. The term alkoxy refers to radicals in which the alkyl radical is as described above, as, for example, the radicals methoxy, ethoxy, propyloxy or isopropoxy and linear secondary or tertiary, butoxy, pentyloxy. The term alkoxycarbonyl preferably designates the radicals in which the alkoxy radical is the same as described above, as, for example, methoxycarbonyl, etoxycarbonyl.

Cycloalkyl radicals selected from saturated or unsaturated monocyclic cycloalkyl. Saturated monocyclic cycloalkyl radicals can be chosen from radicals containing from 3 to 7 carbon atoms, such as radicals cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. Unsaturated cycloalkyl radicals can be chosen from the radicals: cyclobutene, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene. The term cycloalkane means radicals, in which the radical cycloalkyl is such as described above, as, for example, radicals of cyclopropylamine, cyclobutylamine, cyclopentyloxy, cyclohexyloxy, cycloheptylamine, cyclobutanone, Cyclopentanone, cyclohexanone, cyclopentadienyls, cyclohexadienone. The term cycloalkylcarbonyl designates the radicals in which the radical of cycloalkane is such as you described is e, as, for example, radicals: cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexyloxycarbonyl, cyclohexyloxycarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexyloxycarbonyl.

Aryl radicals can be mono - or polycyclic type. Monocyclic aryl Radicati you can choose from phenyl radicals, optionally substituted by one or more alkyl radicals, such as tolyl, xylyl, mesityl, cumenyl. Polycyclic aryl radicals can be chosen from naphthyl, Anttila, financila. The term aryloxy designates the radicals in which the aryl moiety is as described above, as, for example, radicals of phenyloxy, tolyloxy, naphthyloxy, antioxi, phenanthridone. The term aryloxyalkyl preferably designates the radicals in which the radical of aryloxy is such as described above, as, for example, vinyloxycarbonyl, tolylacetylene.

In this application the term (co)polymerization means a polymerization or copolymerization. Thus (co)polymerization of lactide and glycolide covers the polymerization of lactide, polymerization glycolide, as well as the copolymerization of lactide and glycolide.

Preferably the catalytic system according to the present invention, the number of (co)polimerizuet supplements what about the relation to the catalyst is from 0.05 to 5 molar equivalents and more preferably from 0.5 to 2 molar equivalents.

More specifically the object of the invention is a catalytic system, such as described above, containing the compound of formula (1)in which R1denotes either a hydrogen atom or a group of formula-S14(R14)(R'14)(R14).

Preferably R1denotes the hydrogen atom and the compound (1) denotes triftormetilfullerenov acid. Also preferably, R1denotes a group of formula-S14(R14)(R'14)(R14), in which E14denotes the carbon atom or silicon, and more preferably E14denotes the carbon atom, and R14, R'14and R14independently represent a hydrogen atom or an alkyl radical.

According to the present invention (with)polimerizuet additive of the formula (2)used, therefore, performs the function of the initiator (or coinitiator) (co)polymerization. Her presence is necessary, because without such compounds of formula (2) reaction (co)polymerization proceed much more slowly, have significantly lower yields are reproducible and, therefore, unsuitable for industrial applications.

More specifically the object of the invention is a catalytic system, such as described above, containing the compound of the formula (2), in which

E denotes an oxygen atom or sulfur;

R2denotes the atom of water is ode;

R3denotes a hydrogen atom or a group of formula-E'14(T14)(T'14)(T"14);

E'14denotes the carbon atom or silicon;

T14, T'14and T14independently represent a hydrogen atom or one of the following substituted or unsubstituted radicals: alkyl, cycloalkyl or aryl, in which one or more substituents selected from: halogen, alkyl, cycloalkyl, phenyl, naphthyl, carboxy and alkoxycarbonyl,

and more specifically

E denotes an oxygen atom;

R2denotes a hydrogen atom;

R3denotes a hydrogen atom or a group of formula-E'14(T14)(T'14) (T"14), where E'14denotes the carbon atom, and T14T'14and T14independently represent a hydrogen atom or an alkyl radical.

More specifically the object of the invention is a catalytic system, such as described above and characterized in that the (co)primerisima additive of General formula (2) is water or an aliphatic alcohol. Of the aliphatic alcohols can for example be mentioned methanol, ethanol, n-propanol, isopropanol, n-butanol or pentane-1-ol. Preferably an aliphatic alcohol selected from isopropanol and pentane-1-ol.

