Birthdaaay complex polyester and method thereof (options)

 

(57) Abstract:

Describes the new birthdaaay complex polyester containing units of lactic acid units and glycolic acid and at least one unit hydroxypolycarboxylic acid selected from the group consisting of tartaric acid, pambou acid complex ester of tartaric acid and complex ether of pambou acid. Also describes how to obtain it (options). Biorstwami polymers are used as excipient in the compositions of continuous selections for medicines. As the main drug lithium acid conjugated with the polymer, increasing the acidity of the polymer is important to facilitate the formation of the conjugate. 13 C. and 21 C.p. f-crystals, 11 PL.

The present invention relates to biorazlagaemykh complex polyesters and methods for their preparation.

ART

Biorstwami polymers are used, for example, as eccipienti in the compositions of continuous selections for medicines (for example, U.S. patents NN 3,773,919 and 4,767,628). Examples of such polymers are copolymers of lactic acid and glycolic acid, which are produced either by polycondensation of lactic acid and glycolic acid, or poms Press, London 1979)).

In International publication N WO 94/15587 described ionic conjugates continuous discharge of polymers and drugs. As the main drug lithium acid conjugated with the polymer, increasing the acidity of the polymer is important to facilitate the formation of the conjugate.

THE INVENTION

One aspect of the present invention reflects birthdaaay complex polyester containing units of lactic acid, which includes 4-100 (for example, 4-40) carboxyl groups and has an average molecular weight of from 1000 to 200,000 g/mol. In one example of a complex polyester also includes units of glycolic acid or additionally includes a unit hydroxypolycarboxylic acid (i.e., one or more units acids such as tartaric acid, pamula acid or ester of these acids). Complex polyester may contain from 45 to 99.9 mol.% units of lactic acid, from 0 to 50 mol. % of units of glycolic acid and from 0.1 to 10 mol. % units hydroxypolycarboxylic acid, in which hydroxypolycarboxylic acid contains from 1 to 20 (for example, from 2 to 20 hydroxyl groups and from 2 to 40 carboxyl groups (for example, from 2 to 20).

In another aspect of the infusion of the manual includes a reaction polyhydroxyalkanoic acid, such as tartaric acid, pamula acid or complex acid ester, lactic acid or lactide to obtain a complex of the polyester, for example heating of the reagent at a temperature of from 100 to 250oC. If required, can also simultaneously be the reaction polyhydroxyalkanoic acid and glycolic acid or glycolide. The method may additionally include etherification of hydroxyl groups in a complex polyester formed in this way, the second polycarboxylic acid or with a second anhydride, or alkylation with polyepoxy.

The third aspect of this invention relates to a method for deriving biorazlagaemykh complex polyester. This method involves the reaction of a polyol (for example, glucose, sorbitol, lactose, mannitol or gluconic acid with lactic acid or lactide to obtain a complex of the polyester (for example, heating of the reagent at a temperature of from 80 to 250oC); and the etherification of the free hydroxyl groups of a complex of the polyester formed in this way, with a polycarboxylic acid (e.g., succinic acid) or anhydride (for example, succinic anhydride or 1,2,4,5 - benzylaminocarbonyl a dianhydride, or glutaric anhydride is required may incidentally be the reaction of the polyol with glycolic acid or glycolide.

Still another aspect of the present invention reflects a way of getting bioaerosol complex polyester. This method involves the reaction of a polyol with a polycarboxylic acid or anhydride to obtain hydroxypolycarboxylic acid, where the polyol has at least three hydroxyl groups; and reaction of the thus obtained hydroxypolycarboxylic acid with lactic acid or lactide to obtain a complex of the polyester (for example, heating of the reagent at a temperature of from 80 to 250oC). If you want, may incidentally be the reaction hydroxypolycarboxylic acid and glycolic acid or glycolide, and optionally the remaining hydroxyl group in compound polyester can be tarifitsirovana with the second polycarboxylic acid (e.g., succinic acid) or with the second anhydride (for example, succinic anhydride or 1,2,4,5-benzylaminocarbonyl a dianhydride) or alkylated, polyepoxy (for example, 1,2,7,8-diepoxyoctane). Second polycarboxylic acid or the second anhydride may be included at the end of the chain complex of the polyester (for example, acid finish), or W is, recondensation).

