SU1685952A1 - Method for preparation of complex polyesters - Google Patents

Abstract

The invention relates to the creation of biodistrusable medical purpose polymers based on glycolide and lactide. The invention makes it possible to obtain these polymers according to a simplified technology due to the fact that the melt of lactide or glycolide or their mixtures containing (1-15) 10 mol / l hydroxy acids, is incubated with calcium oxide, hydroxide or hydride for 0.5-1, 0 h at a molar ratio of Ca COOH 3.5 and 90-130 ° C, followed by polymerization of the mixture at 160-220 ° C in mass

Description

This invention relates to the synthesis of biodegradable medical grade polymers based on glycolide and lactide, which can be used to make absorbable suture, dowel pins for osteosynthesis of bone fractures and other products that are biodestructive in a living organism without the formation of toxic products.

The purpose of the invention is to simplify the technology for producing a high molecular weight polymer that does not contain toxic impurities and is suitable for the manufacture of high strength biodestructive products for medical purposes.

Glycolic and lactic acids, as well as their linear dimers and oligomers present as impurities in the raw glycolide and lactide, cause a significant decrease in the molecular weight of the resulting polymers, which makes them unsuitable for the manufacture of biodegradable products for medical purposes.

The solid inorganic calcium compound, when interacting with the melt of monomers, neutralizes the impurities of organic acids by chemically binding them in the form of salts of acids or their oligomeric derivatives. The temperature of this interaction is slightly higher than the melting point of the monomers, for example, for glycolide it is 90 ° C, for lactide 130 ° C. At the same time, a catalytic complex is formed, which, after raising the temperature of the reaction mixture to 140-160 ° C, is able to initiate the process of polymerization of lactones.

The processing time of the monomers with the calcium compound is 30-60 minutes and depends on the initial content of organic acid in the monomer and the molar ratio of Ca and organic acid. The latter value ranges from 3.0 to 5.0, depending on the nature of the calcium compound. AT

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Calcium oxide, calcium hydroxide or calcium hydride are used as the active impurity acceptor.

Special experiments have shown that the residual content of organic acids in the monomers after such treatment does not exceed 5–10 mol / l, which makes it possible to obtain on their basis high-molecular polymers with fiber-forming properties.

At the temperature of pre-treatment (90-130 ° C) there is no formation of polymers. The polymerization of glycolide and lactide after treatment and preparation of the catalyst is carried out in the melt in the range of 140-220 ° C.

PRI me R 1. A. 10.0 g of raw glycolide containing, according to potentiometric titration 5.0 10 mol / l glycolic acid, are placed in a glass ampoule and this amount of CaO is added to it so that the molar ratio Ca: COOH was 4.0. The mixture was evacuated (Growth -0.01 mm Hg), heated at 90 ° C for 1 hour, while the glycolic acid content was reduced to 4.0 mol / L. Next, the temperature is raised to 160 ° C and the glycolide is polymerized by the action of the prepared catalyst. The yield of crystalline polyglycolide with fiber-forming properties of 98.4% for 1 h.

B. For comparison, a similar experiment was carried out in a manner known per se. For this, 10.0 g of raw glycolide is loaded in a stream of argon into a previously evacuated recrystallization vessel, the required amount of dried ethyl acetate is added and the number of recrystallization that is necessary to obtain a conforming monomer is sequentially carried out. After four recrystallization cycles, the content of glycolic acid in the monomer decreased from 5.0 to 4.5 mol / L, which is quite enough to produce a high molecular weight polymer. The yield of purified monomer 45%.

SnCte 2H20 is added to 1.0 g of purified glycolide in a stream of argon in such a quantity that its concentration is 1.0 mol / l, the mixture is evacuated (Height - 0.01 mm Hg) and the melt is polymerized at 160 ° C for 1 h. The yield of crystalline polyglycolide with fiber-forming properties 57%.

Thus, the proposed method makes it possible to halve the loss of monomer during purification and to obtain a high molecular weight polymer with fiber-forming properties without the participation of toxic compounds of heavy metals.

EXAMPLE 2 A. In Example 1A, lactide is polymerized. For this, 10.0 lac ™ of raw material containing 15.0 mol / l of lactic acid is mixed with CaO at a molar ratio of Ca: COOH of 3.0. The mixture is heated in vacuum (Height: 0.01 mm Hg) for 1 h at 130 ° C. The content of lactic acid is reduced to 4.5 10 mol / l (according to potentiometric titration). Next, the temperature is raised to 160 ° C and the lactide is polymerized by the action of the formed

catalyst for 1 hour. High molecular weight polymer yield 55%.