The object of the invention is also a method of (co)polymerization of lactide and glycolide, which is carried out in the presence od the CSO or neskolkih monomers, question, catalytic systems, such as described above, containing the compound of General formula (1) and (co)polymerized additive of General formula (2) and possibly solvent polymerization.

(Co)polymerization of lactide and glycolide according to the invention carry out (co)polymerization by breaking the cycle. This method can be carried out either in solution, or in conditions of hypothermia. If the (co)polymerization is carried out in solution, for reaction in the solvent used, the substrate (or substrates)used in the catalytic reaction. Solvents that do not interfere with the catalytic reaction, are also suitable. As examples of such solvents can be called aromatic hydrocarbons (such as toluene, xylene or mesitylene), possibly substituted by one or more nitro groups (such as nitrobenzene), ethers (such as methyl tertiary butyl ether, tetrahydrofuran or dioxane), aliphatic or aromatic halides (such as dichloromethane, chloroform, dichloroethane or dichlorobenzene).

In accordance with the present invention the reaction is carried out at temperatures from -20 to about 150°C. if the (co)polymerization is conducted in solution, the temperature is preferably from 0 to 30°C. the duration of the reaction is from NESCO is gcih minutes to 48 hours, preferably from 30 minutes to 20 hours. The number of (co)polimerizuet additive with respect to the catalyst is preferably from 0.05 to 5 molar equivalents and more preferably from 0.5 to 2 molar equivalents. The output of the method (co)polymerization according to the present invention is usually more than 80% and can even reach 100% under relatively mild conditions (room temperature, for several hours), as shown in the examples.

More specifically the object of the invention is also a method, such as described above, using a catalytic system, such as described above, containing the compound of formula (1)in which R1denotes either a hydrogen atom or a group of formula-S14(R14)(R'14)(R14).

Preferably the object of the invention is a method, such as described above, wherein R1denotes a hydrogen atom, in this case, the compound (1) is triftormetilfullerenov acid. Preferably also an object of the invention is a method, such as described above, wherein R1denotes a group of formula-S14(R14)(R'14)(R14), in which E14denotes the carbon atom or silicon, and more preferably E14denotes the carbon atom, and R14, R'14and R14independently denote an atom is odorata or alkyl radical.

More specifically the object of the invention is also a method, such as described above, using a catalytic system, such as described above, containing the compound of General formula (2), in which

E denotes an oxygen atom or sulfur;

R2denotes a hydrogen atom;

R3denotes a hydrogen atom or a group of formula-E'14(T14)(T'14)(T"14),

E'14denotes the carbon atom or sulfur;

T14, T'14and T14independently represent a hydrogen atom or one of the following substituted or unsubstituted radicals: alkyl, cycloalkyl or aryl, in which one or more substituents selected from: halogen, alkyl, cycloalkyl, phenyl, naphthyl, carboxy and alkoxycarbonyl,

and more specifically

E denotes an oxygen atom;

R2denotes a hydrogen atom;

R3denotes a hydrogen atom or a group of formula-E'14(T14)(T'14)(T"14), where E'14denotes the carbon atom, and T14, T'14and T14independently represent a hydrogen atom or an alkyl radical.

More specifically the object of the invention is a method of (co)polymerization of lactide and glycolide, such as described above, using a catalytic system, (with)polimerizuet additive which is either water or an aliphatic alcohol, and p is edocfile aliphatic alcohol is selected from methanol, ethanol, propanol and butanol.

The method of (co)polymerization of lactide and glycolide according to the present invention allows thus to regulate the nature of the final links of the (co)polymer chain and is very well suited to produce (co)polymers, the end parts of which are acid-alcohol or ester-alcohol, as shown in the experimental part.

The method of (co)polymerization of lactide and glycolide according to the present invention is also very well suited to produce (co)polymers, the weight of which ranges from 500 to 50,000 daltons, more specifically from 1000 to 20000 daltons.