Another aspect of the present invention reflects the communication method of polyesters, containing, as a minimum, units of lactic acid, in the presence or absence of other units, such as units of glycolic acid. The method includes the etherification of the free hydroxyl group on each of the polyesters with a polycarboxylic acid (e.g., succinic acid) or anhydride (for example, succinic anhydride, or 1,2,4,5-benzylaminocarbonyl a dianhydride, or glutaric anhydride, optionally catalyzed with acid, for example p-toluensulfonate acid), or by etherification of the free hydroxyl groups on the complex polyesters with polyepoxy (for example, 1,2,7,8-diepoxyoctane). In one embodiment, the free hydroxyl group tarifitsiruetsya with succinic acid under reduced pressure. In another embodiment, the free hydroxyl group tarifitsiruetsya with 1,2,4,5-benzylaminocarbonyl the dianhydride.

Another aspect of the present invention reflects the increase of free hydroxyl groups in borisloseso complex polyester described above. The method includes substantial complex of the polyester polycarboxylic acid is first dianhydride), when the polycarboxylic acid or anhydride cleaves the ester bond in a complex polyester and atrificial obtained hydroxyl group to split complex polyester.

In this description, "axiolichbiala acid contains at least one hydroxyl group (for example, from 1 to 20 hydroxyl groups and at least two carboxyl groups (for example, from 2 to 40 carboxyl groups); "polyhydroxyalkanoate acid contains at least two hydroxyl groups (for example, from 2 to 20 hydroxyl groups and at least two carboxyl groups (for example, from 2 to 40 carboxyl groups); "polycarboxylic acid" contains at least two carboxyl groups, polyepoxy contains at least two epoxy groups (for example, two epoxy groups); and "polyol contains at least two hydroxyl groups (for example, from 2 to 20 hydroxyl groups). The term "anhydride" refers to how monoamide and polyanhydride.

In the absence of specific instructions lactic acid may be a D-lactic acid or L-lactic acid and lactide can be D-lactide, L-lactide or DL-lactide.

Other characteristics and advantages of the present invention budow this area may, on the basis of this description to apply the present invention to the full extent. The following specific options for implementation are therefore illustrative, but not restrictive in nature.

In the absence of specific instructions, all used here is the technical and scientific terms have the meaning which is generally accepted in the field to which this invention. Additionally, here are links to all publications, patent applications, patents, and other materials.

PREFERRED EMBODIMENTS OF THE INVENTION

Example 1

Polymerization disclosure cycle L-tartaric acid.

In a glass reactor with a capacity of 500 ml was placed is 203.2 g of L-lactide (Cilag AG, Schaffhausen, Switzerland), 81,1 g glycolide (Cilag) and 15.0 g of L-tartaric acid (Riedel de Haen, Seelze, Germany). L-tartaric acid was then dehydrated by means of phosphorus pentoxide in the device Abderhalden (Aldrich, Milwaukee, WI, U. S. A. ). Added with 5.3 ml of 0.1 M solution of 2-ethylhexanoate tin in toluene (stoichiometric ratio of 200 parts per million). After drying in vacuum at room temperature for one hour to remove toluene reactor was placed in a nitrogen atmosphere and immersed in an oil bath, preheated to a temperature of 200oC, and kept at 200oC for 4 h under mechanical paramesh and 2,31% units tartaric acid (56/33/2 PLGTA). Acid number of the copolymer, which was determined by titration, was 0,630 meq/g (for example, an acid number (milliequivalent/g) = normality of NaOH, multiplied by the volume of NaOH needed to neutralize a gram of complex polyester).

Example 2

Polycondensation with succinic acid

In a glass reactor with a capacity of 500 ml was placed in 100.0 g (65/33/2) PLGTA with molecular weight of 3000 g/mol (acid number = 0,630 meq/g) and of 3.78 g of succinic acid (stoichiometric ratio of acid groups of succinic acid to the hydroxyl group of the copolymer = 1,06). The reactor was immersed in an oil bath at 200oC. After melting the mixture was intensively mixed and maintained in a vacuum for distillation of water condensate (0,10 mbar). The samples were removed and subjected to analysis every half hour. After 4 h the reaction was stopped due to a significant increase in the viscosity of the copolymer. Monitoring polycondensation shown in table 1. The evolution of the acid number and srednekamennogo molecular weight (AVG. Mn) were determined by gel permeation chromatography (GPC) in tetrahydrofuran (THF) using sensor light scattering Wyatt.

Example 3

Polycondensation with 1,2,4,5-benzylaminocarbonyl the dianhydride

In a glass reactor acostumbrados of dianhydride (Aldrich Chemical Co., St. Louis, MO). The mixture is then immersed in an oil bath, preheated to 220oC. After complete melting of the mixture was intensively stirred for 30 minutes Average molecular mass determined sterile exclusion chromatography (SEC) was 10500. It was determined acid number, which was 0,951 meq/g.