B. For comparison, a similar experiment was conducted in Example 1B. For this, 10.0 g of raw dj-lactide containing 15.0

mol / l of lactic acid, is subjected to recrystallization from a hot solution of ethyl acetate by a known method. After four cycles of recrystallization, the residual content of lactic acid in the lacquer is 4.6 mol / l, the yield of the purified monomer is 50%.

SnCl2 2Н20 (concentration 1.0 mol / l) is added to 1.0 g of purified d.l-lactide and melt polymerized at 160 ° C for 1 hour. The yield of the high molecular weight polymer is 36%.

Thus, the proposed method allows halving the loss of monomer and obtaining high molecular weight polylactide without the participation of toxic heavy metal based catalysts.

Example 3: In Example 1A, glycolide is polymerized in the presence of Ca (OH2) with a molar ratio of Ca:

COOH 4.0. After preliminarily incubating the Ca (OH) 2 mixture with the molten monomer for 0.5 h, the residual glycolic acid content is 4.2 mol / L. The yield of crystalline polyglycolide with fiber-forming properties of 88% at 160 ° Сза 1 h.

Example 4. In Example 2A, d.l-lactide is polymerized at a molar ratio of Ca (OH) 2: lactic acid equal to 3.0. The residual content of lactic acid after preliminary keeping in the melt a mixture of lactide and Ca (OH) z and preparation of the catalyst is 4.0–10 mol / l. The yield of high molecular weight popylactide is 48% at 160 ° C for 1 h.

Example 5: In Example 1A, glycolide is polymerized in the presence of CaH2 at a molar ratio of CaiCOOH of 5.0. Residual glycol content

acid after pre-melting the mixture of CaH2 with glycolide for 0.5 h is 4.4 1 (G3 mol / l. The yield of crystalline fiber-forming polymer is 48% in 1 h at 160 ° C.

Example 6. According to Example 2A, d.l-lactide is polymerized in the presence of CaH2 at a molar ratio of Ca: COOH - - 4.0. After preliminary melting at 130 ° C for 1 h of a mixture of CaH2 and lactide, the residual content of lactic acid is 4.7 1 (G3 mol / l. The yield of the high molecular weight polymer is 46.7% for 1 h at 160 ° C.

Example 7. In Example 1A, the polymerization of equimolar amounts of glycolide and d, l-lactide and the presence of CaO is carried out at a molar ratio of Ca: COOH 4.0. After keeping the molten monomer mixture with CaO at 130 ° C for 1 hour, the total residual content of organic hydroxy acids in the reaction mixture is 4.6-10 mol / L. Next, the temperature of the mixture is raised to 160 ° C and the glycolide and lactide are copolymerized under the action of the prepared catalyst. The yield of high molecular weight copolymer is 78% in 6 hours at 160 ° C.

Example 8. In Example 7, 75 mol.% Glycolide and 25 mol.% Lactide are copolymerized in the presence of Ca (OH) 2 at a molar ratio of Ca: COOH of 3.0. The residual content of organic acids after keeping in the melt the mixture of monomers with Ca (OH) 2 at 100 ° C for 1 h is equal to 4.5 10 mol / l. Yield of high molecular weight fiber-forming copolymer 89% for 6 hours at 160 ° C.

EXAMPLE 9 In Example 7, 25 mol.% Glycolide and 75 mol.% D.l-lactide are copolymerized in the presence of CaHg at a molar ratio of Ca: COOH of 5.70. The residual content of organic acids after keeping in the melt at 130 ° C for half an hour the mixture of monomers with CaHz is 4.8 mol / l. The yield of high molecular weight copolymer is 65% in 6 hours at

160 ° C.

Claims (1)

DETAILED DESCRIPTION OF THE INVENTION Method for producing polyesters by polymerization or copolymerization of glycolide and lactide in bulk in the presence of a catalyst at 160 ° C, characterized in that, in order to simplify the technology for producing a high molecular weight polymer that does not contain toxic impurities and suitable for the manufacture of high-strength, biodegradable medical devices, the melt of a monomer or a mixture of monomers containing (1-15) x 10 mol / l hydroxy acids, previously incubated with calcium oxide, hydroxide or hydride for 0.5-1, 0 h at molar ratio Ca: COOH - 3.0: 5.0 and 90-130 ° С.