The method of (co)polymerization of lactide and glycolide according to the present invention has several advantages, in particular:

catalytic system consists of a catalyst and (co)polimerizuet supplements that are readily available and inexpensive;

- the use of additives in inhibiting (co)polymerization allows not only significantly improve the course of the (co)polymerization, but also to precisely adjust the length of the chain, which is almost equal to the initial ratio of monomer and initiator;

- the use of additives in inhibiting (co)polymerization also allows you to adjust the nature of the final link in the chain of the obtained (co)polymer;

- (co)polymerization can be carried out at a very gentle pace is atornic conditions, such as room temperature, and the duration of reaction required for almost complete conversion of one or more monomers does not exceed a few hours and maximum 24 hours;

- (co)polymerization can really conduct in a homogeneous medium so that the weight distribution of the obtained (co)polymer is limited; indices of polydispersity obtained according to the present invention (co)polymers are from 1.0 to 1.5;

- obtained from (co)polymers can be easy, fast and effective cleaning without changing their properties. Traces of residual monomers and residues of catalysts indeed removed quantitatively by conventional filtration through alkaline alumina and/or rinsing in two stages with an aqueous solution of bicarbonate.

Finally, the invention relates to polymers or copolymers of lactide and glycolide obtained or obtainable by the method such as described above. Such (co)polymers can have adjustable end groups of the acid/alcohol or ester/alcohol. Such (co)polymers may also have a small weight from 500 to 50,000 daltons, and preferably from 1,000 to 20,000 daltons.

The object of the present invention are (co)polymers of lactide and glycolide with adjustable finite group and acid/alcohol or ester/alcohol. The object of the present invention are (co)polymers of lactide and glycolide, the weight of which ranges from 500 to 50,000 daltons, and preferably from 1,000 to 20,000 daltons. More preferably, the object of the present invention are (co)polymers of lactide and glycolide with adjustable end-groups of the acid/alcohol or ester/alcohol, the weight of which ranges from 500 to 50,000 daltons, and preferably from 1,000 to 20,000 daltons.

The products of General formula (1) and (2) are commercial or can be obtained well-known specialist of ways.

If any other meaning is not specified, all technical and scientific terms used in this application, have the meaning commonly understood by the average person skilled in the art to which the invention belongs. Also, all publications, patent applications and all other references mentioned in the present description, is included as a reference.

To illustrate the methods are the following examples, which in no case should not be construed as limiting the scope of the invention.

Example 1: obtaining the polymer (D,L-lactide) with the end groups of the acid-alcohol

In the tube Slinka with a magnetic bar, purged with argon, is injected successively 22 g of D,L-lactide (0,153 mol), 150 ml of dichloromethane, to 1.35 ml triftormetilfullerenov acid (0,0153 say what) and 0.3 ml of water (0,0153 mol). The reaction mixture was stirred at room temperature. The progress of polymerization is controlled proton NMR. After three hours from the beginning of the reaction, the conversion of monomer is 100%. Then the reaction mixture is injected alkaline alumina. Stirred for an hour, after which the medium was filtered through a Frit and the solvent is removed under reduced pressure. According to GPC analysis (gel permeation chromatography) by the calibration carried out in accordance with the standards of polystyrene (PS)having a weight from 761 to 400,000, the sample contains polymers having close values of the masses (Mw=2600 daltons, Mw/Mn=1,48). The nature of the final link in the chain of the acid/alcohol define mass spectrometry (ionization electrospray, detection in the positive ion mode, the sample is dissolved in acetonitrile with traces of ammonium hydroxide).

Example 2: obtain the polymer (D,L-lactide) with the end groups of the ester-alcohol

In the tube Slinka with a magnetic bar, purged with argon, is injected successively 22 g of D,L-lactide (0,153 mol), 150 ml of dichloromethane, to 1.35 ml triftormetilfullerenov acid (0,0153 mol) and of 1.17 ml isopropanol (0,0153 mol). The reaction mixture was stirred at room temperature for three hours. Then the reaction mixture is injected alkaline alumina. Stirred for an hour, after which the medium was filtered through a Frit and the solvent UD is given under reduced pressure. The polymer is determined using proton NMR; conversion of the monomer is 100%. According to GPC analysis (gel permeation chromatography) by the calibration carried out in accordance with the standards of polystyrene (PS)having a weight from 761 to 400,000, the sample contains polymers having close values of the masses (Mw=2070 daltons, Mw/Mn=1,25). The nature of the final link in the chain ester/alcohol define mass spectrometry (ionization electrospray, detection in the positive ion mode, the sample is dissolved in acetonitrile with traces of ammonium hydroxide).