Example 4

Polycondensation with 1,2,7,8-diepoxyoctane

60,0 g (65/33/2) PLGTA with molecular weight of 10000 g/mol (acid number = 0,431 meq/g) was melted at 180oC in a glass reactor. Using a Gilson pipette, added 1.5 ml of 1,2,7,8-diepoxyoctane drops 300 μl every 15 minutes and the Mixture was stirred at this temperature for another 4 h table 2I shows the increase in the molecular weight of the copolymer and a minor change in acid number.

Example 5

Polymerization erection cycle with malic acid

In a glass reactor with a capacity of 500 ml was placed 209,1 g of L - lactide (Cilag), 84,2 g glycolide (Cilag), 6.7 g of D,L-malic acid (Aldrich) and 4.45 ml of 0.1 M solution of 2-ethylhexanoate tin in toluene. Then everything took place in the scheme of Example 1, except that the temperature of the oil bath maintained at 180oC during the first four hours and then increased to 200oC. Poly is acted, had an acid number of 0.45 meq/g and an average molecular weight of 6000 g/mol. The copolymer contained 65,91% of the units of lactic acid, 32,95% of residues of glycolic acid and 1.14% malic acid residues. Its structure was linear with one hydroxyl end and two acid functions on the unit D,L-malic acid on the other end.

Example 6

Polycondensation with succinic acid

The mixture is 60.0 g of the copolymer from example 5 and 0.82 g of succinic acid (Aldrich) was melted at 200oC, kept at reduced pressure and was intensively stirred for 4,75 including the evolution of the acid number and the average molecular weight of the polymer was determined by GPC in THF using sensor light scattering Wyatt. The results are presented in table 3.

Example 7

Synthesis of the special initiator for the polymerization reaction to the disclosure of cycle

A mixture of 22,61 g of L-tartaric acid and 27,39 g benzene 1,2,4,5-tetracarbon of dianhydride was added to the reaction vessel and immersed in an oil bath at 200oC. After melting the mixture temperature in the vessel was increased to 220oC for 40 min and held at this temperature for another 30 min under vigorous stirring. After cooling to room temperature BNDES special initiator for the polymerization reaction to the disclosure of cycle

The solution 13,50 g of L-tartaric acid in 200 ml of acetone (pre-dehydrated calcium chloride) was heated to reflux distilled. 11,50 g 1,2,7,8-diepoxyoctane was added in drops when using misleading funnel within 30 minutes the Solution is then subjected to reflux distilled for 3 hours Oligomers were recovered by evaporation of the acetone and then dehydrated in a vacuum. The measured acid number was 4,03 meq/g.

Example 9

Polymerization erection cycle with a conventional polymerization initiator

In a glass reactor with a capacity of 500 ml of 203.2 put glycolide, 81,8 g of L-lactide and 14.9 g of the initiator in accordance with example 7. Then applied the scheme in example 1, except that the oil bath was kept at 220oC and the polymerization was carried out in a total of 8 hours the Final copolymer had only 8.5 wt.% the residual L-lactide, had an acid number of 0.77 meq/g and an average molecular weight 12900 g/mol.

Example 10

Polymerization erection cycle with a conventional polymerization initiator.

In a glass reactor with a capacity of 500 ml was placed 129.4 g of glycolide, to 52.1 g of L-lactide and 18.5 g of the initiator in accordance with example 8. Used the same pattern as in example 1, except that mass who ate only 10.6 wt.% the residual L - lactide, had an acid number 0,472 meq/g and an average molecular weight 30500 g/mol.

Example 11

Polymerization disclosure cycle when using polyols

In a glass reactor with a capacity of 500 ml was placed in a dry atmosphere glycolide, L-lactide and various Paleologue initiators to obtain 300 g of a copolymer 66/33 PLGA of different molecular weight. The mixture was heated to a temperature typically exceeding 30oC melting point used Paleologo initiator, and was stirred for 4 to 8 h, depending on the kinetics of polymerization. All reaction conditions and characteristics of the obtained copolymers are shown in table 4. Residual monomers (wt%) represent the weight percent of residual monomers (for example, glycolide or lactide) polymer sample.

Example 12

The formation of acid end with succinic anhydride

Each of the copolymers synthesized in accordance with example 11, was further subjected to reaction with succinic anhydride (more than 1.5 times greater than the number of hydroxyl groups originally introduced into the mixture for synthesis) at 150oC for 30 min and intensively stirred. The modified copolymer was then dissolved in the copolymer. Then the copolymer was besieged from solution by slow addition of cold deionized water. The suspension is completely besieged (5000 rpm) at 0oC for 30 min and subjected to freeze-drying. Through this washing removed the residual monomers from the polymerization, and the excess of succinic anhydride was converted to sodium succinate, which is also removed when washing. The leaching efficiency was confirmed by SEC. Table 5 presents the characteristics of the final copolymers.