Example 3: obtaining the copolymer (D,L-lactide/glycolide) 75/25 with the end groups of the ester-alcohol

In the tube Slinka with a magnetic bar, purged with argon, is injected 16.5 g of D,L-lactide (0,115 mol) and 4.4 g of glycolide (of 0.038 mol), dissolved in 150 ml of dichloromethane. Then enter to 1.35 ml triftormetilfullerenov acid (0,0153 mol) and of 1.17 ml isopropanol (0,0153 mol). The reaction mixture was stirred at room temperature for two hours. Then the reaction mixture is injected alkaline alumina. Stirred for an hour, after which the medium was filtered through a Frit and the solvent is removed under reduced pressure. The polymer is determined using proton NMR; converting each of the monomers is more than 95%. The ratio of the integrals of the signals corresponding frequent is polylactide (to 5.2 ppm) and polyglycolide (4,85 ppm), allows you to determine the composition of the copolymer: 79% lactide and 21% of glycolide. According to GPC analysis (gel permeation chromatography) by the calibration carried out in accordance with the standards of polystyrene (PS)having a weight from 761 to 400,000, the sample contains copolymers having close values of the masses (Mw=2100 daltons, Mw/Mn=1,34). The nature of the final links define mass spectrometry (ionization electrospray, detection in the positive ion mode, the sample is dissolved in acetonitrile with traces of ammonium hydroxide).

Example 4: production of polymer (D,L-lactide) with the end groups of the ester-alcohol

In the tube Slinka with a magnetic bar, purged with argon, is injected successively 22 g of D,L-lactide (0,153 mol), 150 ml of dichloromethane, 190 μl triftormetilfullerenov acid (0.002 mol) and 170 μl of isopropanol (0.002 mol). The reaction mixture was stirred at room temperature for ten hours. Then the reaction mixture is injected alkaline alumina. Stirred for an hour, after which the medium was filtered through a Frit and the solvent is removed under reduced pressure. The polymer is determined using proton NMR; conversion of the monomer is 100%. The presence at the end of the chain complex of isopropyl ether also detected using proton NMR. According to GPC analysis (gel permeation chromatography) by calibration, assests is imago in accordance with the standards of polystyrene (PS), having a mass of from 761 to 400,000, the sample contains polymers having close values of the masses (Mw=13000 daltons, Mw/Mn=1,15).

Example 5: Receiving oligomer (D,L-lactide) with the end groups of the ester-alcohol (Mw approximately 1000 Yes)

In the tube Slinka with a magnetic bar, purged with argon, is injected sequentially 19,39 g D,L-lactide (is 0.135 mol), 160 ml of dichloromethane, 3,00 ml triftormetilfullerenov acid (0,0336 mol) and the 3.65 ml pentane-1-ol (0,0336 mol). The reaction mixture was stirred at room temperature for one hour. Then the reaction mixture is injected alkaline alumina. Stirred for an hour, after which the medium was filtered through a Frit and the solvent is removed under reduced pressure. The polymer is determined using proton NMR; conversion of the monomer is 100%. According to GPC analysis (gel permeation chromatography) by the calibration carried out in accordance with the standards of polystyrene (PS)having a weight from 761 to 400,000, the sample contains polymers having close values of the masses (Mw=1008 daltons, Mw/Mn=1,13). The nature of the final link in the chain ester-alcohol define mass spectrometry (ionization electrospray, detection in the positive ion mode, the sample is dissolved in acetonitrile with traces of ammonium hydroxide).