Example 13

Synthesis of specially obtained initiator for polymerization with the disclosure of cycle

Various hydroxyl groups contained in the initiators, were subjected to acid funkcionisanje using actinophage anhydride by melting of both reagents and their intensive mixing for 30 minutes. Placed in the reactor substances and temperature are presented in table 6.

Example 14

Polymerization erection cycle with a conventional polymerization initiator.

In a reactor with a capacity of 500 ml was placed in a dry atmosphere glycolide, L-lactide and three modified initiator in accordance with example 13 to obtain 200 g of a copolymer with different molekularbiologie initiator, and was stirred for 4 to 8 h, depending on the kinetics of polymerization. All reaction conditions and characteristics of the obtained copolymers are presented in table 7.

Example 15

Polymerization disclosure cycle when using hexadecanol and 1,2-propane diol

Synthesized two copolymer as described in example 11 using hexadecanol or 1,2-propane diol as Paleologo initiator. Reaction conditions and results are shown in table 8.

Example 16

Polycondensation with BTCDA

Two of the copolymer according to example 15 or copolymer obtained when using the initiator 1,2-propane diol from example 15 were mixed in a glass reactor with a capacity of 500 ml with benzene 1,2,4,5-tetracarbonyl a dianhydride (BTCDA). The copolymer initiated hexadecanol to contain only one hydroxyl group, and thus acted as a limiter circuit when polycondensate. In both experiments the reaction mixture was stirred at 200oC for 4 h Conditions and characteristics are presented in table 9.

Example 17

Synthesis of initiator

In a glass reactor with a capacity of 500 ml was placed 36,13 g of 1,2,4,5-benzylaminocarbonyl of dianhydride (BTCDA) and 13,87 g of 1,2-propane diol for p is x ends. The mixture was left at room temperature under mechanical stirring for 30 min, to gently initiate the polycondensation. The mixture is then immersed in an oil bath at 160oC until complete melting of the mixture. The temperature was then raised and maintained at 180oC for 20 min, until the viscosity of the mixture does not become too high to allow mixing. The mixture is then cooled to room temperature and analyzed by SEC in acetone and titration of the acid functions. The resulting polymer had an acid number of 6.2 meq/g, average molecular weight 3020 g/mol and a melting point 240oC.

Example 18

Polymerization erection cycle with a conventional polymerization initiator

In a glass reactor with a capacity of 500 ml was placed 131,8 g glycolide, 53,1 g of L-lactide and 15.1 g of the initiator in accordance with example 17. Then the mixture was heated to 220oC and stirred for 5.5 h of the Final copolymer had only 8.7 wt.% the residual L-lactide, an acid number of 0.77 meq/g and an average molecular weight 15200 g/mol.

Example 19

Polymerization erection cycle with glycolic acid

In a glass reactor with a capacity of 500 ml was placed a mixture of glycolide, l-lactide and picolinate tin was used as the catalyst in a molar ratio of 200 parts per million. Then the mixture was obezvozhivani in vacuum for one hour to remove the toluene, and then immersed in an oil bath. The polymerization was carried out at intensive stirring for 6 hours the reaction Conditions and characteristics of the final copolymer are presented in table X.

Example 20

Polycondensation with succinic acid or HCACH

The copolymer of example 19 was mixed with succinic acid or cyclohexane hexacarbonyl acid (HCACH) when the stoichiometric ratio of 1: 1 and 3:2, melted at 200oC and was stirred for 2 to 4 h before until analysis SEC did not cease to show the peak elution for succinic acid or HCACH. Conditions and characteristics are presented in table 11.

It should be understood that since the invention has been described according to its description, the previous description is provided for illustrative purposes and does not restrict the scope of the invention, which is defined by the scope of the attached claims. Other aspects, advantages and modifications presented within the claims.

Example 21

Synthesis of copolymer 66/33/1 RLGTA with a molecular weight of 12,000 g/mol, initiated tartaric acid

The reactor was placed the second divalent tin 2-ethylhexanoate (Sigma, St. Louis, Missouri, USA, article number S-3252) in toluene (Riedel-de Haen) solution (0,1043 M, of 4.25 ml). L(+)- tartaric acid was previously dehydrated silicagel in the drying device Abderhalden for 9 hours the Reactor (connected to the pump through the separator liquid nitrogen) and then placed in a vacuum of 0.04 mbar) with stirring (34 rpm, stirrer Scientific bioblock is used, Strasbourg, France, model 94412) for approximately 40 minutes to remove toluene. Then the reactor was placed in an oil bath (temperature about 40oC) for 30 minutes the Reactor under oxygen atmosphere without nitrogen (BOC gases, moisture content 8VPM) then immersed in an oil bath (temperature of 20oC), and stirring is increased to about 125 rpm Before diving for cover placed ribbon heating element (input control of thermolyne type 45500, the setting position of -4). The time required to fully melt the contents of the reactor was typically 10 min to the reactor contents in the amount of 300 g 200oC. Samples were taken during the reaction every 2 h and were analyzed by GPC to determine the percentage of residual monomer and retrieve values srednekamennogo molecular weight (Mn) and srednevekovoi molecular weight (Mw). Octid, 33,15% of the units glycolide and 0.56% units tartaric acid (66/33/1 PLGTA). It was determined that acid number titration was 0,267 meq/g. Srednekislye molecular weight of the copolymer was 12360, and srednevekovaja molecular weight of the copolymer was 14060, i.e., the ratio Mw/Mn was $ 1,37.

Example 22

The formation of acid end 66/33/1 PLGTA with a molecular weight of 12,000 g/mol by glutaric anhydride

The reactor was placed a specified copolymer PLGTA (19.01 in g) and glutaric anhydride (Aldrich, of 0.47 g). The reactor contents were purged until such time as the pressure indication is not accounted for approximately 0,04 mbar. The reactor was sequentially placed in a nitrogen atmosphere without oxygen (BOC gases, moisture content 8VPM) and immersed in an oil bath (temperature = 160oC) ribbon heating element on the cover (the setting position = 4, the model is the same as in the previous case) in a convenient and time specified. The contents of the reactor melted after 10 min at 160oC. the Reaction was carried out for another 30 minutes Final acid number patriciaanne PLGTA was 0,353 meq/g. The values of Mn, Mw and Mw/Mn were determined respectively 11850, 12500 and 1,055. The percentage of hydroxyl groups PLGTA that were patrilineage, sokolovas acid and at least one unit hydroxypolycarboxylic acid selected from the group consisting of tartaric acid, pambou acid complex ester of tartaric acid and complex ether of pambou acid.

2. Birthdaaay complex polyester under item 1, characterized in that the complex polyester mainly contains 65 mol.% units of lactic acid, 33 mol.% units of glycolic acid and 2 mol.% units of tartaric acid.

3. Birthdaaay complex polyester containing units of lactic, glycolic acids and at least one unit hydroxypolycarboxylic acid containing from 2 to 20 hydroxyl groups and from 2 to 20 carboxyl groups.

4. Birthdaaay complex polyester containing units of lactic acid units and glycolic acid and a conventional polymerization initiator.

5. Birthdaaay complex polyester under item 4, characterized in that the initiator contains units of tartaric acid and units 1,2,4,5-benzylaminocarbonyl acid.

6. Birthdaaay complex polyester under item 4, characterized in that the initiator contains units of tartaric acid and units 1,2,7,8-diepoxyoctane.

7. Birthdaaay complex polyester under item 4, characterized eraut from the group consisting of glucose, lactose and mannitol.

8. Birthdaaay complex polyester containing units of lactic acid units and glycolic acid and initiator containing hexadecanol.

9. Birthdaaay complex polyester containing units of lactic acid units and glycolic acid and initiator containing 1,2-propandiol.

10. Birthdaaay complex polyester under item 9, characterized in that it additionally contains units 1,2,4,5-benzylaminocarbonyl acid.

11. Birthdaaay complex polyester under item 10, characterized in that it further comprises a unit hexadecanol.

12. The initiator for polymerization containing units 1,2,4,5-benzylaminocarbonyl acid and units of 1,2-propane diol.

13. Birthdaaay complex polyester containing units of lactic acid units and glycolic acid units cyclohexanedicarboxylic acid or basic initiator containing units 1,2,4,5-benzylaminocarbonyl acid and units of 1,2-propane diol.

14. Birthdaaay complex polyester containing units of lactic acid units and glycolic acid units tartaric acid, and he allerban with glutaric anhydride.

15. give the reaction hydroxypolycarboxylic acid with lactic acid or lactide and glycolic acid or glycolide, moreover, the specified hydroxypolycarboxylic acid selected from the group consisting of tartaric acid, pambou acid complex ester of tartaric acid and complex ether of pambou acid.