Example 6: Getting cooligomers (D,L-lactide/glycolide) 80/20 end groups ester-what Peart (Mw approximately 1000 Yes)

In the tube Slinka with a magnetic bar, purged with argon, is injected 18,81 g D,L-lactide (0,128 mol), 4,00 g glycolide (0,031 mol) and 160 ml of dichloromethane. Then enter 3.5 ml triftormetilfullerenov acid (0,039 mol) and 3.4 ml of pentane-1-ol (0,039 mol). The reaction mixture was stirred at room temperature for one hour. Then the reaction mixture is injected alkaline alumina. Stirred for an hour, after which the medium was filtered through a Frit and the solvent is removed under reduced pressure. The polymer is determined using proton NMR; converting each of the monomers is more than 95%. The ratio of the integrals of the signals corresponding part of polylactide (to 5.2 ppm) and polyglycolide (4,85 ppm), allows to determine the composition of the copolymer: 80% lactide and 20% of glycolide. According to GPC analysis (gel permeation chromatography) by the calibration carried out in accordance with the standards of polystyrene (PS)having a weight from 761 to 400,000, the sample contains copolymers having close values of the masses (Mw=1030 daltons, Mw/Mn=1,23). The nature of the final links define mass spectrometry (ionization electrospray, detection in the positive ion mode, the sample is dissolved in acetonitrile with traces of ammonium hydroxide).

Example 7: Getting cooligomers (D,L-lactide/glycolide) 60/40 with the end groups of the ester-alcohol (Mw is primer the 1000 Yes)

In the tube Slinka with a magnetic bar, purged with argon, is injected 2,68 g D,L-lactide (0,0186 mol), 1.44 g glycolide (0,0124 mol) and 40 ml of dichloromethane. Then enter 0,69 ml triftormetilfullerenov acid (0,0077 mol) and 0,85 ml pentane-1-ol (0,0077 mol). The reaction mixture was stirred at room temperature for two hours. Then the reaction mixture is injected alkaline alumina. Stirred for an hour, after which the medium was filtered through a Frit and the solvent is removed under reduced pressure. The polymer is determined using proton NMR; converting each of the monomers is more than 95%. The ratio of the integrals of the signals corresponding part of polylactide (to 5.2 ppm) and polyglycolide (4,85 ppm), allows to determine the composition of the copolymer: 60% lactide and 40% of glycolide. According to GPC analysis (gel permeation chromatography) by the calibration carried out in accordance with the standards of polystyrene (PS)having a weight from 761 to 400,000, the sample contains copolymers having close values of the masses (Mw=953 daltons, Mw/Mn=1.26 in). The nature of the final links define mass spectrometry (ionization electrospray, detection in the positive ion mode, the sample is dissolved in acetonitrile with traces of ammonium hydroxide).

Example 8: production of polymer (D,L-lactide) with the end groups of the acid-alcohol and Mw, comprising about 7000 Yes

In the tube Slinka with a magnetic bar, purged with argon, consistently give 22.1 g of D,L-lactide (0,153 mol), 140 ml of dichloromethane, 0,486 ml triftormetilfullerenov acid (0,0055 mol) and 0.10 ml of water (0,0055 mol). The reaction mixture was stirred at room temperature. The progress of polymerization is controlled proton NMR. Six hours from the beginning of the reaction, the monomer conversion is greater than 95%. The reaction mixture is poured into a separating funnel and washed with saturated aqueous NaHCO3and then brine. The solution is dried on anhydrous Na2SO4, filtered and the solvent is removed under reduced pressure. According to GPC analysis (gel permeation chromatography) by the calibration carried out in accordance with the standards of polystyrene (PS)having a weight from 761 to 400,000, the sample contains polymers having close values of the masses (Mw=7200 daltons, Mw/Mn=1,32).

1. Catalytic system consisting of

(a) triftoratsetata General formula (1)

in which R1denotes a hydrogen atom or deuterium as a catalyst and polymerization of lactide and glycolide (b) additive (co)polymerization of the General formula (2)

where E denotes an oxygen atom or sulfur;

R2denotes a hydrogen atom;

R 3denotes a hydrogen atom or a group of the formula

E'14(T14)(T'14)(T"14);

E'14is a carbon atom or silicon;

T14, T'14and T14independently represent a hydrogen atom or one of the following substituted or unsubstituted radicals: alkyl, cycloalkyl or aryl, in which one or more substituents selected from halogen, alkyl, cycloalkyl, phenyl, naphthyl, carboxy and alkoxycarbonyl,

moreover, the amount of additive (co)polymerization with respect to the catalyst is from 0.05 to 5 molar equivalents,

for (co)polymerization of lactide and glycolide.