16. The method according to p. 15, characterized in that it further carry out the etherification of hydroxyl groups in the specified complex obtained polyester with a second polycarboxylic acid or anhydride or alkylation with polyepoxides.

17. The method according to p. 16, wherein conducting the etherification of hydroxyl groups in the specified complicated polyester with glutaric anhydride and an acid catalyst.

18. The method of obtaining biorazlagaemykh complex polyester, namely, that carry out the reaction of the polyol with lactic acid or lactide and the etherification of the free hydroxyl groups of the specified complex obtained polyester with polycarboxylic acid or anhydride.

19. The method according to p. 18, characterized in that conduct the reaction of the polyol with lactic acid or lactide and glycolic acid or glycolide.

20. The method according to p. 18 or 19, characterized in that the polyol is a glucose, sorbitol, lactose, mannitol or gluconic acid.

21. FPIC is the anhydride is succinic anhydride or 1,2,4,5-benzylaminocarbonyl the dianhydride.

22. The method of obtaining biorazlagaemykh complex polyester, namely, that carry out the reaction of a polyol with a polycarboxylic acid or anhydride to obtain hydroxypolycarboxylic acid, where the specified polyol has at least three hydroxyl groups and the reaction of the specified received hydroxypolycarboxylic acid with lactic acid or lactide.

23. The method according to p. 22, characterized in that conduct the reaction specified hydroxypolycarboxylic acid and glycolic acid or glycolide.

24. The method according to p. 22 or 23, characterized in that the polyol is a glucose, sorbitol, lactose, mannitol or gluconic acid.

25. The method according to PP.22 to 24, characterized in that carry out the etherification of hydroxyl groups in the specified complicated polyester with a second polycarboxylic acid or with a second anhydride or alkylate with the second polyepoxide.

26. The method according to p. 25, characterized in that the polycarboxylic acid is succinic acid and the specified second anhydride is succinic anhydride or 1,2,4,5-benzylaminocarbonyl the dianhydride or the specified second polyepoxide is 1,2,7,8-diepoxyoctane.

27. Specificatio free hydroxyl group on each of these polyesters with polycarboxylic acid or anhydride or etherification of the free hydroxyl group on the specified complex polyesters with polyepoxides.

28. The method according to p. 27, characterized in that the polycarboxylic acid is succinic acid, the said anhydride is succinic anhydride or 1,2,4,5-benzylaminocarbonyl a dianhydride, and the specified polyepoxide is 1,2,7,8-diepoxyoctane.

29. The method according to p. 27 or 28, characterized in that carry out the etherification specified free hydroxyl groups with succinic acid under reduced pressure.

30. The method according to PP.27 to 29, characterized in that the complex polyester additionally contains units of glycolic acid.

31. The method according to p. 27, characterized in that the free hydroxyl group atrificial with 1,2,4,5-benzylaminocarbonyl the dianhydride.

32. The way to increase the available carboxyl groups biorazlagaemykh complex polyester containing units of lactic acid, which consists in the fact that carry out the esterification of the specified complex of the polyester polycarboxylic acid or anhydride, and mentioned polycarboxylic acid or anhydride cleaves the ester bond in the specified complicated polyester and atrificial obtained hydroxyl group on the specified split complex polyester.

33. Elote.

34. The method according to p. 32, characterized in that the polycarboxylic acid is succinic acid, and the anhydride is succinic anhydride or 1,2,4,5-benzylaminocarbonyl the dianhydride.

 

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FIELD: chemistry.

SUBSTANCE: present invention relates to a composition for moulding articles and a method of producing said composition. The composition contains 100 pts.wt of a polymer component A, which consists of 5-100 wt % of a lactic acid polymer (component A-α) and 95-0 wt % of thermoplastic resin (component A-β), 0.001-5 of pts.wt of a phosphoric-fatty acid ester (component B), 0.01-5 pts.wt of metal phosphate salt (component C), 0.001-2 pts.wt of at least one antioxidant (component D), 0.001-10 pts.wt of a chain end closing agent (component E) and 0.01-0.3 pts.wt of hydrotalcite. The antioxidant is selected from a group comprising a phosphite-based compound, phosphonite-based compounds, a hindered phenol-based compound and a thioether-based compound. The method of producing the composition involves mixing, at 250-300°C, composition-1, which contains poly-1-lactic acid and a phosphoric-fatty acid ester, and composition-2, which contains poly-d-lactic acid and a phosphoric-fatty acid ester, in the presence of a metal phosphate salt to obtain a stereo-complex lactic acid polymer. Further, component A, which consists of the obtained stereo-complex polymer and a thermoplastic resin, is mixed with the antioxidant and the chain end closing agent.