2. The catalytic system according to claim 1, characterized in that the amount of additive (co)polymerization with respect to the catalyst is from 0.5 to 2 molar equivalents.

3. The catalytic system according to claim 1, wherein R1denotes a hydrogen atom.

4. The catalytic system according to claim 1, characterized in that

E denotes an oxygen atom;

R2denotes a hydrogen atom;

R3denotes a hydrogen atom or a group of the formula E'14(T14)(T'14)(T"14), where E'14denotes the carbon atom, and T14T'14and T14independently represent a hydrogen atom or an alkyl radical.

5. The catalytic system p is any of claims 1 to 4, characterized in that the compound of General formula (2) is either water or an aliphatic alcohol.

6. The catalytic system according to claim 5, characterized in that the compound of General formula (2) is an aliphatic alcohol selected from isopropanol or pentane-1-ol.

7. The method of (co)polymerization of lactide and glycolide, which is carried out in the presence of one or more of the considered monomers, catalyst system, such as described in one of claims 1 to 6, and possibly solvent polymerization.

8. The method according to claim 7, characterized in that the method is carried out at a temperature of from 0 to 30°C.

9. The method according to one of claims 7 and 8, characterized in that the duration of the reaction is from several minutes to 48 hours, and preferably from 30 minutes to 20 hours

10. Polymers or copolymers of lactide and glycolide obtained by the method according to one of claims 7 to 9.



 

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EFFECT: valuable properties of catalysts, improved method of synthesis.

8 cl, 7 ex

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4 cl, 12 ex, 3 tbl

FIELD: chemical industry; methods of production of polyester.

SUBSTANCE: the invention is pertaining to the field of chemical industry, in particular, to the method of production of polyester. The true invention is pertaining to the synergetic compositions of titanium-containing catalytic agents and the promoters for the catalytic agents consisting of the carboxylic acid or the oxalic acid or their salts, which are used at production of polyesters. The invention presents the catalytic composition for production of the polyesters containing titanyl oxalate,XmTiO(C2O4)2(H2O)n , where X= Li, K, Rb, Cs and Ca, To, Rb, Cs and Ca, m=1 or 2; the promoter of the catalystic agent containing oxalic acid or carboxylic acid containing from 1 up to 26 carbonic atoms, or their corresponding salt containing Li, Na, K or ammonium; Sodium oxalate of the promoter of the catalystic agent makes from 0.1 up to 80 mass shares from the composition of the mass of titanium. There is a description of the activated catalytic agent containing titanium compound XmTiYo , where X=H, Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba and ammonium; m=0.1 or 2, Y = bis (2, 2, 6, 6 - tetramethyl-3.5- heptanedionate) and acetylacetonate; and the promoter of the catalytic agent consisting of an oxalic acid or its corresponding salt containing Li, Na, K or the ammonium. At that the promoter of the catalytic agent makes 0.1 mass share up to 80 mass shares from the composition of the mass titanium. The invention describes the composition of the activated catalytic agent including the catalytic agent and the promoter of the catalytic agent and the composition including germanium containing the catalytic agent and the promoter of the catalytic agent. The invention also describes the method of production of the polyester by polycondensation of the reactants at the presence of the above described catalytic agent and the produced polyesters. The technical result of the invention is production of the improved polyester with the smaller acetaldehyde number and the good coloration.

EFFECT: the invention ensures production of the improved polyester with the smaller acetaldehyde number and the good coloration.

22 cl, 1 tbl, 24 ex

The invention relates to the field of Bioorganic chemistry, namely to new biologically active substances and methods of production thereof

The invention relates to a new ORGANOMETALLIC catalyst to obtain a complex ester comprising the reaction product, including interaction and complex orthoevra or condensed complex orthoevra titanium, zirconium, or aluminum; b) an alcohol containing at least two hydroxyl groups; b) organophosphorus compounds containing at least one group R-HE, and g) of the Foundation by mixing the above components; in addition, the ORGANOMETALLIC catalyst comprises the reaction product with 2-hydroxycarboxylic acid

FIELD: biodegradable polymers, medicine.