EFFECT: obtained composition has good thermal stability, especially in humid conditions.

14 cl, 22 tbl, 70 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method for thermal stabilisation of a polymer obtained by ring-opening polymerisation, as well as a method of producing polyhydroxy acids, a method of analysing metal residues in a polymer and polylactide. Said polymer contains residues of a Sn(II), Sb(III), Pb(II), Bi(III), Fe(II), Ti(II), Ti(III), Mn(II), Mn(III) or Ge(II)-containing catalyst. Thermal stabilisation is carried by treating the polymer at temperature higher than melting point thereof with a peroxide in amount of at least 0.2 wt % based on the weight of the polymer. The peroxide is selected from a group consisting of ketone peroxides, organic hydroperoxides, peracids, hydrogen peroxide and mixtures thereof. Molar ratio of peroxy functional groups from said peroxide to metal ranges from 1 to 100. Said metal is selected from a group consisting of Sn(II), Sb(III), Pb(II), Bi(III), Fe(II), Ti(II), Ti(III), Mn(II), Mn(III) and Ge(II). The method of producing polyhydroxy acids involves converting one or more monomers, dimers and/or oligomers of a hydroxy acid to a polyhydroxy acid using a Sn(II), Sb(III), Pb(II), Bi(III), Fe(II), Ti(Il), Ti(III), Mn(II), Mn(III) or Ge(II)-containing catalyst and treating the obtained polyhydroxy acid with a peroxide. The method of analysing metal residues in a polymer involves dissolving the polymer in an organic solvent, adding Fe(III), oxidising the metal and reducing Fe(III) to Fe(II), adding water, complexing the Fe(II) to form a coloured complex, determining content of Fe(II) and establishing content of metal in the polymer.

EFFECT: optimising a method for thermal stabilisation of polymers obtained by ring-opening polymerisation, particularly polylactic acid.

16 cl, 5 tbl, 3 dwg, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a biodegradable mixed aliphatic-aromatic polyester suitable for an extrusion coating, which contains links formed from at least a dicarboxylic acid and at least a diol, with long-chain branches, and substantially free from gel, characterised by shear viscosity of 800-1600 Pa*s, heat-resistance constant of less than 1.5*10-4, melt strength of 2-4.5 g and ultimate elongation greater than 30. The biodegradable polyester can be obtained by reactive extrusion from a linear polyester precursor containing links formed by dicarboxylic acid and diol and having melt flow index from 5 g/10 min to 30 g/10 min and terminal unsaturation content of 0.1-1% mol/mol. The method is realised by adding peroxides, epoxides and carbodiimides. The invention also relates to a layered article consisting of at least a base and at least a first layer consisting of the polyester disclosed herein, an extensible film, multilayer films and a composition suitable for extrusion coating, which consists of a biodegradable mixed aliphatic-aromatic ester and polylactic acid.

EFFECT: obtaining biodegradable polyesters, having physical and chemical properties which enable to obtain thin films with high melt stability and high transparency.

21 cl, 7 dwg, 4 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to method of continuous obtaining of polyesters. Described is method of continuous polymerisation with opening of ring of cyclic ester monomers with formation of aliphatic polyesters based on monomers of cyclic ester, which includes the following operations: a) continuous supply of cyclic ester monomer and polymerisation catalyst into continuous stirred loop reactor, reactor working under efficient for polymerisation conditions with formation of prepolymerised reaction mixture with polymerisation degree between 40% and 90% at temperature from 100 to 240°C; b) continuous discharge of prepolymerised reaction mixture from continuous stirred reactor and continuous supply of prepolymerised reaction mixture into plug flow reactor, with plug flow reactor working under conditions of polymerisation, under which reaction mixture is polymerized to polymerisation degree of at least 90%, with formation of polymer at temperature from 100 to 240°C; c) continuous discharge of polymer from plug flow reactor.

EFFECT: obtaining high quality polyesters from the point of view of molecular weight, structure of polymer chain, colour and content of residual monomer.

14 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: method relates to biodegradable material production. Biodegradable material, which is a chemical bond-crosslinked product, formed by a multivalent compound A, which includes 3 or more functional groups X, selected from a group consisting of a hydroxyl group, a thiol group and an amino group, and a multivalent compound B, which includes 3 or more functional groups Y, selected from a group consisting of a carboxyl group, an isocyanate group and a thioisocyanate group, where the chemical cross links are formed via condensation reaction of said functional group(s) X and said functional group(s) Y, where the value (y+z)/(x+z) ranges from 1.2 to 4.0, if MA≥MB, and the value (x+z)/(y+z) ranges from 1.2 to 4.0, if MA<MB, where x denotes the number of functional groups X not involved in the condensation reaction with said functional groups Y, y denotes the number of functional groups Y not involved in the condensation reaction with said functional groups X, z denotes the number of said cross links, MA denotes the weight-average molecular weight of said multivalent compound A and MB denotes the weight-average molecular weight of said multivalent compound B. The invention also discloses a vessel embolisation material, an anti-adhesive material, a wound-dressing material, a blood-staunching material and a material which prevents involuntary urination.

EFFECT: material has high compression force, high degree of recovery, high complex modulus of elasticity and short gel time.

13 cl, 1 tbl, 18 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

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: 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

FIELD: chemistry.

SUBSTANCE: effect is achieved by using compositions based on different stereoregular amorphous biodegradable polymers - polylactides and copolymers of lactides with glycolides (18-72 mass ratio) as the second component of biocompatible mineral filler - hydroxyapatite with particle size of the main fraction of 1-12 mcm (8-41 mass ratio), as well as an organic solvent with boiling temperature equal to or higher than softening temperature by 3-20°C (20-41 mass ratio). After preparation of a homogenous mixture, the composition is undergoes thermal treatment at 80-130°C in a vacuum in a shaping vessel with the required shape. A porous product is obtained due to removal of solvent. Density of the obtained porous product is about 0.4-0.8 g/cm3.

EFFECT: design of a method of obtaining porous biodegradable composite polymer products based on polylactides or copolymers of lactides and gylcolides.

3 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention concerns polymerisation catalysts, particularly lactide polymerisation catalysts. Claimed metal compounds can be applied in chemical industry as catalysts, particularly for obtainment of biodegradable polymers (polylactides) applicable in food industry, medical technology, pharmaceutics etc. Invention claims catalyst for polylactide obtainment, including metal compound of the formula , where M is one of the following metals: Zn(II), Mg(II), Ca(II), Sr(II), Ba(II), Al(III), Ga(III), Ge(II); R1 and R2 are hydrocarbon substitute; R3 is alkyl, dualky, aryl or heterocycle; Y is oxygen or nitroge; X is a fragment of unsaturated C6-C22 hydrocarbon; S is present in the compound in some instances as coordinated solvent. Also invention claims method of polylactide synthesis by affecting lactide monomer by the claimed catalyst.

EFFECT: enhanced efficiency of catalyst.

16 cl, 3 tbl, 6 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: description is given of use of a catalyst system for (co)oligomerisation of lactide or glycolide with ring opening. The catalyst system is formed by a polymer catalyst based on a strongly acidic ion-exchange resin (1) and a (co)oligomerisation additive of formula (2) R1-E-R2, in which E is an element of the 16th group, R1 is a hydrogen or deuterium atom, R2 is a hydrogen or deuterium atom or a group in formula - E14(R14)(R'14)(R"14), where E14 is an element of the 14th group, R14, R'14, R"14 - represent a hydrogen atom, a deuterium atom, substituted or unsubstituted alkyl, cycloalkyl or aryl.

EFFECT: proposed catalyst system allows for controlling chain length and nature of terminal groups of compounds, separate compounds from a catalyst using a simple and efficient method and prevent loss of catalyst activity.

14 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of preparing a polymer-containing composition which can be used in medicine, packing, textile industry and motor-car construction. The method of preparing a polymer-containing composition involves preparation of a mixture of inorganic anionic clay from the hydrotalcite family and a monomer from the family of cylclic esters, and polymerisation of the said monomer at 50-250°C. Also described is a polymer-containing composition obtained using the said method.

EFFECT: obtaining a polymer-containing composition with improved fire-resistance and impact-strength properties.

14 cl, 9 dwg, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to production of biodegradable polymers, particularly to a method of producing polylactides from a catalyst system, used in the food industry, medical engineering, pharmacology etc. The method involves opening and then polymerisation of rac- or L-lactide in a monomer melt at 120-200°C in the presence of a metal and with or without additives RxYyR'z. The metal has low electronic work function. , where M, M' and Y denote a metal selected from Li, Na, K, Mg, Ca, Fe, Al, Ga, Zn, La, Nd, Sm; RxYyR'z denote an adamantyl alcohol or an inorganic compound, R, R', A denote oxygen, halogen ion, hydroxide ion and an acid residue.

EFFECT: invention enables to obtain polylactide with a faster polymerisation process, high degree of monomer conversion and minimisation of formation of by-products.

14 cl, 2 tbl, 5 dwg, 7 ex

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