SUBSTANCE: claimed product is obtained by polymerization of alpha-angelicalactone in presence of sodium butylate at 18-25°C for 220-315 hours. Further product is purified with diethyl ether, volatile matters are removed by heating up to 80°C for 4 h under pressure of 14 Hg mm and product is exposed with gamma- or ultraviolet irradiation. Obtained product is characterized with two kinds of interunit bonds, namely carbon-carbon polyolefin bonds and carbon-carbon polyester bonds and contains polyester bonds in amount of 0.01-0.99 as calculated to monomer unit and cross-links between chains in amount of 0-1,94 as calculated to monomer unit. Polymers of present invention are useful in medicine in production of pharmaceutical preparations, surgery filaments, packing materials, etc.

EFFECT: polymer with controlled biodegradation.

7 ex

FIELD: polymers.

SUBSTANCE: invention relates to method for production of polyesters having several free acid functions in the middle of chain and based on cyclic esters such as lactides and glycosides. Disclosed is production of abovementioned polyesters by ring opening polymerization in presence of chain initiator, namely tartaric acid benzyl diester, having optionally substituted phenyl radical; and removing of protective group from carboxylic functions of chain initiator.

EFFECT: improved method for polyester production.

4 cl, 12 ex, 3 tbl

The invention relates to a complex of the polyester containing one or more free carboxyl groups and characterized by the ratio of carboxyl and hydroxyl groups greater than one

The invention relates to complex polyesters containing one or more free COOH groups and having a ratio of carboxyl groups to hydroxyl groups is greater than one, where specified complicated polyester contains an element selected from the group comprising L-lactic acid, D-lactic acid, DL-lactic acid,-caprolactone, p-dioxanone,-Caproic acid, alkylaromatic, cycloalkylation, alkylresorcinol,-hydroxybutyrate, substituted or unsubstituted trimethylantimony, 1,5-dioxan-2-it, 1,4-dioxan-2-it, glycolide, glycolic acid, L-lactide, D-lactide, DL-lactide, mesolectal and any optically active isomers, racemates or copolymers, and the element selected from malic acid, citric acid or 1,6-hexandiol and any optically active isomers, racemates or copolymers, where specified complicated polyester has an average degree of polymerization between 10 and 300 and an average molecular weight from about 1200 to about 40,000; and the complex conjugates of polyester ion associated with a biologically active polypeptide containing at least one group ionogenic amine, where at least 50

The invention relates to a film comprising a biodegradable copolymer, where the copolymer includes at least two statistically recurring Monomeric level, where the first link has the formula

< / BR>
and the second link has the formula

< / BR>
and at least 50% of the units have the formula of the first link

The invention relates to biodegradiruemym the copolymers and plastic products, including biodegradable copolymers

FIELD: chemistry of polymers, chemical technology.

SUBSTANCE: invention relates to a method for polymerization of one or some monomers one of that is vinyl chloride monomer. Method involves addition of the standard system of organic peroxides to polymerization mixture in the first step of polymerization, and one or some of additional organic peroxides and, optionally, surfactant are added to the polymerization mixture at the reaction temperature value when pressure in the polymerization reactor falls due to depletion of vinyl chloride monomer amount. Indicated additional organic peroxides have half-time value less 1 h at the polymerization temperature under condition that formed polymer is not subjected for radio-frequency dielectric heating in the presence of additional organic peroxide. The proposed method provides decreasing the polymerization time owing to higher rate value of the pressure drop in the end the polymerization reaction. Also, invention provides the enhanced effectiveness of cooling capacity of polymerization solution.

EFFECT: improved effectiveness of polymerization process.

5 cl, 1 tbl, 1 ex

FIELD: chemistry of polymers, chemical technology.

SUBSTANCE: invention relates to a polymerization method of vinyl chloride monomer and optionally additional monomers by using a single or some organic peroxides. This method involves dosing at least one organic peroxide compound with half-time value from 0.0001 h to less 0.050 h at the polymerization point to the polymerization mixture. Dosing such initiating agent allows achievement of improving the polymerization rate regulation and higher rate of polymerization. By using this method vinyl chloride-base (co)polymer is prepared having less 50 mass parts of residual initiating agent per one million of mass parts of (co)polymer in measuring after polymerization and drying (co)polymer at 60°C for 1 h directly. (Co)polymer can be used in the molding process involving heating a (co)polymer to temperature exceeding its boiling point.

EFFECT: improved method for polymerization.

8 cl, 2 tbl

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